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  • American Society of Hematology  (19)
  • American Association for the Advancement of Science (AAAS)
  • 1
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    Genomic agonism and phenotypic antagonism between estrogen and progesterone receptors in breast cancer (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-06-25
    Description: The functional role of progesterone receptor (PR) and its impact on estrogen signaling in breast cancer remain controversial. In primary ER + (estrogen receptor–positive)/PR + human tumors, we report that PR reprograms estrogen signaling as a genomic agonist and a phenotypic antagonist. In isolation, estrogen and progestin act as genomic agonists by regulating the expression of common target genes in similar directions, but at different levels. Similarly, in isolation, progestin is also a weak phenotypic agonist of estrogen action. However, in the presence of both hormones, progestin behaves as a phenotypic estrogen antagonist. PR remodels nucleosomes to noncompetitively redirect ER genomic binding to distal enhancers enriched for BRCA1 binding motifs and sites that link PR and ER/PR complexes. When both hormones are present, progestin modulates estrogen action, such that responsive transcriptomes, cellular processes, and ER/PR recruitment to genomic sites correlate with those observed with PR alone, but not ER alone. Despite this overall correlation, the transcriptome patterns modulated by dual treatment are sufficiently different from individual treatments, such that antagonism of oncogenic processes is both predicted and observed. Combination therapies using the selective PR modulator/antagonist (SPRM) CDB4124 in combination with tamoxifen elicited 70% cytotoxic tumor regression of T47D tumor xenografts, whereas individual therapies inhibited tumor growth without net regression. Our findings demonstrate that PR redirects ER chromatin binding to antagonize estrogen signaling and that SPRMs can potentiate responses to antiestrogens, suggesting that cotargeting of ER and PR in ER + /PR + breast cancers should be explored.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Supertetrahedral sulfide crystals with giant cavities and channels (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-02-19
    Description: Although aluminosilicates and metal phosphates can form porous open-framework materials such as zeolites, sulfide analogs usually form high-density phases because of the relatively small tetrahedral angle at sulfur atoms. One strategy to overcome this limitation is to use tetrahedral clusters as the building blocks to achieve porous sulfide-based networks. The preparation and crystal structures of two indium sulfide open frameworks (ASU-31 and ASU-32) built of supertetrahedral clusters around organic template and water guests are described. ASU-31, based on the sodalite-tetrahedrite network, contains cavities 25.6 angstroms in diameter, and ASU-32, based on the tetragonal CrB4 network, contains channels with a minimum diameter of 14.7 angstroms. The organic cations can be completely exchanged with sodium ions in aqueous solution at room temperature without degradation of the crystals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li -- Laine -- O'Keeffe -- Yaghi -- New York, N.Y. -- Science. 1999 Feb 19;283(5405):1145-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Supramolecular Design and Discovery Group, Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10024236" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Effects of working-memory training on striatal dopamine release (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-08-06
    Description: Updating of working memory has been associated with striato-frontal brain regions and phasic dopaminergic neurotransmission. We assessed raclopride binding to striatal dopamine (DA) D2 receptors during a letter-updating task and a control condition before and after 5 weeks of updating training. Results showed that updating affected DA activity before training and that training further increased striatal DA release during updating. These findings highlight the pivotal role of transient neural processes associated with D2 receptor activity in working memory.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Backman, Lars -- Nyberg, Lars -- Soveri, Anna -- Johansson, Jarkko -- Andersson, Micael -- Dahlin, Erika -- Neely, Anna S -- Virta, Jere -- Laine, Matti -- Rinne, Juha O -- New York, N.Y. -- Science. 2011 Aug 5;333(6043):718. doi: 10.1126/science.1204978.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Aging Research Center, Karolinska Institute, 171 77 Stockholm, Sweden. lars.backman.1@ki.se〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21817043" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Corpus Striatum/*metabolism/radionuclide imaging ; Dopamine/*metabolism ; Humans ; *Learning ; Male ; *Memory, Short-Term ; Positron-Emission Tomography ; Raclopride/metabolism ; Receptors, Dopamine D2/*metabolism ; Young Adult
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    Disease ecology. Ecological and evolutionary effects of fragmentation on infectious disease dynamics (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-06-14
    Description: Ecological theory predicts that disease incidence increases with increasing density of host networks, yet evolutionary theory suggests that host resistance increases accordingly. To test the combined effects of ecological and evolutionary forces on host-pathogen systems, we analyzed the spatiotemporal dynamics of a plant (Plantago lanceolata)-fungal pathogen (Podosphaera plantaginis)relationship for 12 years in over 4000 host populations. Disease prevalence at the metapopulation level was low, with high annual pathogen extinction rates balanced by frequent (re-)colonizations. Highly connected host populations experienced less pathogen colonization and higher pathogen extinction rates than expected; a laboratory assay confirmed that this phenomenon was caused by higher levels of disease resistance in highly connected host populations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jousimo, Jussi -- Tack, Ayco J M -- Ovaskainen, Otso -- Mononen, Tommi -- Susi, Hanna -- Tollenaere, Charlotte -- Laine, Anna-Liisa -- New York, N.Y. -- Science. 2014 Jun 13;344(6189):1289-93. doi: 10.1126/science.1253621.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Metapopulation Research Group, Department of Biosciences, University of Helsinki, Post Office Box 65 (Viikinkaari 1), FI-00014 University of Helsinki, Helsinki, Finland. ; Metapopulation Research Group, Department of Biosciences, University of Helsinki, Post Office Box 65 (Viikinkaari 1), FI-00014 University of Helsinki, Helsinki, Finland. Department of Biomedical Engineering and Computational Science, Aalto University School of Science, FI-00076 Aalto, Finland. ; Metapopulation Research Group, Department of Biosciences, University of Helsinki, Post Office Box 65 (Viikinkaari 1), FI-00014 University of Helsinki, Helsinki, Finland. anna-liisa.laine@helsinki.fi.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24926021" target="_blank"〉PubMed〈/a〉
    Keywords: Ascomycota/*pathogenicity ; *Biological Evolution ; *Ecological and Environmental Processes ; Extinction, Biological ; *Host-Pathogen Interactions ; Plant Diseases/*microbiology ; Plantago/*microbiology ; Seasons
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    Eicosapentaenoic and Arachidonic Acids from Phytophthora infestans Elicit Fungitoxic Sesquiterpenes in the Potato (1981)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1981-04-03
    Description: Mycelial extracts from Phytophthora infestans caused necrosis and elicited the accumulation of antimicrobial stress metabolites in potato tubers. A portion of the material with elicitor activity could be extracted from the mycelium by a mixture of chloroform and methanol. The most active elicitors of stress metabolites in these extracts were eicosapentaenoic and arachidonic acids. These fatty acids were found in either free or esterified form in all active fractions of the mycelial extracts.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bostock, R M -- Kuc, J A -- Laine, R A -- New York, N.Y. -- Science. 1981 Apr 3;212(4490):67-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17747631" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    Evidence for a malarial parasite interaction site on the major transmembrane protein of the human erythrocyte (1985)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1985-04-05
    Description: Soluble oligosaccharides derived from the surface of human erythrocytes were tested for their ability to competitively inhibit invasion of erythrocytes by Plasmodium falciparum, a malarial parasite. Invasion was most effectively inhibited by erythroglycan, a carbohydrate component of the band 3 transmembrane protein. The lactosamine chains of erythroglycan contributed much of the inhibitory activity. This indication of a primary parasite interaction site on band 3 supports a role for this protein in mediating the radical alterations of the erythrocyte cytoskeleton that accompany invasion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Friedman, M J -- Fukuda, M -- Laine, R A -- New York, N.Y. -- Science. 1985 Apr 5;228(4695):75-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3883494" target="_blank"〉PubMed〈/a〉
    Keywords: Anion Exchange Protein 1, Erythrocyte/*physiology ; Endocytosis ; Erythrocyte Membrane/*parasitology ; Humans ; Malaria/physiopathology ; Membrane Proteins/physiology ; Plasmodium falciparum/*physiology ; Spectrin/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    Recent natural selection causes adaptive evolution of an avian polygenic trait (2017)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2017-10-20
    Description: We used extensive data from a long-term study of great tits ( Parus major ) in the United Kingdom and Netherlands to better understand how genetic signatures of selection translate into variation in fitness and phenotypes. We found that genomic regions under differential selection contained candidate genes for bill morphology and used genetic architecture analyses to confirm that these genes, especially the collagen gene COL4A5 , explained variation in bill length. COL4A5 variation was associated with reproductive success, which, combined with spatiotemporal patterns of bill length, suggested ongoing selection for longer bills in the United Kingdom. Last, bill length and COL4A5 variation were associated with usage of feeders, suggesting that longer bills may have evolved in the United Kingdom as a response to supplementary feeding.
    Keywords: Evolution
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    Evaluation of hMICL As a Marker Associated with Disease Progression in BCR-ABL Negative Myeloproliferative Neoplasms (2012)
    American Society of Hematology
    Details
    Publication Date: 2012-11-16
    Description: Abstract 1724 Introduction: BCR-ABL negative myeloproliferative neoplasms (MPNs) (polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF)) have preponderance to progress to hematopoietic insufficiency with fibrosis and/or blast transformation. This progression is often difficult to detect, but can be preceded by a stage of variable duration commonly termed acceleration, which is not homogeneously defined, but characterized by worsening cytopenias and constitutional symptoms. The monitoration of this process is clearly important, but at the present time biomarkers for this are lacking. We and others have described the human myeloid inhibitory C-type lectin-like receptor (hMICL) (also known as CLL-1) to be a very stable marker for the malignant cells in acute myeloid leukemia (AML), even in CD34- cases (van Rhenen et al. Leukemia 2007, Roug et al. Cytometry 2011). Given the need for new markers in MPN we hypothesized that determining the level of circulating hMICL expressing stem cells could be predictive of disease progression in MPN. Materials and Methods: Peripheral blood (PB) was obtained from 37 PV-, 19 ET-, and 8 PMF patients. A total of 57 (36 PV, 16 ET, and 5 PMF) patients were in stable phase while 7 (1 PV, 3 ET, and 3 PMF) were defined as being in an accelerated phase. Samples were prepared for five-color flow cytometry protocols using the antibodies anti-CD34, anti-CD38, anti-CD45, anti-CD14, and anti-hMICL. Acquisition was performed on a BD FACSCanto II and data analyses were carried out in FlowJo software. We focused on the following subsets: CD45lowSSClowCD14-CD34+hMICL+ and CD45lowSSClowCD14-CD34+CD38-hMICL+. Gates defining hMICL positivity were established on the basis of hMICL- lymphocytes as internal controls. One million cells were analyzed per sample and subsets of interest were calculated as percentage of these. Results: We found a percentage of CD34+hMICL+ (mean 1.176%, SD 0.908) and CD34+CD38-hMICL+ (mean 0.256%, SD 0.329) in PMF patients, which was statistically different from both PV- (mean 0.038%, SD 0.101, and mean 0.005%, SD 0.018, respectively) (p=0.0002 and p
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 9
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    Interleukin-15 Is an Autocrine/Paracrine Viability Factor for Cutaneous T-Cell Lymphoma Cells (1998)
    American Society of Hematology
    Details
    Publication Date: 1998-07-01
    Description: In this study we investigated the role of interleukin-15 (IL-15) in the immunobiology of cutaneous T-cell lymphoma (CTCL) cells. Using cell culture techniques, reverse transcriptase-polymerase chain reaction (RT-PCR), and immunhistochemistry we found that IL-15, like IL-7, is a growth factor for the Sézary cell line SeAx and that both cytokines prolonged the survival of malignant T cells directly isolated from Sézary syndrome (SS) patients. Both IL-15 and IL-7 were more potent than IL-2. IL-4 and IL-9, whose receptors share the same gamma chain with the receptors of IL-2, IL-7, and IL-15, did not sustain the growth of CTCL cells, indicating that signaling through the common gamma chain (γc) is not sufficient for continuous growth. IL-13 and tumor necrosis factor-α (TNF-α) had no effect. IL-7 and IL-15 also supported the growth of SeAx cells in the presence of the apoptosis inducing agents dexamethasone and retinoic acid. The analysis of patient Sézary cells and three CTCL cell lines by RT-PCR showed that all these cells expressed IL-15 mRNA, but only a few (25%) produced IL-7 mRNA. Immunohistological analyses of skin biopsy samples of SS and Mycosis fungoides patients showed immunoreactivity for IL-15 in basal cell layer keratinocytes and in the infiltrating lymphocytes. We conclude that IL-15 is a growth or viability factor for CTCL-derived cell lines or shortly cultivated Sézary cells. The findings that IL-15 mRNA can be detected in Sézary syndrome peripheral blood mononuclear cells and that the IL-15 protein is detected in skin sections from CTCL patients suggest that IL-15 plays an important role in the biology of CTCL.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 10
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    A Prospective Phase II, Open-Label, Single-Arm, Multicenter Study to Assess the Efficacy and Safety of SEG101 (Crizanlizumab) in Sickle Cell Disease Patients with Priapism (SPARTAN) (2019)
    American Society of Hematology
    Details
    Publication Date: 2019-11-13
    Description: Background: Sickle cell disease (SCD) is the most common single-gene disorder in African Americans and can lead to complications, including acute pain and chronic organ damage. Approximately 40% of men with SCD experience priapism, a clinical disorder characterized by prolonged, painful penile erection in the absence of sexual stimulation. Vaso-occlusion-induced ischemia is generally thought to account for SCD-associated priapism. Crizanlizumab, a humanized monoclonal antibody that binds P-selectin and blocks interaction with its ligands (including leukocyte PSGL-1). Crizanlizumab significantly decreased vaso-occlusive crises (VOCs) leading to healthcare visit vs placebo, and was well tolerated in SUSTAIN, a phase 2 study in adults with SCD. This SPARTAN study aims to evaluate the clinical efficacy of intravenous (IV) crizanlizumab 5 mg/kg in reducing priapic events in patients with SCD and a history of priapism utilizing a modern electronic reporting system. Electronic reporting tools have advantages over the paper format in regards to accuracy of and compliance in recording PROs (Stone et al, 2003). The study design and details of PRO collection methods are presented here. Study Design and Methods: This is a Phase 2, multicenter, open-label, single arm study of crizanlizumab in male patients aged ≥16 years with SCD-related priapism. The study will consist of 14 weeks prescreening, 12 weeks screening, and 52 weeks of treatment. The primary endpoint is percent reduction from baseline of priapic events frequency (unwanted/painful erection lasting 〉60 minutes) by 26 weeks. It is expected that crizanlizumab treatment reduces priapic events by ≥ 25% in SCD patients with priapism by 26 weeks. Demonstration of significant percent reduction from baseline in priapic events will be evaluated statistically. Priapic events will be self-reported in real time via a restricted and secure study-issued smart watch and smart phone with a study-specific digital application (app). The patient records the start of a priapic event using a button on the pin code-protected app, which triggers a report in a database, creates a date/time stamp, and records the patient's identification. The patient is then prompted to complete an event reporting survey in one of three ways: using the app on the watch/phone, by a personal call with an operator, or by paper diary. Event reporting surveys will record priapic event occurrences, time and length of events, how the event was relieved, if there was a trigger, and the patient-reported pain at its worst during the event (scale of 0-10). Paper diaries are available as a back-up. Secondary endpoints include safety, as well as the following outcomes at 26 and 52 weeks: rate of priapic events, percent reduction in ≥4-hour erections requiring an ER visit, rate of VOC at 26 and 52 weeks, rate of uncomplicated VOC events, and rate of complicated crises. Approximately 56 patients are planned to be enrolled across 28 sites. Eligible patients must be ≥ 16 years old, have ≥4 events during prescreening, ≥3 during screening with 1 event occurring within 4 weeks prior to first treatment. Patients will be treated with IV crizanlizumab 5 mg/kg on the first day of Week 1, Week 3 (loading dose), Week 7, and then every 4 weeks until final treatment at Week 51. Primary analysis will be conducted after patients receive 26 weeks of treatment. Mandatory safety follow-ups will be conducted until 15 weeks after last dose. Patient feedback was considered and incorporated into the trial design. Results: This Phase 2 study (ClinicalTrials.gov Identifier: NCT03938454) has been successfully designed and approved by the institutional review board. Trial is ongoing. Conclusions: This study, which incorporates electronic PRO collection methods, has been designed to address the unmet treatment need in male patients 〉16 years old with SCD-related priapism. Figure 1. SPARTAN Study Design Disclosures Darbari: Novartis: Membership on an entity's Board of Directors or advisory committees; Hilton Publishing: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Other: one day advisory board meeting . Paulose:Novartis Pharmaceuticals Corporation: Employment. Laine:Novartis: Employment. Purkayastha:Novartis Pharmaceuticals: Employment. Kato:Novartis, Global Blood Therapeutics: Consultancy, Research Funding; Bayer: Research Funding.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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