tbuckley/cabot-search huggingface dataset:
Abstract #2378: ERR\#947;/AP1 signaling drives cholesterol production and Tamoxifen resistance in breast cancer
Authors: Rebecca Riggins, Jennifer Lan, Julie Dunderdale, Alan Zwart, Robert Clarke
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Breast cancer is a heterogeneous disease, with several histologic or molecular subtypes. Two of the major classifications are invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). In comparison to IDC, a significantly greater percentage of ILCs are estrogen receptor alpha-positive (ER+) and progesterone receptor-positive. However it has been suggested that ILC patients with ER+ breast cancer may not experience significantly improved survival following endocrine therapy when compared to IDC patients, and the reason(s) for this are not understood. We have recently published that expression of the orphan nuclear receptor estrogen-related receptor gamma (ERR\#947;) is significantly increased in an ILC-specific cell culture model of Tamoxifen (TAM) resistance, and that ERR\#947; plays a functional role in the resistant phenotype through the activation of AP1. However, the signal transduction networks regulated by ERR\#947;/AP1 in this context remain unknown. One putative target gene of ERR\#947;/AP1 is HMGCS2, a mitochondrial enzyme that generates key precursors for the synthesis of cholesterol, which is important for plasma membrane fluidity and signal transduction. Given that cholesterol-lowering drugs like statins have anti-tumor effects and can inhibit components of the AP1 pathway, we hypothesize that ERR\#947;/AP1 signaling mediates TAM resistance by stimulating cholesterol production via HMGCS2. We have found that LCCTam (resistant) breast cancer cells, which exhibit high levels of ERR\#947; and HMGCS2 expression as well as AP1 activity, contain significantly greater levels of cholesterol than SUM44 (sensitive) breast cancer cells. Importantly, siRNA-mediated knockdown of ERR\#947; in LCCTam cells (which restores TAM sensitivity) decreases HMGCS2 expression and significantly reduces cholesterol content. Preliminary studies also indicate that pharmacological inhibition of AP1 decreases cholesterol content while reducing HMGCS2 expression in LCCTam cells. Together these findings represent an important enhancement in our knowledge of breast cancer biology and endocrine response, and future studies will focus on further elucidating the molecular mechanism(s) of ERR\#947;/AP1 action in TAM resistance.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2378.
<i>EXTL3</i> mutations cause skeletal dysplasia, immune deficiency, and developmental delay
Authors: Stefano Volpi, Yasuhiro Yamazaki, Patrick M. Brauer, Ellen van Rooijen, Atsuko Hayashida, Anne Slavotinek, Hye Sun Kuehn, Maja Di Rocco, Carlo Rivolta, Ileana Bortolomai, Likun Du, Kerstin Felgentreff, Lisa Ott de Bruin, Kazutaka Hayashida, George Freedman, Genni Enza Marcovecchio, Kelly Capuder, Prisni Rath, Nicole Luche, Elliott J. Hagedorn, Antonella Buoncompagni, Beryl Royer-Bertrand, Silvia Giliani, Pietro Luigi Poliani, Luisa Imberti, Kerry Dobbs, Fabienne E. Poulain, Alberto Martini, John Manis, Robert J. Linhardt, Marita Bosticardo, Sergio Damian Rosenzweig, Hane Lee, Jennifer M. Puck, Juan Carlos Zúñiga-Pflücker, Leonard Zon, Pyong Woo Park, Andrea Superti-Furga, Luigi D. Notarangelo
Journal: The Journal of Experimental Medicine (2017)

We studied three patients with severe skeletal dysplasia, T cell immunodeficiency, and developmental delay. Whole-exome sequencing revealed homozygous missense mutations affecting exostosin-like 3 (EXTL3), a glycosyltransferase involved in heparan sulfate (HS) biosynthesis. Patient-derived fibroblasts showed abnormal HS composition and altered fibroblast growth factor 2 signaling, which was rescued by overexpression of wild-type EXTL3 cDNA. Interleukin-2–mediated STAT5 phosphorylation in patients’ lymphocytes was markedly reduced. Interbreeding of the extl3-mutant zebrafish (box) with Tg(rag2:green fluorescent protein) transgenic zebrafish revealed defective thymopoiesis, which was rescued by injection of wild-type human EXTL3 RNA. Targeted differentiation of patient-derived induced pluripotent stem cells showed a reduced expansion of lymphohematopoietic progenitor cells and defects of thymic epithelial progenitor cell differentiation. These data identify EXTL3 mutations as a novel cause of severe immune deficiency with skeletal dysplasia and developmental delay and underline a crucial role of HS in thymopoiesis and skeletal and brain development.
Co-Existing Gene Mutations at Diagnosis and at Relapse in De Novo Acute Myeloid Leukemia with MLL Translocations
Authors: Der-Cherng Liang, Lee-Yung Shih, Ming-Chung Kuo, Chao-Ping Yang, Hsi-Che Liu, Tang-Her Jaing, Jen-Fen Fu, Yu-Shu Shih, Tung-Huei Lin
Journal: Blood (2014)
Bortezomib and Methotrexate Interfere with the DNA Repair Signaling Transduction Pathways and Induce Apoptosis in Cutaneous T-Cell Lymphoma
Authors: Vassiliki Mpakou, Evangelia Papadavid, Evi Konsta, Vikentiou Murofora, Frieda Kontsioti, Sotiris Papageorgiou, Dikea-Eleni Ioannidou, Eleni Bazani, Christina Economopoulou, Diamantina Vasilatou, Maria Atta, Nikos Papanikolaou, Christoforos Roubakis, Panagiotis Tsirigotis, Christina Antoniou, Dimitris Rigopoulos, George Dimitriadis, Vassiliki Pappa
Journal: Blood (2014)
Disruption of Reward Processing in Addiction
Authors: Maartje Luijten, Arnt F. Schellekens, Simone Kühn, Marise W. J. Machielse, Guillaume Sescousse
Journal: JAMA Psychiatry (2017)

Disrupted reward processing, mainly driven by striatal dysfunction, is a key characteristic of addictive behaviors. However, functional magnetic resonance imaging (fMRI) studies have reported conflicting results, with both hypoactivations and hyperactivations during anticipation and outcome notification of monetary rewards in addiction.To determine the nature and direction of reward-processing disruptions during anticipation and outcome notification of monetary rewards in individuals with addiction using image-based meta-analyses of fMRI studies.Relevant publications were identified searching PubMed (inclusion until March 2015) using the following terms: reward, fMRI, substance use, cocaine, cannabis, opiates, alcohol, nicotine, smokers, gambling, gamblers, gaming, and gamers. Authors of included articles were contacted to obtain statistical fMRI maps.Inclusion criteria: reward task involving monetary reward anticipation and/or outcome; participants showing addictive behaviors; and healthy control group. Exclusion criteria: participants aged younger than 18 years; recreational substance use or gambling; participants at risk for addictive behaviors; and studies using the same patient data as other included studies.Study procedures were conducted in accordance with the Meta-analysis of Observational Studies in Epidemiology guidelines. Using Seed-based d Mapping software, meta-analyses were performed using random-effect nonparametric statistics with group whole brain T-maps from individual studies as input. Analyses were performed across all addictions and for substance and gambling addictions separately.Group differences (individuals with addiction vs control individuals) in reward-related brain activation during reward anticipation and outcome using fMRI (planned before data collection).Twenty-five studies were included in the meta-analysis, representing 643 individuals with addictive behaviors and 609 healthy control individuals. During reward anticipation, individuals with substance and gambling addictions showed decreased striatal activation compared with healthy control individuals. During reward outcome, individuals with substance addiction showed increased activation in the ventral striatum, whereas individuals with gambling addiction showed decreased activation in the dorsal striatum compared with healthy control individuals.Striatal hypoactivation in individuals with addiction during reward anticipation and in individuals with gambling addiction during reward outcome is in line with the reward-deficiency theory of addiction. However, the combination of hypoactivation during reward anticipation and hyperactivation during reward outcome in the striatum of individuals with substance addiction may be explained using learning-deficit theory.
METB-07CLASSIFICATION OF HIGH GRADE GLIOMA USING MATRIX-ASSISTED LASER DESORPTION/IONIZATION MASS SPECTROMETRY IMAGING (MALDI MSI): INTERIM RESULTS OF THE GLIOMIC STUDY
Authors: Emilie Le Rhun, Marie Duhamel, Maxence Wisztorski, Fahed Zairi, Claude Alain Maurage, Isabelle Fournier, Nicolas Reyns, Michel Salzet
Journal: Neuro-Oncology (2015)

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) allows to determine spatial localization of molecules along tissue sections. The aim of the Gliomic study is to classify high-grade gliomas (HGG) by MALDI-MSI according to their prognosis. Until now, samples from 13 patients have been analyzed after tumor resection. According to the OMS 2007 classification, 3 tumors were grade 3 (2 oligoastrocytoma and 1 astrocytoma) and 10 were grade 4. An isocitrate dehydrogenase 1 (IDH1) mutation was found in 31% of the cases, a O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation in 20% (median value: 5%, range 2-93%). Frozen tissue sections of 12 µm thickness were realized and matrix was then deposited homogeneously with a manual sprayer to cover the entire surface. Tissues were prepared for analysis of low-weighted molecules, particularly lipids. Tumor-specific mass spectra were acquired with 70 µm spatial resolution. After molecular image acquisition, matrix was removed, tissues were stained and annotated by a pathologist. The imaging datasets were spatially segmented by clustering all spectra by their molecular profiles similarity. Individual tissue segmentations were compared with histological annotations and revealed new regions of interest. A low concordance between the histological annotations and the MS imaging data was found for tumor regions. Global segmentations were generated using all the tissues and revealed 3 molecularly different groups. Known low infiltrated regions and necrotic regions were still grouped together respectively after this global segmentation. Pre-necrotic regions were divided between necrotic and tumor regions. Moreover, we highlighted sub-regions within the tumor area which were not histologically annotated. This analysis provided new insights into HGG tissue organization. The data obtained from MALDI MSI analysis may provide specific information and allow a more accurate diagnosis. A total of 21 patients have been enrolled and updated results will be presented taking account histological and molecular biology data.
Effect of Reverse Triage on Creation of Surge Capacity in a Pediatric Hospital
Authors: Gabor D. Kelen, Ruben Troncoso, Joshua Trebach, Scott Levin, Gai Cole, Caitlin M. Delaney, J. Lee Jenkins, James Fackler, Lauren Sauer
Journal: JAMA Pediatrics (2017)

The capacity of pediatric hospitals to provide treatment to large numbers of patients during a large-scale disaster remains a concern. Hospitals are expected to function independently for as long as 96 hours. Reverse triage (early discharge), a strategy that creates surge bed capacity while conserving resources, has been modeled for adults but not pediatric patients.To estimate the potential of reverse triage for surge capacity in an academic pediatric hospital.In this retrospective cohort study, a blocked, randomized sampling scheme was used including inpatients from 7 units during 196 mock disaster days distributed across the 1-year period from December 21, 2012, through December 20, 2013. Patients not requiring any critical interventions for 4 successive days were considered to be suitable for low-risk immediate reverse triage. Data were analyzed from November 1, 2014, through November 21, 2016.Proportionate contribution of reverse triage to the creation of surge capacity measured as a percentage of beds newly available in each unit and in aggregate.Of 3996 inpatients, 501 were sampled (268 boys [53.5%] and 233 girls [46.5%]; mean [SD] age, 7.8 [6.6] years), with 10.8% eligible for immediate low-risk reverse triage and 13.2% for discharge by 96 hours. The psychiatry unit had the most patients eligible for immediate reverse triage (72.7%; 95% CI, 59.6%-85.9%), accounting for more than half of the reverse triage effect. The oncology (1.3%; 95% CI, 0.0%-3.9%) and pediatric intensive care (0%) units had the least effect. Gross surge capacity using all strategies (routine patient discharges, full use of staffed and unstaffed licensed beds, and cancellation of elective and transfer admissions) was estimated at 57.7% (95% CI, 38.2%-80.2%) within 24 hours and 84.1% (95% CI, 63.9%-100%) by day 4. Net surge capacity, estimated by adjusting for routine emergency department admissions, was about 50% (range, 49.1%-52.6%) throughout the 96-hour period. By accepting higher-risk patients only (considering only major critical interventions as limiting), reverse triage would increase surge capacity by nearly 50%.Our estimates indicate considerable potential pediatric surge capacity by using combined strategic initiatives. Reverse triage adds a meaningful but modest contribution and may depend on psychiatric space. Large volumes of pediatric patients discharged early to the community during disasters could challenge pediatricians owing to the close follow-up likely to be required.
Prognosis of Patients with Primary Central Nervous System Post-Transplant Lymphoproliferative Disorder (PTLD-CNS) Treated with Immunossupression Reduction, Intrathecal Chemotherapy and Whole-Brain Radiotherapy: An Analysis of 23 Patients in a Brazilian Cohort
Authors: Guilherme Fleury Perini, Joao Garibaldi Junior, Adriana M. Damasco Penna, Marina P Cristelli, Adriana Bruscato, Egyla M Cavalcanti, Jose Osmar Medina Pestana, Gisele W. B. Colleoni, Jose Pedro Zampieri Filho, Rodrigo Vaez, Otavio C. G. Baiocchi, Jose Orlando Bordin
Journal: Blood (2015)
The Y-Specific Gene PRY Is Expressed in Normal Blood Cells as Well as Leukemia Cells and Can Elicit a Specific Antibody Response in Male Recipients of Hematopoietic Stem Cells from Female Donors.
Authors: Emmanuel Zorn, Blair Floyd, Andrew Tweel, David B. Miklos, Roberto Bellucci, Christine Canning, Robert J. Soiffer, Joseph Antin, Jerome Ritz
Journal: Blood (2004)
Anticoagulation Therapy for Venous Thrombotic Events in Patients with Myeloproliferative Neoplasms
Authors: Noa Lavi, Maya Koren-Michowitz, Avi Leader, Adi Shacham-Abulafia, Shirley Shapira, Najib Dally, Evgeni Chubar, Elena Mishchenko, Martin H. Ellis
Journal: Blood (2015)
Nanoparticular delivery system for a secretoneurin derivative induces angiogenesis in a hind limb ischemia model
Authors: Karin Albrecht-Schgoer, Jan Barthelmes, Wilfried Schgoer, Markus Theurl, Isabelle Nardin, Daniela Lener, Clemens Gutmann, Sarah Dünnhaupt, Andreas Bernkop-Schnürch, Rudolf Kirchmair
Journal: Journal of Controlled Release (2017)
Ultrasociality, class, threat, and intentionality in human society
Authors: Roger A McCain
Journal: Behavioral and Brain Sciences (2016)

Gowdy & Krall neglect an important aspect of human societies, which is that class systems are not genetically based but rather based on threat. In turn, threat presupposes intentionality, so seems to distinguish human from arthropod ultrasociality. Class systems, in turn, seem to explain the distinctive mixture of persistence and instability characteristic of human, but not arthropod, ultrasocial populations.
Perception, cognition, and delusion
Authors: Robert M. Ross, Ryan McKay, Max Coltheart, Robyn Langdon
Journal: Behavioral and Brain Sciences (2016)

Firestone & Scholl's (F&S) critique of putative empirical evidence for the cognitive penetrability of perception focuses on studies of neurologically normal populations. We suggest that a comprehensive exploration of the cognition-perception relationship also incorporate work on abnormal perception and cognition. We highlight the prominence of these issues in contemporary debates about the formation and maintenance of delusions.
Increased Osteocyte Apoptosis in Multiple Myeloma Patients: A Potential Role in Bone Remodeling Alterations Related to Osteolytic Bone Lesions.
Authors: Nicola Giuliani, Marzia Ferretti, Manuela Abeltino, Cristina Mancini, Eugenia Martella, Benedetta Dalla Palma, Marina Bolzoni, Valentina Sgobba, Paola Storti, Vittorio Rizzoli, Carla Palumbo
Journal: Blood (2009)
131I-Anti-CD45 Antibody Plus Busulfan/Cyclophosphamide in Matched Related Transplants for Acute Myeloid Leukemia in First Remission.
Authors: John M. Pagel, Frederick R. Appelbaum, Janet F. Eary, Joseph G. Rajendran, Darrell R. Fisher, Ted Gooley, Eneida Nemecek, Katherine Ruffner, Eileen Sickle, Larry Durack, Jeanette Carreras, Mary M. Horowitz, Ajay K. Gopal, Oliver W. Press, Paul J. Martin, Irwin D. Bernstein, Dana C. Matthews
Journal: Blood (2004)
Imatinib Followed by Reduced Intensity Stem Cell Transplantation and Donor Lymphocyte Infusions Is Effective in Chronic Phase CML with Less Toxicity Than Standard Allogeneic Transplantation.
Authors: Mhairi Copland, Nicholas Heaney, Karen Stewart, Judith Godden, Graeme Smith, Charles Crawley, Tessa L. Holyoake
Journal: Blood (2005)
CBIO-29TARGETING A Plk1-CONTROLLED POLARITY CHECKPOINT IN GLIOBLASTOMA MULTIFORME
Authors: Banafsheh Kadhkodaei, Robin Lerner, Stefan Grossauer, Katharina Koeck, Ian Meyers, C. David James, Claudia Petritsch
Journal: Neuro-Oncology (2015)

Stem-like glioma cells, frequently referred to as tumor-propagating cells or cancer stem cells are culprits for recurrence due to their intrinsic resistance to standard therapy and their ability to regrow the parental tumor in xenografts. Similar to normal neural stem cells CD133+ tumor-propagating cells undergo asymmetric, self-sustaining cell divisions (Gomez-Lopez S. et al, Cell Mol Life Sci, 2014, 71(4):575-97). Cancer-associated changes in cell division mode contribute to neoplastic transformation of glioma precursors (Sugiarto S. et al, Cancer Cell, 2011 20(3):328-40). While increased symmetric, self-renewing divisions of glioma precursors correlate with therapy sensitivity, asymmetric self-sustaining divisions potentially maintain the pool of tumor-propagating cells and contribute to therapy evasion. How pharmacological MAPK pathway inhibitors clinically evaluated for the treatment of GBM affect the division mode of tumor-propagating cells is unknown. We investigate CD133+ tumor-propagating cell responses to novel targeted therapies, in specifically, small molecule inhibitors of BRAFV600E, a mutant kinase frequently found in pediatric malignant astrocytoma. Our investigations showed that CD133+ tumor-propagating cells have higher asymmetric divisions than progenitor-like glioma cells. CD133+ stem-like GBM subpopulation exhibit decreased sensitivity to the anti-proliferative effects of MAPK pathway inhibition and show extended G2/M phase. We find that the mitotic checkpoint kinase and polarity regulator Plk1 is more active in CD133+ tumor-propagating cells. Plk1 activity links asymmetric division and mitotic entry. In an orthotopic GBM xenograft model, combined MAPK-pathway and PLK1 inhibition showed increased anti-proliferative effects and cell death frequency towards CD133+ cells beyond that achieved by either inhibitor alone. Ongoing work is investigating if Plk1 controls a polarity checkpoint, the integrity of which is especially important in the therapy–evasive compartment in GBM and that provides a rationale for combination therapy.
Risk-Adapted Intravenous Melphalan Followed by Adjuvant Dexamethasone (D) and Thalidomide (T) for Newly Diagnosed Patients with Systemic AL Amyloidosis (AL): Interim Results of a Phase II Study.
Authors: Adam D. Cohen, Ping Zhou, Lillian Reich, Alice Quinn, Sophia Fircanis, Lisa Drake, Cyrus Hedvat, Julie Teruya-Feldstein, Daniel A. Filippa, Martin Fleisher, Raymond L. Comenzo
Journal: Blood (2004)
Equivalence of BCR-ABL Transcript Levels &lt;1% According to the International Scale with Complete Cytogenetic Response in Chronic Phase CML Patients.
Authors: Michael Lauseker, Benjamin Hanfstein, Claudia Haferlach, Susanne Schnittger, Markus Pfirrmann, Alice Fabarius, Brigitte Schlegelberger, Susanne Saussele, Philipp Erben, Rüdiger Hehlmann, Joerg Hasford, Andreas Hochhaus, Martin C Müller
Journal: Blood (2012)
The likelihood of death from prostate cancer in men with favorable or unfavorable intermediate-risk disease.
Authors: Florence K. Keane, Ming-Hui Chen, Danjie Zhang, Marian J. Loffredo, Philip W. Kantoff, Andrew A. Renshaw, Anthony Victor D'Amico
Journal: Journal of Clinical Oncology (2014)

42 Background: Recently men with intermediate-risk prostate cancer (PC) were classified into favorable and unfavorable categories but whether the risk of PC-specific mortality (PCSM) amongst men with high-risk PC is higher compared to men with unfavorable intermediate-risk PC is unknown. Methods: In a prospective randomized trial conducted between 1995 and 2001, 206 men with intermediate or high-risk PC were randomized to 70 Gy with or without six months of androgen suppression therapy (AST). The subgroup of 197 patients with available information on percent positive biopsies formed the study cohort. Fine and Gray’s regression was used to assess whether men with high-risk PC had a significantly higher risk of PCSM compared to men with unfavorable intermediate-risk PC, adjusting for age, treatment, and comorbidity category. Results: After a median follow-up of 14.3 years there were 127 deaths (64.5%), of which 22 (17.3%) were from PC. There were no PC deaths in the favorable intermediate-risk group. There was no significant increase in the risk of PCSM in men with high-risk compared to unfavorable intermediate-risk PC (Adjusted Hazard Ratio: 1.59; 95% Confidence Interval: 0.66 to 3.83; P= 0.30) after adjusting for age, randomized treatment arm and comorbidity. Conclusions: Given no significant difference in the risk of PCSM in unfavorable intermediate compared with high-risk PC, these patients may merit treatment with RT and long-term AST. The lack of PC deaths in the favorable intermediate-risk group suggests that adding AST may not reduce the risk of PCSM in these patients. [Table: see text]
Elevated Cyclin D1 (CCND1) Expression in the Plasma Cells of Patients with Systemic AL Amyloidosis at Diagnosis Is Associated with Higher Brain Natriuretic Peptide (BNP) Levels, Increased Plasma Cells and Significantly Poorer Survival.
Authors: Ping Zhou, James E Hoffman, Hani Hassoun, Heather Landau, Raymond L Comenzo
Journal: Blood (2009)
HHV6-Associated Limbic Encephalitis after Reduced-Intensity Umbilical Cord Blood Transplantation.
Authors: Kazuya Ishiwata, Hisashi Yamamoto, Shinsuke Takagi, Masanori Tsuji, Daisuke Kato, Hideki Araoka, Mayumi Yoshimi, Madoka Narita, Kimiko Sagawa, Naofumi Matsuno, Naoyuki Uchida, Kazuhiro Masuoka, Atsushi Wake, Akiko Yoneyama, Shigeyoshi Makino, Shuichi Taniguchi
Journal: Blood (2008)