tbuckley/cabot-search huggingface dataset:
Abstract A39: Sall2 tumor suppressor protein is a novel Casein Kinase 2 target
Authors: Viviana Hermosilla, Adam Rabalski, Laszlo Gyenis, David W. Litchfield, Roxana Pincheira
Journal: Cancer Research (2016)

Abstract Sall2 is a transcription factor with critical roles during development, including neurogenesis and eye formation. Importantly, Sall2 has also been associated with cancer, although its contribution to the disease remains controversial. Sall2 is down-regulated in several tumor types and its activity promotes cell cycle arrest and cell death. Despite its role as a tumor suppressor, little is known about its regulation. In order to identify regulatory mechanisms of Sall2 protein, bioinformatic analysis were performed. Preliminary data lead to the identification of several putative phosphorylation sites within a potential and highly conserved PEST motif. All of these sites match the consensus sequence for Casein Kinase 2 (CK2)-mediated phosphorylation. CK2 is a ubiquitous and constitutively active kinase whose activity is increased in cancer cells. CK2 promotes both cell survival and proliferation by regulating stability, activity and/or subcellular localization of its target proteins, including tumor suppressors. With the aim of determining whether Sall2 is regulated by CK2, several approaches such as pharmacological inhibition of CK2, mass spectrometry analysis, immunofluorescence, immunoprecipitation, in vitro kinase assays and site directed mutagenesis were used. Our results indicate that Sall2 is a CK2 target in vitro. In cells, CK2 interacts with Sall2 and triggers the ubiquitination and subsequent degradation of Sall2 in a proteasome-mediated fashion. Moreover, phosphorylation of Sall2 at S763 and T778 was greatly reduced under CK2 inhibition, suggesting that these are the most important CK2-dependent phospho-sites in vivo. In conclusion, we have identified Sall2 as a new CK2 target. Our results support a novel regulatory mechanism for Sall2 degradation and provide new insights into the means by which CK2 promotes cell survival and proliferation, two characteristic requirements of cancer cells. FUNDING: FONDECYT1151031, CIHR Citation Format: Viviana Hermosilla, Adam Rabalski, Laszlo Gyenis, David W. Litchfield, Roxana Pincheira. Sall2 tumor suppressor protein is a novel Casein Kinase 2 target. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr A39.
Lying Low
Authors: John J. Ross, Anand Vaidya, Ursula B. Kaiser
Journal: New England Journal of Medicine (2011)

An 88-year-old woman presented to the emergency room with confusion. She began having transient episodes of confusion, dizziness, tremors, and anxiety a year earlier. These episodes were unpredictable, lasting for minutes and then abating spontaneously, and had been increasing in frequency since they began. The patient felt well between episodes and reported no abnormal sensation . . .
Splicing Factor 3b Subunit 1 (SF3B1) mediates Mitochondrial Iron Overload In Myelodysplastic Syndromes With Ring Sideroblasts By Alternative Splicing Of Mitoferrin-1 (SLC25A37)
Authors: Valeria Visconte, Reda Z Mahfouz, John Barnard, Ali Tabarroki, Li Zhang, Edy Hasrouni, Heesun J. Rogers, Nanthawan Avishai, Jonathan Cowen, Reza Sharghi-Moshtaghin, Midori Hitomi, Daniel Lindner, Arthur Heuer, Alan E. Lichtin, Anjali S. Advani, Eitan Fibach, Eliezer A. Rachmilewitz, Matt Kalaycio, Mikkael A. Sekeres, Yogen Saunthararajah, Ramon V. Tiu
Journal: Blood (2013)
Imipramine treatment of borderline children: case reports with a controlled study
Authors: T A Petti, A Unis
Journal: American Journal of Psychiatry (1981)

The authors discuss the borderline syndrome of childhood, review the pertinent literature, and present three case histories demonstrating the salient features of the clinical syndrome. Each patient failed to benefit from intensive hospital treatment until imipramine (5 mg/kg/day) was added to the treatment regimen. One child was treated in a double-blind, imipramine-placebo crossover protocol. Substantial improvement with imipramine was demonstrated in adaptive peer interactions, compliance, and bizarre behaviors. This strongly supports consideration of imipramine a part of the intensive inpatient treatment of the borderline syndrome in children.
Structure of C-Type Virus Particles in Lymphocyte Cultures of Bovine Origin2
Authors: Jero Calafat, Philomena C. Hageman, A. A. Ressang
Journal: JNCI Journal of the National Cancer Institute (1974)

Virus particles, primarily extracellular, were observed in 14 of 15 lymphocyte cultures from cows with hyperlymphocytosis. A detailed morphologic study was done on these particles after different fixations and negative staining with phosphotungstic acid. After glutaraldehyde and osmium fixation, the virion was roughly spherical (diameter ≈ 103 nm) and enclosed in an envelope that sometimes had a high electron density and quite often had surface projections. A core with a diameter of 40–90 nm was central and often separated from the intermediate membrane by a translucent space. After fixation with osmium or osmium followed by uranyl acetate treatment during dehydration, the intermediate membrane was not visible and the outline of the nucleoid was fuzzy. After negative staining, the clear surface projections were ≈ 114 Å long. Two morphologic features showed that the maturation of this virus particle differed from that described for the C-type particles: We found 1) particles with an electron-dense, central nucleoid (like mature C-type) still attached to the cell membrane and 2) no immature C-type particles. This suggests that the bovine particle matured when still attached to the cell membrane.
Doctors, drug companies, and gifts
Authors: M M Chren, C S Landefeld
Journal: JAMA (1990)

This paper by Chren and Landefeld was originally presented at the Miriam Hospital on March 21, 1991, as the 1991 Lichtman Oration, an annual meeting devoted to ethical problems in medicine honoring Herbert C. Lichtman, MD, former physician-in-chief at the hospital. Because of the importance of this paper, and its controversial character, the Journal has asked a number of practicing physicians and other concerned persons to offer their opinions on this paper. These commentaries will then be published in a subsequent issue of the Journal, along with reactions by our readers.
Diagnosing schizophrenia in 1982: the effect of DSM-III
Authors: M H Lipkowitz, S Idupuganti
Journal: American Journal of Psychiatry (1985)

In 1982, 2 years after the introduction of DSM-III, the authors sent questionnaires to 1,313 psychiatrists in the United States asking what criteria they used to diagnose schizophrenia. They received responses from 341 and compared these with responses of 301 psychiatrists to the same question in October 1980, 3 months after the introduction of DSM-III. The results indicate that DSM-III did not have a major effect on the diagnostic practices of psychiatrists from 1980 to 1982. A high number of psychiatrists continued to approach the diagnosis of schizophrenia in an individualistic, unsystematic way.
Abstract P1-03-02: Estrogens contribute to cytokine upregulation and cancer stem cell recruitment upon breast cancer contact with mature human mammary adipocytes: Effects of estrogen type and adipocyte donor weight
Authors: J Slingerland, M Picon-Ruiz, K Jang, C Morata-Tarifa, C Pan, A Besser, M Kim, TA Ince, GA Howard, D El-Ashry
Journal: Cancer Research (2016)

Abstract Consequences of the obesity epidemic on cancer morbidity and mortality are not fully appreciated. While obesity confers increased cancer risk and worse outcome, mechanisms thereof are not fully known. We show prolonged co-culture of fat cells (human adipocyte stem cells, differentiated adipocytes or mature adipocytes) from breast tissue together with breast cancer lines or cultured primary dissociated human breast tumor cells increases secretion of six different pro-inflammatory cytokines, each of which contributes to tumor progression through cancer stem cell recruitment. Prolonged exposure to fat cells or to each cytokine increases the proportion of cells that form mammosphere and express ALDH1 activity in vitro and that can initiate primary orthotopic tumors and metastasis in vivo. Adipocyte and cytokine exposures activate Src, and Src family kinase activity leads to induction of embryonic transcription factors that upregulate miR302b. miR302b induction is Sox2-dependent, promotes cytokine-driven sphere formation, and in turn, stimulates cMYC and SOX2 expression. Src is not only activated by adipocyte or cytokine exposures, it is also required to sustain cytokine induction, since Src inhibitors decrease cytokine production after co-culture. Cytokine upregulation was much greater after co-culture of ER+ breast cancer cells with mature, aromatase positive, adipocytes than with adipocyte stem cells. Cytokine induction was estrogen regulated. The mechanisms of cytokine induction, ER-coactivation and effects of different estrogenic ligands will be presented. Present data illuminate the increased risk of breast cancer after menopause, particularly in obese women and the increased breast cancer mortality with obesity: cancer cell invasion into local fat, in the presence of high local aromatase and intracellular estrogen would establish feed-forward loops to activate Src, maintain pro-inflammatory cytokine production and increase tumor initiating cell abundance, tumor growth and metastasis. These data link obesity related pro-inflammatory cytokines to Src activation and cancer initiating cell abundance, and provide a novel rationale for Src inhibitors together with endocrine therapy for breast cancer. Citation Format: Slingerland J, Picon-Ruiz M, Jang K, Morata-Tarifa C, Pan C, Besser A, Kim M, Ince TA, Howard GA, El-Ashry D. Estrogens contribute to cytokine upregulation and cancer stem cell recruitment upon breast cancer contact with mature human mammary adipocytes: Effects of estrogen type and adipocyte donor weight. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-03-02.
Prediction of response to haloperidol dose reduction by Span of Apprehension measures for treatment-refractory schizophrenic patients
Authors: M F Green, J Mintz, L Bowen, B D Marshall, T G Kuehnel, J L Hayden, R P Liberman
Journal: American Journal of Psychiatry (1993)

Thirteen treatment-refractory schizophrenic patients participated in a haloperidol reduction study. Two of the subjects were unable to tolerate medication reduction. These subjects were comparable to the other patients in terms of initial clinical variables but were outliers on baseline accuracy and reaction time measures from the Span of Apprehension. The results suggest that aspects of basic visual processing and motor response speed may identify patients who require higher neuroleptic doses.
Progress in inflammatory breast cancer: cause for cautious optimism.
Authors: G N Hortobagyi, A U Buzdar
Journal: Journal of Clinical Oncology (1986)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1986.4.12.1727 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3783199 Progress in inflammatory breast cancer: cause for cautious optimism. G N HortobagyixG N HortobagyiSearch for articles by this author , A U BuzdarxA U BuzdarSearch for articles by this author https://doi.org/10.1200/JCO.1986.4.12.1727 First Page PDF © 1986 by American Society of Clinical Oncology
Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study
Authors: Robin L Carhart-Harris, Mark Bolstridge, James Rucker, Camilla M J Day, David Erritzoe, Mendel Kaelen, Michael Bloomfield, James A Rickard, Ben Forbes, Amanda Feilding, David Taylor, Steve Pilling, Valerie H Curran, David J Nutt
Journal: The Lancet Psychiatry (2016)

Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression.In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797.Psilocybin's acute psychedelic effects typically became detectable 30-60 min after dosing, peaked 2-3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0-1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1 week (mean QIDS difference -11·8, 95% CI -9·15 to -14·35, p=0·002, Hedges' g=3·1) and 3 months (-9·2, 95% CI -5·69 to -12·71, p=0·003, Hedges' g=2) after high-dose treatment. Marked and sustained improvements in anxiety and anhedonia were also noted.This study provides preliminary support for the safety and efficacy of psilocybin for treatment-resistant depression and motivates further trials, with more rigorous designs, to better examine the therapeutic potential of this approach.Medical Research Council.
Investigational Therapies for Metastatic Thyroid Carcinoma
Authors: R. Michael Tuttle, R. Leboeuf
Journal: Journal of the National Comprehensive Cancer Network (2007)

Although traditional chemotherapy has yielded disappointing results in the therapy of progressive metastatic thyroid cancer, the recent development of a wide range of novel therapies targeting critical steps in the pathogenesis of thyroid cancer has led to a renewed interest in thyroid cancer clinical trials. This review provides an overview of the pathogenesis of thyroid cancer with particular emphasis on specific molecular targets that can be modulated with these novel agents. The article reviews the results for the small number of thyroid cancer patients included in published therapeutic trials and critically examines patient selection criteria for inclusion in clinical trials. Given the dramatic increase in availability of thyroid cancer clinical trials, all patients with radioactive iodine-refractory, progressive metastatic thyroid cancer should be considered for inclusion in a novel therapy trial.
Abstract A10: LncRNA MIR222HG transcribed from the miR-221/222 promoter are associated with the development of castration resistant prostate cancer
Authors: Fangfang Qu, Tong Sun, Xiaodong Wang, Gwo-Shu Mary Lee, Philip W. Kantoff
Journal: Cancer Research (2016)

Abstract We previously found that microRNA-221 and 222 play a crucial role in regulating the AR function during the castration resistant prostate cancer (CRPC) development. We further investigated mechanisms involved in the differential expression of miR-221/222 in prostate cancer cell lines. Based on transcriptome and histone modification data, we recognized a putative promoter region located at 23.3 kb upstream of the miR-221/222. By further characterizing transcriptional events occurred in this promoter region, we identified a two- exonic, polyadenylated long non-coding RNA (lncRNA), MIR222HG. Forced over-expression MIR222HG significantly increased androgen-independent cell growth and repressed DHT induced PSA expression in LNCaP cells, a hallmark of CRPC phenotype. Expression level of MIR222HG is significantly associated with human prostate cancer progression from localized hormone sensitive prostate cancer (HSPC) to CRPC. Taken together, lncRNA MIR222HG, which is co-transcribed from miR-221/222 promoter region, mediated AR transcriptional regulation and may involved in transformation process from HSPC to CRPC. Further study on MIR222HG may help understand the CRPC development processes. Citation Format: Fangfang Qu, Tong Sun, Xiaodong Wang, Gwo-Shu Mary Lee, Philip W. Kantoff. LncRNA MIR222HG transcribed from the miR-221/222 promoter are associated with the development of castration resistant prostate cancer. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr A10.
Abstract PR02: Transcriptional regulation mediated by biochemically distinct forms of SWI/SNF
Authors: Jesse R. Raab, Samuel Resnick, Terry Magnuson
Journal: Cancer Research (2016)

Abstract Background: We often consider the SWI/SNF complex as a single entity with a single function in a particular cell type. This model ignores that multiple positions within the SWI/SNF chromatin remodeling complex can be filled by mutually exclusive subunits. Inclusion or exclusion of such subunits gives rise to an array of biochemically distinct chromatin remodeling complexes, some of which have profound functional consequences on gene regulation and differentiation. Here, we examine the functional relationships among three complex-specific ARID (AT-Rich Interacting Domain) subunits of the SWI/SNF complex in a human hepatocellular carcinoma cell line using ChIP-seq, RNA-seq, and public data on transcription factor binding. Results: Using RNAi directed at each of the three subunits, we identify widespread overlap in transcriptional regulation mediated by SWI/SNF. The ARID subunits are commonly bound together at the promoters of active genes, with more variable binding associated with distal regulatory elements. ARID1B and ARID2 cooperate to repress the expression of hundreds of genes. Additionally, we identify many examples of competitive interactions between ARID1A and ARID1B or ARID2, and show that gene expression changes following loss of one ARID are dependent on the function of an alternative ARID. These distinct regulatory modalities are correlated with differential occupancy by transcription factors. Together these data suggest distinct SWI/SNF complexes dictate gene-specific transcription through interactions between different forms of SWI/SNF and specific co-factors. The ARID subunits are among the most frequently mutated chromatin regulators in cancer. Understanding the functional relationship between distinct forms of the complex is a necessary first step for identifying their potentially unique roles in oncogenesis. Citation Format: Jesse R. Raab, Samuel Resnick, Terry Magnuson. Transcriptional regulation mediated by biochemically distinct forms of SWI/SNF. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr PR02.
To the Editors:
Authors: C. D. Hingston, T. W. Holmes, A. G. Saayman, M. P. Wise
Journal: European Respiratory Journal (2011)

We read with interest the recent report by KORNUM et al. [1] investigating the link between community-acquired pneumonia and obesity in a large cohort of Danish patients.The authors observed that the increased risk of pulmonary infection no longer existed for obesity when other major chronic diseases were included in the regression model.Cohort studies that describe comorbid associations become more meaningful when one can assign an underlying pathophysiological process.In this context, we would suggest that there are a number of plausible mechanisms that are confounders with obesity.Insulin resistance and hyperglycaemia are more prevalent amongst obese individuals.Airway surface fluid glucose is normally strictly maintained at low levels, which may be as much as 20 times lower than that of plasma, by means of a process of active transport.Elevation of glucose in airway surface fluid, which can occur with even mild hyperglycaemia, promotes bacterial growth within the airway in a dose-dependent manner and predisposes to pneumonia [2].It was also suggested that gastro-oesophageal reflux related to obesity increases the risk of community-acquired pneumonia by the aspiration of gastric contents into the lung.The situation may be rather more complex, as gastric contents by nature of their acidity are usually sterile.However, the use of acidsuppressing drugs, such as proton pump inhibitors and, to a lesser extent, H 2 -antagonists, raise gastric pH and promote the survival and growth of bacteria colonising the aerodigestive tract [3].Use of the more potent proton pump inhibitors has increased in obese patients [4] and this group of drugs is strongly associated with the development of communityacquired pneumonia.One may also consider other drugs that are more frequently prescribed in the obese; for example, the statins.This class of drug may be beneficial in both preventing and reducing the severity of community-acquired pneumonia, thus decreasing the need for hospitalisation [5].Improving the outcome of community-acquired pneumonia will require exploration of these and other mechanisms where plausible risk factors are identified by cohort studies.
Endpiece: Common doctors
Authors: Peter Morrell
Journal: BMJ (2005)

When I say “common doctors” I mean those whom we can also call “textbook” doctors, since indeed they have their whole medicine not in their heart and mind but laid aside in books and manuscripts; and they do not know how to apply their hands to the curing of a disease unless, having first found its name, they look for the remedies under that appropriate to it in their books. Whereas true doctors, inasmuch as they prosecute their art by methods having but scant regard for names, investigate the substance and causes of diseases by division and resolution in order to elicit therefrom therapeutic indications and frame intentions by which they have recourse to books; they do not, as do the former, allow themselves to be led like blind men by names to them as judges, but putting what they read to the refinement of reason they do not obey writings as though they were masters, but rather drag the writings themselves like slaves toward the forwarding of their own purpose: the result is that this exact knowledge of names is necessary for both schools; for the former because they know no other way of healing; for the latter to enable them to enter into discussion with others and to dispute with them the method of effecting a cure.

Giovanni Manardi, Concerning the names of disease afflicting the outward parts (1535), quoted in Bullough VL. Universities, medicine and science in the medieval west. Aldershot: Ashgate Publishing, 2004:97