tbuckley/cabot-search huggingface dataset:
Abstract SY38-03: Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukemia
Authors: Brian Huntly
Journal: Cancer Research (2012)

Abstract Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukemia Recurrent chromosomal translocations involving the mixed lineage leukemia (MLL) gene initiate aggressive forms of leukemia, which are often refractory to conventional therapies. Many MLL-fusion partners are members of the super elongation complex (SEC), a critical regulator of transcriptional elongation, suggesting that aberrant control of this process plays an important role in leukemia induction. Here we will describe a global proteomic strategy to demonstrate that MLL-fusions, as part of SEC and the polymerase associated factor (PAFc) complex are associated with the BET family of acetyl-lysine recognising, chromatin “adaptor” proteins. These data provided the basis for therapeutic intervention in MLL-fusion leukemia, via the displacement of the BET family of proteins from chromatin. We will show that a novel small molecule inhibitor of the BET family GSK1210151A (I-BET151) has profound efficacy against human and murine MLL-fusion leukemic cell lines, through the induction of early cell cycle arrest and apoptosis. I-BET151 treatment in two human leukemia cell lines with different MLL-fusions alters the expression of a common set of genes whose function may account for these phenotypic changes. The mode of action of I-BET151 is, at least in part, due to the inhibition of transcription at key genes (BCL2, C-MYC and CDK6) through the displacement of BRD3/4, PAFc and SEC components from chromatin. In vivo studies will demonstrate that I-BET151 has significant therapeutic value, providing survival benefit in two distinct mouse models of murine MLL-AF9 and human MLL-AF4 leukemia. In addition, the efficacy of I-BET151 against human leukemia stem cells (LSC) will be shown, providing further evidence of its potent therapeutic potential. These findings establish the displacement of BET proteins from chromatin as a promising epigenetic therapy for these aggressive leukemias. To extend the applications of our work, we will also present preliminary data to demonstrate that inhibition of BET proteins has therapeutic promise in a larger number of AML subtypes. We will speculate on potential mechanisms for this, the investigation of which is ongoing. Finally, we will discuss extension of the paradigm of BET inhibition to the numerous other epigenetic “readers” implicated in the induction and progression of cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY38-03. doi:1538-7445.AM2012-SY38-03
International Cancer Information Services Step Up Collaboration
Authors: E. Dixon
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article International Cancer Information Services Step Up Collaboration Get access Eleanor Dixon Eleanor Dixon Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 1, 2 January 1991, Page 13, https://doi.org/10.1093/jnci/83.1.13 Published: 02 January 1991
Understanding Cancer: From Basic Science to Clinical Practice, by Malcolm Alison, Catherine Sarraf
Authors: P. Selby
Journal: BMJ (1997)

Malcolm Alison, Catherine Sarraf Cambridge University Press, £19.95, pp 277 ISBN 0 521 56751 3

It is getting harder to write comprehensive textbooks covering research into cancer and clinical practice for its management. The explosion in knowledge of basic science that is relevant to cancer is well recognised. The increasing complexity of clinical practice and clinical research is equally pressing. Against this background, Malcolm Alison and Catherine Sarraf have taken a major challenge to write a postgraduate text that will allow people to understand cancer. They have succeeded certainly to a substantial degree.

The book is structured in the traditional way for textbooks on this subject, going through causes, genetics, tumour biology, cell proliferation, the pathological assessments of tumours, and some discussion of cancer treatments. It is clearly written and benefits from a consistency possible when two authors do all the work and …
Circulatory and Ventilatory Response to Exercise in Thyrotoxicosis
Authors: D. G. Massey, Margaret R. Becklake, J. M. McKenzie, D. V. Bates
Journal: New England Journal of Medicine (1967)

THYROTOXICOSIS is characterized by an increased basal metabolism. To provide the increased oxygen requirement, the respiratory and cardiovascular systems augment their minute output. However, at rest, both cardiac output1 , 2 and minute ventilation3 are increased disproportionately to the increase in oxygen consumption. In the case of minute ventilation, the rapid and shallow breathing pattern characteristic of thyrotoxicosis results in increased dead-space ventilation, the alveolar ventilation remaining normal.4 The elevation of cardiac output has been attributed to increased blood flow through the skin,1 , 2 , 5 and it has been suggested that both the increased respiratory and the circulatory responses serve a useful function by . . .
FASTING REMNANT LIPOPROTEIN CHOLESTEROL IS INDEPENDENTLY ASSOCIATED WITH SUBCLINICAL ATHEROSCLEROSIS: THE ELSA-BRASIL STUDY
Authors: Marcio Sommer Bittencourt, Raul Santos, Henrique Staniak, Kausik Ray, Steven Jones, Seth Martin, Peter Toth, Michael Blaha, Isabela Bensenor, Paulo Lotufo
Journal: Journal of the American College of Cardiology (2016)
Splenic Hamartoma Presenting as a "Hot Spot" on Tc-99m Phytate SPECT Imaging
Authors: KENSAKU SHIMUZU, KAZUYOSHI SUGA, NAOFUMI MATSUNAGA, NORIHIKO KUME, KAZUYA NISHIGAUCHI, KAZUMITSU HONJO, SHIGERU YONESHIRO
Journal: Clinical Nuclear Medicine (1998)

The cases of two patients with surgically proven splenic hamartomas with "hot spots" on Tc-99m phytate SPECT imaging are presented. There was intense radiocolloid accumulation in the peripheral portion of a large single tumor in one patient, and in each of three isolated tumors in the other patient. The intense uptake might be related to the function of proliferated reticuloendothelial cells in the tumors. These unique findings were not clearly identified on the planar images.
Texas anesthesiologist who billed when off work is convicted of defrauding insurers
Authors: Owen Dyer
Journal: BMJ (2016)

A prominent anesthesiologist faces as long as 10 years in prison after being convicted of seven counts of fraud in a Dallas federal court.

Richard Toussaint, the wealthy cofounder of a bankrupt Texas luxury hospital chain, was found guilty of submitting fraudulent bills worth roughly $10m (£7m; €9m) to Blue Cross Blue Shield of Texas, UnitedHealthcare, Humana, Aetna, Cigna, and the Federal Employees Health Benefits Program.

Toussaint billed, the court found, as if he had been present for procedures that took place when he was at another hospital, while asleep in bed, while in …
Abstract 1705: Diagnosis of chronic lymphoid leukemia on unstained blood smears using Raman microspectroscopy and supervised classification
Authors: Teddy Happillon
Journal: Cancer Research (2012)

Abstract Chronic Lymphoid Leukemia (CLL) is a blood cancerous disease characterized by the proliferation of lymphocytes (lymphocytosis). This is the most common leukemia, preferentially affecting people aged over 50 years old. It is incurable and in most cases shows no clinical signs. Thus, it is often discovered by chance during a blood test. If necessary, morphological and immunological studies are led by analyzing blood smears colored with May-Grünwald Giemsa, by making a complete blood count and by computing a Matutes scores. These studies are necessary because it is impossible to distinguish a healthy cell from a cancerous one only using a conventional microscope even if the cells are stained. In order to establish the diagnosis of the disease reliably and automatically, a new approach based on the Raman microspectroscopy is introduced in this study. Based on the interaction between matter and light, this technology acquires a real molecular and biochemical signature of the analyzed sample in a label-free manner (no staining or marking of the sample). Recently, Raman microspectroscopy has shown a promising potential to highlight the pathophysiological states in both human and animal since differences between different pathophysiological states occur at the molecular level. From unstained blood smears, obtained by spreading a drop of blood of CLL patients and healthy persons on standard glass slides, Raman spectra are acquired on the nucleus of white blood cells. Using a supervised classification algorithm such as the “Support Vector Machine” (SVM), a spectral model is established to distinguish spectra obtained from healthy or pathological cells. This model is computed using a population of spectra called “training set” and consists of 513 spectra from 6 CLL patients and 347 spectra from 4 healthy persons. Then, a classification of the “validation set” composed of 2820 spectra from 33 CLL patients and 1074 spectra from13 healthy individuals was achieved. A sensitivity of 84.84% and a specificity of 84.61% were obtained on the patient. Finally, a “blind set” composed of 721 spectra from 8 cases is classified. The sensitivity and specificity are respectively equal to 80% and 100%. The results obtained on the differentiation between healthy and pathological cells show the real potential of Raman spectroscopy coupled with supervised classification for the diagnosis of CLL. Future studies will concentrate on the prognosis, and if possible the prediction of CLL. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1705. doi:1538-7445.AM2012-1705
140 IMPACT OF SARCOPENIA ON MORTALITY AFTER LIVER TRANSPLANTATION IN HIV INFECTED PATIENTS
Authors: T.M. Antonini, O. Ciacio, P. Bucur, S. Bivol, A. Coilly, P. Ichai, G. Pittau, E. Teicher, A.-M. Roque-Afonso, A. Sa Cunha, R. Adam, D. Castaing, D. Samuel, J.-C. Duclos-Vallee, E. Vibert
Journal: Journal of Hepatology (2013)
Regression of Coronary Artery Disease as a Result of Intensive Lipid-Lowering Therapy in Men with High Levels of Apolipoprotein B
Authors: Greg Brown, John J. Albers, Lloyd D. Fisher, Susan M. Schaefer, Jiin-Tarng Lin, Cheryl Kaplan, Xue-Qiao Zhao, Brad D. Bisson, Virginia F. Fitzpatrick, Harold T. Dodge
Journal: New England Journal of Medicine (1990)

The effect of intensive lipid-lowering therapy on coronary atherosclerosis among men at high risk for cardiovascular events was assessed by quantitative arteriography. Of 146 men no more than 62 years of age who had apolipoprotein B levels ≥125 mg per deciliter, documented coronary artery disease, and a family history of vascular disease, 120 completed the 2 1/2-year double-blind study, which included arteriography at base line and after treatment. Patients were given dietary counseling and were randomly assigned to one of three treatments: lovastatin (20 mg twice a day) and colestipol (10 g three times a day); niacin (1 g four times a day) and colestipol (10 g three times a day); or conventional therapy with placebo (or colestipol if the low-density lipoprotein [LDL] cholesterol level was elevated).
Abstract 4613: Targeting ER-KDM1 axis to sensitize therapy resistant breast cancer cells to hormonal therapy
Authors: Valerie Cortez, Sujit S. Nair, Seshidar Rao Tekmal, Ratna K. Vadlamudi
Journal: Cancer Research (2010)

Abstract Estrogen-induced breast carcinogenesis is characterized by global changes in histone modifications. KDM1 (also known as LSD1) a histone demethylase enzyme, plays a key role in establishing specific histone methylation marks at ERα target gene promoters. Emerging evidence suggests histone methylation imposes ligand dependency; and deregulation of this epigenetic pathway potentially contributes to hormonal independence and adaptive resistance in breast cancer. Our study examined the therapeutic efficacy of pargyline, a KDM1 inhibiting drug, and evaluated the therapeutic benefit to curb growth of therapy resistant breast cancer cells. We used several model cell lines shown to exhibit resistance to hormonal therapy including MCF7-HER2, MCF7-Tam, MCF7-Ca-LTLT, MCF7-PELP1 and parental MCF7 cells as controls. Reporter gene assays showed KDM1 enhanced ERα- mediated transcription in therapy resistant cells. KDM1 functionally interacts with ERα coregulator PELP1 and is co-recruited with PELP1 to ERα target genes. Pargyline treatment substantially inhibited ERα transactivation functions. ChIP analysis revealed distinct activating histone methylation modifications at growth regulatory ERα target genes in aggressively growing and therapy resistant breast cancer cells. Breast cancer models treated with pargyline facilitated reversal of the observed specific modifications and thereby inhibited the growth of breast cancer cells in vitro and in vivo nude mice models. Pargyline also showed significant effect in blocking local estrogen synthesis via alterations in histone methylation modifications at the aromatase promoter. Combinational therapy using three agents that: (a) block ERα's nuclear actions (tamoxifen or letrozole), (b) ERα's extranuclear actions (dasatinib) and (c) ERα's epigenetic modifications (pargyline) showed most promising therapeutic effect compared to single agent therapy on the growth of therapy resistant cells. Our results suggest that histone methylation modifications play a role in therapy resistance and validate the therapeutic potential of pargyline in combinational therapies. Collectively, our results suggests targeting KDM1 axis with pargyline in combination with current endocrine therapies will have better therapeutic effect and may inhibit or delay development of hormonal resistance. This study is funded by Komen grant KG090447. 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 4613.
Abstract 2861: Pitavastatin inhibits azoxymethane-induced colonic preneoplastic lesions in C57BL/KsJ-<i>db/db</i> obese mice
Authors: Yoichi Yasuda, Masahito Shimizu, Hiroyasu Sakai, Masaya Kubota, Takuji Tanaka, Hisataka Moriwaki
Journal: Cancer Research (2010)

Abstract Obesity and related metabolic abnormalities are risk factors for colorectal cancer. A state of chronic inflammation and adipocytokine imbalance may play a role in this carcinogenesis. Statins, which are commonly used for the treatment of hyperlipidemia, are known to possess anti-inflammatory effects. Statins also exert chemopreventive properties against various cancers. The present study examined the effects of pitavastatin, a recently developed lipophilic statin, on the development of azoxymethane (AOM)-initiated colonic premalignant lesions in C57BL/KsJ-db/db (db/db) obese mice. Male db/db mice were administrated weekly subcutaneous injections of AOM (15 mg/kg body weight) for 4 weeks and then were subsequently fed a diet containing 1 ppm or 10 ppm pitavastatin for 8 weeks. Feeding with either dose of pitavastatin significantly reduced the number of colonic premalignant lesions, β-catenin accumulated crypts, by inhibiting their proliferation and surrounding inflammation. Pitavastatin increased the serum levels of adiponectin while conversely decreasing the serum levels of total cholesterol, TNF-α and leptin. In addition, pitavastatin caused a significant decrease in the expression of TNF-α, IL-6, IL-18 and COX-2 mRNAs on the colonic mucosa of AOM-treated mice. These findings suggest that pitavastatin attenuates chronic inflammation and improves the imbalance of adipocytokines, thereby preventing the development of colonic premalignancies in an obesity-related colon cancer model. Therefore, some types of statin, including pitavastatin, may be a useful chemoprevention modality for colon cancer in obese individuals. 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 2861.
AB0658 The Effects of Infliximab Treatment on Depression, Anxiety and Sleep Disorders in Patients with Ankylosing Spondylitis
Authors: E.D. Ersozlu Bozkirli, S.O. Keskek, E. Bozkirli, A.E. Yucel
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Ankylosing spondylitis (AS) is a chronic inflammatory disease which physically, psychologically, and socially affect the patient9s life. <h3>Objectives</h3> Previous studies have reported a correlation between severity of AS and depression, anxiety, and sleep disorders. In this study we aimed to investigate the effects of infliximab on depression, anxiety and sleep disorders in patients with AS. <h3>Methods</h3> A total of 29 AS patients whose BASDAI≥4 were enrolled. Patients were treated with intravenous infliximab (5mg/kg) at 0, 2nd and 6th week. The scores of VAS pain assessment, VAS-sleep, BASDAI, BASFI, ASQoL, mSchober, Beck depression (BDI) and Beck anxiety inventory (BAI), and the levels of chest expansion, morning stiffness, ESR, CRP were evaluated before initiation of therapy and 6 weeks after the last infusion (at 12th week). <h3>Results</h3> There were 6 (20.7%) women and 23 (79.3%) men. There were statistically significant decrement between all measurements before and after the treatment (p&lt;0.001 for each; Table 1). There were 25 (86.2%) patients with clinically significant depression (cut-off point 17), 20 (68.96%) patients with clinically significant anxiety (cut-off point 16) before treatment. These numbers decreased to 8 (27.58%) and 4 (13.79%) respectively at 12th week. The scores of BASDAI, VAS-sleep, BDI and BAI after 6 weeks from last dose were lower than those before the treatment. There were significant correlations between BDI and BASDAI, BASFI, chest expansion, duration of morning stiffness, ASQoL (p&lt;0.05 for each; Table 2). BAI also significantly correlated with BDI, and ASQoL (p&lt;0.05 for each; Table 2). <h3>Conclusions</h3> In this study, we have shown significant improvements in VAS-sleep, BDI and BAI scores after infliximab treatment. This improvement seems to be related to healing of the disease rather than the direct effect of the drug because it was correlated with the imrovement in disease activity scores. The most significant correlation was found with ASQoL supporting the accuracy of this relation. <h3>References</h3> Persoons P, Vermeire S, Demyttenaere K et al. The impact of major depressive disorder on the short and long term outcome of Crohn9s disease treatment with infliximab. Aliment Pharmacol Ther 2005;22:101-10 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2682
Abstract 765: Costimulatory SA-4-1BBL and monophosphoryl lipid A as novel adjuvant system for the development of cancer vaccines with robust therapeutic efficacy
Authors: Abhishek Srivastava, Rajesh Sharma, Hong Zhao, Esma Yolcu, Haval Shirwan
Journal: Cancer Research (2011)

Abstract Subunit vaccines based on tumor-associated antigens (TAAs) represent an attractive alternative to conventional treatments for cancer due to their safety profile and ability to control recurrences by establishing long-term immunological memory. However, the efficacy of TAA-based therapeutic vaccines is limited by weak immunogenic nature of these antigens and various immune evasion mechanisms employed by the progressing tumor. To overcome these limitations, we herein used SA-4-1BBL costimulatory molecule and toll-like receptor 4 agonist monophosphoryl lipid A (MPL) as two immunomodulators with distinct mechanisms of action as a novel adjuvant system for the development of HPV16 E7 and survivin TAA-based therapeutic vaccines against TC-1 cervical and 3LL pulmonary carcinoma mouse models, respectively. A single immunization with a vaccine formulation containing E7 protein plus SA-4-1BBL and MPL resulted in the eradication of established E7 expressing TC-1 tumors in 100% of mice. Similarly, a single vaccination with survivin, as a bona fide self-TAA, resulted in control and/or eradication of established 3LL pulmonary metastases and the efficacy of the vaccine was further improved by a booster injection. Combined adjuvants had better therapeutic efficacy over the individual agents while SA-4-1BBL significantly performed better than MPL. The therapeutic efficacy achieved with the combinatorial use of both adjuvants and SA-4-1BBL as monotherapy was correlated with elevated levels of IFN-γ+TNF-α+IL-2+ triple positive antigen-specific CD8+ T cells, cytotoxic response, long-term immune memory, and most importantly an increase in the intratumoral number of CD8+ T effector cells with simultaneous decrease in the number of CD4+FoxP3+ T regulatory cells, resulting in a favorable T effector/T regulatory cell ratio. In marked contrast, although MPL as monotherpay improved the effector function of CD8+ T cells, it did not increase the infiltration of these cells into the tumor. Surprisingly, MPL as monotherapy increased the number of CD4+FoxP3+ T regulatory cells infiltrating into the tumor, resulting in an unfavorable T effector/T regulatory cell ratio. Taken together, these data demonstrate the utility of using SA-4-1BBL and MPL as a novel adjuvant system for the development of therapeutic TAA-based subunit cancer vaccines with strong clinical implications. Work is in part funded by NIH 2R44 AI071618-02, R43 AI074176, R41 CA121665, KLCP, the W.M. Keck Foundation, and the Commonwealth of Kentucky Research Challenge Trust Fund. 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 765. doi:10.1158/1538-7445.AM2011-765
LEFT ATRIAL APPENDAGE OCCLUSION DEVICE AND NOVEL ORAL ANTICOAGULANTS VERSUS WARFARIN FOR STROKE PREVENTION IN NON-VALVULAR ATRIAL FIBRILLATION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROL TRIALS
Authors: David Felipe Briceno, Pedro Villablanca Spinetto, Nicole Cyrille, Daniele Massera, Eric Bader, Eric Manheimer, Philip Aagaard, Kevin Ferrick, Jay Gross, Soo Gyum Kim, Andrew Krumerman, Eugen Palma, Nils Guttenplan, John Fisher, Mario Garcia, Andrea Natale, Luigi Di Biase
Journal: Journal of the American College of Cardiology (2015)
Review of Michael L. Gross. Bioethics and Armed Conflict/Moral Dilemmas of Medicine and War.<sup>1</sup>
Authors: Edmund G. Howe
Journal: The American Journal of Bioethics (2008)

"Review of Michael L. Gross. Bioethics and Armed Conflict/Moral Dilemmas of Medicine and War. 1 ." , 8(10), pp. 82–83