tbuckley/cabot-search huggingface dataset:
Abstract LB-303: Berubicin, a brain tumor targeting anthracycline: Discovery and clinical evaluation
Authors: Waldemar Priebe, Timothy Madden, Charles A. Conrad
Journal: Cancer Research (2008)

Abstract Development of effective chemotherapeutic strategies to treat brain tumors has been limited in part by the inaccessibility of the CNS to pharmacological intervention. Topoisomerase II (topo II) overexpression has been well documented in human gliomas and is correlated to poor survival, but to date no effective topo II poison, capable of reaching the target tissue after systemic administration, has been developed. We hypothesized that the presence of ATP-binding cassette (ABC) transporters in the blood-brain barrier (BBB) might, in part, be responsible for limiting the CNS penetration of most anticancer drugs including topo II poisons like doxorubicin (DOX). To identify new agents effective in vivo against brain tumors, we have used our innovative modular design of DNA-binding agents to create unique libraries of potential topo II poisons. By systematically screening such libraries, we have identified highly apoptotic compounds that can circumvent P-gp and MRP1-mediated resistance mechanisms, suggesting that such compounds will be potent cytotoxins against gliomas, through their ability to cross the BBB.Synthesis and in vitro screening of a library of over 400 DNA binding agents in a panel of cells overexpressing P-gp and MRP1 led to identification of 10 compounds possessing the necessary characteristics from which the compound Berubicin (RTA744, WP744) was selected for detailed preclinical evaluation. Berubicin (BRB) is structurally related to the well-known anticancer drug DOX, but is significantly more apoptotic than DOX against multidrug-resistant tumor cell lines with the MDR1 and MRP1 phenotypes and can cross the BBB, achieving CNS and brain tumor concentrations exceeding that of plasma. Subsequent preclinical development led to IND and Phase I clinical studies in humans. In the first Phase I trial dose escalation of BRB proceeded according to an accelerated titration design, with single patient cohorts and 100% dose escalations until evidence of drug-related Grade 2 or greater toxicities were observed. The MTD of berubicin administered on a qd X 3 schedule was 7.5 mg/m2/day (22.5 mg/m2/cycle). Toxicities appear consistent with the anthracycline class, with no unexpected toxicities observed. Of interest no neurotoxicity or cardiotoxicity have been reported. Median time to progression in the Phase I study as of 5/21/ 2007 was 7.4 weeks with one complete response (CR), one partial response (PR)) and 7 minor response or stable disease patients, observed. Because of the unique biological characteristics of BRB (potent topo II poison, ability to cross BBB, activity against multidrug resistant tumors) and the results of Phase I clinical studies this agent is uniquely placed to become an effective therapeutic agent for the treatment of brain tumors.
Abstract SY29-02: The Mdm2/Mdm4 complex: A rheostat for p53 activity
Authors: Guillermina Lozano
Journal: Cancer Research (2010)

Abstract The activity of the p53 tumor suppressor is regulated by multiple factors. Two of these, Mdm2 and Mdm4, function as p53 inhibitors in vivo in multiple cell types. Loss of Mdm2 or Mdm4 in mice leads to embryo and cell lethal phenotypes that are rescued by deletion of p53. Additionally, haplo insufficiency at these loci results in elevated p53 activity, delayed lymphomagenesis, and developmental defects in some cases. On the other hand, over expression of Mdm2 and Mdm4 occurs in many tumors most of which retain wild type p53. Mdm2 and Mdm4 transgenic mice are tumor prone. Additionally, a single nucleotide polymorphism (SNP) in the human MDM2 promoter increases the levels of MDM2 expression is associated with increased cancer risk. A mouse model with this SNP shows increased Mdm2 levels, decreased p53 activity, and an enhanced tumor phenotype. These data emphasize the exquisite sensitivity of the p53 pathway to changes in Mdm2 and Mdm4 gene dosage, and the consequences of those effects on development and tumorigenesis. Citation Format: Guillermina Lozano. The Mdm2/Mdm4 complex: A rheostat for p53 activity [abstract]. In: Proceedings of the AACR 101st Annual Meeting 2010; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr SY29-02
A hearty tale of blood and gore
Authors: Toby Pitts-Tucker
Journal: BMJ (2012)

“I will affirm, my most excellent Doctors, the blood to pass forth and return by unwonted tracts . . .”

With these words William Harvey, the subject of Thomas Wright’s spellbinding biography, would proceed to show in gory detail his revolutionary theory of circulation. By performing vivisections in front of enrapt audiences, Harvey demonstrated that blood must be pumped around the body in a circuit. It was this revelation that would shatter existing theories on anatomy and physiology and usher in a new era in medicine.

Wright leads us through the colourful years of Harvey’s life as an undergraduate at Gonville and Caius College, Cambridge. With sore eyes and fingers numb with cold, Harvey would read avidly into the night, pausing only to look down with envy and contempt at the “gentlemen” undergraduates, the sons of noblemen, lords, …
Abstract 5083: Klotho Gene Delivery Delays and Attenuates Spontaneous Hypertension
Authors: Zhongjie Sun
Journal: Circulation (2009)

Background - Klotho is a recently-discovered anti-aging gene. Knockout of klotho gene shortens the lifespan while over-expression of klotho gene extends lifespan of mice. The prevalence of hypertension increases with age. Therefore, hypertension and related cardiovascular diseases are aging disorders. The expression of klotho was decreased significantly in SHRs. The purpose of this experiment was to test our hypothesis that klotho gene delivery attenuates spontaneous hypertension. Methods and Results- Recombinant adeno-associated virus (AAV-2) carrying mouse klotho full-length cDNA (AAV.mKL) was constructed for in vivo expression of klotho. Four groups of male SHR (4 weeks) (8 rats/group) and 1 group of age-matched WKY rats (5 rats/group) were used. Blood pressure (BP) and body weight (BW) were measured twice in all animals before gene delivery in SHR. Briefly, the 4 groups of SHR received IV injection of AAV.mKL, AAV.LacZ, AAV.GFP, and PBS, respectively. The WKY group received PBS as a control. Following gene delivery, BP and BW was monitored weekly. BPs of SHR groups treated with AAV.LacZ, AAV.GFP, or PBS were significantly higher than that of the WKY group treated with PBS. AAV.mKL delayed and significantly attenuated the elevation of BP without affecting the body weight gain in SHRs. One single dose of AAV.mKL attenuated spontaneous hypertension for up to 12 weeks (length of the study). The systolic BP was 140±3.6, 174±4, and 126±2.8 mmHg for SHR-mKL, SHR-LacZ, and WKY-PBS groups, respectively. AAV.mKL also significantly increased hypotensive responses to acetylcholine, suggesting that klotho gene delivery improved endothelial function. AAV.mKL significantly decreased NADPH oxidase activity and superoxide production in mesenteric resistance arteries. Klotho gene delivery abolished renal damage in SHRs. Conclusion- AAV delivery of mouse klotho gene delayed and attenuated hypertension in SHR. The antihypertensive effect of klotho may be mediated by inhibition of NADPH oxidases. Klotho deficiency may play a role in the development of spontaneous hypertension. This research has received full or partial funding support from the American Heart Association, Greater Southeast Affiliate (Alabama, Florida, Georgia, Louisiana, Mississippi, Puerto Rico &amp; Tennessee).
Abstract P2-01-17: Not presented
Authors: CP Dravis, C-Y Chung, GM Wahl
Journal: Cancer Research (2019)

Abstract This abstract was not presented at the conference. Citation Format: Dravis CP, Chung C-Y, Wahl GM. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-01-17.
Abstract P4-08-18: Not presented
Authors: Y Liu, S Chen, Y Jiang, J Wu, Z Shao
Journal: Cancer Research (2019)

Abstract This abstract was not presented at the conference. Citation Format: Liu Y, Chen S, Jiang Y, Wu J, Shao Z. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-18.
Abstract P2-14-27: Impact of surgery on survival in patients with stage IV breast cancer: A population-based study from the SEER database
Authors: C-G Song, Y-X Lin, J Zhang, Q Zeng, M-Y Chen, L-L Chen, X-X Wang, Q-X Chen
Journal: Cancer Research (2019)

Abstract Surgical treatment for stage IV breast cancer remains controversial. Therefore, we aimed to further explore the impact of surgery on survival in patients with stage IV breast cancer using the Surveillance, Epidemiology, and End Results (SEER) database. We selected 3,822 patients diagnosed with stage IV breast cancer from 2010 to 2012 in the SEER database who were divided into surgery and non-surgery groups. We assessed the breast cancer-specific survival (BCSS) and overall survival (OS) of the two groups using Kaplan-Meier plots and Cox proportional hazard regression models. In addition, we performed stratification analyses of breast subtype, tumor size and status of distant metastasis to identify the effects of these factors on surgical outcomes. The median survival times were 30 and 24 months in the surgery and non-surgery groups, respectively. The Kaplan-Meier curves showed that the surgery group survived longer than the non-surgery group. The hazard ratios (HR) of the surgery group were 0.504 for BCSS and 0.507 for OS (P&amp;lt;0.001). Furthermore, patients in the surgery group still experienced significantly better survival than those in the non-surgery group when stratified according to breast subtype, tumor size and status of distant metastasis. Surgical treatment appears to be associated with improved survival in patients with stage IV breast cancer, independently of breast subtype, tumor size and status of distant metastasis. Citation Format: Song C-G, Lin Y-X, Zhang J, Zeng Q, Chen M-Y, Chen L-L, Wang X-X, Chen Q-X. Impact of surgery on survival in patients with stage IV breast cancer: A population-based study from the SEER database [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-14-27.
TRAF3IP3 at the trans-Golgi network regulates NKT2 maturation via the MEK/ERK signaling pathway
Authors: Xinwei Zhang, Ke Wang, Weijia Zhao, Li Cao, Shusong Zhang, Rong Jin, Xiuyuan Sun, Jie Hao, Xiaojun Huang, Mingzhao Zhu, Hounan Wu, Hongshan Zhao, Qing Ge
Journal: Cellular and Molecular Immunology (2019)
Let’s talk about sex, and relations with industry
Authors: Fiona Godlee
Journal: BMJ (2019)

How much sex are people having, and is it enough?Published in The BMJ this week, new results from a British survey of sexual frequency and attitudes find that people aged 16-44 are having less sex than people of the same age 10 years ago (doi:10.1136/bmj.l1525).Other developed countries report similar trends.Possible explanations vary by age and socioeconomic group, as explored by Peter Leusink (doi:10.1136/bmj.l1961
The FMS-like tyrosine kinase-3 ligand/lung dendritic cell axis contributes to regulation of pulmonary fibrosis
Authors: Meritxell Tort Tarrés, Franziska Aschenbrenner, Regina Maus, Jennifer Stolper, Lisanne Schuette, Lars Knudsen, Elena Lopez Rodriguez, Danny Jonigk, Mark Philipp Kühnel, David DeLuca, Antje Prasse, Tobias Welte, Jack Gauldie, Martin RJ Kolb, Ulrich A Maus
Journal: Thorax (2019)

Dendritic cells (DC) accumulate in the lungs of patients with idiopathic lung fibrosis, but their pathogenetic relevance is poorly defined.To assess the role of the FMS-like tyrosine kinase-3 ligand (Flt3L)-lung dendritic cell axis in lung fibrosis.We demonstrate in a model of adenoviral gene transfer of active TGF-β1 that established lung fibrosis was accompanied by elevated serum Flt3L levels and subsequent accumulation of CD11bpos DC in the lungs of mice. Patients with idiopathic pulmonary fibrosis also demonstrated increased levels of Flt3L protein in serum and lung tissue and accumulation of lung DC in explant subpleural lung tissue specimen. Mice lacking Flt3L showed significantly reduced lung DC along with worsened lung fibrosis and reduced lung function relative to wild-type (WT) mice, which could be inhibited by administration of recombinant Flt3L. Moreover, therapeutic Flt3L increased numbers of CD11bpos DC and improved lung fibrosis in WT mice exposed to AdTGF-β1. In this line, RNA-sequencing analysis of CD11bpos DC revealed significantly enriched differentially expressed genes within extracellular matrix degrading enzyme and matrix metalloprotease gene clusters. In contrast, the CD103pos DC subset did not appear to be involved in pulmonary fibrogenesis.We show that Flt3L protein and numbers of lung DC are upregulated in mice and humans during pulmonary fibrogenesis, and increased mobilisation of lung CD11bpos DC limits the severity of lung fibrosis in mice. The current study helps to inform the development of DC-based immunotherapy as a novel intervention against lung fibrosis in humans.
Correction: RAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors
Authors: Sherene Loi, Sathana Dushyanthen, Paul A. Beavis, Roberto Salgado, Carsten Denkert, Peter Savas, Susan Combs, David L. Rimm, Jennifer M. Giltnane, Monica V. Estrada, Violeta Sánchez, Melinda E. Sanders, Rebecca S. Cook, Mark A. Pilkinton, Simon A. Mallal, Kai Wang, Vincent A. Miller, Phil J. Stephens, Roman Yelensky, Franco D. Doimi, Henry Gómez, Sergey V. Ryzhov, Phillip K. Darcy, Carlos L. Arteaga, Justin M. Balko
Journal: Clinical Cancer Research (2019)

In the original version of this article (1), the stated disclosure of the author Carlos L. Arteaga is incorrect. The error has been corrected in the latest online HTML and PDF versions of the article. The authors regret this error.
Abstract 12659: Long-Term Outcomes of Patients With ST-Elevation Myocardial Infarction (STEMI) Complicated by Cardiac Arrest and Cardiogenic Shock
Authors: Anirudh Kumar, Chetan P Huded, Michael J Johnson, Venu Menon, Stephen G Ellis, Samir R Kapadia, Umesh N Khot
Journal: Circulation (2018)

Background: Cardiac arrest (CA) and cardiogenic shock (CS) are known complications of ST-elevation myocardial infarction (STEMI) associated with significant mortality. Long-term outcomes and the in...
Abstract P1-08-13: A prospective evaluation of HLA expression in breast implant associated anaplastic large cell lymphoma to identify disease susceptibility
Authors: SE Tevis, KK Hunt, RN Miranda, CE Butler, MW Clemens
Journal: Cancer Research (2019)

Abstract Background: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare T-cell lymphoma found to occur in association with breast implants. Proposed pathogenic factors for BIA-ALCL include immunologic reaction to textured implants, bacteria and biofilm, chronic inflammation, autoimmune disease, or genetic predisposition. While HLA alleles have been found to be associated with other forms of lymphoma, the frequency of HLA allele polymorphisms have not been described for BIA-ALCL. The aim of this study is to evaluate the frequency of HLA alleles in patients with BIA-ALCL. Methods: We prospectively evaluated HLA alleles in 13 patients with BIA-ALCL seen at a single institution from 2017 to 2018. HLA testing was carried out using probe based sequence specific testing and sequence based typing. The frequency of HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 were evaluated in the study population. Allele frequencies in the Caucasian European general population were obtained from the National Marrow Donor Program for normative controls. We estimated the relative risk of BIA-ALCL with 95% confidence intervals for each HLA allele using a t test. All statistics were performed using SPSS. Results: Thirteen patients with BIA-ALCL and HLA testing were identified with ages ranging from 37 – 76 years. We identified 10, 11, and 9 HLA A, B, and C alleles respectively. There were 8 DRB1 alleles and 5 DQB1 alleles in the BIA-ALCL patients. The following alleles occurred more than two times more frequently in patients with BIA-ALCL as compared with the general population: A*31, A*32, A*68, B*27, B*39, B*49, B*51, and C*15. Conversely, the A*01, A*24, and B*35 alleles occurred less frequently in patients with BIA-ALCL. The A*26 allele was found to occur significantly less often in BIA-ALCL patients (0.2992 vs. 0.07692, p&amp;lt;0.001) versus normative controls. Conclusions: Our results identify differences in the frequency of specific HLA alleles in patients who develop BIA-ALCL compared with the general population. These alleles may signify genetic susceptibility factors for germline genetic variation in HLA in Caucasian patients with BIA-ALCL. Further work is needed to elucidate if these alleles confer susceptibility or resistance and are predictive for the disease in women with textured surface breast implants. Citation Format: Tevis SE, Hunt KK, Miranda RN, Butler CE, Clemens MW. A prospective evaluation of HLA expression in breast implant associated anaplastic large cell lymphoma to identify disease susceptibility [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-13.
Type 1 Diabetes: BTNL2‐Ig Protein Attenuates Type 1 Diabetes in Non‐Obese Diabetic (NOD) Mice (Adv. Healthcare Mater. 9/2019)
Authors: Xiaohong Tian, Yujun Lin, Cheng Cui, Min Su, Laijun Lai
Journal: Advanced Healthcare Materials (2019)

In article number 1800987 by Laijun Lai and co-workers, recombinant butyrophilin-like 2 (BTNL2)-IgG2a Fc (rBTNL2-Ig) fusion protein is examined for its effect on Type 1 diabetes (T1D), a T cell-mediated autoimmune disease. rBTNL2-Ig ameliorates T1D in non-obese diabetic (NOD) mice, which correlates with its ability to inhibit T cell function; consequently, rBTNL2-Ig may provide a useful treatment of T1D patients.
Abstract P3-10-21: Withdrawn
Authors: MM Manai, JJ Thomassin-Piana, PP Finetti, AA Gammoudi, MM Manai, KK Rahal, DD Birnbaum, HH Boussen, FF Bertucci
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Manai MM, Thomassin-Piana JJ, Finetti PP, Gammoudi AA, Manai MM, Rahal KK, Birnbaum DD, Boussen HH, Bertucci FF. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-21.
A man vomiting bright red blood
Authors: Kristen Davies, Kofi Oppong
Journal: BMJ (2018)

A 58 year old man was admitted to the emergency department after a sudden onset of vomiting bright red blood and an episode of black, tarry stools. His medical history included an appendicectomy 20 years ago and alcoholic liver disease. He took no regular drugs, drank 90 units of alcohol a week, and did not smoke.

On examination his body temperature was normal (36.6°C), he was hypotensive (90/56 mm Hg), and he had tachycardia (110 beats/min). He also had palmar erythema, gynaecomastia, and spider naevi on his chest. His abdomen was soft, with no evidence of rebound tenderness or organomegaly. He had tenderness in the epigastric region and his bowel sounds were normal. A digital rectal examination showed black tarry stool.

His haemoglobin concentration was 60 g/L (130-180), and two units of blood were transfused. Once he had been made haemodynamically stable, and after resuscitation with intravenous fluids and administration of packed red cells, he was taken for urgent endoscopy (fig 1⇓).



Fig 1  Endoscopy



1.  What does the image show?

2.  What are the differential diagnoses for an upper gastrointestinal bleed?

3.  What …
Abstract 20186: Estimation of Biatrial Volume Using Cardiac Magnetic Resonance Imaging Predicts Atrial Fibrillation Recurrence After Pulmonary Vein Isolation
Authors: Yu Kumagai, Takanori Arimoto, Daisuke Kutsuzawa, Hiroki Takahashi, Tetsurou Shishido, Tamon Yamanaka, Takuya Miyamoto, Tetsu Watanabe, Isao Kubota
Journal: Circulation (2017)

Introduction: Predictive value of left atrial volume in atrial fibrillation (AF) patients underwent pulmonary vein isolation (PVI) has been established. However, the relationship among right atrial...
Allergens of <i>Pityrosporum ovale</i> and <i>Candida albicans</i>
Authors: G. Doekes, M. J. H. Kaal, A. G. van Ieperen‐van Dijk
Journal: Allergy (1993)

Pityrosporum ovale has recently been recognized as a source of allergens to which many patients with atopic dermatitis (AD) show type I skin reactions and specific IgE antibodies. In this study the IgE‐binding components and/or epitopes in P. ovale extract were shown to be partially sensitive to pronase or trypsin treatment, whereas periodate oxidation resulted in a complete loss of IgE‐binding capacity, thus suggesting the involvement of carbohydrate structures. In Con A affinity chromatography most of the IgE‐binding capacity of crude P. ovale extract bound to the column, and could be eluted with mannoside. Gel filtration on Sephacryl S‐400 revealed a marked heterogeneity with respect to molecular mass, with most of the IgE‐binding activity associated with high‐mol.‐mass fractions (from 5 × 10 4 up to 2 × 10 6 Da). A similar heterogeneity was found after chromatofocusing, with IgE‐binding in the whole pI‐range from 7.0 to 4.0. Essentially identical results were obtained with extracts of Candida albicans , in agreement with the previously shown cross‐reactivity of IgE‐binding components in the two yeast extracts. In inhibition ELISA, gel filtration and chromatofocusing fractions containing components with widely different mol. mass or pi showed complete reciprocal cross‐inhibition, and were all capable of inhibiting the binding of IgE to unfractionated extracts. We therefore conclude that the cross‐reacting anti‐ P. ovale/anti‐C. albicans IgE antibodies in the sera of AD patients are mainly directed at a restricted number of carbohydrate epitope that are expressed on a heterodisperse range of high‐mol‐mass components, probably mannans or mannoproteins.