tbuckley/cabot-search huggingface dataset:
Molecular basis for the accelerated senescence response to Adriamycin in MCF-7 breast and HCT-116 tumor cells
Authors: Xu Di, Lynne W. Elmore, Teneille D. Walker, Robert P. Shiu, David A. Gewirtz
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4989 

Rationale. An accelerated or premature senescence response to antitumor drugs and ionizing radiation has been reported in tumor cell lines, tumor xenografts and in clinical samples. The response appears to be, in large part (but not exclusively) dependent on functional p53, induction of p21, and potentially the down regulation of cdc2 (cdk1). Previous work in our laboratory has demonstrated that induction of Adriamycin- and irradiation-induced senescence is accompanied by downregulation of c-myc protein. The current studies were designed to test the roles of p21, c-myc, cdc2, and reactive oxygen species in Adriamycin-induced senescence. We also examined whether interference with apoptosis might be permissive for senescence. Results. c -myc : A 2-hour exposure to 0.75μM Adriamycin suppressed c-myc protein in MCF-7/E6 and p53 mutant MDA-MB231 breast tumor cells. This drug-induced suppression of c-myc is likely to be a component of the accelerated senescence detected in the residual cell population that remains in a growth arrested state - whereas the bulk of the cell population dies through apoptosis. Unexpectedly, MCF-7 cells expressing exogenous c-myc (via a doxycycline-inducible promoter) also senesced in response to acute Adriamycin exposure. Furhermore, c-myc protein levels were unchanged in p53 wild-type HCT-116 cell undergoing senescence in response to Adriamycin. cdc2 : Adriamycin suppressed cdc2 expression in MCF-7/E6 cells, MDA-MB231 cells and HCT-116 cells; the effect on cdc2 was generally transient, with a partial restoration of cdc2 levels in cells that recovered proliferative capacity. p53 and p21: Adriamycin promoted accelerated senescence in HCT-116 cells; the senescence response was delayed in p53 knockout HCT-116 cells and eliminated in p21 knockout HCT-116 cells. Apoptosis was detected in both the p53 and p21 knockouts but not the wild-type cells. Reactive oxygen: The reactive oxygen scavenger, N-acetyl cysteine, blocked reactive oxygen generation in MCF-7 cells exposed to Adriamycin, but did not attenuate the accelerated senescence response. Interference with apoptosis: Blocking apoptosis in MDA-MB231 or MCF-7/E6 cells with the pan-caspase inhibitor zVAD-FMK failed to consistently increase the senescent cell population or reduce the antiproliferative activity of Adriamycin. Conclusions. Our studies suggest that suppression of c-myc and generation of reactive oxygen play limited roles in the accelerated senescence response to Adriamycin. In contrast, induction of p21 and down regulation of cdc2 may be key components of this response pathway. Senescence does not appear to be the default response when apoptosis is blocked; however, other death pathways (i.e., mitotic catastrophe or autophagy) may contribute to the antiproliferative and cytotoxic actions of Adriamycin when the senescence response pathway is abrogated.
Abstract 11186: Vitamin-D Deficiency in Coronary Artery Disease and Peripheral Artery Disease
Authors: Shikhar Agarwal, Navkaranbir S Bajaj, Tarique Zaman, E M Tuzcu, Samir R Kapadia
Journal: Circulation (2011)

Vitamin-D deficiency has recently been implicated to play a major role in etiopathogenesis of atherosclerosis. We aimed to explore the relationship between coronary artery disease (CAD) and periphe...
Abstract P1-12-09: Possibility of GnRH agonist plus tamoxifen as an alternative treatment to AC (adriamycin plus cyclophosphamide) chemotherapy plus tamoxifen treatment in premenopausal hormone responsive HER2 negative breast cancer patients
Authors: Heeseung Park, Guiyun Sohn, Byung Ho Son, Jong Won Lee, SeiHyun Ahn
Journal: Cancer Research (2015)

Abstract Background: The purpose of this study is to compare the treatment outcomes using GnRH agonist plus tamoxifen, and adriamycin and cyclophopsphamide(AC) containing chemotherapy plus tamoxifen in hormone responsive premenopausal node negative breast cancer patients. Methods: Total 1027 premenopausal women with node negative, hormone receptor positive, Her-2 negative breast cancer were included in this retrospective cohort study. 595 patients (57.9%) were treated with GnRH agonist together with tamoxifen, and 432 patients (42.1%) were treated with adriamycin and cyclophsophamide containing chemotherapy with tamoxifen. Results: A median follow up period was81 months. In pT1 disease, 7 year DFS (disease free survival)was 98.9% for GnRH agonist plus tamoxifen group and 97.4% for chemotherapy plus tamoxifen group, and in pT2 disease, 7 year DSS was 99.1% for GnRH agonist plus tamoxifen group, and 96.9% for chemotherapy plus tamoxifen groupwith nostatisticalsignificance (p=0.252 &amp; 0.230).In pT1 disease, 7 year RFS was 95.4% for GnRH agonist plus tamoxifen group and 92.9% for chemotherapy plus tamoxifen group, and in pT2 disease, 7 year RFS was 91.6% for GnRH agonist plus tamoxifen group, and 91.7% for chemotherapy plus tamoxifen group with no statistical difference between two treatment groups (p=0.353 &amp; 0.836). In subgroup analysis, ER+/PR+ patients and patientsyounger than 40 years old showed slightly better survival inGnRHagnonist plus tamoxifen group when compared to chemotherapy plus tamoxifen group with p-value of 0.046 &amp; 0.018. Conclusion: Adding GnRH agonist to tamoxifen is reasonable alternative to adding AC chemotherapy to tamoxifen in premenopausal luminal type node negative breast cancer patients. Citation Format: Heeseung Park, Guiyun Sohn, Byung Ho Son, Jong Won Lee, SeiHyun Ahn. Possibility of GnRH agonist plus tamoxifen as an alternative treatment to AC (adriamycin plus cyclophosphamide) chemotherapy plus tamoxifen treatment in premenopausal hormone responsive HER2 negative breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-12-09.
Abstract 14963: Prevention of Neointimal Hyperplasia After Angioplasty Using NF-kappaB Decoy Oligodeoxynucleotides-Coated Balloon Catheter in Rabbit Restenosis Model
Authors: Takashi Miyake, Munehisa Shimamura, Hironori Nakagami, Ryuichi Morishita
Journal: Circulation (2011)

Restenosis after endovascular intervention is a major limitation of this minimally invasive technique and hampers the procedure's efficacy for treating cardiovascular disease. To overcome this prob...
THE FEMALE HORMONES
Authors: Elmer L. Sevringhaus
Journal: Annals of Internal Medicine (1942)

Editorial1 July 1942THE FEMALE HORMONESELMER L. SEVRINGHAUSELMER L. SEVRINGHAUSSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-17-1-153 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptBecause there is still much misapprehension as to the conditions in which these hormones are effective and as to their limitations, a brief authoritative discussion of the available pertinent facts concerning them seems desirable. The following summary has been prepared by Dr. Elmer L. Sevringhaus* and is published as an editorial in order to help toward a clearer understanding and more intelligent use of these preparations.The hormones which are distinctively female are the estrogens and progesterone. The first group includes estradiol (the most potent), estrone (next in potency but more commonly known and used), and estriol (still less potent).... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Summary of a lecture delivered before the American College of Physicians, April 22, 1942, at St. Paul, Minnesota.For further details regarding these hormones, readers are referred to: (1) ALLEN, E., DANFORTH, C. H., and DOISY, E. A.: Sex and internal secretions, second edition, 1939, Williams and Wilkins, Baltimore; and (2) Glandular physiology and therapy, second edition, 1942, American Medical Association, Chicago. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1942Volume 17, Issue 1Page: 153-155KeywordsEstradiolEstrogensHormonesProgesterone ePublished: 1 December 2008 Issue Published: 1 July 1942 PDF downloadLoading ...
Problems with the diagnostic algorithm for hypercalcaemia
Authors: Michaël R Laurent
Journal: BMJ (2015)

The diagnostic algorithm in Minisola and colleagues’ excellent review of hypercalcaemia contains several debateable points.1

Firstly, the authors suggest confirming hypercalcaemia after vitamin D supplements are discontinued, but high vitamin D rarely contributes to hypercalcaemia if supplementation is not excessive. Directly proceeding to calcidiol measurements provides more certainty and avoids unnecessary delays.

The authors …
Serogroup A Meningococcal Conjugate Vaccine Coverage After the First National Mass Immunization Campaign—Burkina Faso, 2011
Authors: I. Médah, D. Yélbeogo, J.L. Kambou, K. Wannemuehle, J.L. Goodson, B. Flannery, A. Cohn, R.T. Novak, T. Clark, N.E. Messonnier, S.A. Meyer
Journal: JAMA (2013)
Discovery of direct inhibitors of Keap1–Nrf2 protein–protein interaction as potential therapeutic and preventive agents
Authors: Dhulfiqar Ali Abed, Melanie Goldstein, Haifa Albanyan, Huijuan Jin, Longqin Hu
Journal: Acta Pharmaceutica Sinica B (2015)

The Keap1–Nrf2–ARE pathway is an important antioxidant defense mechanism that protects cells from oxidative stress and the Keap1–Nrf2 protein–protein interaction (PPI) has become an important drug target to upregulate the expression of ARE-controlled cytoprotective oxidative stress response enzymes in the development of therapeutic and preventive agents for a number of diseases and conditions. However, most known Nrf2 activators/ARE inducers are indirect inhibitors of Keap1–Nrf2 PPI and they are electrophilic species that act by modifying the sulfhydryl groups of Keap1׳s cysteine residues. The electrophilicity of these indirect inhibitors may cause "off-target" side effects by reacting with cysteine residues of other important cellular proteins. Efforts have recently been focused on the development of direct inhibitors of Keap1–Nrf2 PPI. This article reviews these recent research efforts including the development of high throughput screening assays, the discovery of peptide and small molecule direct inhibitors, and the biophysical characterization of the binding of these inhibitors to the target Keap1 Kelch domain protein. These non-covalent direct inhibitors of Keap1–Nrf2 PPI could potentially be developed into effective therapeutic or preventive agents for a variety of diseases and conditions.
Abstract 6181: ST Segment Resolution and Pathological Findings of Aspirated Materials in Patients with ST Elevation Acute Myocardial Infarction
Authors: Asami Suzuki, Tsunekazu Kakuta, Taishi Yonetsu, Tetsumin Lee, Taro Iwamoto, Naohiko Kawaguchi
Journal: Circulation (2008)

Early resolution of ST-segment elevation (STR) is a potent predictor of better clinical outcome after PCI in ST elevation acute myocardial infarction (STEMI). The aim of this study was to determine the association of aspirated materials and serial change of ST elevation. We studied 150 consecutive STEMI patients with assessable ECG recording, in whom standard PCI was performed with the adjunctive use of aspiration thrombectomy. STR(+) was defined as more than 50% resolution of ST-segment elevation at 60min after PCI. Aspirated materials were pathologically classified into thrombus only group (fresh, lytic, or organized) or thrombus and atheroma complex group, and compared between STR(+) and STR(−). TIMI flow grade, IVUS findings after aspiration(ruptured plaque, calcification, thrombus and echo signal attenuation), area under the curve (AUC) of CK-MB release, and pathological findings were also compared between the two groups. Seventy-six patients (50.6%) showed STR and 74 patients didn’t. RCA culprit lesion was significantly more frequent in STR(+)(P&lt;0.05). There was no significant difference in other patient characteristics or IVUS findings in the present cohort. AUC of CK-MB was lower in STR(+)(p=0.02). TIMI 3 flow was more frequently achieved in STR(+)(p&lt;0.05). Fresh thrombus was more frequent in STR(+)(p&lt;0.05), whereas atheromatous component and lytic or organized thrombus were frequently observed in STR(−)(p&lt;0.05). Culprit lesions in STEMI, when atheroma and thrombus complex with lytic or organized thrombus was aspirated, caused more myocardial damage and less frequent STR.
Revaccination may cause relapse
Authors: V S Neil
Journal: BMJ (1994)

antibodies, particularly their opsonising activity.Assays are available in our unit to measure the ability of patients' serum to opsonise pneumococci and enhance the ingestion of these organisms by phagocytes.These tests may supplement quanti- tative antibody tests in determining the need for reimmunisation.As pneumococcal vaccine contains capsular polysaccharide from only 23 serotypes of Streptococcus pneumoniae it does not provide full protection against pneumococcal septicaemia, and lifelong prophylaxis with antibiotics must be recommended.The reported incidence of pneu- mococcus that is resistant to penicillin, however, is over 40% in Spain,' which makes it crucial to recommend antibiotics resistant to penicillinase for high risk patients.Finally, Capnocytophage canimorsus must be added to the list of organisms of which people who have undergone splenectomy and have contact with animals should be aware.This organism can be transmitted by animal bites, especially dog bites, and can lead to septicaemia and death.It remains susceptible to penicillin.
Meditation and psychotherapy: a rationale for the integration of dynamic psychotherapy, the relaxation response, and mindfulness meditation
Authors: Ilan Kutz, Joan Z. Borysenko, Herbert Benson
Journal: American Journal of Psychiatry (1985)

A framework for the integration of meditation and psychotherapy is presented through a consideration of the psychobiological nature of meditation (the relaxation response) and discussion of a traditional meditation practice (mindfulness meditation) as an effective cognitive technique for the development of self-awareness. The mechanisms by which the emotional and cognitive changes of meditation can be of therapeutic value are explored and the synergistic advantages of the combination of psychotherapy and meditation are discussed.
Celecoxib potentiates in vitro and in vivo radiosensitivity in squamous cell carcinoma of the head and neck.
Authors: Jonathan Bock, Andrew Heaford, Douglas Trask
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

2814 

Squamous cell carcinoma of the head and neck (SCCHN) is characterized by aggressive growth and early lymphatic metastasis, necessitating the addition of radiation therapy (XRT) for the control of local and regional disease in patients with these cancers. Any adjuvant therapies that augment radiosensitivity could have significant impact on cancer treatment protocols for patients with SCCHN. Previous data from our lab have shown that celecoxib, a COX-2 specific non-steroidal anti-inflammatory drug, induces S-phase specific toxicity in SCCHN, suggesting a mechanism for therapeutic synergism. These studies were conducted to evaluate possible mechanisms of in vitro and in vivo synergism with celecoxib and XRT in an SCCHN model. In vitro clonogenic survival assays combining celecoxib with XRT in the UM-SCC-1 cell line showed synergistic toxicity, and in vivo mouse xenograft experiments demonstrated significantly decreased tumor growth with combination therapy compared to XRT or celecoxib alone. Further in vitro clonogenic survival assays were performed to analyze the effects of the timing of celecoxib administration on SCCHN toxicity. Combination therapy with celecoxib and XRT lead to increased in vitro apoptosis as determined by caspase-3 activation, and cell cycle analysis showed enhancement of XRT-induced G2 phase accumulation following celecoxib administration. These studies describe a mechanism for therapeutic synergism with celecoxib and XRT, and provide a basis for the development of clinical trials combining celecoxib with standard radiation treatment for patients with SCCHN.
Abstract 17298: MicroRNA-411 Targets Foxo1 to Induce Hepatic Glucose Production in Type 2 Diabetes
Authors: Nikhil C Adi, Jennipher N Adi, Paul Kurlansky, Arthur Agatston, Keith A Webster
Journal: Circulation (2011)

Introduction: miRNAs are a class of short, NC, single-stranded RNA molecules that negatively regulate gene expression. A hallmark of T2D is excessive HGP that plays an important role in the development of hyperglycemia and hyperlipidemia. FOXO1 has been shown to bind directly to the promoters of gluconeogenic genes and activate HGP. Hypothesis: miR-411 is down regulated in liver of mice with polygenic susceptibility for T2D leading to FOXO1 OE and induction of gluconeogenesis. Methods: NONcNZO10 (NZ10) mice with polygenic susceptibility to T2D or SWR controls were fed Control (CD) or South Beach (SD; high protein/unsaturated fat) diets for 25 weeks. After 12 hr. fasting the mice were sacrificed and liver was collected. Total RNA was isolated and subjected to Sanger 14 multi-species miRNA microarray. RESULTS: Diabesity was not induced in control SWR mice fed either diet or in NZ10 mice fed SD as evidenced by serum glucose and insulin levels and normal GTT. NZ10 mice fed CD were hyperglycemic (blood glucose &gt;350mg/dL) with impaired GTT and hyperinsulinemia; gene expression analysis showed significant induction of key gluconeogenic genes; PEPCK, G6Pase and FBP1 in the livers of these mice (all, p&lt;0.05). Protein and mRNA levels of FOXO1 were significantly up-regulated in the liver of these mice (p&lt;0.05). Western blot analysis showed significantly increased glycogen phosphorylase and decreased glycogen synthase in livers of insulin-treated NZ10 mice fed CD, with increased CREB-133 phosphorylation and suppressed phosphorylation of AMPKα (all p&lt;0.05). NZ10 mice fed CD had fatty liver and elevated gene transcripts of SREBF1 and PGC1alpha. miRNA analysis showed significant down-regulation of miR-411 in liver of NZ10 mice fed CD (p&lt;0.05). In Silico analysis using Targetscan revealed FOXO1 as a target for miR-411. Overexpression of miR-411 in HepG2 cells eliminated FOXO1 expression and suppressed the expression of gluconeogenic enzymes. Conclusions: miR-411 targets FOXO1 and negatively regulates the expression of gluconeogenic genes. In NZ10 mice fed CD miR-411 is down-regulated causing hyperglycemia; this can be prevented by SD that promotes glucose homeostasis and reversal of the diabetic phenotype.
Dasatanib (D) in patients (pts) with chronic myelogenous leukemia (CML) in lymphoid blast crisis (LB-CML) or Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ALL) who are imatinib (IM)-resistant (IM-R) or intolerant (IM-I): The CA180015 ‘START-L’ study
Authors: S. Coutre, G. Martinelli, H. Dombret, A. Hochhaus, R. Larson, G. Saglio, A. Gollerkeri, A. Apanovitch, O. G. Ottman
Journal: Journal of Clinical Oncology (2006)

6528 Background: Dasatinib (D) (BMS-354825) is a multi-targeted kinase inhibitor of BCR-ABL and SRC. Preliminary data from a phase I study suggest high efficacy of D in IM pretreated pts. Methods: START L is an open label phase II study of D in IM-R or IM-I pts with LB-CML and Ph+ALL conducted at 42 centers worldwide. D was given orally, 70 mg twice a day (bid), with escalation to 100 mg bid for poor response or reductions to 50 mg and 40 mg bid for toxicity. Pts had weekly blood counts and monthly bone marrow exams, including cytogenetics. The primary endpoint was confirmed (sustained for at least 4 weeks) major hematologic response (MaHR) rates. Results: From January to June 2005, 101 pts were accrued. Data are available on the first 78 treated pts (42 LB-CML, 36 Ph+ALL). Of the 42 LB-CML pts, 37 were IM-R, 52% were male with median (med) age of 47 years. Prior therapy included IM &gt;600 mg/day in 52% and stem-cell transplant (SCT) in 33% of pts. Med baseline platelet (plt) count was 32.5/nl, med BM blasts were 82%, Bcr-Abl mutations were seen in 48%, and extramedullary disease (EMD) was seen in 29% of pts. The D dose was reduced in 14%, temporarily interrupted in 33%, and escalated in 26% of pts. At 6-months, the MaHR rate was 31% including 26% complete hematologic response (CHR), the MCyR rate was 50%, and 17% of pts remained on study. Of the 36 Ph+ALL pts, 34 were IM-R, 64% were male with med age 46 years. Prior therapy included IM&gt; 600 mg/day in 47% and SCT in 42% of pts. Baseline plt count was 53.5/nl, med BM blasts were 69%, Bcr-Abl mutations were seen in 47% and EMD was seen in 31% of pts. The D dose was reduced in 28%, temporarily interrupted in 39%, and escalated in 47% of the pts. At 6-months, the MaHR rate was 42% including 31% CHR, the MCyR rate was 58%, and 33% pts remained on study. Among all 78 pts, grade 3–4 thrombocytopenia and neutropenia was seen in 82% and 76% of pts, respectively. The most frequent D-related non-hematologic toxicities were diarrhea (30%), nausea (23%), fatigue (19%), rash (17%) and pleural effusion (13%). Conclusions: D is active in IM pretreated LB-CML and Ph+ALL pts. Data on all 101 pts will be presented at the meeting. [Table: see text]
Abstract 675: MDCT Immediately After Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction is Useful in Assessing Infarct Extent
Authors: Youngkeun Ahn, Doo Sun Sim, Yun Hyeon Kim, Song Choi, Hyun Ju Seon, Jum Suk Ko, Min Goo Lee, Keun Ho Park, Hyun Ju Yoon, Nam Sik Yoon, Young Joon Hong, Hyung Wook Park, Ju Han Kim, Myung Ho Jeong, Jeong Gwan Cho, Jong Chum Park, Jung Chaee Kang
Journal: Circulation (2009)
Abstract 1453: LXR-623, a novel Liver X Receptor modulator, displays neutral lipid effects in Cholesteryl Ester Transfer Protein-expressing species and inhibits atherosclerotic lesion progression in Low Density Lipoprotein receptor knockout mice
Authors: Ponnal Nambi, Michael D Basso, Liang Chen, Qiang-Yuan Liu, Anita Halpern, Valerie Clerin, Christine Resmini, James C Keith, Irene Feingold, Robert J Steffan, Jay Wrobel, Elaine Quinet
Journal: Circulation (2007)

LXRα and LXRα are ligand-activated transcription factors involved in the upregulation of genes involved in reverse cholesterol transport (RCT), a process involved in cholesterol homeostasis. Unfort...