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https://www.readbyqxmd.com/read/27865938/pdmp-a-ceramide-analogue-acts-as-an-inhibitor-of-mtorc1-by-inducing-its-translocation-from-lysosome-to-endoplasmic-reticulum
#1
Takashi Ode, Katarzyna A Podyma-Inoue, Kazue Terasawa, Jin-Ichi Inokuchi, Toshihide Kobayashi, Tetsuro Watabe, Yuichi Izumi, Miki Hara-Yokoyama
Mammalian or mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth, metabolism, and cell differentiation. Recent studies have revealed that the recruitment of mTORC1 to lysosomes is essential for its activation. The ceramide analogue 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), a well known glycosphingolipid synthesis inhibitor, also affects the structures and functions of various organelles, including lysosomes and endoplasmic reticulum (ER). We investigated whether PDMP regulates the mTORC1 activity through its effects on organellar behavior...
November 16, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27852416/-effects-and-mechanism-ofitraconazole-on-prostate-cancer-pc-3-cell-apoptosis
#2
Z W Zhao, L L Yang, J S Ji, L Y Zheng, S J Fang, J L Wang
Objective: To investigate the effects and mechanisms of itraconazole on prostate cancer PC-3 cells proliferation. Methods: The PC-3 cells were divided into four group: control group, itraconazole group, itraconazole+ CerS-1-shRNA group and itraconazole+ PDMP group.3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide(MTT)assay was used to detect the growth of PC-3 cells.Apoptosis was detected by Annexin V-FITC /PI.The intracellular ceramide production was assayed by high performance liquid chromatography(HPLC)...
October 25, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27794549/clinicians-use-of-prescription-drug-monitoring-programs-in-clinical-practice-and-decision-making
#3
Gillian J Leichtling, Jessica M Irvine, Christi Hildebran, Deborah J Cohen, Sara E Hallvik, Richard A Deyo
OBJECTIVES:  Little is known about clinicians' use of prescription drug monitoring program (PDMP) profiles in decision-making. The objective of this qualitative study was to understand how clinicians use, interpret, and integrate PDMP profiles with other information in making clinical decisions. DESIGN : Qualitative interviews of clinician PDMP users. SETTING:  Oregon registrants in the state's PDMP. SUBJECTS:  Thirty-three clinicians practicing in primary care, emergency medicine, pain management, psychiatry, dentistry, and surgery...
October 29, 2016: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/27744401/prevalence-and-factors-associated-with-multiple-provider-episodes-in-texas-an-epidemiological-analysis-of-prescription-drug-monitoring-program-data
#4
Erin A Ferries, Aaron M Gilson, Rajendar R Aparasu, Hua Chen, Michael L Johnson, Marc L Fleming
OBJECTIVE:  Prescription drug abuse has reached epidemic levels, leading to overdose-related morbidity and mortality. Patient and regional-level factors are believed to contribute to higher rates of prescription drug abuse. The objective of this study was to determine the prevalence and factors associated with multiple provider episodes (MPEs) in Texas. METHODS:  This was a retrospective cohort analysis of data from the Texas Prescription Drug Monitoring Program (PDMP) database, linked with Texas county census data...
October 15, 2016: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/27692186/a-survey-of-physicians-perspectives-on-the-new-york-state-mandatory-prescription-monitoring-program-istop
#5
Cary J Blum, Lewis S Nelson, Robert S Hoffman
BACKGROUND: Prescription drug monitoring programs (PDMPs) have emerged as one tool to combat prescription drug misuse and diversion. New York State mandates that prescribers use its PDMP (called ISTOP) before prescribing controlled substances. We surveyed physicians to assess their experiences with mandatory PDMP use. METHODS: Electronic survey of attending physicians, from multiple clinical specialties, at one large urban academic medical center. RESULTS: Of 207 responding physicians, 89...
November 2016: Journal of Substance Abuse Treatment
https://www.readbyqxmd.com/read/27673162/poster-410-incidence-of-patients-testing-positive-for-methadone-in-a-pain-clinic-with-a-negative-prescription-drug-monitoring-program-pdmp-report
#6
Francis P Lagattuta, Jason Williford, Physician Assistant
No abstract text is available yet for this article.
September 2016: PM & R: the Journal of Injury, Function, and Rehabilitation
https://www.readbyqxmd.com/read/27658522/physician-attitudes-and-experiences-with-maryland-s-prescription-drug-monitoring-program-pdmp
#7
Dora H Lin, Eleanor Lucas, Irene B Murimi, Katherine Jackson, Michael Baier, Shannon Frattaroli, Andrea C Gielen, Patience Moyo, Linda Simoni-Wastila, G Caleb Alexander
AIMS: Physicians' use of prescription drug monitoring programs (PDMPs) varies by state. Among Maryland physicians, we sought to (1) estimate the PDMP impact on changes in opioid prescribing, (2) approximate the scope of PDMP utility and (3) determine the barriers to PDMP use after its 2013 implementation. DESIGN: Cross-sectional postal survey linking responses to state records of PDMP registration and use, randomly sampling physicians within specialty and registration strata...
September 23, 2016: Addiction
https://www.readbyqxmd.com/read/27647699/prescription-drug-monitoring-program-data-tracking-of-opioid-addiction-treatment-outcomes-in-integrated-dual-diagnosis-care-involving-injectable-naltrexone
#8
Ayesha Sajid, Aaron Whiteman, Richard L Bell, Marion S Greene, Eric A Engleman, R Andrew Chambers
BACKGROUND AND OBJECTIVES: Fourfold increases in opioid prescribing and dispensations over 2 decades in the U.S. has paralleled increases in opioid addictions and overdoses, requiring new preventative, diagnostic, and treatment strategies. This study examines Prescription Drug Monitoring Program (PDMP) tracking as a novel measure of opioid addiction treatment outcomes in a university-affiliated integrated mental health-addiction treatment clinic. METHODS: Repeated measure parametrics examined PDMP and urine drug screening (UDS) data before and after first injection for all patients (N = 68) who received at least one long-acting naltrexone injection (380 mg/IM) according to diagnostic groupings of having either (i) alcohol (control); (ii) opioid; or (iii) combined alcohol and opioid use disorders...
October 2016: American Journal on Addictions
https://www.readbyqxmd.com/read/27539856/induction-of-glycosphingolipid-gm3-expression-by-valproic-acid-suppresses-cancer-cell-growth
#9
Nagako Kawashima, Yoshiyuki Nishimiya, Shouta Takahata, Ken-Ichi Nakayama
Glycosphingolipid GM3, a known suppressor of epidermal growth factor receptor (EGFR) phosphorylation, inhibits cell proliferation. Valproic acid, conversely, is known as an up-regulator of GM3 synthase gene (ST3GAL5). To test the possibility that valproic acid could inhibit EGFR phosphorylation by increasing the level of GM3 in cells, we treated A431 epidermoid carcinoma cells with valproic acid and found that valproic acid treatment caused an about 6-fold increase in the GM3 level but only a marginal increase in the GM2 level in these cells and that the observed increase in GM3 level was valproic acid dose-dependent...
October 7, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27517620/inhibition-of-glucosylceramide-synthase-eliminates-the-oncogenic-function-of-p53-r273h-mutant-in-the-epithelial-mesenchymal-transition-and-induced-pluripotency-of-colon-cancer-cells
#10
Salman B Hosain, Sachin K Khiste, Mohammad B Uddin, Vindya Vorubindi, Catherine Ingram, Sifang Zhang, Ronald A Hill, Xin Gu, Yong-Yu Liu
Missense mutation of tumor suppressor p53, which exhibits oncogenic gain-of-function (GOF), not only promotes tumor progression, but also diminishes therapeutic efficacies of cancer treatments. However, it remains unclear how a p53 missense mutant contributes to induced pluripotency of cancer stem cells (CSCs) in tumors exposed to chemotherapeutic agents. More importantly, it may be possible to abrogate the GOF by restoring wild-type p53 activity, thereby overcoming the deleterious effects resulting from heterotetramer formation, which often compromises the efficacies of current approaches being used to reactivate p53 function...
August 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27517152/a-recombinantly-tailored-%C3%AE-defensin-that-displays-intensive-macropinocytosis-mediated-uptake-exerting-potent-efficacy-against-k-ras-mutant-pancreatic-cancer
#11
Salman B Hosain, Sachin K Khiste, Mohammad B Uddin, Vindya Vorubindi, Catherine Ingram, Sifang Zhang, Ronald A Hill, Xin Gu, Yong-Yu Liu
Missense mutation of tumor suppressor p53, which exhibits oncogenic gain-of-function (GOF), not only promotes tumor progression, but also diminishes therapeutic efficacies of cancer treatments. However, it remains unclear how a p53 missense mutant contributes to induced pluripotency of cancer stem cells (CSCs) in tumors exposed to chemotherapeutic agents. More importantly, it may be possible to abrogate the GOF by restoring wild-type p53 activity, thereby overcoming the deleterious effects resulting from heterotetramer formation, which often compromises the efficacies of current approaches being used to reactivate p53 function...
August 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27373967/anti-amyloidogenic-effects-of-glycosphingolipid-synthesis-inhibitors-occur-independently-of-ganglioside-alterations
#12
Anastasia Noel, Sabrina Ingrand, Laurence Barrier
Evidence has suggested that ganglioside abnormalities may be linked to the proteolytic processing of amyloid precursor protein (APP) in Alzheimer's disease (AD) and that pharmacological inhibition of ganglioside synthesis may reduce amyloid β-peptide (Aβ) production. In this study, we assessed the usefulness of two well-established glycosphingolipid (GSL) synthesis inhibitors, the synthetic ceramide analog D-PDMP (1-phenyl 2-decanoylamino-3-morpholino-1-propanol) and the iminosugar N-butyldeoxynojirimycin (NB-DNJ or miglustat), as anti-amyloidogenic drugs in a human cellular model of AD...
September 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27273809/preparing-a-prescription-drug-monitoring-program-data-set-for-research-purposes
#13
Nicole O'Kane, Sara E Hallvik, Miguel Marino, Joshua Van Otterloo, Christi Hildebran, Gillian Leichtling, Richard A Deyo
PURPOSE: To develop a complete and consistent prescription drug monitoring program (PDMP) data set for use by drug safety researchers in evaluating patterns of high-risk use and potential abuse of scheduled drugs. METHODS: Using publically available data references from the US Food and Drug Administration and the Centers for Disease Control and Prevention, we developed a strategic methodology to assign drug categories based on pharmaceutical class for the majority of prescriptions in the PDMP data set...
September 2016: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/27221045/inhibition-of-ceramide-glucosylation-sensitizes-lung-cancer-cells-to-abc294640-a-first-in-class-small-molecule-sphk2-inhibitor
#14
Shuhong Guan, Yuan Y Liu, Tingzan Yan, Jun Zhou
Sphingosine kinase 2 (SphK2) is proposed as a novel oncotarget for lung cancer. Here, we studied the anti-lung cancer cell activity by ABC294640, a first-in-class SphK2 inhibitor. We showed that ABC294640 suppressed growth of primary and A549 human lung cancer cells, but sparing SphK2-low lung epithelial cells. Inhibition of SphK2 by ABC294640 increased ceramide accumulation, but decreased pro-survival sphingosine-1-phosphate (S1P) content, leading to lung cancer cell apoptosis activation. Significantly, we show that glucosylceramide synthase (GCS) might be a major resistance factor of ABC294640...
August 5, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27172362/glucosylceramide-synthase-inhibitors-d-pdmp-and-d-etdo-p4-decrease-the-gm3-ganglioside-level-differ-in-their-effects-on-insulin-receptor-autophosphorylation-but-increase-akt1-kinase-phosphorylation-in-human-hepatoma-hepg2-cells
#15
Natalia Fedoryszak-Kuśka, Mirosława Panasiewicz, Hanna Domek, Tadeusz Pacuszka
Gangliosides function as modulators of several cell growth related receptors. It was shown for caveolin-rich adipocytes, that GM3 ganglioside binds to insulin receptor (IR), dissociates its complex with caveolin, and thus lowers IR autophosphorylation following insulin treatment. We extended those studies into human hepatocyte-derived HepG2 cells, characterized by a high level of IR but low of caveolin. To lower the glycosphingolipid content, estimated by GM3 concentration, two glucosylceramide synthase inhibitors d-threo-1-pheny-2-decanoylamino-3-morpholino-1-propanol (d-PDMP) and d-threo-1-(3,4,-ethylenedioxy)phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (d-EtDO-P4) were used...
2016: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/27098615/opioid-related-policies-in-new-england-emergency-departments
#16
Scott G Weiner, Ali S Raja, Jane C Bittner, Kevin M Curtis, Peter Weimersheimer, Kohei Hasegawa, Janice A Espinola, Carlos A Camargo
OBJECTIVES: The opioid abuse and overdose epidemic in the United States has led to the need for new practice policies to guide clinicians. We describe implementation of opioid-related policies in emergency departments (EDs) in New England to gauge progress and determine where further work is needed. METHODS: This study analyzed data from the 2015 National Emergency Department Inventory-New England survey. The survey queried directors of every ED (n = 195) in the six New England states to determine the implementation of five specific policies related to opioid management...
September 2016: Academic Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine
https://www.readbyqxmd.com/read/27061342/characteristics-of-state-prescription-drug-monitoring-programs-a-state-by-state-survey
#17
A Travis Manasco, Christopher Griggs, Rebecca Leeds, Breanne K Langlois, Alan H Breaud, Patricia M Mitchell, Scott G Weiner
OBJECTIVES: Prescription drug monitoring programs (PDMPs) are state-based data collection systems recording controlled substance medications. Currently, 49 states have PDMPs. There are discrepancies in reporting patterns, infrastructure, and oversight between programs. We characterized aspects of each state's PDMP. METHODS: A web search of each state's PDMP was conducted, and a list of all PDMP administrators was obtained. From August 1 to November 31, 2014, a link to a web-based survey was sent to each PDMP administrator...
July 2016: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/27009292/clinical-styles-and-practice-policies-influence-on-communication-with-patients-regarding-worrisome-prescription-drug-monitoring-program-data
#18
Christi Hildebran, Gillian Leichtling, Jessica M Irvine, Deborah J Cohen, Sara E Hallvik, Richard A Deyo
OBJECTIVES: Clinician communication with patients regarding worrisome findings in Prescription Drug Monitoring Programs (PDMPs) may influence patient responses and subsequent care. The authors studied the range of approaches clinicians report when communicating with patients in this situation and how practice policies and procedures may influence this communication. DESIGN: Qualitative interviews of clinician PDMP users. SETTING: Oregon registrants in the state's PDMP...
November 2016: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/26995800/the-impact-of-prescription-drug-monitoring-programs-and-prescribing-guidelines-on-emergency-department-opioid-prescribing-a-multi-center-survey
#19
Adam C Pomerleau, Lewis S Nelson, Jason A Hoppe, Matthew Salzman, Paul S Weiss, Jeanmarie Perrone
OBJECTIVE: Emergency department (ED) providers are high volume but low quantity prescribers of opioid analgesics (OA). Few studies have examined differences in opioid prescribing decisions specifically among ED providers. The aim of this study was to describe OA prescribing decisions of ED providers at geographically diverse centers, including utilization of prescribing guidelines and prescription drug monitoring programs (PDMP). METHODS: This was a multi-center cross-sectional Web-based survey of ED providers who prescribe OA...
March 19, 2016: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/26970307/pre-clinical-assessment-of-a-674563-as-an-anti-melanoma-agent
#20
Ying Zou, Guobiao Fan, Xuemin Wang
The present study aims to investigate the anti-melanoma activity by an Akt1 specific inhibitor A-674563. We showed that A-674563 was anti-proliferative and cytotoxic when added to human melanoma cells (A375, WM-115 and SK-Mel-2 lines). A-674563 induced caspase-dependent apoptotic death of human melanoma cells, and its cytotoxicity was inhibited with pre-treatment of caspase inhibitors. Further, A-674563 treatment blocked Akt and its downstream S6 Kinase 1 (S6K1) activation in A375 melanoma cells. Significantly, restoring Akt-S6K1 activation via introduction of constitutively-active Akt1 (ca-Akt1) only partially attenuated A-674563's cytotoxicity against A375 cells...
August 12, 2016: Biochemical and Biophysical Research Communications
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