Database : MEDLINE
Search on : Dilazep [Words]
References found : 415 [refine]
Displaying: 1 .. 10   in format [Detailed]

page 1 of 42 go to page                         

  1 / 415 MEDLINE  
              next record last record
select
to print
Photocopy
Full text

[PMID]: 27210310
[Au] Autor:Sakai N; Kawasaki Y; Waragai T; Oikawa T; Kaneko M; Sato T; Suyama K; Hosoya M
[Ad] Address:Department of Pediatrics, Fukushima Medical University School of Medicine.
[Ti] Title:Successful therapy with tonsillectomy plus pulse therapy for the relapse of pediatric IgA nephropathy treated with multi-drugs combination therapy.
[So] Source:Fukushima J Med Sci;62(1):68-73, 2016 Jun 08.
[Is] ISSN:2185-4610
[Cp] Country of publication:Japan
[La] Language:eng
[Ab] Abstract:Immunoglobulin A nephropathy (IgAN) is the most common form of chronic glomerulonephritis worldwide. In Japan, the treatment for use as an initial therapy was established in Guidelines for the Treatment of Childhood IgA nephropathy; however, no rescue therapy for recurrent or steroid-resistant pediatric IgAN was established. We report here a 15-year-old boy with severe IgAN, who was treated with combination therapy involving prednisolone, mizoribine, warfarin, and dilazep dihydrochloride for 2 years. The response to the combination therapy was good and both proteinuria and hematuria disappeared. The pathological findings at the second renal biopsy were improved and PSL was discontinued. However, due to nonadherence to the treatment regimen and tonsillitis, macrohematuria and an increase of proteinuria were again observed and the pathological findings at the third renal biopsy showed clear deterioration. The patient was, therefore, diagnosed with recurrent IgAN. Tonsillectomy plus methylprednisolone pulse therapy (TMP) was performed as a rescue therapy for the recurrence of severe IgAN. Both the proteinuria or hematuria subsequently disappeared, and no proteinuria or hematuria has been observed and kidney function has remained normal during a 5-year follow-up. The patient experienced no severe side effects associated with the drug regimens. In conclusion, our case suggests that TMP may be an effective and useful rescue therapy for recurrent IgAN after multi-drug combination therapy.
[Mh] MeSH terms primary: Glomerulonephritis, IGA/therapy
Methylprednisolone/administration & dosage
Tonsillectomy
[Mh] MeSH terms secundary: Adolescent
Drug Therapy, Combination
Humans
Male
Recurrence
[Pt] Publication type:CASE REPORTS; JOURNAL ARTICLE
[Nm] Name of substance:X4W7ZR7023 (Methylprednisolone)
[Em] Entry month:1705
[Cu] Class update date: 170501
[Lr] Last revision date:170501
[Js] Journal subset:IM
[Da] Date of entry for processing:160524
[St] Status:MEDLINE
[do] DOI:10.5387/fms.2016-3

  2 / 415 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
PubMed Central Full text
Full text

[PMID]: 26636542
[Au] Autor:Xue C; Zhou C; Dai B; Yu S; Xu C; Mao Z; Ye C; Chen D; Zhao X; Wu J; Chen W; Mei C
[Ad] Address:Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
[Ti] Title:Antihypertensive treatments in adult autosomal dominant polycystic kidney disease: network meta-analysis of the randomized controlled trials.
[So] Source:Oncotarget;6(40):42515-29, 2015 Dec 15.
[Is] ISSN:1949-2553
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Blood pressure (BP) control is one of the most important treatments of Autosomal dominant polycystic kidney disease (ADPKD). The comparative efficacy of antihypertensive treatments in ADPKD patients is inconclusive. METHODS: Network meta-analysis was used to evaluate randomized controlled trials (RCT) which investigated antihypertensive treatments in ADPKD. PubMed, Embase, Ovid, and Cochrane Collaboration were searched. The primary outcome was estimated glomerular filtration rate (eGFR). Secondary outcomes were serum creatinine (Scr), urinary albumin excretion (UAE), systolic BP (SBP), diastolic BP (DBP), mean artery pressure (MAP) and left ventricular mass index (LVMI). RESULTS: We included 10 RCTs with 1386 patients and six interventions: angiotensin-converting enzyme inhibitors (ACEI), Angiotensin II receptor blocker (ARB), combination of ACEI and ARB, calcium channel blockers (CCB), -blockers and dilazep. There was no difference of eGFR in all the treatments in both network and direct comparisons. No significant differences of Scr, SBP, DBP, MAP, and LVMI were found in network comparisons. However, ACEI significantly reduced SBP, DBP, MAP and LVMI when compared to CCB. Significantly increased UAE was observed in CCB compared with ACEI or ARB. Bayesian probability analysis found ARB ranked first in the surrogate measures of eGFR, UAE and SBP. CONCLUSIONS: There is little evidence to detect differences of antihypertensive treatments on kidney disease progression in ADPKD patients. More RCTs will be needed in the future. Use of ARB may be an optimal choice in clinical practice.
[Mh] MeSH terms primary: Angiotensin Receptor Antagonists/therapeutic use
Angiotensin-Converting Enzyme Inhibitors/therapeutic use
Antihypertensive Agents/therapeutic use
Polycystic Kidney, Autosomal Dominant/drug therapy
[Mh] MeSH terms secundary: Disease Progression
Humans
Hypertension/drug therapy
Hypertension/etiology
Polycystic Kidney, Autosomal Dominant/complications
Randomized Controlled Trials as Topic
Treatment Outcome
[Pt] Publication type:JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Angiotensin Receptor Antagonists); 0 (Angiotensin-Converting Enzyme Inhibitors); 0 (Antihypertensive Agents)
[Em] Entry month:1610
[Cu] Class update date: 170220
[Lr] Last revision date:170220
[Js] Journal subset:IM
[Da] Date of entry for processing:151205
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.6452

  3 / 415 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
PubMed Central Full text
Full text

[PMID]: 26447863
[Au] Autor:Sun T; Liu B; Li P
[Ad] Address:Department of Neurosurgery, Zaozhuang Hospital of Zaozhuang Coal Mining Group, Zaozhuang, Shangdong, China (mainland).
[Ti] Title:Nerve Protective Effect of Asiaticoside against Ischemia-Hypoxia in Cultured Rat Cortex Neurons.
[So] Source:Med Sci Monit;21:3036-41, 2015 Oct 08.
[Is] ISSN:1643-3750
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Asiaticoside is one of the main functional components of the natural plant Centella asiatica urban. Studies have reported it has several functions such as anti-depression and nerve cell protection. Asiaticoside can reduce the cerebral infarct size in acute focal cerebral ischemia in a mouse model and asiatic acid glycosides can significantly improve neurobehavioral scores. Currently, there is a lack of understanding of asiaticoside in regard to its neural protective mechanism in cerebral ischemia. This study aimed to solve this problem by using an ischemia-hypoxia cell model in vitro. MATERIAL AND METHODS: An in vitro ischemia hypoxia cell model was successfully established by primary cultured newborn rat cortical neurons. After being treated by asiaticoside for 24 h, cell survival rate, lactate dehydrogenase release quantity, and B-cell lymphoma gene-2 (BCL-2), Bax, and caspase-3 protein expressions was detected. RESULTS: After 10 nmol/L or 100 nmol/L of asiaticoside were given to the cells, cell survival rate increased significantly and presented concentration dependence. Asiaticoside can reduce lactate dehydrogenase release. Lactate dehydrogenase release in model cells is gradually reduced with the increase of asiaticoside concentration. The lactate dehydrogenase release in asiaticoside 10 nmol/L group, asiaticoside 100 nmol/L group and ischemia hypoxia group were 26.751.05, 22.362.87 and 52.355.46%, respectively (p<0.05). It was also found that asiaticoside could modulate the expression of apoptotic factors, including bcl-2, Bax, and caspase-3. CONCLUSIONS: Asiaticoside helps to protect in vitro ischemia hypoxia neurons. This nerve cell protection may be mediated by the BCL-2 protein.
[Mh] MeSH terms primary: Brain Ischemia/drug therapy
Centella/chemistry
Hypoxia-Ischemia, Brain/drug therapy
Neurons/drug effects
Neuroprotective Agents/chemistry
Triterpenes/chemistry
[Mh] MeSH terms secundary: Animals
Animals, Newborn
Apoptosis
Caspase 3/metabolism
Cell Survival
Cells, Cultured
Cerebral Cortex/pathology
Dilazep/chemistry
Frontal Lobe/metabolism
Frontal Lobe/pathology
Gene Expression Regulation/drug effects
L-Lactate Dehydrogenase/metabolism
Memory
Neurons/pathology
Proto-Oncogene Proteins c-bcl-2/biosynthesis
Proto-Oncogene Proteins c-bcl-2/metabolism
Rats
Rats, Sprague-Dawley
bcl-2-Associated X Protein/metabolism
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Bax protein, rat); 0 (Neuroprotective Agents); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (Triterpenes); 0 (bcl-2-Associated X Protein); EC 1.1.1.27 (L-Lactate Dehydrogenase); EC 3.4.22.- (Casp3 protein, rat); EC 3.4.22.- (Caspase 3); F8KLC2BD5Z (Dilazep); PKO39VY215 (asiaticoside)
[Em] Entry month:1608
[Cu] Class update date: 170220
[Lr] Last revision date:170220
[Js] Journal subset:IM
[Da] Date of entry for processing:151009
[St] Status:MEDLINE
[do] DOI:10.12659/MSM.894024

  4 / 415 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 26428002
[Au] Autor:Rehan S; Ashok Y; Nanekar R; Jaakola VP
[Ad] Address:Oulu Biocenter and Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 3000, FI-90014 Oulu, Finland.
[Ti] Title:Thermodynamics and kinetics of inhibitor binding to human equilibrative nucleoside transporter subtype-1.
[So] Source:Biochem Pharmacol;98(4):681-9, 2015 Dec 15.
[Is] ISSN:1873-2968
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Many nucleoside transport inhibitors are in clinical use as anti-cancer, vasodilator and cardioprotective drugs. However, little is known about the binding energetics of these inhibitors to nucleoside transporters (NTs) due to their low endogenous expression levels and difficulties in the biophysical characterization of purified protein with ligands. Here, we present kinetics and thermodynamic analyses of inhibitor binding to the human equilibrative nucleoside transporter-1 (hENT1), also known as SLC29A1. Using a radioligand binding assay, we obtained equilibrium binding and kinetic rate constants of well-known NT inhibitors--[(3)H]nitrobenzylmercaptopurine ribonucleoside ([(3)H]NBMPR), dilazep, and dipyridamole--and the native permeant, adenosine, to hENT1. We observed that the equilibrium binding affinities for all inhibitors decreased whereas, the kinetic rate constants increased with increasing temperature. Furthermore, we found that binding is enthalpy driven and thus, an exothermic reaction, implying that the transporter does not discriminate between its inhibitors and substrates thermodynamically. This predominantly enthalpy-driven binding by four chemically distinct ligands suggests that the transporter may not tolerate diversity in the type of interactions that lead to high affinity binding. Consistent with this, the measured activation energy of [(3)H]NBMPR association was relatively large (20 kcal mol(-1)) suggesting a conformational change upon inhibitor binding. For all three inhibitors the enthalpy (ΔH) and entropy (ΔS) contributions to the reaction energetics were determined by van't Hoff analysis to be roughly similar (25-75% ΔG). Gains in enthalpy with increasing polar surface area of inhibitors suggest that the binding is favored by electrostatic or polar interactions between the ligands and the transporter.
[Mh] MeSH terms primary: Equilibrative Nucleoside Transporter 1/antagonists & inhibitors
Equilibrative Nucleoside Transporter 1/metabolism
Thermodynamics
[Mh] MeSH terms secundary: Animals
Dilazep/pharmacokinetics
Humans
Insecta
Protein Binding/physiology
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Equilibrative Nucleoside Transporter 1); 0 (SLC29A1 protein, human); F8KLC2BD5Z (Dilazep)
[Em] Entry month:1603
[Cu] Class update date: 171116
[Lr] Last revision date:171116
[Js] Journal subset:IM
[Da] Date of entry for processing:151003
[St] Status:MEDLINE

  5 / 415 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 28509205
[Au] Autor:Kanno S; Kawasaki Y; Maeda R; Miyazaki K; Ono A; Suzuki Y; Suyama K; Suzuki S; Hosoya M
[Ad] Address:Department of Pediatrics, Fukushima Medical University School of Medicine, 1 Hikariga-oka, Fukushima City, Fukushima, 960-1295, Japan.
[Ti] Title:An 11-year-old girl with antineutrophil cytoplasmic antibody-associated glomerulonephritis identified by a school urinary screening program.
[So] Source:CEN Case Rep;3(2):232-236, 2014 Nov.
[Is] ISSN:2192-4449
[Cp] Country of publication:Japan
[La] Language:eng
[Ab] Abstract:Antineutrophil cytoplasmic autoantibody-associated glomerulonephritis (GN) in childhood is rare and has a poor prognosis. We report an 11-year-old girl with renal-limited antineutrophil cytoplasmic autoantibody-associated vasculitis. Proteinuria and hematuria were first detected by a school urinary screening (SUS) program. Histopathological examination revealed pauci-immune necrotizing GN. She did not display purpura or peripheral neuropathy. She was diagnosed with antineutrophil cytoplasmic autoantibody-associated GN based on proteinuria, high serum titers of antineutrophil cytoplasmic autoantibodies (ANCAs), and pauci-immune necrotizing GN. The patient was treated with combination therapy, consisting of methylprednisolone and urokinase pulse, prednisolone, mizoribine (MZB), warfarin, and dilazep hydrochloride. At 2months after treatment, urinary protein excretion was decreased and the hematuria had disappeared, while the serum titer of ANCAs was also decreased. The dose of prednisolone was tapered, and proteinuria and hematuria later disappeared at 9months after treatment. In conclusion, we reported an 11-year-old girl with renal-limited antineutrophil cytoplasmic autoantibody-associated vasculitis early identified by a SUS program and treated with multi-drug combination therapy including MZB. On the basis of our results, we believe that a SUS programs may be effective for the early identification and treatment of children with renal-limited antineutrophil cytoplasmic autoantibody-associated vasculitis.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1705
[Cu] Class update date: 170521
[Lr] Last revision date:170521
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.1007/s13730-014-0126-1

  6 / 415 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 25454272
[Au] Autor:Playa H; Lewis TA; Ting A; Suh BC; Muoz B; Matuza R; Passer BJ; Schreiber SL; Buolamwini JK
[Ad] Address:Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Ste 327 Johnson, 847, Monroe, Memphis, TN 38163, USA.
[Ti] Title:Dilazep analogues for the study of equilibrative nucleoside transporters 1 and 2 (ENT1 and ENT2).
[So] Source:Bioorg Med Chem Lett;24(24):5801-5804, 2014 Dec 15.
[Is] ISSN:1464-3405
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:As ENT inhibitors including dilazep have shown efficacy improving oHSV1 targeted oncolytic cancer therapy, a series of dilazep analogues was synthesized and biologically evaluated to examine both ENT1 and ENT2 inhibition. The central diamine core, alkyl chains, ester linkage and substituents on the phenyl ring were all varied. Compounds were screened against ENT1 and ENT2 using a radio-ligand cell-based assay. Dilazep and analogues with minor structural changes are potent and selective ENT1 inhibitors. No selective ENT2 inhibitors were found, although some analogues were more potent against ENT2 than the parent dilazep.
[Mh] MeSH terms primary: Dilazep/analogs & derivatives
Equilibrative Nucleoside Transporter 1/antagonists & inhibitors
Equilibrative-Nucleoside Transporter 2/antagonists & inhibitors
[Mh] MeSH terms secundary: Animals
Biological Transport/drug effects
Cell Line
Dilazep/chemical synthesis
Dilazep/pharmacology
Equilibrative Nucleoside Transporter 1/genetics
Equilibrative Nucleoside Transporter 1/metabolism
Equilibrative-Nucleoside Transporter 2/genetics
Equilibrative-Nucleoside Transporter 2/metabolism
Humans
Protein Binding
Rats
Recombinant Proteins/biosynthesis
Recombinant Proteins/chemistry
Recombinant Proteins/genetics
Swine
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Name of substance:0 (Equilibrative Nucleoside Transporter 1); 0 (Equilibrative-Nucleoside Transporter 2); 0 (Recombinant Proteins); F8KLC2BD5Z (Dilazep)
[Em] Entry month:1508
[Cu] Class update date: 171121
[Lr] Last revision date:171121
[Js] Journal subset:IM
[Da] Date of entry for processing:141203
[St] Status:MEDLINE

  7 / 415 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 25091947
[Au] Autor:Zeng H; Liu S; Wang P; Qu X; Ji H; Wang X; Zhu X; Song Z; Yang X; Ma Z; Zhu H
[Ad] Address:School of Life Sciences, Institute of Genetics, Fudan University, Shanghai, 200433, China.
[Ti] Title:Dilazep synergistically reactivates latent HIV-1 in latently infected cells.
[So] Source:Mol Biol Rep;41(11):7697-704, 2014 Nov.
[Is] ISSN:1573-4978
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:The long-lived latently infected cells persist in spite of prolonged highly active anti-retroviral therapy and present a major barrier to a cure of human immunodeficiency virus type 1 (HIV-1) infection. Elimination of this reservoir requires reactivation of the latent virus. None of the current agents can safely and effectively reactivate latent HIV-1 reservoirs. Dilazep, a nucleoside transport inhibitor, is used to treat ischemic dysfunction. However, little is known about the effect of dilazep in inducing HIV expression in latently infected cells. Using the Jurkat T cell model of HIV-1 latency, we found that dilazep effectively reactivates latent HIV-1 gene expression in a dose manner. We observed that dilazep synergistically reactivated latent HIV-1 transcription with valproic acid. We also found that dilazep activates viral latency without inducing cell surface activation markers CD25 and CD69 activation. In summary, dilazep, alone or in combination with VPA, could be useful in future eradication strategies.
[Mh] MeSH terms primary: Dilazep/pharmacology
Disease Reservoirs/virology
HIV-1/drug effects
Virus Activation/drug effects
Virus Latency/physiology
[Mh] MeSH terms secundary: Drug Synergism
Flow Cytometry
Green Fluorescent Proteins
Humans
Jurkat Cells
Valproic Acid/pharmacology
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:147336-22-9 (Green Fluorescent Proteins); 614OI1Z5WI (Valproic Acid); F8KLC2BD5Z (Dilazep)
[Em] Entry month:1506
[Cu] Class update date: 171030
[Lr] Last revision date:171030
[Js] Journal subset:IM
[Da] Date of entry for processing:140806
[St] Status:MEDLINE
[do] DOI:10.1007/s11033-014-3662-z

  8 / 415 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
Full text

[PMID]: 24646214
[Au] Autor:Kawasaki Y; Suyama K; Miyazaki K; Kanno S; Ono A; Suzuki Y; Sato M; Hashimoto K; Hosoya M
[Ad] Address:Department of Pediatrics, Fukushima Medical University School of Medicine, Fukushima, Japan.
[Ti] Title:Resistance factors for the treatment of immunoglobulin A nephropathy with diffuse mesangial proliferation.
[So] Source:Nephrology (Carlton);19(7):384-91, 2014 Jul.
[Is] ISSN:1440-1797
[Cp] Country of publication:Australia
[La] Language:eng
[Ab] Abstract:AIM: Some patients with severe immunoglobulin A nephropathy (IgAN) are resistant to multi-drug combination therapy; however, there have been few reports on the risk factors for non-responsiveness to treatment for severe IgAN. We, therefore, evaluated the risk factors for non-responsiveness to treatment in cases of severe IgAN. METHODS: We collected data on 44 children who had been diagnosed with IgAN with diffuse mesangial proliferation and treated with multi-drug combination therapy. The children were divided into two groups based on the prognosis at the latest follow-up. Group 1 consisted of 30 children with normal urine and nine children with minor urinary abnormalities and Group 2 consisted of four children with persistent nephropathy and one child with renal insufficiency. The clinical, laboratory, and pathological findings for both groups were analyzed. RESULTS: The age at the onset in Group 2 was higher than that in Group 1. C3 deposits and high chronicity index values at the first renal biopsy were more frequently found in Group 2 than in Group 1 patients. IgA deposits, serum IgA and myeloid-related protein (MRP) 8/14 levels, and glomerular and interstitial MRP8+CD68+ scores at the second biopsy were all higher in Group 2 than in Group 1 patients. CONCLUSIONS: Our results, although based on only a small number of patients in a retrospective study, suggest that age, presence of C3 deposits and interstitial changes at the onset, and persistent renal inflammatory activation may be risk factors for non-responsiveness to treatment for IgAN with diffuse mesangial proliferation.
[Mh] MeSH terms primary: Dilazep/administration & dosage
Drug Resistance, Multiple
Glomerulonephritis, IGA
Prednisolone/administration & dosage
Ribonucleosides/administration & dosage
[Mh] MeSH terms secundary: Age of Onset
Antigens, CD/metabolism
Antigens, Differentiation, Myelomonocytic/metabolism
Biopsy/methods
Calgranulin A/metabolism
Calgranulin B/metabolism
Child
Drug Therapy, Combination/methods
Female
Glomerulonephritis, IGA/blood
Glomerulonephritis, IGA/diagnosis
Glomerulonephritis, IGA/drug therapy
Glomerulonephritis, IGA/epidemiology
Humans
Immunoglobulin A/metabolism
Immunosuppressive Agents/administration & dosage
Japan/epidemiology
Kidney Function Tests/methods
Male
Mesangial Cells/metabolism
Mesangial Cells/pathology
Retrospective Studies
Risk Factors
Severity of Illness Index
Vasodilator Agents/administration & dosage
[Pt] Publication type:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Name of substance:0 (Antigens, CD); 0 (Antigens, Differentiation, Myelomonocytic); 0 (CD68 antigen, human); 0 (Calgranulin A); 0 (Calgranulin B); 0 (Immunoglobulin A); 0 (Immunosuppressive Agents); 0 (Ribonucleosides); 0 (Vasodilator Agents); 4JR41A10VP (mizoribine); 9PHQ9Y1OLM (Prednisolone); F8KLC2BD5Z (Dilazep)
[Em] Entry month:1502
[Cu] Class update date: 171116
[Lr] Last revision date:171116
[Js] Journal subset:IM
[Da] Date of entry for processing:140321
[St] Status:MEDLINE
[do] DOI:10.1111/nep.12232

  9 / 415 MEDLINE  
              first record previous record next record last record
select
to print
Photocopy
PubMed Central Full text
Full text

[PMID]: 23441192
[Au] Autor:Paproski RJ; Yao SY; Favis N; Evans D; Young JD; Cass CE; Zemp RJ
[Ad] Address:Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta, Canada.
[Ti] Title:Human concentrative nucleoside transporter 3 transfection with ultrasound and microbubbles in nucleoside transport deficient HEK293 cells greatly increases gemcitabine uptake.
[So] Source:PLoS One;8(2):e56423, 2013.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Gemcitabine is a hydrophilic clinical anticancer drug that requires nucleoside transporters to cross plasma membranes and enter cells. Pancreatic adenocarcinomas with low levels of nucleoside transporters are generally resistant to gemcitabine and are currently a clinical problem. We tested whether transfection of human concentrative nucleoside transporter 3 (hCNT3) using ultrasound and lipid stabilized microbubbles could increase gemcitabine uptake and sensitivity in HEK293 cells made nucleoside transport deficient by pharmacologic treatment with dilazep. To our knowledge, no published data exists regarding the utility of using hCNT3 as a therapeutic gene to reverse gemcitabine resistance. Our ultrasound transfection system--capable of transfection of cell cultures, mouse muscle and xenograft CEM/araC tumors--increased hCNT3 mRNA and (3)H-gemcitabine uptake by >2,000- and 3,400-fold, respectively, in dilazep-treated HEK293 cells. Interestingly, HEK293 cells with both functional human equilibrative nucleoside transporters and hCNT3 displayed 5% of (3)H-gemcitabine uptake observed in cells with only functional hCNT3, suggesting that equilibrative nucleoside transporters caused significant efflux of (3)H-gemcitabine. Efflux assays confirmed that dilazep could inhibit the majority of (3)H-gemcitabine efflux from HEK293 cells, suggesting that hENTs were responsible for the majority of efflux from the tested cells. Oocyte uptake transport assays were also performed and provided support for our hypothesis. Gemcitabine uptake and efflux assays were also performed on pancreatic cancer AsPC-1 and MIA PaCa-2 cells with similar results to that of HEK293 cells. Using the MTS proliferation assay, dilazep-treated HEK293 cells demonstrated 13-fold greater resistance to gemcitabine compared to dilazep-untreated HEK293 cells and this resistance could be reversed by transfection of hCNT3 cDNA. We propose that transfection of hCNT3 cDNA using ultrasound and microbubbles may be a method to reverse gemcitabine resistance in pancreatic tumors that have little nucleoside transport activity which are resistant to almost all current anticancer therapies.
[Mh] MeSH terms primary: Deoxycytidine/analogs & derivatives
Membrane Transport Proteins/genetics
Membrane Transport Proteins/metabolism
Transfection
[Mh] MeSH terms secundary: Animals
Biological Transport
Cell Survival/drug effects
Deoxycytidine/metabolism
Deoxycytidine/toxicity
Equilibrative Nucleoside Transporter 1/genetics
Equilibrative Nucleoside Transporter 1/metabolism
Gene Expression
HEK293 Cells
Humans
Membrane Transport Proteins/deficiency
Mice
Microbubbles
Oocytes/metabolism
Transfection/instrumentation
Transfection/methods
Xenopus laevis
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Equilibrative Nucleoside Transporter 1); 0 (Membrane Transport Proteins); 0 (cif nucleoside transporter); 0W860991D6 (Deoxycytidine); B76N6SBZ8R (gemcitabine)
[Em] Entry month:1308
[Cu] Class update date: 161019
[Lr] Last revision date:161019
[Js] Journal subset:IM
[Da] Date of entry for processing:130227
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0056423

  10 / 415 MEDLINE  
              first record previous record
select
to print
Photocopy

[PMID]: 23318848
[Au] Autor:Moriyama T; Iwasaki C; Tanaka K; Ochi A; Shimizu A; Shiohira S; Itabashi M; Takei T; Uchida K; Tsuchiya K; Nitta K
[Ad] Address:Department of Medicine, Kidney Center, Tokyo Women's Medical University, Japan. takamori@kc.twmu.ac.jp
[Ti] Title:Effects of combination therapy with renin-angiotensin system inhibitors and eicosapentaenoic acid on IgA nephropathy.
[So] Source:Intern Med;52(2):193-9, 2013.
[Is] ISSN:1349-7235
[Cp] Country of publication:Japan
[La] Language:eng
[Ab] Abstract:OBJECTIVE: The beneficial effects of renin-angiotensin-aldosterone system inhibitors (RASI) and the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) on IgA nephropathy (IgAN) have been reported. However, it is unknown whether these agents have any synergistic interactions. METHODS: We divided 38 IgAN patients into two groups: an EPA group (n=18) treated with RASI plus EPA and a DILAZEP group (n=20) treated with RASI plus dilazep dihydrochloride. We analyzed the clinical and histological background of each patient, any relevant clinical findings obtained one year after treatment and any factors significantly related to decreases in proteinuria. RESULTS: The clinical findings were largely similar between the groups, except for body mass index (24.94.5 in the EPA group vs. 21.42.1 in the DILAZEP group, p=0.0041) and total cholesterol (median: 206.0 vs. 177.5 mg/dL, p=0.0493). The histological findings, evaluated according to the Oxford classification, were also similar between the groups. At one year after treatment, the EPA group demonstrated a significantly decreased mean blood pressure (from 94.79.0 to 86.47.2 mmHg, p=0.0007) and a significantly decreased median level of proteinuria (from 0.80 to 0.41 g/g creatinine, p<0.001). In the DILAZEP group, the mean blood pressure significantly decreased (from 95.213.2 to 88.17.7 mmHg, p<0.001) without any significant decrease in the median level of proteinuria (from 0.88 to 0.60 g/g creatinine). According to a multivariate logistic analysis, EPA was found to be the only independent factor related to decreases in proteinuria (odds ratio = 5.073, 95% CI: 1.18-26.7, p=0.0285). CONCLUSION: We conclude that EPA accelerates the effects of RASI and thus decreases the proteinuria observed in patients with IgAN.
[Mh] MeSH terms primary: Dilazep/administration & dosage
Eicosapentaenoic Acid/administration & dosage
Glomerulonephritis, IGA/drug therapy
Renin-Angiotensin System/drug effects
[Mh] MeSH terms secundary: Adolescent
Adult
Aged
Blood Pressure/drug effects
Blood Pressure/physiology
Cohort Studies
Drug Therapy, Combination
Female
Glomerulonephritis, IGA/blood
Humans
Male
Middle Aged
Renin-Angiotensin System/physiology
Treatment Outcome
Young Adult
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:AAN7QOV9EA (Eicosapentaenoic Acid); F8KLC2BD5Z (Dilazep)
[Em] Entry month:1310
[Cu] Class update date: 131121
[Lr] Last revision date:131121
[Js] Journal subset:IM
[Da] Date of entry for processing:130116
[St] Status:MEDLINE


page 1 of 42 go to page                         
   


Refine the search
  Database : MEDLINE Advanced form   

    Search in field  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/PAHO/WHO - Latin American and Caribbean Center on Health Sciences Information