The antiproliferative effect of cyclosporine on hematopoietic and lymphoblastoid cell lines--common mechanistic elements with interferon-alpha.

Abstract:

:Cyclosporine, but not its nonimmunosuppressive analog cyclosporine H (CsH), caused in a variety of hematopoietic cell types a growth arrest in the G0/G1 phase of the cell cycle. This arrest was associated with a significant reduction in the c-myc mRNA levels, which could be observed already 1 hr following CsA treatment. Similarity between the antiproliferative effects of CsA and IFN-alpha was observed. Thus, the IFN-alpha sensitive human B-lymphoblastoid cell line Daudi was also sensitive to CsA while an IFN-alpha resistant variant of Daudi cells was found to be resistant to CsA as well. Inhibition of protein synthesis with cycloheximide during IFN-alpha or CsA treatment blocked their ability to reduce the expression of c-myc. Depletion of protein kinase C (PKC) activity from cells by pretreatment of Daudi cells with phorbol.12-myristate 13-acetate (PMA) abolished the G0/G1 arrest induced by both CsA and IFN-alpha. Combinations of low concentrations of CsA and IFN-alpha had synergistic effects on cell-cycle distribution and on c-myc mRNA level, suggesting that CsA and IFN-alpha differ in some features of their antiproliferative action. This conclusion was supported by the observation that a CsA-resistant variant of Daudi cells was found to retain its sensitivity to IFN-alpha. In addition, reduction of ornithine decarboxylase mRNA expression was obtained with IFN-alpha but not with CsA. Taken together, our results suggest that CsA and IFN-alpha share some common element(s) in the pathways of their antiproliferative activity. The possible mechanisms of their antigrowth effects and the clinical significance of our findings are discussed.

journal_name

Transplantation

journal_title

Transplantation

authors

Yonish-Rouach E,Kimchi A,Rubinstein M

doi

10.1097/00007890-199106000-00025

subject

Has Abstract

pub_date

1991-06-01 00:00:00

pages

1276-82

issue

6

eissn

0041-1337

issn

1534-6080

journal_volume

51

pub_type

杂志文章
  • Cyclosporine and anti-interleukin 2 receptor monoclonal antibody therapy suppress accelerated rejection of rat cardiac allografts through different effector mechanisms.

    abstract::Increasing numbers of sensitized patients are either precluded from receiving an allograft or experience accelerated rejection which may be refractory to conventional therapy. Using a rat model, we have shown that accelerated (24 hr) rejection of LBN cardiac Tx in LEW rats sensitized with BN skin grafts 7 days earlier...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199002000-00037

    authors: Hancock WW,DiStefano R,Braun P,Schweizer RT,Tilney NL,Kupiec-Weglinski JW

    更新日期:1990-02-01 00:00:00

  • Release of tumor necrosis factor, interleukin-2, and gamma-interferon in serum after injection of OKT3 monoclonal antibody in kidney transplant recipients.

    abstract::High levels of tumor necrosis factor-alpha, interleukin-2, and gamma-interferon appeared in the circulation of kidney transplant recipients after the first injection of the monoclonal antibody OKT3. This initial injection was systematically followed by fever. The three cytokines were released in all patients (n = 9), ...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-198904000-00008

    authors: Abramowicz D,Schandene L,Goldman M,Crusiaux A,Vereerstraeten P,De Pauw L,Wybran J,Kinnaert P,Dupont E,Toussaint C

    更新日期:1989-04-01 00:00:00

  • Results of renal transplantation in patients with renal cell carcinoma and von Hippel-Lindau disease.

    abstract:BACKGROUND:Patients with von Hippel-Lindau (VHL) disease are at risk for the development of end-stage renal failure from the treatment of localized renal cell carcinoma. Transplantation with its attendant immunosuppression may predispose patients to tumor recurrence; however, there is little information regarding the o...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199712270-00017

    authors: Goldfarb DA,Neumann HP,Penn I,Novick AC

    更新日期:1997-12-27 00:00:00

  • Focal segmental glomerulosclerosis in children: multivariate analysis indicates that donor type does not alter recurrence risk.

    abstract:BACKGROUND:Focal segmental glomerulosclerosis (FSGS), the second leading cause of end stage renal disease in children, appears to be increasing. Moreover, posttransplantation FSGS recurrence is a major problem, and there is concern that children receiving kidneys from living donors (LD) have increased recurrence risk. ...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0b013e31829c2431

    authors: Nehus EJ,Goebel JW,Succop PS,Abraham EC

    更新日期:2013-09-01 00:00:00

  • Abnormal B-cell regulation in highly sensitized patients with sustained serum levels of antibody to HLA class I antigens.

    abstract:BACKGROUND:There are anti-idiotypes in the sera of highly sensitized (HS) patients that stimulate B cells to produce antibody to HLA class I antigens. The purpose of this study is to determine if there is an abnormality in B cell responses to these anti-idiotypes. METHODS:Supernatants from normal and HS B cells expose...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/01.tp.0000179640.06825.bf

    authors: Hack N,Angra S,McKnight TL,den Hollander N,Cardella CJ

    更新日期:2005-11-15 00:00:00

  • Antibody testing strategies for deceased donor kidney transplantation after immunomodulatory therapy.

    abstract:BACKGROUND:Immunomodulatory protocols including intravenous immunoglobulin/rituximab (IVIG/R) are employed to decrease anti-human leukocyte antigen (HLA) antibody levels for patients broadly sensitized to HLA and increase chances for transplantation with a compatible deceased donor (DD). The aim of our study was to ide...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0b013e31821eab8a

    authors: Lai CH,Cao K,Ong G,Naim M,Wang Q,Mirocha J,Vo A,Jordan SC,Reinsmoen NL

    更新日期:2011-07-15 00:00:00

  • Maturation and function of human fetal pancreatic cells after cryopreservation.

    abstract::If transplantation of endocrine tissue is to become a therapy for a significant number of insulin-dependent diabetic individuals, tissue sources other than adult human islets will be required. Because human fetal pancreatic cells may offer that alternative, we have tried to find the optimal combination of tissue cultu...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199312000-00011

    authors: Beattie GM,Otonkoski T,Lopez AD,Hayek A

    更新日期:1993-12-01 00:00:00

  • Comparisons of alloreactive potential of clinical hematopoietic grafts.

    abstract:BACKGROUND:We sought to compare the immunoreactive potential of human cord blood (CB) versus normal adult bone marrow (BM) versus mobilized blood (peripheral blood stem cells; PBSC) from cancer patients. METHODS:Forty mice were randomized to receive a range of doses of T cell-replete cell preparations from one of the ...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199909150-00006

    authors: Leung W,Ramírez M,Mukherjee G,Perlman EJ,Civin CI

    更新日期:1999-09-15 00:00:00

  • Impact of cytochrome p450 3A5 genetic polymorphism on tacrolimus doses and concentration-to-dose ratio in renal transplant recipients.

    abstract:BACKGROUND:Tacrolimus pharmacokinetic characteristics vary greatly among individuals. Tacrolimus is a substrate of cytochrome p450 (CYP), of subfamily CYP3A. CYP3A activity is the sum of the activities of the family of CYP3A genes, including CYP3A5. Subjects with the CYP3A5*1/*1 genotype express large amounts of CYP3A5...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/01.TP.0000090753.99170.89

    authors: Thervet E,Anglicheau D,King B,Schlageter MH,Cassinat B,Beaune P,Legendre C,Daly AK

    更新日期:2003-10-27 00:00:00

  • Modulation of accelerated rejection of cardiac allografts in sensitized rats by anti-interleukin 2 receptor monoclonal antibody and cyclosporine therapy.

    abstract:UNLABELLED:LBNF1 cardiac allografts (Tx) are rejected within 36 hr in LEW rats sensitized with BN skin Tx 7 days earlier, compared to 8-day rejection in unmodified hosts. Treatment with cyclosporine or ART-18, an anti-interleukin 2 receptor (IL-2[R]) mAb monoclonal antibody, abrogates accelerated rejection and prolongs...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199102000-00004

    authors: Kupiec-Weglinski JW,Sablinski T,Hancock WW,Di Stefano R,Mariani G,Mix CT,Tilney NL

    更新日期:1991-02-01 00:00:00

  • Spontaneous anti-tubular-basement-membrane antibody production by lymphocytes isolated from a rejected allograft.

    abstract::The immunological events mediated by, and antigen specificity of, allograft-bound lymphocytes (ABLs) are poorly understood. To further define the role of antibody-mediated rejection, a rejected allograft from a patient with primary anti-TBM disease was sterilely minced and pressed through a microscreen. The ABLs were ...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-198602000-00008

    authors: Jordan SC,Barkley SC,Lemire JM,Sakai RS,Cohen A,Fine RN

    更新日期:1986-02-01 00:00:00

  • Recall response to cytomegalovirus in allograft recipients: mobilization of CD57+, CD28+ cells before expansion of CD57+, CD28- cells within the CD8+ T lymphocyte compartment.

    abstract:BACKGROUND:Strong correlations have been described between persistently elevated proportions of CD57+ (CD28-) CD8+high T lymphocytes and cytomegalovirus (CMV) infection, in healthy individuals as well as in transplant patients. We investigated whether secondary exposure to CMV triggers recall responses within the CD8 T...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199703150-00014

    authors: Hazzan M,Labalette M,Noel C,Lelievre G,Dessaint JP

    更新日期:1997-03-15 00:00:00

  • Immunosuppression of the elderly kidney transplant recipient.

    abstract::The growing number of elderly patients with end-stage kidney disease awaiting transplantation has resulted in a corresponding rise in the number of elderly transplant recipients. In this paper, we review existing literature on age-related changes, transplant outcomes, and complications in the elderly in an attempt to ...

    journal_title:Transplantation

    pub_type: 杂志文章,评审

    doi:10.1097/01.tp.0000275423.69689.dc

    authors: Danovitch GM,Gill J,Bunnapradist S

    更新日期:2007-08-15 00:00:00

  • Bcl-2 protection of islet allografts is unmasked by costimulation blockade.

    abstract::One major limitation in pancreatic islet transplantation is availability of donor tissue. Donor shortage is exacerbated by islet apoptosis from the stresses of islet isolation and transplantation. Furthermore, the side effects of immunosuppressive drugs preclude transplants into patients whose diabetes is controlled b...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/01.tp.0000132283.95107.9c

    authors: Sutherland RM,Allison J,Thomas HE,Brady JL,Kay TW,Lew AM

    更新日期:2004-05-27 00:00:00

  • The protective effects of the thromboxane synthetase inhibitor Dazmegrel on nephrotoxicity in cyclosporine-treated rats.

    abstract::Renal vasoconstriction has been implicated as a major contributing factor for the nephrotoxic effects of cyclosporine. In an attempt to assess the relative contribution of thromboxane (Tx), the effects of coadministering CsA with the selective Tx synthetase inhibitor, Dazmegrel (DAZ) (Pfizer, Inc.), were determined. R...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199111000-00016

    authors: Gladue RP,Newborg MF

    更新日期:1991-11-01 00:00:00

  • Transplantation of pediatric en bloc cadaver kidneys into adult recipients.

    abstract:BACKGROUND:To maximize the renal donor pool, cadaveric pediatric en bloc kidneys have been transplanted as a dual unit by some transplant centers. We compared the short- and long-term outcomes of adult recipients of cadaveric pediatric en bloc renal transplants versus those of matched recipients of cadaveric adult kidn...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199812270-00020

    authors: Hobart MG,Modlin CS,Kapoor A,Boparai N,Mastroianni B,Papajcik D,Flechner SM,Goldfarb DA,Fischer R,O'Malley KJ,Novick AC

    更新日期:1998-12-27 00:00:00

  • Comparison of specific radioimmunoassays for cyclosporine.

    abstract::This study compares two recently introduced radioimmunoassay kits involving specific monoclonal antibodies to cyclosporine. One kit (Sandimmun) involved 3H-labeled CsA (3H-CsA) as tracer and the other (CY-CLO-Trac-SP) involved a 125I-labeled conjugated derivative of CsA. The kits were nearly equivalent in method perfo...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-198904000-00019

    authors: Sgoutas DS,Hammarstrom M

    更新日期:1989-04-01 00:00:00

  • Effects of steroid hormones on phytohemagglutinin-stimulated human peripheral blood lymphocytes.

    abstract::The interactions of steroid hormones and human peripheral blood lymphocytes (PBLs) have been investigated following glass-wool column separation of PBLs and incubation in a serum-free medium in the presence of phytohemagglutinin (PHA). Addition of hydrocortisone or progesterone above physiological concentrations resul...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-197905000-00004

    authors: Neifeld JP,Tormey DC

    更新日期:1979-05-01 00:00:00

  • Delayed hepatic artery thrombosis in adult orthotopic liver transplantation-a 12-year experience.

    abstract:BACKGROUND:Although the clinical features of early hepatic artery thrombosis (HAT) are well defined, the features of delayed (more than 4 weeks after transplantation) hepatic artery thrombosis are less clearly defined. The aim of our study was to identify risk factors, clinical presentation, and outcome of management o...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-200106150-00018

    authors: Bhattacharjya S,Gunson BK,Mirza DF,Mayer DA,Buckels JA,McMaster P,Neuberger JM

    更新日期:2001-06-15 00:00:00

  • Adverse presensitization to renal transplants. Detection by utilization of a D locus antigen-defined lymphoblastoid cell panel as targets in antibody-dependent cell-mediated cytotoxicity assays.

    abstract::Sera obtained before transplantation from 52 consecutive renal allograft recipients were tested for antibody-dependent cell-mediated cytotoxicity (ADCC) and for complement-dependent cytotoxic antibodies (CDC). A D locus antigen-defined lymphoblastoid cell panel (B lymphoblastoid cell panel) was used as targets for the...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:

    authors: Suthanthiran M,Fotino M,Cheigh JS,Rubin AL,Novogrodsky A,Stenzel KH

    更新日期:1979-05-01 00:00:00

  • Morphometric analysis of neointimal formation in murine cardiac grafts: III. Dissociation of intestitial fibrosis from neointimal formation.

    abstract:BACKGROUND:This study examined the relationship between transplant vascular sclerosis (TVS) and tissue fibrosis, features of chronic rejection that can develop rapidly in accepted heterotopic murine cardiac allografts. METHODS:The rate of development of interstitial fibrosis or TVS development was determined by comput...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199710270-00020

    authors: Armstrong AT,Strauch AR,Starling RC,Sedmak DD,Orosz CG

    更新日期:1997-10-27 00:00:00

  • Separate clones of cytotoxic T lymphocytes are generated against private and public H-2 antigens.

    abstract::By cytolysis and monolayer absorption tests, the kinetics of the generation of CBA/H cytotoxic lymphocytes (Tc) in response to stimulation by H-2b antigens have been analyzed in vitro. The Tc population which reacts with public antigens of H-2b and H-2d strains shows peak activity in culture at 4 to 5 days, then rapi...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-198006000-00012

    authors: Schnagl HY,Boyle W

    更新日期:1980-06-01 00:00:00

  • Utility of colonoscopy in the evaluation of diarrhea in solid organ transplant recipients.

    abstract:BACKGROUND:Diarrhea is common in solid organ transplant recipients. Colonoscopy with random biopsies is performed frequently in the diagnostic evaluation of the posttransplant population with diarrhea. The purpose of this study was to determine the sensitivity of colonoscopy with random biopsy in determining a specific...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0b013e3181ae98ab

    authors: Rice JP,Spier BJ,Cornett DD,Walker AJ,Richie K,Pfau PR

    更新日期:2009-08-15 00:00:00

  • Cardiovascular risk profile of patients with acute liver failure after liver transplantation when compared with the general population.

    abstract:BACKGROUND:As opposed to most solid-organ transplant recipients, patients with acute liver failure exhibit a pretransplant health status more comparable with the general population, and any posttransplant cardiovascular risk excess should thus be more attributable to transplantation-related factors alone. METHODS:This...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0b013e3181bcd682

    authors: Aberg F,Jula A,Höckerstedt K,Isoniemi H

    更新日期:2010-01-15 00:00:00

  • Long-term improvement in renal function after cyclosporine reduction in renal transplant recipients with histologically proven chronic cyclosporine nephropathy.

    abstract:BACKGROUND:Chronic cyclosporine (CsA) nephropathy, which has been unequivocally documented in recipients of heart, heart-lung, liver, or bone marrow transplants, as well as in nontransplant situations, usually results in a progressive deterioration of renal function. In this study, we assessed the potential reversibili...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199803150-00010

    authors: Mourad G,Vela C,Ribstein J,Mimran A

    更新日期:1998-03-15 00:00:00

  • Dual-kidney transplantation with organs from expanded criteria donors: a long-term follow-up.

    abstract:BACKGROUND:Since 1995, dual-kidney transplantation using organs from marginal donors has been used at our center to expand the organ donor pool and decrease the waiting time for deceased donor kidney transplantation. This approach has allowed for a shorter waiting period without compromising outcome in the early posttr...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/01.tp.0000130452.01521.b1

    authors: Tan JC,Alfrey EJ,Dafoe DC,Millan MT,Scandling JD

    更新日期:2004-09-15 00:00:00

  • Everolimus interferes with healing of experimental intestinal anastomoses.

    abstract:BACKGROUND:Although clinical data suggest its existence, little is known about the effect of rapamycin derivatives on wound repair. This study aims to delineate the influence of the mammalian target of rapamycin inhibitor everolimus on wound healing in the rat intestine. METHODS:Four groups of 26 male Wistar rats rece...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/01.tp.0000246078.09845.9c

    authors: van der Vliet JA,Willems MC,de Man BM,Lomme RM,Hendriks T

    更新日期:2006-12-15 00:00:00

  • Pathophysiological Trends During Withdrawal of Life Support: Implications for Organ Donation After Circulatory Death.

    abstract:BACKGROUND:Donation after circulatory death (DCD) provides an alternative pathway to deceased organ transplantation. Although clinical DCD lung, liver, and kidney transplantation are well established, transplantation of hearts retrieved from DCD donors has reached clinical translation only recently. Progress has been l...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0000000000001396

    authors: Iyer A,Chew HC,Gao L,Villanueva J,Hicks M,Doyle A,Kumarasinghe G,Jabbour A,Jansz PC,Feneley MP,Harvey RP,Graham RM,Dhital KK,Macdonald PS

    更新日期:2016-12-01 00:00:00

  • Exercise training in solid organ transplant recipients: a systematic review and meta-analysis.

    abstract:BACKGROUND:Exercise training is effective in improving the cardiovascular risk profiles of nontransplanted patients, but the health benefits and potential harms of routine exercise training after solid organ transplantation are unclear. This study aims to assess the health benefits and harms of supervised exercise trai...

    journal_title:Transplantation

    pub_type: 杂志文章,meta分析,评审

    doi:10.1097/TP.0b013e31827a3d3e

    authors: Didsbury M,McGee RG,Tong A,Craig JC,Chapman JR,Chadban S,Wong G

    更新日期:2013-03-15 00:00:00

  • Analysis of factors affecting recurrence of hepatocellular carcinoma after liver transplantation with a special focus on inflammation markers.

    abstract:BACKGROUND:Systemic inflammation markers, such as neutrophil-to-lymphocyte ratio (NLR), have recently emerged as the prognostic factors for recurrence of liver tumors. METHODS:We assessed the ability of NLR and of other variables to predict the outcomes of orthotopic liver transplantation (OLT) for hepatocellular carc...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0b013e3182187cf0

    authors: Bertuzzo VR,Cescon M,Ravaioli M,Grazi GL,Ercolani G,Del Gaudio M,Cucchetti A,D'Errico-Grigioni A,Golfieri R,Pinna AD

    更新日期:2011-06-15 00:00:00