Tacrolimus enhances transforming growth factor-beta1 expression and promotes tumor progression.

Abstract:

BACKGROUND:Immunosuppressive therapy is a risk factor for the increased incidence and metastatic progression of malignancies in organ graft recipients. Transforming growth factor (TGF)-beta(1) has been associated with tumor invasion and metastasis, and we have implicated cyclosporine-associated TGF-beta(1) hyperexpression in tumor progression in mice. METHODS:BALB/c mice or severe combined immunodeficient-beige mice were treated with 2 or 4 mg/kg of tacrolimus, and the effect of treatment on mouse renal cancer cell pulmonary metastasis was investigated. We also determined whether tacrolimus induces TGF-beta(1) expression. Spleens from tacrolimus-treated mice were analyzed for level of expression of TGF-beta(1) mRNA with the use of competitive-quantitative polymerase chain reaction assay, and circulating levels of TGF-beta(1) protein were measured with the use of an enzyme-linked immunosorbent assay. RESULTS:Treatment with tacrolimus resulted in a dose-dependent increase in the number of pulmonary metastases in the BALB/c mice (197+/-16 in untreated mice, 281+/-26 in mice treated with 2 mg/kg of tacrolimus, and 339+/-25 in mice treated with 4 mg/kg of tacrolimus; no treatment vs. 4 mg/kg tacrolimus, Bonferroni's P<0.001) and in the severe combined immunodeficient-beige mice (117+/-18 in untreated mice, 137+/-19 in mice treated with 2 mg/kg of tacrolimus, and 216+/-29 in mice treated with 4 mg/kg of tacrolimus; no treatment vs. 4 mg/kg tacrolimus, P<0.05). Treatment with 4 mg/kg but not 2 mg/kg of tacrolimus resulted in a significant increase in the levels of expression of TGF-beta(1) mRNA and circulating levels of TGF-beta(1) protein. CONCLUSIONS:Tacrolimus has a dose-dependent effect on tumor progression and TGF-beta(1) expression, and tacrolimus-induced TGF-beta(1) overexpression may be a pathogenetic mechanism in tumor progression.

journal_name

Transplantation

journal_title

Transplantation

authors

Maluccio M,Sharma V,Lagman M,Vyas S,Yang H,Li B,Suthanthiran M

doi

10.1097/01.TP.0000081399.75231.3B

subject

Has Abstract

pub_date

2003-08-15 00:00:00

pages

597-602

issue

3

eissn

0041-1337

issn

1534-6080

journal_volume

76

pub_type

杂志文章
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    authors: Madayag RM,Johnson LB,Bartlett ST,Schweitzer EJ,Constantine NT,McCarter RJ Jr,Kuo PC,Keay S,Oldach DW

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  • Flow cytometry cross-match: a method for predicting graft rejection.

    abstract::Long-term graft survival is mainly influenced by early graft rejection and posttransplant graft function. The ability of both complement-dependent cytotoxicity cross-match (CDC) and flow cytometry cross-match (FCXM) to predict acute rejection episodes has been evaluated by cross-matching 40 patients who received cadav...

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    authors: Utzig MJ,Blümke M,Wolff-Vorbeck G,Lang H,Kirste G

    更新日期:1997-02-27 00:00:00

  • Selection and outcome of living donors for adult to adult right lobe transplantation.

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    authors: Marcos A,Fisher RA,Ham JM,Olzinski AT,Shiffman ML,Sanyal AJ,Luketic VA,Sterling RK,Olbrisch ME,Posner MP

    更新日期:2000-06-15 00:00:00

  • Immune response, accommodation, and tolerance to transplantation carbohydrate antigens.

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  • Tendinitis--a common complication after renal transplantation.

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    doi:

    authors: Murison MS,Eardley I,Slapak M

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  • CMV-specific Cell-mediated Immunity at 3-month Prophylaxis Withdrawal Discriminates D+/R+ Kidney Transplants at Risk of Late-onset CMV Infection Regardless the Type of Induction Therapy.

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    doi:10.1097/TP.0000000000002421

    authors: Jarque M,Melilli E,Crespo E,Manonelles A,Montero N,Torras J,Cruzado JM,Luque S,Gil-Vernet S,Grinyó JM,Bestard O

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  • Liver transplantation restores endocrine cells in patients with familial amyloidotic polyneuropathy.

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    authors: Anan I,El-Salhy M,Nyhlin N,Suhr OB

    更新日期:2000-09-15 00:00:00

  • Nutritional immunomodulation enhances cardiac allograft survival in rats treated with donor-specific transfusion and cyclosporine.

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    journal_title:Transplantation

    pub_type: 杂志文章

    doi:

    authors: Levy AE,Alexander JW

    更新日期:1995-10-27 00:00:00

  • The high incidence of BK polyoma virus infection among renal transplant recipients in India.

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    pub_type: 杂志文章

    doi:10.1097/01.TP.0000113163.02039.30

    authors: Sachdeva MS,Nada R,Jha V,Sakhuja V,Joshi K

    更新日期:2004-02-15 00:00:00

  • Hemostatic complications in bone marrow transplantation: a retrospective analysis of 447 patients.

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    journal_title:Transplantation

    pub_type: 杂志文章

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    authors: Pihusch R,Salat C,Schmidt E,Göhring P,Pihusch M,Hiller E,Holler E,Kolb HJ

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  • Improved metabolic control and quality of life in seven patients with type 1 diabetes following islet after kidney transplantation.

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    authors: Cure P,Pileggi A,Froud T,Messinger S,Faradji RN,Baidal DA,Cardani R,Curry A,Poggioli R,Pugliese A,Betancourt A,Esquenazi V,Ciancio G,Selvaggi G,Burke GW 3rd,Ricordi C,Alejandro R

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  • Predominant role of the Fab fragment in delaying hyperacute rejection in guinea pig-to-rat xenotransplantation.

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    authors: Urbani L,Fabre M,Cardoso J,Lambin P,Devillier P,Soubrane O,Houssin D,Gautreau C

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    authors: Aranda JM Jr,Scornik JC,Normann SJ,Lottenberg R,Schofield RS,Pauly DF,Miles M,Hill JA,Sleasman JW,Skoda-Smith S

    更新日期:2002-03-27 00:00:00

  • Failure to alter neonatal transplantation tolerance by the injection of interleukin 2.

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    pub_type: 杂志文章

    doi:10.1097/00007890-198802000-00041

    authors: Tempelis CH,Hála K,Krömer G,Schauenstein K,Wick G

    更新日期:1988-02-01 00:00:00

  • Long-term outcome of controlled, non-heart-beating donor liver transplantation.

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    journal_title:Transplantation

    pub_type: 杂志文章

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    authors: Manzarbeitia CY,Ortiz JA,Jeon H,Rothstein KD,Martinez O,Araya VR,Munoz SJ,Reich DJ

    更新日期:2004-07-27 00:00:00

  • Human hepatic stellate cells inhibit T-cell response through B7-H1 pathway.

    abstract:BACKGROUND:The liver is an immunologic privileged organ; liver allografts are accepted across major histocompatibility complex barriers in many species. However, hepatocyte transplants are acutely rejected, suggesting a role for liver nonparenchymal cells in regulating the immunoresponse. We have shown potent immunoreg...

    journal_title:Transplantation

    pub_type: 杂志文章

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    authors: Charles R,Chou HS,Wang L,Fung JJ,Lu L,Qian S

    更新日期:2013-07-15 00:00:00

  • Cell and extracellular matrix rejection in arterial concordant and discordant xenografts in the rat.

    abstract::Vascularized xenografts are rejected acutely and hyperacutely in concordant or discordant combinations, respectively. We investigated the impact of the donor-recipient combination on the rejection of arterial xenografts, analyzing the cellular and extracellular matricial compartments. Aortic xenografts were performed ...

    journal_title:Transplantation

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    authors: Allaire E,Mandet C,Bruneval P,Bensenane S,Becquemin JP,Michel JB

    更新日期:1996-09-27 00:00:00

  • Different kinetics of obliterative airway disease development in heterotopic murine tracheal allografts induced by CD4+ and CD8+ T cells.

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    journal_title:Transplantation

    pub_type: 杂志文章

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    authors: Higuchi T,Jaramillo A,Kaleem Z,Patterson GA,Mohanakumar T

    更新日期:2002-09-15 00:00:00

  • CD4+CD25+ cells regulate CD8 cell anergy in neonatal tolerant mice.

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    journal_title:Transplantation

    pub_type: 杂志文章

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    authors: Gao Q,Rouse TM,Kazmerzak K,Field EH

    更新日期:1999-12-27 00:00:00

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    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-198809000-00011

    authors: Peest D,Schaper B,Nashan B,Wonigeit K,Raude E,Pichlmayr R,Haverich A,Deicher H

    更新日期:1988-09-01 00:00:00

  • Magnetic resonance-defined perinephric edema after clinical islet transplantation: a benign finding associated with mild renal impairment.

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    pub_type: 杂志文章

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    更新日期:2004-09-27 00:00:00

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    pub_type: 杂志文章

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    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0b013e31821cdf0d

    authors: Hönger G,Hopfer H,Arnold ML,Spriewald BM,Schaub S,Amico P

    更新日期:2011-07-15 00:00:00

  • Cardiovascular Parameters to 2 years After Kidney Transplantation Following Early Switch to Everolimus Without Calcineurin Inhibitor Therapy: An Analysis of the Randomized ELEVATE Study.

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    pub_type: 杂志文章,多中心研究,随机对照试验

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    doi:

    authors: van der Hem LG,van der Vliet JA,Bocken CF,Kino K,Hoitsma AJ,Tax WJ

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

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    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

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    pub_type: 杂志文章

    doi:10.1097/00007890-199410270-00015

    authors: Everett JP,Shipley GD,Mauck KA,Wagner CR,Morris TE,Hosenpud JD

    更新日期:1994-10-27 00:00:00

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    journal_title:Transplantation

    pub_type: 杂志文章

    doi:

    authors: Almond PS,Moss A,Nakhleh RE,Melin M,Chen S,Salazar A,Shirabe K,Matas AJ

    更新日期:1993-08-01 00:00:00

  • Regulatory T cells: potential in organ transplantation.

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    pub_type: 杂志文章,评审

    doi:10.1097/01.TP.0000106477.70852.29

    authors: Wood KJ,Luo S,Akl A

    更新日期:2004-01-15 00:00:00

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    pub_type: 杂志文章

    doi:

    authors: Sutton P,Moreland A,Hutchinson IV,Müllbacher A

    更新日期:1995-11-15 00:00:00