Gemcitabine-a Novel Immunosuppressive Agent-Prevents Rejection in a Rat Cardiac Transplantation Model1

Margreiter, Raimund; Fischer, Michael A.; Roberts, Kurt E.; Schmid, Thomas; Hittmair, A; Schirmer, Michael; Geisen, Francoise; Tiefenthaler, Martin; Konwalinka, G

doi:10.1097/00007890-199910150-00025

Cited by 12 publications

(8 citation statements)

References 9 publications

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“…dFdC has already been widely used in humans as an anticancer drug because of its cytotoxic potential with few side effects. As an immunosuppressive drug, dFdC was successfully tested in a rat cardiac transplantation model to prevent GVHD (12). In these rats, however, dFdC was started even before cardiac transplantation, ensuring higher levels of dFdC during the onset of GVHD.…”

Section: Discussionmentioning

confidence: 99%

“…As a cytotoxic agent, dFdC is widely used for the treatment of solid malignancies and refractory hematologic malignancies (9,10). Besides, in vitro studies revealed an inhibitory effect of dFdC on lymphocytes and bone marrow progenitors (11), and an immunosuppressive effect was described in a rat cardiac transplantation model (12). Therefore, we hypothesized that dFdC may also be a promising alternative for treatment of ABD lesions.…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic effects of gemcitabine on cutaneous manifestations in an Adamantiades–Behçet's disease‐like mouse model

Sohn

Lutz²,

Kwon

et al. 2004

Experimental Dermatology

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The aim of this work was to study the effects and side effects of gemcitabine (2 0 ,2 0 -difluorodeoxycytidine, dFdC), a pyrimidine synthesis inhibitor, on skin lesions of a herpes simplex virus (HSV)-induced Adamantiades-Behc¸et's disease (ABD)-like mouse model. For the doseescalation study, ICR mice were treated intraperitoneally with dFdC over 5 days. For the efficacy study, ICR mice were inoculated with HSV and classified as having ABD according to a revised Japanese classification, and then 18 ABD mice were randomly assigned to placebo, 0.06 or 0.12 mg of dFdC/day over 5 days. Serum levels of interleukin-4 (IL-4), IL-6, IL-10, interferon-g (IFN-g), and tumor necrosis factor-a (TNF-a) were determined using enzyme-linked immunosorbent assay. After application of 3 mg of dFdC over 5 days, alanine aminotransferase increased (P ¼ 0.032), but all other kidney and liver parameters were unchanged. In ABD mice, 5 days of dFdC treatment with 0.06 or 0.12 mg of dFdC/day resulted in a dose-dependent improvement of cutaneous manifestations by more than 60% (P ¼ 0.017). There was no significant change in cytokine levels, and none of the cytokine levels correlated with response to treatment. Moreover, dFdC shows promising effects to improve cutaneous lesions in the HSV-induced ABD-like mouse model. In this animal model, effects of dFdC on the cytokine profile remained inconclusive.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Therapeutic effects of gemcitabine on cutaneous manifestations in an Adamantiades–Behçet's disease‐like mouse model

Sohn

Lutz²,

Kwon

et al. 2004

Experimental Dermatology

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“…One of these agents could be gemcitabine, a drug showing, at standard cytotoxic dose, relatively low total toxicity. Its immunosuppressive action was first assessed by a team headed by Margreiter [3] in a model of heart transplantation in the rat, with encouraging preliminary results. They confirmed the hypothesis that multiple administration of low-dose dFdC has a primary effect on immunocompetent cells.…”

Section: Discussionmentioning

confidence: 99%

Gemcitabine does not prevent acute rejection of the transplanted liver in rats

et al. 2004

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Our study was designed to determine effect of gemcitabine on acute rejection of liver in rats. Liver transplantation was performed in rats of the Dark Agouti (DA) and Lewis (LEW) strains. Recipients were divided into three groups: A, DA-to-LEW without inimunosuppression; B, DA-to-LEW, treated with cyclosporine A; C, DA-to-LEW, treated with gemcitabine. Immunosuppressants were subcutaneously injected for seven consecutive days after transplantation. On day 7, blood samples and liver graft tissue specimens were harvested. Group A showed severe rejection changes (RAI 8/9); in group B no rejection changes were present (RAI 0/9), and in group C moderate rejection changes were observed (RAI 6/9). Differences were significant between B vs C and A vs C groups; P < 0.05. Serum creatinine and urea levels in the gemcitabine group were significantly lower than those in the cyclosporine A group. We did not confirm gemcitabine ability to prevent liver allograft rejection.

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“…Initial studies on the effects of the drug in lymphocyte colony-forming assays showed that the drug inhibited the PHA-induced lymphocyte proliferation in vitro and that it prolonged significantly the survival of rats implanted an allogeneic heart [236]. Gemcitabine (2,2'difluorodeoxycytidine) (dFdC) is an antimetabolite which is useful in the treatment of pancreatic cancer.…”

Section: Fluorouracil (5fu)mentioning

confidence: 99%

Anticancer Drug-Induced Immunomodulation and Cancer Therapeutics

Mihich

2007

CCTR

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In the light of increasing knowledge on the regulation of the efferent and afferent branches of antitumor immunity, on tumor-induced imbalances of immune response and on tumor escape mechanisms, it seem important to review the information available on the immunomodulating effects of anticancer drugs and their possible exploitation in cancer therapeutics.The immunomodulation induced by several antitumor antibiotics is considered with particular emphasis on the effects of Doxorubicin and their therapeutic exploitation. The immunomodulating effects of anticancer drugs considered include those of cyclophosphamide and other alkylating agents, of 6-mercaptopurine and other antimetabolities, of Vinca alkaloida, Taxanes, Thalidomide, Gleevec and Difluoromethyl ornithine. The positive effects on tumor immunity are discussed with reference to their potential exploitation in the therapeutics. The effects of certain anticancer drugs on tumor antigen expression are also discussed as a mechanism by which these agents increase tumor immunogenicity with consequent advantages for therapeutic exploitation and vaccine effectiveness. The need for increased molecular and clinical studies of anticancer drugs-induced immunomodulation is emphasized.

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Gemcitabine-a Novel Immunosuppressive Agent-Prevents Rejection in a Rat Cardiac Transplantation Model1

Abstract: DFdC is a new immunosuppressive agent that can successfully prevent cardiac rejection in a rat transplantation model.

Cited by 12 publications

References 9 publications

Therapeutic effects of gemcitabine on cutaneous manifestations in an Adamantiades–Behçet's disease‐like mouse model

Therapeutic effects of gemcitabine on cutaneous manifestations in an Adamantiades–Behçet's disease‐like mouse model

Gemcitabine does not prevent acute rejection of the transplanted liver in rats

Anticancer Drug-Induced Immunomodulation and Cancer Therapeutics

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