Immunosuppressive action of FTY720 for renal allograft a rat model

Kunikata, S; Nagano, Tomoya; Nishioka, Tsukasa; Akiyama, Takahiro; Kurita, Takashi

doi:10.1016/s0041-1345(98)01944-7

Cited by 10 publications

(2 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to its properties, FTY720 has been investigated as an immunosuppressive agent in organ and tissue transplants [ 382 – 386 ]. In particular, FTY720 accumulates in lymph nodes and inhibits the egress of lymphocytes [ 387 ].…”

Section: Sphingosine-1-phosphatementioning

confidence: 99%

New extracellular factors in glioblastoma multiforme development: neurotensin, growth differentiation factor-15, sphingosine-1-phosphate and cytomegalovirus infection

et al. 2018

View full text Add to dashboard Cite

Recent years have seen considerable progress in understanding the biochemistry of cancer. For example, more significance is now assigned to the tumor microenvironment, especially with regard to intercellular signaling in the tumor niche which depends on many factors secreted by tumor cells. In addition, great progress has been made in understanding the influence of factors such as neurotensin, growth differentiation factor-15 (GDF-15), sphingosine-1-phosphate (S1P), and infection with cytomegalovirus (CMV) on the ‘hallmarks of cancer’ in glioblastoma multiforme.Therefore, in the present work we describe the influence of these factors on the proliferation and apoptosis of neoplastic cells, cancer stem cells, angiogenesis, migration and invasion, and cancer immune evasion in a glioblastoma multiforme tumor. In particular, we discuss the effect of neurotensin, GDF-15, S1P (including the drug FTY720), and infection with CMV on tumor-associated macrophages (TAM), microglial cells, neutrophil and regulatory T cells (Treg), on the tumor microenvironment. In order to better understand the role of the aforementioned factors in tumoral processes, we outline the latest models of intratumoral heterogeneity in glioblastoma multiforme. Based on the most recent reports, we discuss the problems of multi-drug therapy in treating glioblastoma multiforme.

show abstract

Section: Sphingosine-1-phosphatementioning

confidence: 99%

New extracellular factors in glioblastoma multiforme development: neurotensin, growth differentiation factor-15, sphingosine-1-phosphate and cytomegalovirus infection

et al. 2018

View full text Add to dashboard Cite

show abstract

“…However, in combination with suboptimal doses of cyclosporin or tacrolimus it has synergistic action and potentiates the immunosuppressive effects of either drug, without inducing drug-related adverse events such as nephro-and neurotoxicity. [167][168][169] Further clinical trials are in progress to evaluate the potential of FTY720 for clinical application in organ transplantation in humans.…”

Section: Fty720mentioning

confidence: 99%

Immunosuppressive Drugs in Paediatric Liver Transplantation

Mourik

Kelly

2001

Paediatric Drugs

View full text Add to dashboard Cite

Orthotopic liver transplantation is established treatment for children with acute and chronic liver failure. Despite advances in pre- and postoperative management, innovative surgical techniques and new immunosuppressive drugs, acute and chronic rejection remains a problem. In addition, well established adverse effects of commonly used immunosuppressive drugs are no longer accept able. More potent, but less toxic, immunosuppressive agents have been developed and some novel compounds are now entering routine practice. Cyclosporin was the cornerstone of immunosuppressive therapy until the introduction of its novel pharmaceutical form (Neoral) with improved bioavailability, lower inter- and intraindividual pharmacokinetic variability and improved graft survival. Recently, tacrolimus, a macrolide drug with a similar mode of action, but much higher potency, was introduced and, at present, is the only agent which can successfully replace cyclosporin as a first-line immunosuppressive drug. Mycophenolate mofetil has recently been approved for use in adult and paediatric renal transplant recipients. It has a similar mode of action to cyclosporin and tacrolimus, but acts at a later stage of the T cell activation pathway. Administration with standard immunosuppressive drugs reduces the incidence of acute rejection and enables cyclosporin and tacrolimus dose reduction, thus reducing the risk of associated toxic effects. Phase I and II trials with sirolimus (rapamycin), a macrolide antibiotic, have shown comparable immunosuppressive action, when administered in conjunction with standard immunosuppressants. Further clinical trials need to be carried out to establish efficacy, tolerability and pharmacokinetics in paediatric transplant recipients. Monoclonal antibody therapy (daclizumab and basiliximab) is an exciting new development whereby T cell proliferation is inhibited by selective blockade of interleukin (IL)-2 receptors. Preliminary results, when used in combination with a standard immunosuppressive regimen, are good with respect to incidence of acute graft rejection, host immune response and adverse effects. FTY720 is a novel synthetic immunosuppressive compound which induces a reduction in peripheral blood lymphocyte count through apoptotic T cell death or accelerated trafficking of T cells into lymphatic tissues. Experimental animal studies demonstrated synergistic action in combination with low dose cyclosporin or tacrolimus, potentiating their immunosuppressive effects. Further studies are being carried out to determine its potential for application in organ transplantation. Despite this rapid development of novel compounds, it will take many years before they may become part of standard protocols in paediatric transplantation medicine. Further development and research of efficacy and tolerability of existing drugs is, therefore, vital.

show abstract

Organ TransplantDrugs

Kundu

2003

Burger's Medicinal Chemistry and Drug Discovery

View full text Add to dashboard Cite

In recent years several new immunosuppressive agents for organ transplantation have been introduced for clinical usage. They have greater efficacy and fewer side effects than those of the classical therapies involving corticosteroids, azathioprine, and cyclosporine. The new maintenance immunosuppressive drugs are either immunophilin‐binding drugs or are inhibitors of de novo synthesis of nucleotides (purines or pyrimidines) that inhibit signal transduction in lymphocytes. The immunophilin‐binding drugs are cyclosporine, tacrolimus, and rapamycin, whereas inhibitors of de novo nucleotide synthesis include mycophenolate mofetil, mizoribine, brequinar, and leflunomide. Gusperimus (deoxyspergualin), which inhibits IL‐1 synthesis, was useful in reversing early and late acute rejection in clinical trials. FTY‐720, another promising drug, prolonged the survival of allografts and synergized with cyclosporin and sirolimus in experimental models. Antibody preparations such as OKT3, as well as the newer recombinant products, which specifically bind to the IL‐2 receptor, basiliximab, and daclizumab, not only reduced acute rejection but were associated with few adverse effects. Antisense oligonucleotides that interfere with the intercellular adhesion molecules involved in rejection gave encouraging results in primate renal allografts. Use of stem cells, donor bone marrow, and xenotransplantation are some of the alternatives that are likely to find application in organ transplantation in the near future.

show abstract

Immunosuppressive action of FTY720 for renal allograft a rat model

Cited by 10 publications

References 7 publications

New extracellular factors in glioblastoma multiforme development: neurotensin, growth differentiation factor-15, sphingosine-1-phosphate and cytomegalovirus infection

New extracellular factors in glioblastoma multiforme development: neurotensin, growth differentiation factor-15, sphingosine-1-phosphate and cytomegalovirus infection

Immunosuppressive Drugs in Paediatric Liver Transplantation

Organ TransplantDrugs

Contact Info

Product

Resources

About