Comparison of effects of sirolimus on cytokine dependent and cytokine independent proliferation

Molnar-Kimber, Katherine L.; Rhoad, A.; Warner, L.; Chen, H.; Sehgal, Suren N.

doi:10.1007/bf01778325

Cited by 2 publications

(1 citation statement)

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“…It has been shown that SRL can reduce the likelihood of metastasis by increasing the expression of E‐cadherin, which increases the binding affinity of tumor cells to each other (15). Regarding the antitumoral activity of SRL, it has been shown that SRL inhibits the proliferation of transformed cell lines of lymphoid, CNS, hepatic, melanocytic, osteoblastic, myogenic, renal, and connective tissue origin as well as proliferation of T and B cells transformed by HTLV‐1 and EBV (16). In experimental studies, it has been shown that SRL has antiproliferative effects on certain types of tumors like renal cell cancer, rhabdomyosarcoma, B‐ and T‐cell lymphoma, glioma, breast cancer, colon carcinoma, multiple myeloma, ovarian cancer, prostate cancer, bladder cell carcinoma, non‐small cell lung cancer, pancreatic cancer, melanoma and hepatocellular carcinoma and it also has antiangiogenic capability by which it could prevent tumor growth (4, 17).…”

Section: Sirolimus (Rapamune®)mentioning

confidence: 99%

The role and value of sirolimus administration in kidney and liver transplantation

Mehrabi¹,

Fonouni²,

Kashfi³

et al. 2006

Clinical Transplantation

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Enormous advancements in visceral transplantation have led to significant improvements in the quality of life of patients. However, despite these developments, the average graft half-life after transplantation has remained almost unchanged and chronic rejection is still considered a major problem. In this regard, more concerns have shifted to factors influencing long-term graft survival, patient survival, and quality of life. To achieve this goal, detrimental effects of immunosuppressive (IS) agents, which have deleterious influence on the quality of life and/or patient survival, should be reduced. In the course of recent years, the transplant community has worked on reducing these side effects by developing new ISs, employing new combination regimens, or finding and adjusting optimal dosages and blood level concentrations. Among the IS agents, the antifungal, antitumoral and IS activity of mammalian target of rapamycin (mTOR) inhibitors without nephrotoxicity, have received special attention regarding this new class of IS. Sirolimus (SRL), as the first member of mTOR inhibitors, has been utilized in many clinical trials with respect to its benefit-risk assessment. In our review, the clinical evolution of SRL, as well as the evidence-based clinical benefits of SRL in kidney and liver transplantation (KTx, LTx), are summarized. Various studies of SRL in KTx and LTx have shown that combination therapy with SRL will enrich the variety of IS modalities. It also can be regarded as a safe base therapy to which other necessary drugs can be added. In addition to the enhanced acute rejection prophylaxis, and in contrast to the calcineurin inhibitors (CNI) and steroids, this drug solely does not have common side effects such as nephrotoxicity, neurotoxicity, diabetes mellitus and hypertension. Moreover, this agent might diminish vasculopathic processes that mediate chronic allograft nephropathy (CAN). Therefore, by reducing the likelihood of CAN it can decrease the rate of long-term organ failure. One possibly desirable characteristic of SRL is its antiproliferative effect, which could provoke antitumoral or antiatherogenic activity following transplantation. Despite all promising impacts of SRL in organ transplantation, there are some concerns regarding the adverse effects of this drug, for instance dyslipidemia, pneumonitis and wound healing problems. However, the majority of these side effects can be reduced or ceased by careful dose adjustments and correct timing of use. In conclusion, after a decade of both in vivo and in vitro studies on SRL, it can be advocated that SRL is a promising, potent and effective IS agent as it reduces the rate of acute rejection episodes in de novo transplants. It could improve the quality of life, graft and patient survival rate, and achieve excellent outcomes with few adverse effects when wisely used in combination with other immunosuppressants.

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Section: Sirolimus (Rapamune®)mentioning

confidence: 99%