A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.
Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.
A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.
The transference of a kidney from one human or animal to another.
A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).
An antibiotic substance derived from Penicillium stoloniferum, and related species. It blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase. Mycophenolic acid is important because of its selective effects on the immune system. It prevents the proliferation of T-cells, lymphocytes, and the formation of antibodies from B-cells. It also may inhibit recruitment of leukocytes to inflammatory sites. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1301)
A CALCIUM and CALMODULIN-dependent serine/threonine protein phosphatase that is composed of the calcineurin A catalytic subunit and the calcineurin B regulatory subunit. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including HISTONES; MYOSIN LIGHT CHAIN; and the regulatory subunits of CAMP-DEPENDENT PROTEIN KINASES. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes.
An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient.
The practice of replacing one prescribed drug with another that is expected to have the same clinical or psychological effect.
A disease characterized by the progressive invasion of SMOOTH MUSCLE CELLS into the LYMPHATIC VESSELS, and the BLOOD VESSELS. The majority of the cases occur in the LUNGS of women of child-bearing age, eventually blocking the flow of air, blood, and lymph. The common symptom is shortness of breath (DYSPNEA).
A benign tumor containing vascular, adipose, and muscle elements. It occurs most often in the kidney with smooth muscle elements (angiolipoleiomyoma) in association with tuberous sclerosis. (Dorland, 27th ed)
A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.
The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host.
A tumorlike condition characterized by SMOOTH MUSCLE and ENDOTHELIUM proliferation of LYMPHATIC VESSELS and LYMPH NODES in the MEDIASTINUM and retroperitoneum, also in the lung. It may be manifested by chylous PLEURAL EFFUSION and ASCITES.
The administration of substances into the eye with a hypodermic syringe.
Recurrent narrowing or constriction of a coronary artery following surgical procedures performed to alleviate a prior obstruction.
Therapy with two or more separate preparations given for a combined effect.
Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.
An opaque, milky-white fluid consisting mainly of emulsified fats that passes through the lacteals of the small intestines into the lymphatic system.
The transference of a part of or an entire liver from one human or animal to another.
Hydrocarbons with more than one double bond. They are a reduced form of POLYYNES.
Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals.
Stents that are covered with materials that are embedded with chemicals that are gradually released into the surrounding milieu.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
Agents that affect the rate or intensity of cardiac contraction, blood vessel diameter, or blood volume.
Elements of limited time intervals, contributing to particular results or situations.
The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically.
The transference of pancreatic islets within an individual, between individuals of the same species, or between individuals of different species.
Small containers or pellets of a solid drug implanted in the body to achieve sustained release of the drug.
The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to INULIN clearance.
Transference of a tissue or organ from either an alive or deceased donor, within an individual, between individuals of the same species, or between individuals of different species.
Fluoroimmunoassay where detection of the hapten-antibody reaction is based on measurement of the increased polarization of fluorescence-labeled hapten when it is combined with antibody. The assay is very useful for the measurement of small haptenic antigens such as drugs at low concentrations.
Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.
Devices that provide support for tubular structures that are being anastomosed or for body cavities during skin grafting.
Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs.
Diseases that result in THROMBOSIS in MICROVASCULATURE. The two most prominent diseases are PURPURA, THROMBOTIC THROMBOCYTOPENIC; and HEMOLYTIC-UREMIC SYNDROME. Multiple etiological factors include VASCULAR ENDOTHELIAL CELL damage due to SHIGA TOXIN; FACTOR H deficiency; and aberrant VON WILLEBRAND FACTOR formation.
Agents that interact with TUBULIN to inhibit or promote polymerization of MICROTUBULES.
A dicarboxylic acid ketone that is an important metabolic intermediate of the CITRIC ACID CYCLE. It can be converted to ASPARTIC ACID by ASPARTATE TRANSAMINASE.
Biocompatible materials usually used in dental and bone implants that enhance biologic fixation, thereby increasing the bond strength between the coated material and bone, and minimize possible biological effects that may result from the implant itself.
A plant species of the genus CITRUS, family RUTACEAE that produces the familiar grapefruit. There is evidence that grapefruit inhibits CYTOCHROME P-450 CYP3A4, resulting in delayed metabolism and higher blood levels of a variety of drugs.
Kidney disorders with autosomal dominant inheritance and characterized by multiple CYSTS in both KIDNEYS with progressive deterioration of renal function.
An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance has been listed as a known carcinogen. (Merck Index, 11th ed)
Compounds used extensively as acetylation, oxidation and dehydrating agents and in the modification of proteins and enzymes.
The transference of a heart from one human or animal to another.
Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
Providers of tissues for transplant to non-related individuals.
Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.
Serum containing GAMMA-GLOBULINS which are antibodies for lymphocyte ANTIGENS. It is used both as a test for HISTOCOMPATIBILITY and therapeutically in TRANSPLANTATION.
Autosomal dominant neurocutaneous syndrome classically characterized by MENTAL RETARDATION; EPILEPSY; and skin lesions (e.g., adenoma sebaceum and hypomelanotic macules). There is, however, considerable heterogeneity in the neurologic manifestations. It is also associated with cortical tuber and HAMARTOMAS formation throughout the body, especially the heart, kidneys, and eyes. Mutations in two loci TSC1 and TSC2 that encode hamartin and tuberin, respectively, are associated with the disease.
A loss of mucous substance of the mouth showing local excavation of the surface, resulting from the sloughing of inflammatory necrotic tissue. It is the result of a variety of causes, e.g., denture irritation, aphthous stomatitis (STOMATITIS, APHTHOUS); NOMA; necrotizing gingivitis (GINGIVITIS, NECROTIZING ULCERATIVE); TOOTHBRUSHING; and various irritants. (From Jablonski, Dictionary of Dentistry, 1992, p842)
Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.
Laboratory tests used to evaluate how well the kidneys are working through examination of blood and urine.
A family of mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. These cells do not have a normal anatomic homolog. (From Fletcher CDM, et. al., World Health Organization Classification of Tumors: Pathology and Genetics of Tumors of Soft Tissue and Bone, 2002).
A family of ribosomal protein S6 kinases that are considered the major physiological kinases for RIBOSOMAL PROTEIN S6. Unlike RIBOSOMAL PROTEIN S6 KINASES, 90KDa the proteins in this family are sensitive to the inhibitory effects of RAPAMYCIN and contain a single kinase domain. They are referred to as 70kDa proteins, however ALTERNATIVE SPLICING of mRNAs for proteins in this class also results in 85kDa variants being formed.
A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.
Abnormal passage in any organ of the biliary tract or between biliary organs and other organs.
Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body.
A detailed review and evaluation of selected clinical records by qualified professional personnel to improve the quality of patient care and outcomes. The clinical audit was formally introduced in 1993 into the United Kingdom's National Health Service.
Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.
Abnormally infrequent menstruation.
Preparative treatment of transplant recipient with various conditioning regimens including radiation, immune sera, chemotherapy, and/or immunosuppressive agents, prior to transplantation. Transplantation conditioning is very common before bone marrow transplantation.
Drugs used for their effects on the respiratory system.
An order of zygomycetous fungi, usually saprophytic, causing damage to food in storage, but which may cause respiratory infection or MUCORMYCOSIS in persons suffering from other debilitating diseases.
Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.
A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)
Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery.
Implants constructed of materials designed to be absorbed by the body without producing an immune response. They are usually composed of plastics and are frequently used in orthopedics and orthodontics.
A cytochrome P-450 suptype that has specificity for a broad variety of lipophilic compounds, including STEROIDS; FATTY ACIDS; and XENOBIOTICS. This enzyme has clinical significance due to its ability to metabolize a diverse array of clinically important drugs such as CYCLOSPORINE; VERAPAMIL; and MIDAZOLAM. This enzyme also catalyzes the N-demethylation of ERYTHROMYCIN.
Non-cadaveric providers of organs for transplant to related or non-related recipients.
Organic salts and esters of benzenesulfonic acid.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Strategy for the analysis of RANDOMIZED CONTROLLED TRIALS AS TOPIC that compares patients in the groups to which they were originally randomly assigned.
Obstruction of flow in biological or prosthetic vascular grafts.
Radiography of the vascular system of the heart muscle after injection of a contrast medium.
The presence of proteins in the urine, an indicator of KIDNEY DISEASES.

High-throughput screening of small molecules in miniaturized mammalian cell-based assays involving post-translational modifications. (1/4814)

BACKGROUND: Fully adapting a forward genetic approach to mammalian systems requires efficient methods to alter systematically gene products without prior knowledge of gene sequences, while allowing for the subsequent characterization of these alterations. Ideally, these methods would also allow function to be altered in a temporally controlled manner. RESULTS: We report the development of a miniaturized cell-based assay format that enables a genetic-like approach to understanding cellular pathways in mammalian systems using small molecules, rather than mutations, as the source of gene-product alterations. This whole-cell immunodetection assay can sensitively detect changes in specific cellular macromolecules in high-density arrays of mammalian cells. Furthermore, it is compatible with screening large numbers of small molecules in nanoliter to microliter culture volumes. We refer to this assay format as a 'cytoblot', and demonstrate the use of cytoblotting to monitor biosynthetic processes such as DNA synthesis, and post-translational processes such as acetylation and phosphorylation. Finally, we demonstrate the applicability of these assays to natural-product screening through the identification of marine sponge extracts exhibiting genotype-specific inhibition of 5-bromodeoxyuridine incorporation and suppression of the anti-proliferative effect of rapamycin. CONCLUSIONS: We show that cytoblots can be used for high-throughput screening of small molecules in cell-based assays. Together with small-molecule libraries, the cytoblot assay can be used to perform chemical genetic screens analogous to those used in classical genetics and thus should be applicable to understanding a wide variety of cellular processes, especially those involving post-transitional modifications.  (+info)

Rapamycin causes poorly reversible inhibition of mTOR and induces p53-independent apoptosis in human rhabdomyosarcoma cells. (2/4814)

The mammalian target of rapamycin (mTOR) has been shown to link growth factor signaling and posttranscriptional control of translation of proteins that are frequently involved in cell cycle progression. However, the role of this pathway in cell survival has not been demonstrated. Here, we report that rapamycin, a specific inhibitor of mTOR kinase, induces G1 cell cycle arrest and apoptosis in two rhabdomyosarcoma cell lines (Rh1 and Rh30) under conditions of autocrine cell growth. To examine the kinetics of rapamycin action, we next determined the rapamycin sensitivity of rhabdomyosarcoma cells exposed briefly (1 h) or continuously (6 days). Results demonstrate that Rh1 and Rh30 cells were equally sensitive to rapamycin-induced growth arrest and apoptosis under either condition. Apoptosis was detected between 24 and 144 h of exposure to rapamycin. Both cell lines have mutant p53; hence, rapamycin-induced apoptosis appears to be a p53-independent process. To determine whether induction of apoptosis by rapamycin was specifically due to inhibition of mTOR signaling, we engineered Rh1 and Rh30 clones to stably express a mutant form of mTOR that was resistant to rapamycin (Ser2035-->Ile; designated mTOR-rr). Rh1 and Rh30 mTOR-rr clones were highly resistant (>3000-fold) to both growth inhibition and apoptosis induced by rapamycin. These results are the first to indicate that rapamycin-induced apoptosis is mediated by inhibition of mTOR. Exogenous insulin-like growth factor (IGF)-I protected both Rh1 and Rh30 from apoptosis, without reactivating ribosomal p70 S6 kinase (p70S6K) downstream of mTOR. However, in rapamycin-treated cultures, the response to IGF-I differed between the cell lines: Rh1 cells proliferated normally, whereas Rh30 cells remained arrested in G1 phase but viable. Rapamycin is known to inhibit synthesis of specific proteins but did not inhibit synthesis or alter the levels of mTOR. To examine the rate at which the mTOR pathway recovered, the ability of IGF-I to stimulate p70S6K activity was followed in cells treated for 1 h with rapamycin and then allowed to recover in medium containing > or =100-fold excess of FK506 (to prevent rapamycin from rebinding to its cytosolic receptor FKBP-12). Our results indicate that, in Rh1 cells, rapamycin dissociates relatively slowly from FKBP-12, with a t1/2 of approximately 17.5 h. in the presence of FK506, whereas there was no recovery of p70S6K activity in the absence of this competitor. This was of interest because rapamycin was relatively unstable under conditions of cell culture having a biological t1/2 of approximately 9.9 h. These results help to explain why cells are sensitive following short exposures to rapamycin and may be useful in guiding the use of rapamycin analogues that are entering clinical trials as novel antitumor agents.  (+info)

Hmo1p, a high mobility group 1/2 homolog, genetically and physically interacts with the yeast FKBP12 prolyl isomerase. (3/4814)

The immunosuppressive drugs FK506 and rapamycin bind to the cellular protein FKBP12, and the resulting FKBP12-drug complexes inhibit signal transduction. FKBP12 is a ubiquitous, highly conserved, abundant enzyme that catalyzes a rate-limiting step in protein folding: peptidyl-prolyl cis-trans isomerization. However, FKBP12 is dispensible for viability in both yeast and mice, and therefore does not play an essential role in protein folding. The functions of FKBP12 may involve interactions with a number of partner proteins, and a few proteins that interact with FKBP12 in the absence of FK506 or rapamycin have been identified, including the ryanodine receptor, aspartokinase, and the type II TGF-beta receptor; however, none of these are conserved from yeast to humans. To identify other targets and functions of FKBP12, we have screened for mutations that are synthetically lethal with an FKBP12 mutation in yeast. We find that mutations in HMO1, which encodes a high mobility group 1/2 homolog, are synthetically lethal with mutations in the yeast FPR1 gene encoding FKBP12. Deltahmo1 and Deltafpr1 mutants share two phenotypes: an increased rate of plasmid loss and slow growth. In addition, Hmo1p and FKBP12 physically interact in FKBP12 affinity chromatography experiments, and two-hybrid experiments suggest that FKBP12 regulates Hmo1p-Hmo1p or Hmo1p-DNA interactions. Because HMG1/2 proteins are conserved from yeast to humans, our findings suggest that FKBP12-HMG1/2 interactions could represent the first conserved function of FKBP12 other than mediating FK506 and rapamycin actions.  (+info)

Interaction of asparagine and EGF in the regulation of ornithine decarboxylase in IEC-6 cells. (4/4814)

Our laboratory has shown that asparagine (ASN) stimulates both ornithine decarboxylase (ODC) activity and gene expression in an intestinal epithelial cell line (IEC-6). The effect of ASN is specific, and other A- and N-system amino acids are almost as effective as ASN when added alone. In the present study, epidermal growth factor (EGF) was unable to increase ODC activity in cells maintained in a salt-glucose solution (Earle's balanced salt solution). However, the addition of ASN (10 mM) in the presence of EGF (30 ng/ml) increased the activity of ODC 0.5- to 4-fold over that stimulated by ASN alone. EGF also showed induction of ODC with glutamine and alpha-aminoisobutyric acid, but ODC induction was maximum with ASN and EGF. Thus the mechanism of the interaction between ASN and EGF is important for understanding the regulation of ODC under physiological conditions. Therefore, we examined the expression of the ODC gene and those for several protooncogenes under the same conditions. Increased expression of the genes for c-Jun and c-Fos but not for ODC occurred with EGF alone. The addition of ASN did not further increase the expression of the protooncogenes, but the combination of EGF and ASN further increased the expression of ODC over that of ASN alone. Western analysis showed no significant difference in the level of ODC protein in Earle's balanced salt solution, ASN, EGF, or EGF plus ASN. Addition of cycloheximide during ASN and ASN plus EGF treatment completely inhibited ODC activity without affecting the level of ODC protein. These results indicated that 1) the increased expression of protooncogenes in response to EGF is independent of increases in ODC activity and 2) potentiation between EGF and ASN on ODC activity may not be due to increased gene transcription but to posttranslational regulation and the requirement of ongoing protein synthesis involving a specific factor dependent on ASN.  (+info)

Cyclosporin A treatment alters characteristics of Ca2+-release channel in cardiac sarcoplasmic reticulum. (5/4814)

Chronic treatment with cyclosporin A (CsA) has been reported (H. S. Banijamali, M. H. ter Keurs, L. C. Paul, and H. E. ter Keurs. Cardiovasc. Res. 27: 1845-1854, 1993; I. Kingma, E. Harmsen, H. E. ter Keurs, H. Benediktsson, and L. C. Paul. Int. J. Cardiol. 31: 15-22, 1991) to induce reversible alterations of contractile properties in rat hearts. To define the molecular mechanisms underlying the physiological alterations, the Ca2+-release channel (CRC) and Ca2+-ATPase from sarcoplasmic reticulum in rats were examined. Ryanodine binding to whole homogenates of rat hearts shows time- and dose-dependent alterations in CRC properties by CsA. On 3 wk of treatment with 15 mg CsA. kg body wt-1. day-1, 1) maximal ryanodine binding (Bmax) decreased, 2) the dissociation constant of ryanodine (Kd) increased, 3) caffeine sensitivity of CRC increased, and 4) ruthenium red sensitivity of CRC decreased. On the other hand, Bmax and Kd of ryanodine binding in rat skeletal muscles were not changed. Ryanodine-sensitive oxalate-supported Ca2+ uptake in whole homogenates was lower in CsA-treated rat hearts than in control hearts, whereas total Ca2+ uptake in the presence of 500 M ryanodine was not changed. Functional experiments with rapamycin and Western blot analysis suggest that the CsA-induced alteration of ryanodine binding is due at least in part to an upregulation of calcineurin. The heart muscle-specific alterations of CRC could be responsible for the previously reported contractile changes of CsA-treated rat hearts.  (+info)

Inhibition of cell cycle progression by rapamycin induces T cell clonal anergy even in the presence of costimulation. (6/4814)

Costimulation (signal 2) has been proposed to inhibit the induction of T cell clonal anergy by either directly antagonizing negative signals arising from TCR engagement (signal 1) or by synergizing with signal 1 to produce IL-2, which in turn leads to proliferation and dilution of negative regulatory factors. To better define the cellular events that lead to the induction of anergy, we used the immunosuppressive agent rapamycin, which blocks T cell proliferation in late G1 phase but does not affect costimulation-dependent IL-2 production. Our data demonstrate that full T cell activation (signal 1 plus 2) in the presence of rapamycin results in profound T cell anergy, despite the fact that these cells produce copious amounts of IL-2. Similar to conventional anergy (induction by signal 1 alone), the rapamycin-induced anergic cells show a decrease in mitogen-activated protein kinase activation, and these cells can be rescued by culture in IL-2. Interestingly, the rapamycin-induced anergic cells display a more profound block in IL-3 and IFN-gamma production upon rechallenge. Finally, in contrast to rapamycin, full T cell activation in the presence of hydroxyurea (which inhibits the cell cycle in early S phase) did not result in anergy. These data suggest that it is neither the direct effect of costimulation nor the subsequent T cell proliferation that prevents anergy induction, but rather the biochemical events that occur upon progression through the cell cycle from G1 into S phase.  (+info)

p70(S6K) controls selective mRNA translation during oocyte maturation and early embryogenesis in Xenopus laevis. (7/4814)

In mammalian cells, p70(S6K) plays a key role in translational control of cell proliferation in response to growth factors. Because of the reliance on translational control in early vertebrate development, we cloned a Xenopus homolog of p70(S6K) and investigated the activity profile of p70(S6K) during Xenopus oocyte maturation and early embryogenesis. p70(S6K) activity is high in resting oocytes and decreases to background levels upon stimulation of maturation with progesterone. During embryonic development, three peaks of activity were observed: immediately after fertilization, shortly before the midblastula transition, and during gastrulation. Rapamycin, an inhibitor of p70(S6K) activation, caused oocytes to undergo germinal vesicle breakdown earlier than control oocytes, and sensitivity to progesterone was increased. Injection of a rapamycin-insensitive, constitutively active mutant of p70(S6K) reversed the effects of rapamycin. However, increases in S6 phosphorylation were not significantly affected by rapamycin during maturation. mos mRNA, which does not contain a 5'-terminal oligopyrimidine tract (5'-TOP), was translated earlier, and a larger amount of Mos protein was produced in rapamycin-treated oocytes. In fertilized eggs rapamycin treatment increased the translation of the Cdc25A phosphatase, which lacks a 5'-TOP. Translation assays in vivo using both DNA and RNA reporter constructs with the 5'-TOP from elongation factor 2 showed decreased translational activity with rapamycin, whereas constructs without a 5'-TOP or with an internal ribosome entry site were translated more efficiently upon rapamycin treatment. These results suggest that changes in p70(S6K) activity during oocyte maturation and early embryogenesis selectively alter the translational capacity available for mRNAs lacking a 5'-TOP region.  (+info)

Growth hormone-dependent differentiation of 3T3-F442A preadipocytes requires Janus kinase/signal transducer and activator of transcription but not mitogen-activated protein kinase or p70 S6 kinase signaling. (8/4814)

The signals mediating growth hormone (GH)-dependent differentiation of 3T3-F442A preadipocytes under serum-free conditions have been studied. GH priming of cells was required before the induction of terminal differentiation by a combination of epidermal growth factor, tri-iodothyronine, and insulin. Cellular depletion of Janus kinase-2 (JAK-2) using antisense oligodeoxynucleotides (ODNs) prevented GH-stimulated JAK-2 and signal transducer and activator of transcription (STAT)-5 tyrosine phosphorylation and severely attenuated the ability of GH to promote differentiation. Although p42(MAPK)/p44(MAPK) mitogen-activated protein kinases were activated during GH priming, treatment of cells with PD 098059, which prevented activation of these kinases, did not block GH priming. However, antisense ODN-mediated depletion of mitogen-activated protein kinases from the cells showed that their expression was necessary for terminal differentiation. Similarly, although p70(s6k) was activated during GH priming, pretreatment of cells with rapamycin, which prevented the activation of p70(s6k), had no effect on GH priming. However, rapamycin did partially block epidermal growth factor, tri-iodothyronine, and insulin-stimulated terminal differentiation. By contrast, cellular depletion of STAT-5 with antisense ODNs completely abolished the ability of GH to promote differentiation. These results indicate that JAK-2, acting specifically via STAT-5, is necessary for GH-dependent differentiation of 3T3-F442A preadipocytes. Activation of p42(MAPK)/p44(MAPK) and p70(s6k) is not essential for the promotion of differentiation by GH, although these signals are required for GH-independent terminal differentiation.  (+info)

Background Diabetics are known to have an accelerated and more aggressive form of atherosclerosis. Both paclitaxel- and sirolimus-eluting stents (PES and SES respectively) showed to reduce clinical and angiographic restenosis as compared to bare metal stents (BMS) up until 1 year. Due to the different mechanisms of action of both drugs and the interference with the PI3-kinase pathway, which is degraded in diabetic patients, it is currently unknown which device is the best option to treat these high-risk patients.. Methods The present study compares the 2-year outcome of a series of 708 consecutive diabetic patients (25% insulin treated) treated with either a BMS, a SES or a PES, as part of the Rapamycin-Eluting Stent Evaluated at Rotterdam Cardiology Hospital (RESEARCH) and Taxus-Stent Evaluated at Rotterdam Cardiology Hospital (T-SEARCH) registries respectively.. Results All-cause mortality did not differ significantly between the 3 groups. As compared to BMS, the use of PES but not SES, was ...
TY - JOUR. T1 - Maintenance of long-term clinical benefit with sirolimus-eluting coronary stents. T2 - Three-year results of the RAVEL trial. AU - Fajadet, Jean. AU - Morice, Marie Claude. AU - Bode, Christoph. AU - Barragan, Paul. AU - Serruys, Patrick W.. AU - Wijns, William. AU - Constantini, Constantino R.. AU - Guermonprez, Jean Léon. AU - Eltchaninoff, Hélène. AU - Blanchard, Didier. AU - Bartorelli, Antonio. AU - Laarman, Gert Jan. AU - Perin, MarcoAntonio. AU - Sousa, J. Eduardo. AU - Schuler, Gerhard. AU - Molnar, Ferenc. AU - Guagliumi, Giulio. AU - Colombo, Antonio. AU - Hayashi, Ernesto Ban. AU - Wülfert, Egon. PY - 2005/3/1. Y1 - 2005/3/1. N2 - Background - The use of sirolimus-eluting coronary stents has been associated with a nearly complete elimination of restenosis at 6 months and with a very low 1-year incidence of major adverse cardiac events (MACE). This analysis examined whether these beneficial effects persist over the longer term. Methods and Results - This multicenter ...
TY - JOUR. T1 - Stent thrombosis and bleeding complications after implantation of sirolimus-eluting coronary stents in an unselected worldwide population. T2 - A report from the e-SELECT (Multi-center Post-Market Surveillance) registry. AU - Urban, Philip. AU - Abizaid, Alexandre. AU - Banning, Adrian. AU - Bartorelli, Antonio L.. AU - Baux, Ana Cebrian. AU - Davk, Vladimr. AU - Ellis, Stephen. AU - Gao, Runlin. AU - Holmes, David. AU - Jeong, Myung Ho. AU - Legrand, Victor. AU - Neumann, Franz Josef. AU - Nyakern, Maria. AU - Spaulding, Christian. AU - Worthley, Stephen. PY - 2011/3/29. Y1 - 2011/3/29. N2 - Objectives: The aim of this study was to ascertain the 1-year incidence of stent thrombosis (ST) and major bleeding (MB) in a large, unselected population treated with sirolimus-eluting stents (SES). Background: Stent thrombosis and MB are major potential complications of drug-eluting stent implantation. Their relative incidence and predisposing factors among large populations treated ...
BRIDGEWATER, N.J., June 15, 2011 /PRNewswire-FirstCall/ -- Cordis Corporation, a worldwide leader in the development and manufacture of interventional vascular technology, today announced it will no longer pursue the development of the NEVO™ Sirolimus-Eluting Coronary Stent in order to focus on other cardiovascular therapies where significant patient need exists. The company will also stop the manufacture of CYPHER® and CYPHER SELECT® Plus Sirolimus-Eluting Coronary Stents by the end of 2011.. Due to evolving market dynamics in the drug-eluting stent (DES) business, we see greater opportunities to benefit patients and grow our business in other areas of the cardiovascular device market, said Seth Fischer, Company Group Chair and Worldwide Chairman, Cordis Corporation. Cordis has been a leader in establishing many markets including diagnostic and guiding catheters, bare metal and drug-eluting stents, carotid stenting, and treatment of peripheral vascular disease and arrhythmias. These ...
TY - JOUR. T1 - A phase II trial of the oral mTOR inhibitor everolimus in relapsed aggressive lymphoma. AU - Witzig, T. E.. AU - Reeder, C. B.. AU - Laplant, B. R.. AU - Gupta, M.. AU - Johnston, P. B.. AU - Micallef, I. N.. AU - Porrata, L. F.. AU - Ansell, S. M.. AU - Colgan, J. P.. AU - Jacobsen, E. D.. AU - Ghobrial, I. M.. AU - Habermann, T. M.. N1 - Funding Information: Research supported in part by the NIH grants CA127433, CA112904 and CA97274, and the Predolin Foundation.. PY - 2011/2. Y1 - 2011/2. N2 - The phosphatidylinositol 3-kinase signal transduction pathway members are often activated in tumor samples from patients with non-Hodgkins lymphoma (NHL). Everolimus is an oral agent that targets the raptor mammalian target of rapamycin (mTORC1). The goal of this trial was to learn the antitumor activity and toxicity of single-agent everolimus in patients with relapsed/refractory aggressive NHL. Patients received everolimus 10 mg PO daily. Response was assessed after two and six cycles, ...
The PROTECT TRIAL is a randomized stent trial with 8800 patients in approximately 200 hospitals, which is designed to evaluate whether the Endeavor stent PROTECTS against late stent thrombosis resulting in less deaths and myocardial infarctions.. Study Stents:. Medtronic Endeavor® Zotarolimus Eluting Coronary Stent System or next generation model Cordis Cypher® Sirolimus-eluting Coronary Stent, Cordis Cypher Select® Sirolimus-eluting Coronary Stent or next generation model. Primary Objective: To compare overall stent thrombosis rate of the Endeavor® Zotarolimus Eluting Coronary Stent System versus the Cypher® Sirolimus-eluting Coronary Stent in a patient population requiring stent implantation. Secondary Objective: To compare the composite endpoint of total death or cardiac death combined with the number of patients with all non-fatal myocardial infarctions as well as the number of patients with large non-fatal myocardial infarctions for Endeavor® Zotarolimus Eluting Coronary Stent System ...
A prospective multicenter registry in real-world Japanese patients undergoing DAPT for three months after stenting. To assess the long-term safety of Endeavor Zotarolimus-eluting stent through noninferiority in the primary endpoint between two different continuous regimen (three and twelve months) groups of DAPT after stenting with Endeavor Zotarolimus-eluting stent in real-world Japanese patients and to examine the optimal duration of DAPT after stenting with Endeavor Zotarolimus-eluting stent. The long-term DAPT group in the present clinical study (to be appropriated from the post-marketing surveillance of Endeavor) should consist of consecutive patients undergoing DAPT for twelve months after stenting, while the short-term DAPT group (to be newly registered in the present clinical study) should consist of patients who are instructed to undergo DAPT for three months after stenting ...
PubMed journal article The effect of immunosuppressive drug rapamycin on regulatory CD4+CD25+Foxp3+T cells in mic were found in PRIME PubMed. Download Prime PubMed App to iPhone, iPad, or Android
RRISC Trial Reduction of Restenosis In Saphenous vein grafts with Cypher sirolimus-eluting stent Prospective, randomized, double-blind, non industry sponsored, trial comparing sirolimus-eluting stents vs. bare metal stents. Prospective, randomized, double-blind, non industry sponsored, trial comparing sirolimus-eluting stents vs. bare metal stents. 75 patients with 96 lesions localized in 80 diseased saphenous vein grafts were included 75 patients with 96 lesions localized in 80 diseased saphenous vein grafts were included Primary endpoint : in-stent late loss Primary endpoint : in-stent late loss Secondary endpoints: Secondary endpoints:  Clinical events (death, MI, TLR, TVR)  Binary angiographic restenosis in-stent/in-segment  IVUS measured neo-intimal hyperplasia volume
Rapamycin derivatives selected among 32(S)-dihydro-rapamycin derivatives and 32-deoxo-rapamycin compounds. Rapamycin derivatives are disclosed of the formula: ##STR1## wherein the variables are in the specification.
Sirolimus is a potent immunosuppressive agent administered as prophylactic agent to prevent rejection after organ transplantation. Sirolimus must be used within a narrow therapeutic window. Due to inter- and intra-variability, sirolimus blood concentrations may be affected, therefore, there is no possibility of predicting the sirolimus blood concentrations based on the dose patients received. Therapeutic drug monitoring (TDM) of whole blood is an important part of immunosuppressive therapy and is mandatory for sirolimus dosage individualization. The objective of this study was to present a validated method for the analysis of sirolimus in human blood by LC/MS spectrometry and also evaluation of correlation between blood sirolimus concentration and laboratory parameters. We examined a group of 32 patients receiving sirolimus at different stages after organ (kidney, liver or pancreas) transplantation. The mean sirolimus concentration was 10.2 ng/ml (range: 1.3- 30.1 ng/ml). The assay was validated for a
This head-to-head trial will assess the non-inferiority of NEVO sirolimus-eluting stent to the XIENCE V everolimus-eluting stent for the prevention of coronary
The main finding of this first-in-human study with the non-polymer-based VES is that sirolimus can be efficiently delivered to the coronary artery without a durable polymer, as demonstrated by the minimum neointimal growth noted at QCA and IVUS.. The development of novel DES systems must be guided by 2 main rationales: 1) to achieve an improved safety profile, and 2) to improve or at least keep the efficacy profile at levels comparable to those of the existing DES devices.. The DES toxicity may be related mainly to 2 aspects: dose/type of the antiproliferative agent delivered to the coronary artery and presence/type of polymer used to carry the antiproliferative drug. In this context, the novel VES carries less than one-half of the dose of the first-generation Cypher sirolimus-eluting stent. As previously demonstrated by Nakamura et al. (22), it is possible to keep the same efficacy of the Cypher stent using 70% or even 45% of its original dose. In a study conducted by that group with 44 ...
Pubmed.ncbi.nlm.nih.gov DA: 23 PA: 10 MOZ Rank: 47. Objectives: This study sought to report the final 5-year outcomes of the ENDEAVOR IV (A Randomized, Controlled Trial of the Medtronic Endeavor Drug [ABT-578] Eluting Coronary Stent System Versus the Taxus Paclitaxel-Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions) trial comparing the Endeavor zotarolimus-eluting stent (E-ZES) (Medtronic, Santa Rosa, California) with … ...
A Prospective Randomized Multicenter Trial to Assess an Everolimus-Eluting Coronary Stent System (PROMUS element) for the Treatment of up to Two De Novo Coronary Artery Lesions - PLATINUM Trial
Results from the PRISON IV Trial Presented at TCT 2016 and Simultaneously Published in JACC: Cardiovascular Interventions. WASHINGTON - November 2, 2016 - Results from a randomized, multicenter trial failed to show non-inferiority of hybrid, ultra-thin strut sirolimus-eluting stents (Osiro SES) with a biodegradable polymer compared to thin-strut everolimus-eluting stents (Xience EES) with a durable polymer in terms of in-segment late lumen loss in successfully treated chronic total occlusions. In addition, although the rate of binary restenosis was low overall in this complex lesion subset, it was higher with the Osirio SES compared with the Xience EES.. Findings from the PRISON IV trial were reported today at the 28th annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium. Sponsored by the Cardiovascular Research Foundation (CRF), TCT is the worlds premier educational meeting specializing in interventional cardiovascular medicine. The study was also published in the ...
Background: A bifurcation lesion has been demonstrated to be the high risk lesion for late stent thrombosis (LST) following drug-eluting stent implantation, resulting from disturbed laminar blood flow and delayed endothelialization of unapposed stent struts. We examined differences in neointimal growth on the stent struts crossing a side branch between sirolimus-eluting stent (SES) and bare-metal stent (BMS) using optical coherence tomography (OCT)... Methods and Results: Of the 41 stents (34 cases) implanted across side branches, 70 struts of 28 SES and 23 struts of 13 BMS, which crossed over a side branch, were analyzed 9 months after stent implantation using OCT. Ten of 28 SES were also analyzed after 3 months. Neointimal growth around the unapposed struts, extending from the adjacent vessel wall, was classified into either complete or incomplete coverage of struts. Neointimal thickness (NIT) on struts was also measured. At 9-month follow-up, complete coverage was observed in 45 struts of SES ...
Everolimus has important clinical activity in various malignancies, but its use can be complicated by respiratory adverse events. Important everolimus-induced respiratory adverse events are interstitial lung disease (ILD) and infections, either typical or opportunistic. Furthermore, non-everolimus-related respiratory events can occur. Due to the non-specific presentation of most of these respiratory disorders, it is often not possible to differentiate between these causes on clinical and radiological grounds only. Considering the potential fatal nature of opportunistic infections, these are especially important to recognize. To be able to distinguish between ILD and (opportunistic) infections as the underlying cause, an aggressive diagnostic workup, including bronchoalveolar lavage, should be performed in patients treated with everolimus who develop respiratory disease. We report three cases of severe opportunistic pulmonary infections during everolimus treatment, concerning two Pneumocystis ...
Journal of Drugs in Dermatology, March, 2006 by Lindsey Warino, James Libecco Abstract Cancer is a major cause of death in immunosuppressed transplant patients. Therefore, sirolimus is frequently used in these patients for its immunosuppressive and antineoplastic properties. However, a variety of cutaneous side effects have resulted from sirolimus therapy. Consequently, dermatologists must be aware of such adverse events and understand the risks and benefits of discontinuing therapy. Introduction Sirolimus (Rapamycin) is an immunosuppressive agent often used in combination with cyclosporine and corticosteroids in renal transplant patients. In contrast to the calcineurin inhibitors, sirolimus, a macrocyclic lactone isolated from Streptomyces Hygroscopicus, has no effect on calcineurin activity. (1-15) Rather, it acts to suppress cytokine-driven T cell proliferation and inhibits the progression from G1 to the S phase of the cell cycle. Not only is sirolimus used for its immunosuppressive ...
Sirolimus weakens your immune system, which increases chances of getting an infection. Watch closely for signs of infection such as a fever, chills, cough, and sore throat. Contact your doctor right away if you notice any signs of infection.. You should not receive any immunizations (vaccines) without your doctors approval.. Sirolimus may make your skin more likely to sunburn. Make sure to cover your skin while outside. You should also use sunscreen with an SPF of 30 or higher to prevent sunburn.. Avoid grapefruit and grapefruit juice while taking sirolimus. They may increase the sirolimus level in your blood and make you more susceptible to certain side effects.. Sirolimus may cause birth defects if it is taken at the time of conception or during pregnancy.. Many other medications may change the blood levels of sirolimus in your body. Check with your doctor before taking any other medicines (prescription, non-prescription, herbal, or natural products).. *Note: The decision to prescribe a ...
Patients with diabetes mellitus have less favourable outcomes after percutaneous coronary intervention (PCI) than non-diabetics. We performed a subgroup analysis of the multicentre RAVEL trial to examine the impact of the sirolimus-eluting stent (SES) on outcomes in diabetic patients. The RAVEL study randomized 238 patients to treatment with either sirolimus-eluting or bare metal stents. Forty-four patients were diabetic; 19 received sirolimus-eluting stents and 25 were treated with bare metal stents. The differences in outcomes between diabetic and non-diabetic patients treated with SES (n=101) were also assessed. Follow-up angiography was performed at 6 months. Major adverse cardiac events (MACE) defined as death, myocardial infarction (MI), or target lesion revascularization (TLR) were analysed at 12-month follow-up. Six-month in-stent late lumen loss was significantly lower for the diabetic SES than the bare stent group (0.07+/-0.2 vs 0.82+/-0.5mm; P,0.001) and similar to that in ...
Rationale: Sirolimus-eluting coronary stents (SESs) and paclitaxel-eluting coronary stents (PESs) are used to reduce restenosis but have different sites of action. The molecular targets of sirolimus overlap with those of the peroxisome proliferator-activated receptor (PPAR)γ agonist rosiglitazone (RSG) but the consequence of this interaction on endothelialization is unknown. Objective: Using the New Zealand white rabbit iliac model of stenting, we examined the effects of RSG on SESs, PESs, and bare metal stents endothelialization. Methods and Results: Animals receiving SESs, PESs, or bare metal stents and either RSG (3 mg/kg per day) or placebo were euthanized at 28 days, and arteries were evaluated by scanning electron microscopy. Fourteen-day organ culture and Western blotting of iliac arteries and tissue culture experiments were conducted. Endothelialization was significantly reduced by RSG in SESs but not in PESs or bare metal stents. Organ culture revealed reduced vascular endothelial ...
This head-to-head noninferiority trial is comparing the efficacy and tolerability of a platinum chromium everolimus-eluting coronary stent system [PROMUS
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Additionally, no patient in the calcified group suffered from stent thrombosis up to 3 years after PCI, while two thrombotic complications occurred in the noncalcified group. Although large population studies with long-term follow-up are mandatory, the authors concluded that EES implantation for calcified culprit lesions appears to be safe up to 3 years. This study also demonstrated that the rates of in-stent ABR (4.3%) and ID-TLR (5.9%) at 6 months for calcified culprit lesions are remarkably lower than that in previous BMS studies, in which these rates ranged from 12 to 23% and from 18 to 23%, respectively, suggesting that EES implantation is more effective for calcified culprit lesions than BMS implantation ...
China Sirolimus Eluting Coronary Stent, Find details about China Sirolimus Eluting Coronary Stent, Drug Eluting Stent from Sirolimus Eluting Coronary Stent - Yilson Medical Technology Co., Ltd.
Figure 5: (a) X-rays of longitudinally cut rabbit iliac arteries at 21 days after placement of overlapping ZES, SES, and PES. The extent of stent coverage by endothelial cells was greatest with ZES, with almost complete coverage in the proximal and distal segments and significantly greater coverage in the overlapped segment compared with SES and PES. (b) Photomicrographs showing the amount of neointimal thickness at 28 days after placement of Endeavor zotarolimus-eluting stents (ZESs), Cypher sirolimus-eluting stents (SESs), Taxus paclitaxel-eluting stents (PESs), and Driver bare metal stents (BMSs) in rabbit iliac arteries. With SES, there were focally uncovered stent struts, which were associated with inflammation consisting of heterophils or eosinophils and giant cells. Adapted from [49 ...
All patients started CNI therapy. Subjects with chronic allograft nephropathy were switched to sirolimus, whereas patients not having chronic allograft nephropathy continued CNI and served as controls (non-randomised trial). The dose of sirolimus was titrated every other week in order to maintain trough levels between 5 and 15 mg/ml ...
The purpose of this study is to elicit the role of oral low-dose sirolimus as a corticosteriod-sparing agent for active uveitis. A retrospective, interventional case series was performed by reviewing the clinical records of all patients treated with oral, low-dose sirolimus (1-4 mg daily) for severe uveitis. Data reviewed included symptomatic improvement, Snellen best-corrected visual acuity, corticosteroid requirement, sirolimus levels, intraocular inflammation, spectral-domain optical coherence tomography, and fluorescein angiogram. Primary outcome measures were determined by the ability to decrease the intraocular inflammation, corticosteroid requirement, and frequency of flares. Eight patients with varied diagnoses were treated with oral low-dose sirolimus for severe, chronic uveitis between 2008 and 2010. In four of the eight patients, there was an improvement of all primary outcome measures. While sirolimus monotherapy was successful in only one patient, a sirolimus/methotrexate combination was
Mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and its derivative, everolimus, are potent immunosuppressive and antiproliferative drugs. Inflammatory diseases are characterized by immunological dysfunction, and monocyte recruitment underlies the mechanism of cell damage. Chemokines attract inflammatory cells to sites of inflammation. Interleukin-8 (IL-8/CXCL8); the monocyte chemoattractant protein-1 (MCP-1/CCL2); the regulated on activation, normal T cell expressed, presumably secreted protein (RANTES/CCL5); the macrophage inflammatory protein (MIP)-1α (CCL3); and MIP-1β (CCL4) are involved in the pathogenesis of inflammation. However, whether mTOR inhibitors moderate the production of chemokines in monocytes remains unclear. A human monocyte cell line, THP-1, and primary monocytes obtained from human volunteers, were stimulated using lipopolysaccharide (LPS), and then treated with sirolimus. The expression of the MCP-1, RANTES, IL-8, MIP-1α, MIP-1β, and TNF-α proteins was
The duration but not the intensity of an inflammatory response to the implantation of sirolimus-eluting coronary stents may predict the restenosis ...
Purpose: Mammalian target of rapamycin (mTOR) inhibitors mediate AKT activation through a type 1 insulin-like growth factor receptor (IGF-1R)-dependent mechanism. Combining the mTOR inhibitor temsirolimus with cixutumumab, a fully human IgG1 monoclonal antibody directed against IGF-1R, was expected to enhance mTOR-targeted anticancer activity by modulating resistance to mTOR inhibition. Objectives of this Phase I study were to evaluate the tolerability and activity of temsirolimus and cixutumumab. Experimental Design: Patients in sequential cohorts (3+3 design) received escalating doses of temsirolimus with cixutumumab weekly for 28 days. At MTD, 21 patients were randomized into three separate drug sequence treatment groups for serial blood draws and FDG-PET/CT scans for pharmacodynamic analyses (PD). Results: Forty-two patients with advanced cancer (19M/23F, median age = 53, median number of prior therapies = 4) were enrolled. MTD was reached at cixutumumab, 6 mg/kg IV and temsirolimus, 25 mg ...
Fingerprint Dive into the research topics of Comparisons of the effects of stent eccentricity on the neointimal hyperplasia between Sirolimus-eluting stent versus Paclitaxel-eluting stent. Together they form a unique fingerprint. ...
There is evidence that rapamycin improves age-related deterioration of cardiac function in laboratory mice. Our study provides the first evidence that rapamycin may partially reverse age-related heart dysfunction in dogs by improving measures of both diastolic and systolic functions...All three outcomes (EF, FS and E/A ratio) showed trends toward improved function following rapamycin treatment and two of them (FS and E/A ratio) reached statistical significance. It appears that FS improvement was most prominent in rapamycin-treated dogs with lowever baseline values, while dogs that had higher values at baseline did not improve as much in response to rapamycin. This may suggest that degree of decline already present in each individual will determine degree of improvement. (greater initial decline, greater improvement).. ...
This weeks topics include favorable lipid-level trends in U.S. adults, an angiotensin receptor neprilysin inhibitor for patients with HF and preserved systolic ejection fraction, and a long-term safety comparison of the Zotarolimus-eluting and Sirolimus-eluting coronary stents.. ...
Background Toll-like receptor 5 (TLR5) is a potentially target related with immunosuppressant rapamycin. Our aim was to evaluate 131I-anti-TLR5 mAb for non-invasive in vivo graft visualization and quantification in rapamycin treated allogeneic transplantation model compared with nonspecific tracer 18F-FDG. Methods Labeling, binding and stability studies were performed. Allografted BALB/c mice were divided into rapamycin-treated and non-treated group, respectively. In vivo dynamic whole-body phosphor-autoradiography and ex vivo biodistribution studies were conducted. Results Phosphor-autoradiography imaging showed clear graft localization from 12 h onward after 131I-anti-TLR5 mAb injection,significantly higher graft uptake in rapamycin-treated group. Pretreatment with anti-TLR5 mAb blocked graft uptake,which were consistent with ex vivo biodistribution studies. As the nonspecific radiotracer, high 18F-FDG uptake was only observed in non-treated allorejection group, not in treated group. The ...
Results: We enrolled 108 patients; 51 received sunitinib and 57 everolimus. Of these, 89 patients had evaluable plasma for 23 angiokines. At the final data cutoff, 87 PFS and 62 mortality events had occurred. Angiokines that were independently adversely prognostic for OS were osteopontin (OPN), hepatocyte growth factor (HGF), and VCAM-1, and these were also associated with poor-risk disease. Stromal derived factor 1 was associated with improved survival. OPN was also significantly associated with worse PFS. No statistically significant angiokine-treatment outcome interactions were observed for sunitinib or everolimus. OPN, HGF, TIMP-1, VCAM-1, PDGF-AA, and IL6 levels increased with progression on everolimus, while OPN, PlGF, TIMP-1, VEGF, and soluble VEGFR-2 and VCAM-1 increased with progression on sunitinib. ...
Adding the mTOR inhibitor everolimus to conventional therapy slowed the progression of trastuzumab-resistant advanced breast cancer, and in the process, provided clues to the origin of trastuzumab resistance.
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Sirolimus, also known as rapamycin, is a natural macrocyclic lactone produced by the bacterium Streptomyces hygroscopicus, with immunosuppressant properties. In cells, sirolimus binds to the immunophilin FK Binding Protein-12 (FKBP-12) to generate an immunosuppressive complex that binds to and inhibits the activation of the mammalian Target Of Rapamycin (mTOR), a key regulatory kinase. This results in inhibition of T lymphocyte activation and proliferation that occurs in response to antigenic and cytokine (IL-2, IL-4, and IL-15) stimulation and inhibition of antibody production..
In the lab, rapamycin is a star geroprotector. In addition to boosting lifespan even when used in late life, its also been found specifically to help prevent cancer, shore up the aging cardiovascular system, and stem cognitive decline. These benefits all derive from suppressing activity of the enzyme mTOR, a regulator of cell growth and survival with some less than desirable side effects on cancers and oxidative stress, among others.. But is rapamycin safe enough for chronic use in humans? Since the drug is well-known to surgeons as an immunosuppressant useful for preventing transplant rejection, fears that it would lead to immune dysfunction have thwarted its path to broad acceptance as a recommendable anti-aging therapy. In particular, previous use in humans has yielded reports of mouth ulcers, diabetes-like symptoms and low platelet count. Like its longevity benefits, these side effects are also thought to derive from rapamycins suppression of mTOR. But evidence surrounding mTORs effects ...
Raj Maturi, MD, reviews a study evaluating intravitreal sirolimus therapy for chronic age-related macular degeneration. The study compared central subfield thickness data of patients who received monotherapy sirolimus versus those who continued with their current anti-VEGF regimen.
Biotronik said yesterday that its Orsiro stent tops the Xience stents made by Abbott (NYSE:ABT) when it comes to target lesion failure, according to data from a clinical trial.. The randomized, controlled BioSTEMI trial was the first direct comparison between the two drug-eluting stents in patients with acute ST-segment elevation myocardial infarction (STEMI). Biotronik announced the results at the European Society of Cardiology Congress in Paris. In 2016, Berlin-based Biotronik claimed the Orsiro device had the edge over Xience in a heart attack subgroup study.. The 12-month study at Geneva University Hospitals included 1,300 patients with acute myocardial infarction. Orsiro had an incidence of 4% target lesion failure (TLF) at 12 months compared to Xiences 6%. The difference in TLF was caused by lower rates of clinically indicated target lesion revascularization in patients treated with Orsiro, compared to Xience. The results were published in The Lancet.. The BioSTEMI trial proves what the ...
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Registry Analysis Published in Journal Heart Finds Taxus StentImplan... ...MIAMI LAKES Fla. June 4 2007 /PRNewswire via COMTEX NewsNetwork/ -...The authors of the analysis sought to identify risk factors forsympto... The major new finding of this study was that the use of theTaxus Ste...,New,Study,Suggests,Better,Patient,Outcomes,with,CYPHER,Sirolimus-Eluting,Coronary,Stent,than,with,Taxus,Stent,in,Real-World,Clinical,Settings,medicine,advanced medical technology,medical laboratory technology,medical device technology,latest medical technology,Health
Sirolimus is a compound produced by the bacteria Streptomyces hygroscopicus. Sirolimus inhibits the response to interleukin-2 (IL-2) and thereby blocks activation of T- and B-cells. In contrast, tacrolimus inhibits the production of IL-2. Sirolimus limits the immune response and helps to prevent organ rejection by inhibiting immune cell activation and proliferation, and antibody production.. The chief advantage sirolimus has over calcineurin inhibitors is that it has low renal toxicity. Transplant patients maintained on calcineurin inhibitors long-term tend to develop impaired kidney function or even chronic renal failure; this can be avoided by using sirolimus instead. It is particularly advantageous in patients with kidney transplants for hemolytic-uremic syndrome, as this disease is likely to recur in the transplanted kidney if a calcineurin-inhibitor is used.. Sirolimus can be taken orally and it is absorbed from the gastrointestinal tract, concentrations peak in the blood within 1 - 2 hours ...
This study shows that use of SES resulted in a significantly lower rate of angiographic binary restenosis than BMS in patients with acute ST-segment elevation MI who underwent angioplasty with or without thrombolysis. Sirolimus-eluting stents also led to a higher rate of 1-year event-free survival.. These findings extend and confirm the positive finding of SES in stable patients to patients with ST-segment elevation MI. In the STRATEGY (Single High-Dose Bolus Tirofiban and Sirolimus-Eluting Stent vs. Abciximab and Bare-Metal Stent in Myocardial Infarction) trial (2), 175 patients with ST-segment elevation MI were randomized to receive single high-dose bolus of tirofiban plus SES or abciximab plus BMS. However, the randomization design was primarily based on economic considerations, with the hope that the lower cost of tirofiban would offset the cost of SES, and binary stent restenosis was not the primary end point, which it was in our study.. Recently, 2 randomized trials specifically studied ...
Definite stent thrombosis definition maximizes specificity, but it may be insufficiently sensitive to capture completely this relatively rare event. Sensitivity can be increased by including probable stent thrombosis in the analysis. There is limited head-to-head data on late stent thromboses for drug-eluting stents with biodegradable polymers. In accordance with the Academic Research Consortium we assessed definite and probable stent thrombosis events in the SORT OUT VII trial, among patient treated with the thin strut cobalt-chromium sirolimus-eluting Orsiro stent (Biotronik, Bülach, Switzerland) and the stainless steel biolimus-eluting Nobori stents (Terumo, Tokyo, Japan). ...
OBJECTIVES The aim of the present study was to evaluate vascular healing of the bioengineered COMBO Dual Therapy Stent compared with a cobalt-chromium (CoCr) everolimus-eluting stent (EES) as assessed by optical coherence tomography in patients with acute coronary syndromes. BACKGROUND CD34+ cells promote endothelial repair after vascular injury. The bioengineered COMBO Dual Therapy Stent combines CD34+ cell-capturing technology with abluminal sirolimus release, but more data from clinical studies evaluating the vascular response are needed. METHODS In a prospective randomized multicenter clinical trial, 60 patients with acute coronary syndromes were randomized 1:1 to COMBO or CoCr EES implantation. The primary endpoint was the percentage of uncovered stent struts per stent. Stent assessment by optical coherence tomography was performed at baseline and at 60 days, followed by independent core laboratory analysis. RESULTS The percentage of uncovered struts per stent was higher with the COMBO than ...
Background RADIANT-3 was a phase III study investigating the effect of the mammalian target of rapamycin inhibitor everolimus on progression-free survival (PFS) in patients with advanced pancreatic neuroendocrine tumors (pNET; Yao et al, NEJM, 2011). Everolimus significantly improved PFS compared with placebo (11 vs 4.6 months, P < .001). Here we investigate the predictive and prognostic effect of soluble VEGF pathway biomarkers among patients treated in this study.. Methods Baseline plasma levels of VEGF-A, PlGF, sVEGFR1, and sVEGFR2 were determined by ELISA using multiplexed MSD platform. The optimal cutoffs for these markers were explored using the survival tree analysis method. Interaction of treatment and baseline marker status (< or ≥ cutoff) was analyzed using a Cox proportional hazards model to assess predictive effects of these markers. P values and hazard ratios for prognostic effects were obtained using stratified log rank test and Cox proportional hazards model, stratified by ...
Although first-generation drug-eluting stents (DES) have significantly reduced the risk of in-stent restenosis, they have also increased the long-term risk of stent thrombosis. This safety concern directly triggered the development of new generation DES, with innovations in stent platforms, polymers, and anti-proliferative drugs. Stent platform materials have evolved from stainless steel to cobalt or platinum-chromium alloys with an improved strut design. Drug-carrying polymers have become biocompatible or biodegradable and even polymer-free DES were introduced. New limus-family drugs (such as everolimus, zotarolimus or biolimus) were adopted to enhance stent performances. As a result, these new DES demonstrated superior vascular healing responses on intracoronary imaging studies and lower stent thrombotic events in actual patients. Recently, fully-bioresorbable stents (scaffolds) have been introduced, and expanding their applications. In this article, the important concepts and clinical results ...
The presentation of atherosclerosis with concomitant hyperthyroidism is not uncommon. Hyperthyroidism predisposes to worse cardiovascular pathologies like systolic hypertension, atrial fibrillation, and hypercoagulability. Drug-eluting stents, on the other hand, have emerged as a miracle treatment choice for patients having atherogenic conditions. They have the highest success rates when it comes to minimizing in-stent restenosis (ISR) during short-term follow-up. There is scarce literature that assesses the correlation of multinodular goiter (MNG) to ISR, especially in Pakistan, and thus any probable association between the two is left untouched. We report a case of a 57-year-old female who is a known hyperthyroid with a massive MNG, presenting with worsening chest pain. She had undergone sirolimus-eluting stent (SES) implantation in left anterior descending artery (LAD) six months back. Cardiac catheterization confirmed restenosis of the SES in the LAD, along with the occlusion of left circumflex and
TCT 2013 presentation of data planned -. DURHAM, N.C., September 30, 2013 - Micell Technologies, Inc. today announced that a peer reviewed article discussing imaging and clinical results of the DESSOLVE I trial of its MiStent Sirolimus Eluting Absorbable Polymer Coronary Stent System (MiStent SES®) was accepted for publication on the JACC Cardiovascular Interventions website. The paper, First-in-Human Evaluation of a Bioabsorbable Polymer-Coated Sirolimus- Eluting Stent: Imaging and Clinical Results of the DESSOLVE I Trial (DES With Sirolimus and a Bioabsorbable Polymer for the Treatment of Patients With De Novo Lesion in the Native Coronary Arteries), is planned to also appear in the October 2013 issue of JACC Cardiovascular Interventions.. The article concluded that, upon 18 months follow-up, the MiStent SES - an absorbable polymer-coated, cobalt chromium, sirolimus-eluting stent - was associated with a low and stable in-stent late lumen loss, complete strut coverage, and no stent ...
Intracellular metabolic pathways dependent upon the mammalian target of rapamycin (mTOR) play a key role in immune-tolerance control. In this study, we focused on long-term mTOR-dependent immune-modulating effects in kidney transplant recipients undergoing conversion from calcineurin inhibitors (CNI) to mTOR inhibitors (everolimus) in a 1-year follow-up. The conversion to everolimus is associated with a decrease of neutrophils and of CD8(+) T cells. In addition, we observed a reduced production of interferon (IFN)-γ by CD8(+) T cells and of interleukin (IL)-17 by CD4(+) T lymphocytes. An increase in CD4(+) CD25(+) forkhead box protein 3 (FoxP3)(+) [regulatory T cell [(Treg )] numbers was also seen. Treg increase correlated with a higher proliferation rate of this regulatory subpopulation when compared with the CD4(+) FoxP3(-) effector counterpart. Basal phosphorylation level of S6 kinase, a major mTOR-dependent molecular target, was substantially maintained in patients treated with everolimus. ...
1. Tacrolimus and sirolimus are potent immunosuppressors used in transplantation. Tacrolimus has been suspected to alter mitochondrial respiration of different tissues but sirolimus has not been evaluated. 2. We evaluated the in vitro effect of tacrolimus and sirolimus on oxidative phosphorylation o …
SAN FRANCISCO -- Chemotherapy-refractory pancreatic neuroendocrine tumors had durable responses and stable disease in patients treated with the mTOR inhibitor RAD001, an open-label study showed.
TY - JOUR. T1 - Sirolimus affects cardiomyocytes to reduce left ventricular mass in heart transplant recipients. AU - Kushwaha, Sudhir S.. AU - Raichlin, Eugenia. AU - Sheinin, Yuri. AU - Kremers, Walter K.. AU - Chandrasekaran, Krishnaswamy. AU - Brunn, Gregory J.. AU - Platt, Jeffrey L.. PY - 2008/11. Y1 - 2008/11. N2 - Aims: The cellular mechanisms underlying cardiac hypertrophy may result from changes in cardiac myocyte growth and differentiation. We tested whether sirolimus, an immunosuppressive agent that inhibits mTOR, a protein that regulates cell division and differentiation, might modify cardiac hypertrophy after cardiac transplantation. Methods and results: Fifty-eight cardiac transplant recipients were withdrawn from treatment with calcineurin inhibitors (CNIs) and treated with sirolimus. Eighty-three control subjects were maintained on CNIs. After 12 months, left ventricular (LV) mass decreased from 196.15 ± 48.28 to 182.21 ± 43.56 g (P = 0.05) and LV mass index from 99.25 ± ...
This pooled analysis suggests a significant and sustained reduction in TVF and MACE among patients treated with EES compared with PES at 3-year follow-up. Furthermore, EES demonstrated improved efficacy and safety over time, with robust reductions in ischemia-driven target lesion revascularization and target vessel revascularization as well as significant and sustained reductions in MI and composite death or MI. It should be noted that the present study is underpowered to definitively examine low-frequency adverse events such as stent thrombosis, MI, and death and comparative trials with emerging DES are required to determine the optimal platform for specific patient and lesion subtypes, particularly patients with diabetes. Based on available data, and the improved clinical outcomes demonstrated in patients receiving EES compared with those receiving PES, EES is an attractive drug-eluting stent choice for clinicians.. ...
The use of rapamycin to extend lifespan and delay age-related disease in mice is well-established despite its potential to impair glucose metabolism which is driven partially due to increased hepatic gluconeogenesis. We tested whether a combination therapeutic approach using rapamycin and metformin could diminish some of the known metabolic defects caused by rapamycin treatment in mice. In genetically heterogeneous HET3 mice, we found that chronic administration of encapsulated rapamycin by diet caused a measurable defect in glucose metabolism in both male and female mice as early as 1 month after treatment. In female mice, this defect was alleviated over time by simultaneous treatment with metformin, also by diet, such that females treated with both drugs where indistinguishable from control mice during glucose tolerance tests. While rapamycin-mediated glucose intolerance was unaffected by metformin in males, we found metformin prevented rapamycin-mediated reduction in insulin and leptin concentrations
March 29, 2012 - Two-year follow-up data from the pivotal PLATINUM Workhorse trial comparing the safety and effectiveness of the Promus Element and Xience V everolimus-eluting coronary stents demonstrated superior efficacy of the Promus. The results were presented at the American College of Cardiology (ACC) Annual Scientific Session by Gregg W. Stone, M.D., professor of medicine and director of research and education at the Center for Interventional Vascular Therapy at Columbia University Medical Center/New York-Presbyterian Hospital. He was the global principal investigator of the trial. The outcomes reported at 12 months remained comparable at two years for the two stents. However, an additional landmark analysis of outcomes from year one to year two demonstrated superior efficacy of the Promus Element during this 12-month period of follow-up. The Promus Element platinum chromium stent continues to demonstrate excellent safety and effectiveness with low rates of cardiac death, myocardial ...
Researchers have shown that the immunosuppressant everolimus provides a potential new treatment option for patients with tuberous sclerosis and associated angiomyolipomas.
The immunosuppressant drug rapamycin blocks progression of the cell cycle at the G1 phase in mammalian cells and yeast. Here we show that rapamycin inhibits cap-dependent, but not cap-independent, translation in NIH 3T3 cells. Cap-dependent translation is also specifically reduced in extracts from r …
Adding an inhibitor of mammalian target of rapamycin (mTOR) to an aromatase inhibitor more than doubled the time to disease progression in patients with advanced, treatment-refractory breast cancer in the phase III BOLERO-2 trial, whose updated results were presented at the San Antonio Breast Cancer Symposium by Gabriel Hortobagyi, MD, of The University of Texas MD Anderson Cancer Center, Houston.1. We believe these results underline the fact that everolimus [Afinitor] is the first agent to significantly enhance the efficacy of hormonal therapy in patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, and could represent a paradigm shift in the management of this patient population, Dr. Hortobagyi predicted.. Virtually all patients with ER-positive advanced disease develop resistance to hormonal therapies, and finding a means of overcoming this resistance is the subject of strong research efforts. Resistance to hormonal therapy in breast cancer has been associated ...
There are two types of diabetes, which at advanced stages may become similar. Insulin resistance may develop in type I diabetes (due to high glucose), whereas insulin insufficiency in type II diabetes (due to loss of beta-cells). Both types of diabetes lead to complications. In comparison, starvation diabetes [28] is only superficially resembles either type of diabetes. Also, diabetes-like symptoms may occur in rapamycin-treated mice and animals with genetically inhibited insulin/IGFI signaling (Fig. 3). To encompass all these cases, I suggest the term type 0 (zero) or benevolent diabetes. It is possible that some patients with diabetes have inactivating mutations in the insulin/IGFI pathway and thus suffer from benevolent diabetes. Furthermore, the condition can be imitated by chronic administration of rapamycin at least in some strains of mice. Both calorie restriction and rapamycin extend life span in mice. Rapamycin prevents retinopathy and nephropathy. Also CR prevents type II diabetes ...
There are two types of diabetes, which at advanced stages may become similar. Insulin resistance may develop in type I diabetes (due to high glucose), whereas insulin insufficiency in type II diabetes (due to loss of beta-cells). Both types of diabetes lead to complications. In comparison, starvation diabetes [28] is only superficially resembles either type of diabetes. Also, diabetes-like symptoms may occur in rapamycin-treated mice and animals with genetically inhibited insulin/IGFI signaling (Fig. 3). To encompass all these cases, I suggest the term type 0 (zero) or benevolent diabetes. It is possible that some patients with diabetes have inactivating mutations in the insulin/IGFI pathway and thus suffer from benevolent diabetes. Furthermore, the condition can be imitated by chronic administration of rapamycin at least in some strains of mice. Both calorie restriction and rapamycin extend life span in mice. Rapamycin prevents retinopathy and nephropathy. Also CR prevents type II diabetes ...
Nine months after the procedure, the numbers of deaths, heart attacks and repeat interventions required because of renewed blood vessel narrowing were equivalent in both treatment groups (9.2% of patients in the biolimus-eluting stent group and 10.5% of patients in the sirolimus-eluting stent group). In the one in four patients given an angiogram, the degree of blood vessel narrowing at the site of stent implantation was also equivalent in both treatment groups.. The drug-eluting stent is designed to treat narrowing of coronary arteries which is one of the principal causes of coronary artery disease. Once implanted, it uses the strength of its cylindrical mesh wall to keep the artery widened and maintain blood flow, and gradually releases its drug into the surrounding tissues. The role of the drug is to inhibit restenosis, a common problem following stent implantation, whereby excessive tissue forms around the stent and may negate the benefit that it provides. First-generation drug-eluting ...
The primary endpoint of TLF (cardiac death, target vessel MI, ischemia-driven target lesion revascularization [TLR]) was significantly lower in the EES arm compared with the PES arm (4.2% vs. 6.8%, hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.46-0.82, p = 0.001 for superiority). This was driven primarily by a significant reduction in ischemia-driven TLR (2.5% vs. 4.6%, HR 0.55, 95% CI 0.38-0.78, p = 0.001). Cardiac death or target vessel MI were similar between the two arms (2.2% vs. 3.2%, p = 0.09). All-cause mortality was similar (1.0% vs. 1.3%, p = 0.61), but EES was associated with a significant reduction in MI (1.9% vs. 3.1%, p = 0.02). EES was also associated with a significant reduction in stent thrombosis (Academic Research Consortium [ARC] or probable) at 1 year, as compared with PES (0.2% vs. 0.8%, p = 0.004). The greatest impact of TLF reduction was noted in patients without diabetes mellitus (DM) (p , 0.05). Two-year follow-up data were available for 3,578 patients (97%). ...
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TY - JOUR. T1 - Immunosuppressants FK506 and rapamycin have different effects on the biosynthesis of cytoplasmic actin during the early period of T cell activation. AU - Miyamoto, Suzanne. AU - Safer, Brian. PY - 1999/12/15. Y1 - 1999/12/15. N2 - FK506 and rapamycin are immunosuppressants that interfere with T cell activation. FK506 inhibits early events of T cell activation such as the induction of cytokine transcription, whereas rapamycin inhibits later interleukin 2 signalling events. However, both reagents either directly or indirectly reduce protein synthesis. Therefore a kinetic study was conducted in human primary T lymphocytes examining increased synthesis of proteins stimulated by either ionomycin + phorbol myristate acetate (PMA) or PMA alone. Three patterns of protein expression were observed. Synthesis of one group of proteins had enhanced synthesis with FK506, but reduced synthesis with rapamycin. A second group had reduced synthesis with rapamycin and either no change or a slight ...
Inhibition of the TOR signalling pathway by genetic or pharmacological intervention extends lifespan in invertebrates, including yeast, nematodes and fruitflies1, 2, 3, 4, 5; however, whether inhibition of mTOR signalling can extend lifespan in a mammalian species was unknown. Here we report that rapamycin, an inhibitor of the mTOR pathway, extends median and maximal lifespan of both male and female mice when fed beginning at 600 days of age. On the basis of age at 90% mortality, rapamycin led to an increase of 14% for females and 9% for males. The effect was seen at three independent test sites in genetically heterogeneous mice, chosen to avoid genotype-specific effects on disease susceptibility. Disease patterns of rapamycin-treated mice did not differ from those of control mice. In a separate study, rapamycin fed to mice beginning at 270 days of age also increased survival in both males and females, based on an interim analysis conducted near the median survival point. Rapamycin may extend ...
TY - JOUR. T1 - Eosinophilic rash secondary to temsirolimus. AU - Gandhi, Mona. AU - Kuzel, Timothy. AU - Lacouture, Mario. PY - 2009/1/1. Y1 - 2009/1/1. N2 - We present a case of a 73-year-old female with metastatic renal cell carcinoma, clear cell histologic subtype, who developed pruritic rash after 2 weeks of 25 mg weekly infusions of temsirolimus. Rash was located on bilateral antecubital areas and posterior knees. Skin biopsy showed spongiotic dermatitis with eosinophils. Based on history and clinical examination, a diagnosis of drug rash secondary to temsirolimus was made. Temsirolimus is a small-molecule inhibitor of the mammalian target of rapamycin (mTOR). Inhibition of mTOR kinase results in cell cycle arrest, antiangiogenesis, and apoptosis. The mechanism of skin toxicity is unknown; however, it can be hypothesized that there is a direct inhibitory effect on signaling pathways that regulate cell growth and tissue repair. The mTOR kinase inhibitor temsirolimus has shown great promise ...
Sirolimus[edit]. Main article: Sirolimus. Sirolimus (rapamycin, trade name Rapamune) is a macrolide lactone, produced by the ... Therefore, sirolimus acts synergistically with ciclosporin and, in combination with other immunosuppressants, has few side ... In a similar manner, Sirolimus prevents B cell differentiation into plasma cells, reducing production of IgM, IgG, and IgA ... Contrary to ciclosporin and tacrolimus, drugs that affect the first phase of T lymphocyte activation, sirolimus affects the ...
Sirolimus[edit]. The bacterial natural product rapamycin or sirolimus,[6] a cytostatic agent, has been used in combination ... "CYPHER Sirolimus-eluting Coronary Stent - P020026". Food and Drug Administration. Retrieved 25 September 2012.. ... The structural characteristics common to temsirolimus and sirolimus; the pipecolic acid, tricarbonyl region from C13-C15, and ... Food and Drug Administration approved sirolimus-eluting coronary stents, which are used in patients with narrowing of coronary ...
... produces sirolimus. List of Streptomyces species LPSN bacterio.net UniProt Deutsche Sammlung von ...
In 2003, the U.S. Food and Drug Administration approved sirolimus-eluting coronary stents, which are used in patients with ... "CYPHER Sirolimus-eluting Coronary Stent - P020026". Food and Drug Administration. Retrieved 25 September 2012. "Torisel". ... Ridaforolimus (AP23573, MK-8669), or deforolimus, is another rapamycin analogue that is not a prodrug for sirolimus. Like ... The bacterial natural product rapamycin or sirolimus, a cytostatic agent, has been used in combination therapy with ...
Sirolimus is used to treat lymphangioma . Treatment with sirolimus can decrease pain and the fullness of venous malformations, ... Sirolimus is a relatively new medical therapy for the treatment of vascular malformations, in recent years, sirolimus has ... Sirolimus (rapamycin, trade name Rapamune) is a macrolide compound. It has immunosuppressant and antiproliferative functions in ... "Sirolimus in the treatment of vascular anomalies." https://www.jvascsurg.org/article/S0741-5214(19)32236-0/fulltext, Journal of ...
e.g. rapamycin (sirolimus) and temsirolimus. Cell lines with known PTEN mutations include: prostate: LNCaP, PC-3 kidney: 786-O ...
H. Mawardi; M. Pavlakis; D.S. Mandelbrot; S.B. Woo (2010). "Sirolimus oral ulcer with Cedecea davisae superinfection". Transpl ... Mawardi, H., Pavlakis, M., Mandelbrot, D., Woo, S. B. (2010). Sirolimus oral ulcer with Cedecea davisae superinfection. Transpl ...
Sirolimus and mycophenolate have less evidence for their use in the treatment of chronic hives but reports have shown them to ... Morgan M (2009). "Treatment of refractory chronic urticaria with sirolimus". Arch Dermatol. 145 (6): 637-9. doi:10.1001/ ... Immunosuppressants used for CU include cyclosporine, tacrolimus, sirolimus, and mycophenolate. Calcineurin inhibitors, such as ... At this point, anti-inflammatory medications (dapsone, sulfasalazine), immunosuppressants (cyclosporin, sirolimus) or other ...
The Combo Dual Therapy Stent is a coronary stent that combines Genous with an antiproliferative, biodegradable sirolimus drug ... Sirolimus-Eluting Stent Found 'Safe,' and 'Effective.'" Cardiology News. "Dual-Therapy Stenting: The Next Step in the Evolution ...
London, Susan (14 November 2011). "Bioengineered, Sirolimus-Eluting Stent Found 'Safe,' and 'Effective.'" Cardiology News. http ... sirolimus drug elution from a biodegradable polymer, was shown to be as effective as a paclitaxel-eluting stent in controlling ... a randomized comparison of a combination sirolimus-eluting endothelial progenitor cell capture stent with a paclitaxel-eluting ...
... biodegradable sirolimus drug elution. The Combo Stent has received CE Mark approval. "Dual-Therapy Stenting: The Next Step in ... Sirolimus-Eluting Stent Found 'Safe,' and 'Effective.'" Cardiology News. First Dual-Therapy Stent Nets CE Mark (Cardiology ...
The first successful trials were of sirolimus-eluting stents. A clinical trial in 2002 led to approval of the sirolimus-eluting ... Both sirolimus and paclitaxel are natural products, making the drug-eluting stents a specific kind of application totally ... 2003). "Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery". New England ... Sirolimus, paclitaxel, and everolimus were previously used for other medical applications and have been included in licensed ...
It is a semi-synthetic derivative of sirolimus (rapamycin). It was designed for use in stents with phosphorylcholine as a ...
Sirolimus (Rapamycin), ascomycin, and tacrolimus were isolated from Streptomyces. Pimecrolimus is a derivative of ascomycin. ...
"Sirolimus in Treating Patients With Angiomyolipoma of the Kidney". ClinicalTrials.gov (NIH). 21 November 2006. Retrieved 10 ... 2002 Treatment with rapamycin (sirolimus) was found to shrink tumours in the Eker rat (TSC2) and mouse (TSC1) models of ... "Multicenter International Lymphangioleiomyomatosis Efficacy of Sirolimus Trial (The MILES Trial)". ClinicalTrials.gov (NIH). 6 ...
Some recipients may instead take ciclosporin, sirolimus, or azathioprine. The risk of early rejection of the transplanted ... These food products are known to interact with the transplant medications, specifically tacrolimus, cyclosporin and sirolimus; ...
Sirolimus may not be as immune suppressive in normal lymphocytes as other agents. Some patients have had improvement in immune ... Sirolimus (rapamycin, rapamune) which is a mTOR (mammalian target of rapamycin) inhibitor can be active in most patients and ... Hypothetically, Sirolimus may have lower risk of secondary cancers as opposed to other immune suppressants and requires ... 2009). "Treatment with sirolimus results in complete responses in patients with autoimmune lymphoproliferative syndrome". ...
Sirolimus. mTOR inhibitor, thereby reducing cytokine-induced lymphocyte proliferation.. PO. C (Au). Neutropenia, hypokalaemia, ... sirolimus, alefacept, and the tyrosine kinase inhibitors, imatinib, nilotinib, and dasatinib.[16][31][32][33][34][35][36][37] ...
Sirolimus: Anti-proliferative effects "Learn about CYPHER Stent, the latest advance in stent technology". Cordis Corporation. ... An anti-rejection-type medication, sirolimus, helps to limit the overgrowth of normal cells while the artery heals which ... CS1 maint: discouraged parameter (link) "CYPHER™ Sirolimus-eluting Coronary Stent - P020026". FDA.gov. U.S. Food and Drug ...
Sirolimus has been effective in improving the quality of life in some people with FAVA. "Fibro-Adipose Vascular Anomaly (FAVA ... Erickson J, McAuliffe W, Blennerhassett L, Halbert A (November 2017). "Fibroadipose vascular anomaly treated with sirolimus: ...
"Cordis' CYPHER TM Sirolimus-eluting Stent Receives CE Mark Approval" (PDF). Cordis Corporation. April 15, 2002. Archived from ... Spaulding C, Daemen J, Boersma E, Cutlip DE, Serruys PW (2007). "A pooled analysis of data comparing sirolimus-eluting stents ... Randomized Study with the Sirolimus-Coated Bx Velocity Balloon-Expandable Stent in the Treatment of Patients with de Novo ... 2002). "A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization". N Engl J ...
Sirolimus (Rapamycin). *Temsirolimus. *Umirolimus. *Zotarolimus; ATP-competitive / indirect: Berberine. *Curcumin. *Dactolisib ...
Sirolimus (Rapamycin). *Temsirolimus. *Umirolimus. *Zotarolimus; ATP-competitive / indirect: Berberine. *Curcumin. *Dactolisib ...
Sirolimus (Rapamycin). *Temsirolimus. *Umirolimus. *Zotarolimus; ATP-competitive / indirect: Berberine. *Curcumin. *Dactolisib ...
The first two drug-eluting stents to be utilized were the paclitaxel-eluting stent and the sirolimus-eluting stent, both of ... Most current FDA-approved drug-eluting stents use sirolimus (also known as rapamycin), everolimus and zotarolimus. Biolimus A9- ... Claessen BE, Henriques JP, Dangas GD (2010). "Clinical studies with sirolimus, zotarolimus, everolimus, and biolimus A9 drug- ...
Sirolimus, a compound that inhibits mTOR signalling, is being studied to treat plexiform neurofibromas. The combination of ... Clinical trial number NCT00652990 for "Sirolimus to Treat Plexiform Neurofibromas in Patients With Neurofibromatosis Type I" at ... erlotinib with sirolimus was studied to treat low-grade gliomas. Early research has shown potential for using the c-kit ... ClinicalTrials.gov Clinical trial number NCT00634270 for "A Phase II Study of the mTOR Inhibitor Sirolimus in Neurofibromatosis ...
Impact of Avoiding Loading Dose of Sirolimus on Wound Complication After Kidney Transplant. A Single Center Experience, Ayran, ... Safety and Efficacy of Sirolimus, Low Dose Tacrolimus and Early Steroid Withdrawal in Patients with Cadaveric Renal Allographs ... M., Jabri, M., El-Ghoroury, M., Oh, H., Provenzano, R., Impact of Avoiding Loading Dose of Sirolimus on Wound Complication ... A Comparative Study, Nagrecha, N., El-Ghoroury, M., Provenzano, R., Safety and Efficacy of Sirolimus, Low Dose Tacrolimus and ...
... thymoglobulin and sirolimus. Newer, so-called "biologic drugs" or monoclonal antibodies, are also used in these conditions and ...
Sirolimus seems to lower the cancer risk in some transplant patients. Sirolimus was shown to inhibit the progression of dermal ... Sirolimus blocks this pathway. The safety and efficacy of sirolimus treatment of LAM were investigated in clinical trials that ... Sirolimus is used to treat venous malformations. Treatment with sirolimus can decrease pain and the fullness of venous ... Sirolimus is a relatively new medical therapy for the treatment of vascular malformations, in recent years, sirolimus has ...
Sirolimus: learn about side effects, dosage, special precautions, and more on MedlinePlus ... while taking sirolimus, and for 12 weeks after stopping sirolimus. If you become pregnant while taking sirolimus, call your ... Before taking sirolimus,. *tell your doctor and pharmacist if you are allergic to sirolimus, any other medications, or any of ... Sirolimus is used in combination with other medications to prevent rejection of kidney transplants. Sirolimus is in a class of ...
Patients with treatment-resistant autoimmune blood conditions may benefit from sirolimus The immunosuppressant sirolimus is an ... Sirolimus chemoprevention supported in organ transplant recipients In solid-organ transplant recipients diagnosed with cancer ... for better x-ray visibility was shown to be non-inferior to an ultrathin-strutted bioresorbable polymer-coated sirolimus- ... post-transplant, treatment with sirolimus reduces the risk of developing a subsequent skin cancer, US investigators report in ...
Successful sirolimus treatment of lymphangioleiomyomatosis in a hepatitis B virus carrier. Internal Medicine 58: 569-574, No. 4 ...
Is sirolimus given to patients who receive organs other than kidneys or have other conditions?. Sirolimus also is used ... Where are sirolimus tests performed?. Sirolimus tests may be performed in a local hospital laboratory but may also be sent to a ... How long will I need to be on sirolimus?. Transplant recipients must take immunosuppressants - including sirolimus or other ... Who orders sirolimus tests?. Sirolimus will usually be monitored by the healthcare provider and transplant team that performed ...
The cover for issue 31 of Oncotarget features Figure 4, "Concentration dose-response curves of sirolimus effect [55 nM-1 nM] on ... cultured in physiological conditions mimicking sirolimus-eluted stent, in order to clarify the effectiveness of sirolimus in ... Gianandrea Pasquinelli from The Bologna University said, "Rapamycin (sirolimus) is a widely used cytostatic drug blocking the ... Oncotarget: Sirolimus-eluting stents -- opposite in vitro effects on the clonogenic cell potential The cover for issue 31 of ...
Detailed drug Information for sirolimus. Includes common brand names, drug descriptions, warnings, side effects and dosing ... Proper Use of sirolimus. Take sirolimus only as directed by your doctor. Do not take more of it, do not take it more often, and ... Sirolimus is available only with your doctors prescription.. Before Using sirolimus. In deciding to use a medicine, the risks ... Uses For sirolimus. Sirolimus is used together with other medicines to prevent the body from rejecting a transplanted kidney. ...
Sirolimus is given in a combination treatment with... ... Sirolimus lowers your bodys immune system. The immune system ... Do not use sirolimus if you are pregnant. Use effective birth control to prevent pregnancy while you are taking sirolimus, and ... What should I discuss with my healthcare provider before taking sirolimus?. Sirolimus may increase your risk of developing ... What is sirolimus?. Sirolimus lowers your bodys immune system. The immune system helps your body fight infections. The immune ...
Find the most comprehensive real-world treatment information on Sirolimus at PatientsLikeMe. 68 patients with fibromyalgia, ... bipolar I disorder or psoriasis currently take Sirolimus. ... Currently taking Sirolimus Duration. Patients. This item is ... Stopped taking Sirolimus Duration. Patients. This item is relevant to you: Less than 1 month 7 * 7 ... Why patients stopped taking Sirolimus. Multiple reasons could be selected. Reason. Patients. This item is relevant to you: ...
Easy-to-read patient leaflet for Sirolimus Tablets. Includes indications, proper use, special instructions, precautions, and ... What do I need to tell my doctor BEFORE I take Sirolimus Tablets?. *If you have an allergy to sirolimus or any other part of ... How is this medicine (Sirolimus Tablets) best taken?. Use this medicine (sirolimus tablets) as ordered by your doctor. Read all ... If you are allergic to this medicine (sirolimus tablets); any part of this medicine (sirolimus tablets); or any other drugs, ...
... sirolimus) from other patients. Learn from their experiences about effectiveness, side effects and cost ...
Among them, octreotide and sirolimus have been shown to be one of the most promising drugs to reduce cyst volume. Sirolimus ... Experimental: Sirolimus Sirolimus administration group starting dose: 2mg/day target trough level: 4-10 ng/dL ... Drug: Sirolimus Sirolimus administration for 12 months followed by conventional therapy alone for additional 12 months ... Sirolimus for Massive Polycystic Liver (SILVER). The recruitment status of this study is unknown. The completion date has ...
Taking sirolimus. *Take sirolimus exactly as directed by your doctor. If you do not understand these directions, ask your ... Sirolimus and pregnancy. Although sirolimus has not been studied in pregnant women, it is not recommended for use during ... How sirolimus works. Sirolimus works by preventing the white blood cells from getting rid of the transplanted organ. ... during sirolimus therapy, and for 12 weeks after sirolimus therapy has stopped. ...
... and sirolimus (Sir), as presented at the IATDMCT 2007 conference. The review focuses on the developmental changes of drug ... Sirolimus half-life and mean residence time (MRT) are shorter than in adults. Similar to that in adults, there is a profound ... Pharmacokinetics of mycophenolate mofetil and sirolimus in children Ther Drug Monit. 2008 Apr;30(2):138-42. doi: 10.1097/FTD. ... and sirolimus (Sir), as presented at the IATDMCT 2007 conference. The review focuses on the developmental changes of drug ...
... Mar 22, 2006, 08:26, Reviewed by: Dr. Priya Saxena. ... The drug is rapamycin, also called sirolimus, and is currently used as an immunosuppressant, to help prevent rejection of a new ...
SOURCE: Sirolimus ( ) Page printed: . Unofficial document if printed. Please refer to SOURCE for latest information. Copyright ... Sirolimus can lower the number of your white blood cells, red blood cells and platelets. You may be at an increased risk for ... Sirolimus may be taken with or without food. Taking it with food will decrease stomach upset. Be consistent, if you take it ... When having sirolimus blood levels drawn, do not take the morning dose of medication until after your blood sample is taken. ...
... ... sirolimus-eluting bioresorbable scaffold (BRS) scaffold, which has a strut thickness in the sub-100-micron range. Dr. Antonio ...
The precise etiology underlying sirolimus-induced pneumonitis remains unknown, but it has been speculated that sirolimus might ... Sirolimus-Induced Interstitial Pneumonitis in an Islet Transplant Recipient. Benigno J. Digon, Kristina I. Rother, Boaz ... Sirolimus-Induced Interstitial Pneumonitis in an Islet Transplant Recipient. Benigno J. Digon, Kristina I. Rother, Boaz ... Sirolimus-Induced Interstitial Pneumonitis in an Islet Transplant Recipient Message Subject (Your Name) has forwarded a page to ...
... Posted on November 17th, 2009 by Deon Scott in All News, asbestos, asbestos ... 1 user commented in Sirolimus can help with Mesothelioma Treatment Follow-up comment rss or Leave a Trackback ... Sirolimus is currently being looked at for the treatment of a number of cancers including mesothelioma. ... These results provide a basis for the clinical evaluation of combined sirolimus and cisplatin chemotherapy in malignant pleural ...
Therapy with sirolimus may be useful in selected patients with LAM. (Funded by the National Institutes of Health and others; ... sirolimus stabilized lung function, reduced serum VEGF-D levels, and was associated with a reduction in symptoms and ... After discontinuation of sirolimus, the decline in lung function resumed in the sirolimus group and paralleled that in the ... Efficacy and safety of sirolimus in lymphangioleiomyomatosis N Engl J Med. 2011 Apr 28;364(17):1595-606. doi: 10.1056/ ...
Sirolimus. Revision as of 20:01, 27 September 2011 by WikiBot. (talk , contribs) (Protected Sirolimus: Protecting pages from ... The anti-proliferative effects of sirolimus may have a role in treating cancer. Recently, it was shown that sirolimus inhibited ... Sirolimus is a macrolide ("-mycin") first discovered as a product of the bacterium Streptomyces hygroscopicus in a soil sample ... The mode of action of sirolimus is to bind the cytosolic protein FK-binding protein 12 (FKBP12) in a manner similar to ...
Paclitaxel-eluting or sirolimus-eluting stents to prevent restenosis in diabetic patients.. Dibra A1, Kastrati A, Mehilli J, ... The study was designed to show noninferiority of the paclitaxel stent as compared with the sirolimus stent, defined as a ... In patients with diabetes mellitus and coronary artery disease, use of the sirolimus-eluting stent is associated with a ... and 125 to receive sirolimus-eluting stents. The primary end point was in-segment late luminal loss. Secondary end points were ...
7. History of hypersensitivity to Sirolimus or any component of the formulation (for. Lapatinib and Sirolimus arm only). 8. ... Sirolimus is designed to block a protein called mTOR (a protein that is thought to cause. cancer cells to grow) inside the ... If you are also taking sirolimus, you will take it by mouth 1 time every day. You should. take it at about the same time each ... A Phase 1 Trial of Lapatinib in Combination With 1) Sirolimus or 2) Metformin in Advanced Cancer. Trial Phase:. Phase 1. ...
Sirolimus and its analogues are drugs that are ... Sirolimus and its analogues are drugs that are commonly used to ... Virtue Sirolimus-Eluting Balloon Helps Prevent Restenosis without Stents. April 25th, 2019 Medgadget Editors Cardiology ... The SEB is an angioplasty balloon, and so is able to push plaque apart, but it also has tiny holes through which sirolimus ... Now a new device, called Virtue Sirolimus-Eluting Balloon (SEB), from Orchestra BioMed, a company based in New Hope, ...
Sirolimus (Rapamune®). (should not be prescribed as rapamycin). Indication. As an adjunct to or substitute to a calcineurin ... Sirolimus is not used de-novo and is generally switched for tacrolimus. The following doses can be started and tacrolimus ...
Sirolimus Clinical Trial The University of Pennsylvania and the University of Arkansas for Medical Sciences are conducting a ...
... the MiStent Sirolimus Eluting Absorbable Polymer Coronary Stent System, in the ... Micell MiStent Sirolimus Eluting Absorbable Polymer Stent Coming to Europe. February 9th, 2015 Medgadget Editors Cardiology ... The MiStent SES includes a proprietary stent coating that contains crystalline drug (sirolimus) and an absorbable polymer. The ... Micell Technologies (Durham, NC) is releasing its flagship product, the MiStent Sirolimus Eluting Absorbable Polymer Coronary ...
Antiplatelet Therapy and Stent Thrombosis After Sirolimus-Eluting Stent Implantation. Takeshi Kimura, Takeshi Morimoto, ... Methods and Results- In an observational study in Japan, 2-year outcomes were assessed in 10 778 patients undergoing sirolimus- ... In the j-Cypher registry, 10 778 Japanese patients treated exclusively by sirolimus-eluting stents were followed up for up to 2 ... Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: data ...
Antiplatelet Therapy and Stent Thrombosis After Sirolimus-Eluting Stent Implantation. Takeshi Kimura, Takeshi Morimoto, ... Antiplatelet Therapy and Stent Thrombosis After Sirolimus-Eluting Stent Implantation. Takeshi Kimura, Takeshi Morimoto, ... Antiplatelet Therapy and Stent Thrombosis After Sirolimus-Eluting Stent Implantation. Takeshi Kimura, Takeshi Morimoto, ...
Tacrolimus/Sirolimus Versus Tacrolimus/Mycophenolate Mofetil (MMF) Versus Neoral/Sirolimus in Adult, Primary Kidney ... A derivative of sirolimus and an inhibitor of TOR SERINE-THREONINE KINASES. It is used to prevent GRAFT REJECTION in heart and ... This study is being done to find out which treatment, tacrolimus or sirolimus, leads to better long-term kidney function. ... The purpose of this study is to compare treatment with the new drug sirolimus (SRL) versus the standard treatment with ...
  • http://www.nelm.nhs.uk/en/NeLM-Area/Other-Lib-Updates/SPC-Changes/Rapamune-sirol. (medworm.com)
  • What is Sirolimus (Rapamune) used for? (everydayhealth.com)
  • Can I take Sirolimus (Rapamune) if I'm pregnant or breastfeeding? (everydayhealth.com)
  • Sirolimus, also known as rapamycin or by the brand name Rapamune, is a medicine that lowers the body's natural immunity. (nephcure.org)
  • The results of the pharmacokinetic study indicate that the SMEDDS formulation shows significantly greater bioavailability than the raw sirolimus powder or commercial product (Rapamune ® oral solution). (dovepress.com)
  • Generic drug Sirolimus is considered just as safe and effective as its brand-name equivalents such as Rapamune. (internationaldrugmart.com)
  • Did you know that buying the generic drug Sirolimus from IDM is much cheaper than buying the Rapamune brand drug? (internationaldrugmart.com)
  • The goal of this clinical research study is to learn if the combination of rabbit anti-thymocyte globulin (Thymoglobulin®), sirolimus (Rapamune®), and mycophenolate mofetil (Cellcept®) can help to prevent graft versus host disease (GVHD). (bioportfolio.com)
  • Sirolimus ( Rapamune ® ) is a prescription medication that belongs to a class of drugs called immunosuppressants. (emedtv.com)
  • Sirolimus (Rapamune) whole blood concentrations can be measured by either chromatographic or immunoassay methodologies. (aruplab.com)
  • Sirolimus, also known as rapamycin, is a macrolide compound that is used to coat coronary stents, prevent organ transplant rejection and treat a rare lung disease called lymphangioleiomyomatosis. (wikipedia.org)
  • The antiproliferative effect of sirolimus has also been used in conjunction with coronary stents to prevent restenosis in coronary arteries following balloon angioplasty. (wikipedia.org)
  • Several large clinical studies have demonstrated lower restenosis rates in patients treated with sirolimus-eluting stents when compared to bare-metal stents, resulting in fewer repeat procedures. (wikipedia.org)
  • Paclitaxel-eluting or sirolimus-eluting stents to prevent restenosis in diabetic patients. (nih.gov)
  • We enrolled 250 patients with diabetes and coronary artery disease: 125 were randomly assigned to receive paclitaxel-eluting stents, and 125 to receive sirolimus-eluting stents. (nih.gov)
  • Because blood flows rapidly through, stents coated with the drug have been used to treat the area by slowly releasing sirolimus and the like into the surrounding vascular tissue. (medgadget.com)
  • The company will also stop the manufacture of CYPHER® and CYPHER SELECT® Plus Sirolimus-Eluting Coronary Stents by the end of 2011. (mdtmag.com)
  • This case underlines the possible need for long term antiplatelet medication among patients receiving sirolimus eluting stents. (bmj.com)
  • Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. (nih.gov)
  • The frequency of neointimal hyperplasia within the stent was also decreased in the group that received sirolimus-eluting stents, as assessed by both angiography and intravascular ultrasonography. (nih.gov)
  • Sirolimus-eluting coronary stents. (nih.gov)
  • We studied the effect of oral sirolimus, administered to prevent and treat in-stent restenosis (ISR), on the variation of serum levels of inflammatory markers following coronary stenting with bare metal stents. (scielo.br)
  • The Partner stent (coated with a permanent polymer) and the Excel stent (coated with a biodegradable polymer) are two different types of sirolimus eluting stents made in China. (bmj.com)
  • The goal of the trial was to evaluate the use of direct stenting compared with predilatation in patients receiving sirolimus-eluting stents for treatment of single, de novo lesions. (acc.org)
  • Patients were enrolled at 16 US sites from April-June 2003 and received sirolimus-eluting stents using direct stenting. (acc.org)
  • Among patients receiving sirolimus-eluting stents for treatment of single, de novo lesions, there was no difference in procedure success, MACE at six months, or late loss at eight months for direct stenting compared with historical controls of predilatation. (acc.org)
  • Several large-scale randomized trials have shown a reduction in restenosis with sirolimus-eluting stents. (acc.org)
  • TUESDAY, Sept. 3, 2019 (HealthDay News) - For patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), there were fewer target lesion failures at one year in those receiving biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents, according to a study published online Sept. 2 in The Lancet . (physiciansweekly.com)
  • A total of 1,300 patients were randomly assigned to receive either biodegradable polymer sirolimus-eluting stents (649 patients with 816 lesions) or durable polymer everolimus-eluting stents (651 patients with 806 lesions). (physiciansweekly.com)
  • In the present study, the difference in the primary end point between the two study groups was largely driven by fewer cases of clinically-indicated target lesion revascularization in patients treated with biodegradable polymer sirolimus-eluting stents compared with durable polymer everolimus-eluting stents," the authors write. (physiciansweekly.com)
  • A subgroup analysis of diabetic patient data from a two-year randomized controlled trial comparing the CYPHER Sirolimus-eluting Coronary Stent to the Taxus Stent showed no statistically significant differences in safety outcomes between the two drug-eluting stents. (webwire.com)
  • The SISR Trial (A Randomized Trial Comparing Sirolimus-Eluting Stent with Vascular Brachytherapy for the Treatment of In-Stent Restenosis Within Bare Metal Stents) is a multi-center, randomized study of 384 patients from 26 academic and community health centers in the United States. (webwire.com)
  • Randomized study comparing everolimus- and sirolimus-eluting stents in patients with bifurcation lesions treated by provisional side-branch stenting. (biomedsearch.com)
  • At the present time, only few randomized studies and some observational reports specifically addressed the issue of bifurcation lesion treatment with sirolimus-eluting stents (SES). (dovepress.com)
  • Serial quantitative intravascular ultrasound and computer-assisted grayscale value analysis for plaque composition over four years were obtained in 23 event-free patients treated with sirolimus-eluting stents. (onlinejacc.org)
  • Background Sirolimus-eluting stents are effective in inhibiting neointimal hyperplasia without affecting plaque volume behind the stent struts at six months. (onlinejacc.org)
  • Methods Serial quantitative intravascular ultrasound and computer-assisted grayscale value analysis over four years were performed in 23 event-free patients treated with sirolimus-eluting stents. (onlinejacc.org)
  • The drug is rapamycin, also called sirolimus, and is currently used as an immunosuppressant, to help prevent rejection of a new, transplanted kidney. (rxpgnews.com)
  • Sirolimus (also called rapamycin) inhibits mTOR and has shown promise in phase 1-2 trials involving patients with LAM. (nih.gov)
  • However, unlike the tacrolimus-FKBP12 complex which inhibits calcineurin (PP2B), the sirolimus-FKBP12 complex inhibits the mammalian target of rapamycin (mTOR) pathway through directly binding the mTOR Complex1 (mTORC1). (wikidoc.org)
  • mammilian target of rapamycin (mTOR) is a very important serine/threonine protein kinase involved in the regulation of energy metabolism, cell growth, angiogenesis and other cellular biological processes.Rapamycin (sirolimus) is a selective inhibitor of mTOR kinase, which can inhibit the activation and proliferation of T lymphocytes to inhibit the immune response.Currently, mTOR inhibitors are also widely used in tumor treatment. (clinicaltrials.gov)
  • We present the first case of the safe coadministration of raltegravir and sirolimus (rapamycin) in an HIV-infected subject who developed renal impairment after liver transplantation. (lww.com)
  • Sirolimus, a more novel agent, inhibits the mammalian target of rapamycin (mTOR) leading to inhibition of lymphocyte growth and differentiation. (hindawi.com)
  • Because of their narrow therapeutic range, many immunosuppressive drugs, including the mammalian target of rapamycin inhibitors everolimus and sirolimus are subject to therapeutic drug monitoring (TDM) to allow for balancing between toxic- and sub-therapeutic drug concentrations. (degruyter.com)
  • Sirolimus, an inhibitor of the mammalian target of rapamycin (mTOR), is increasingly used as an agent for post-transplant immunosuppression and the treatment of solid organ and haematological malignancies and hamartomas. (lymphedemapeople.com)
  • I. Reduction of mammary stem/progenitor cells (MaSC) in ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS), atypical lobular hyperplasia (ALH) or atypical ductal hyperplasia (ADH) in patients receiving sirolimus (rapamycin). (cancer.gov)
  • Sirolimus is an mTOR (mammalian target of rapamycin) inhibitor, which inhibits cell proliferation and reduces allograft rejection resulting in improved long-term graft survival [ 7 , 8 ]. (hindawi.com)
  • 14 C]Sirolimus also degraded to the known ring-opened product, seco-rapamycin. (aspetjournals.org)
  • Sirolimus, seco-rapamycin (basolaterally dosed), and M2 were all actively secreted across the apical membrane, and secretion of each was inhibited by the P-gp inhibitor LY335979 [(2 R )-anti-5-{3-[4-(10,11-difluoromethanodibenzo-suber-5-yl)piperazin-1-yl]-2-hydroxypropoxy}quinoline trihydrochloride]. (aspetjournals.org)
  • Along with CYP3A4-mediated metabolism and P-gp-mediated secretion, we conclude that the following novel pathway, which occurs at least in the intestine, may contribute significantly to the first-pass extraction of sirolimus in humans: intracellular degradation of sirolimus to seco-rapamycin, metabolism of seco-rapamycin to M2 by an unidentified nonmicrosomal enzyme, and P-gp-mediated secretion of M2 and seco-rapamycin. (aspetjournals.org)
  • Preclinical studies showed promising synergistic effects when the mammalian target of rapamycin (mTOR) inhibitor sirolimus was added to pemetrexed. (unl.edu)
  • To help you remember to take sirolimus, take it around the same time every day. (medlineplus.gov)
  • Take sirolimus exactly as directed. (medlineplus.gov)
  • Continue to take sirolimus even if you feel well. (medlineplus.gov)
  • How should I take sirolimus? (cigna.com)
  • If you also take cyclosporine, wait at least 4 hours after your cyclosporine dose before you take sirolimus. (cigna.com)
  • You may take sirolimus with or without food, but take it the same way every time. (cigna.com)
  • What do I need to tell my doctor BEFORE I take Sirolimus Tablets? (drugs.com)
  • What are some things I need to know or do while I take Sirolimus Tablets? (drugs.com)
  • When you start to take sirolimus, ask your doctor what you should do if you forget a dose, and write down these directions so that you can refer to them later. (transplantliving.org)
  • Subjects will take Sirolimus at an initial dose of 2mg followed by dose adjustment to keep Sirolimus trough levels between 5-15ng/ml consistent with the effective dose in the MILES trial. (clinicaltrials.gov)
  • You may take sirolimus with food. (nephcure.org)
  • If your physician has instructed or directed you to take Sirolimus medication in a regular schedule and you have missed a dose of this medicine, take it as soon as you remember. (internationaldrugmart.com)
  • Beginning 2 days before the transplant, you will take sirolimus by mouth once per day. (bioportfolio.com)
  • Your healthcare provider may choose to monitor you more closely if you take sirolimus with a CYP 3A4 inhibitor and adjust your dose as needed. (emedtv.com)
  • If someone takes both sirolimus and cyclosporine (or tacrolimus), then both drug levels will be monitored. (labcorp.com)
  • The use of sirolimus in combination with cyclosporine or tacrolimus was associated with excess mortality, graft loss, and hepatic artery thrombosis in studies in de novo liver transplant patients. (drugs.com)
  • Sirolimus is given in a combination treatment with cyclosporine and a steroid medicine to prevent your body from rejecting a transplanted kidney. (cigna.com)
  • Sirolimus is an immunosuppressant agent used to prevent organ rejection in renal transplants, in combination with corticosteroids and cyclosporine. (patientslikeme.com)
  • The purpose of this study is to compare treatment with the new drug sirolimus (SRL) versus the standard treatment with cyclosporine (CsA) or tacrolimus in children who have received kidney. (bioportfolio.com)
  • Initial studies indicate that sirolimus should be administered with full-doses of cyclosporine and prednisone . (chp.edu)
  • Although sirolimus is not believed to be dangerous to the kidneys, kidney function should be monitored when it is used with other immunosuppressants like cyclosporine. (chp.edu)
  • Twenty kidney recipients on quadruple (mycophenolate mofetil, prednisone, cyclosporine A or tacrolimus, and sirolimus) therapy and 85 on triple therapy where sirolimus was excluded were analyzed for graft rejection or loss within a posttransplant surveillance period of 3 years. (hindawi.com)
  • One regimen comprised a combination of mycophenolate mofetil, prednisone, cyclosporine A or tacroliamus, and sirolimus (quadruple therapy), and the other excluded sirolimus (triple therapy). (hindawi.com)
  • Sirolimus, an inhibitor of the mTOR signaling pathway, has been shown to decrease the incidence of acute rejection when combined with cyclosporine or tacrolimus ( 5-7 ). (wiley.com)
  • We describe the development of this complication in a 56-yr-old woman, who was given an experimental protocol with cyclosporine, sirolimus, steroids, and basiliximab. (lymphedemapeople.com)
  • Following the protocol, after one month, the patient was randomized to the "sirolimus only" group, while cyclosporine was completely suspended and the oral steroids were continued. (lymphedemapeople.com)
  • Sirolimus is used with other medicines called cyclosporine ( Gengraf , Neoral , Sandimmune ), and corticosteroids. (rxwiki.com)
  • When sirolimus is taken with cyclosporine ( Gengraf , Neoral , Sandimmune ), the function of your transplanted kidney may be affected. (rxwiki.com)
  • Your doctor should regularly do tests to check your kidney function while you are taking sirolimus with cyclosporine (Gengraf, Neoral, Sandimmune). (rxwiki.com)
  • When sirolimus is taken with cyclosporine or tacrolimus , you may develop a blood clotting problem. (rxwiki.com)
  • Short and long term in vivo effects of Cyclosporine A and Sirolimus on genes and proteins involved in lipid metabolism in Wistar rats. (sigmaaldrich.com)
  • Cyclosporine A (CsA) and sirolimus (SRL) are immunosuppressive agents (IA) associated with new onset diabetes after transplantation and dyslipidemia. (sigmaaldrich.com)
  • After a phase I trial in stable renal transplant recipients documented that cyclosporine and sirolimus have few overlapping toxicities, we conducted an open-label, single-center, phase I/II dose-escalation trial to examine the safety and efficacy of this drug combination. (ovid.com)
  • Forty mismatched living-donor renal transplant recipients were sequentially assigned to receive escalating initial doses of sirolimus (0.5-7.0 mg/m2/day), in addition to courses of prednisone and a concentration-controlled regimen of cyclosporine. (ovid.com)
  • We conducted surveillance for drug-induced side effects among sirolimus-treated patients and compared their incidence of acute rejection episodes as well as mean laboratory values with those of a historical cohort of 65 consecutive, immediately precedent, demographically similar recipients treated with the same concentration-controlled regimen of cyclosporine and tapering doses of prednisone. (ovid.com)
  • The addition of sirolimus reduced the overall incidence of acute allograft rejection episodes to 7.5% from 32% in the immediately precedent cyclosporine/prednisone-treated patients. (ovid.com)
  • Although sirolimus-treated patients displayed comparatively lower platelet and white blood cell counts and higher levels of serum cholesterol and triglycerides, sirolimus did not augment the nephrotoxic or hypertensive proclivities of cyclosporine. (ovid.com)
  • Sirolimus potentiates the immunosuppressive effects of a cyclosporine-based regimen by reducing the rate of acute rejection episodes. (ovid.com)
  • Combining cyclosporine with sirolimus may increase your blood levels of sirolimus, potentially increasing your risk for side effects. (emedtv.com)
  • To help reduce the risk of this interaction, sirolimus should be taken four hours after cyclosporine. (emedtv.com)
  • Methods and Results- In an observational study in Japan, 2-year outcomes were assessed in 10 778 patients undergoing sirolimus-eluting stent implantation. (ahajournals.org)
  • Landmark analysis did not suggest an apparent clinical benefit of thienopyridine use beyond 6 months after sirolimus-eluting stent implantation. (ahajournals.org)
  • Stent thrombosis after sirolimus eluting stent implantation has been reported to occur at six hours to 375 days after the procedure and usually within the two weeks after discontinuation of antiplatelet medication. (bmj.com)
  • A case is reported of very late stent thrombosis after 17 months of sirolimus eluting stent implantation and eight months after clopidogrel discontinuation despite aspirin continuation. (bmj.com)
  • The proprietary, top-quality coating process allows the integrity of coated polymer after excessive stent expansion and a systemic elution of sirolimus in a well -controlled fashion after the stent implantation. (ecvv.com)
  • Our objective was to assess the vascular response secondary to sirolimus drug-eluting stent implantation using different doses and patterns of elution by means of serial intravascular ultrasound (IVUS) analysis. (scielo.br)
  • Intravascular ultrasound assessment of optimal stent area to prevent in-stent restenosis after zotarolimus-, everolimus- and sirolimus-eluting stent implantation. (biomedsearch.com)
  • Conclusions Sirolimus-eluting stent implantation for unprotected LMCA stenosis appears safe with regard to acute and midterm complications and is more effective in preventing restenosis compared to BMS implantation. (onlinejacc.org)
  • Objectives This study sought to evaluate the long-term arterial response after sirolimus-eluting stent implantation. (onlinejacc.org)
  • Conclusions Between two and four years after sirolimus-eluting stent implantation, peri-stent tissue shrank with a concomitant increase in echogenicity. (onlinejacc.org)
  • These intravascular ultrasound findings suggest that late chronic artery responses may evolve for up to four years after sirolimus-eluting stent implantation. (onlinejacc.org)
  • The effect of sirolimus on mesenchymal cells is unknown, but it is an important issue, since mesenchymal cells such as myofibroblasts and cells promoting vascular calcification play an important role in atherogenesis and vascular restenosis. (eurekalert.org)
  • These mechanisms were also observed in human atherogenesis and could be fundamental to evaluate the in vivo effect of sirolimus too. (eurekalert.org)
  • As impaired wound healing is a possible side effect of sirolimus, some transplant centres prefer not to use it immediately after the transplant operation, and start to give it after a period of weeks or months. (wikidoc.org)
  • Research purpose This clinical trial was designed to evaluate the anti-tumor effect of sirolimus in patients with advanced or postoperative recurrent pancreatic cancer with second-line standard therapy resistance. (clinicaltrials.gov)
  • Before you take a medication for a particular ailment, you should inform the health expert about intake of any other medications including non-prescription medications, over-the-counter medicines that may increase the effect of Sirolimus, and dietary supplements like vitamins, minerals and herbal, so that the doctor can warn you of any possible drug interactions. (internationaldrugmart.com)
  • Generalized lymphedema is an extremely rare effect of sirolimus therapy in renal transplant recipients. (lymphedemapeople.com)
  • We demonstrated a marked renoprotective effect of sirolimus by inhibition of UUO-induced renal tubular apoptosis in vivo. (medsci.org)
  • which reported that the authors evaluated the long-term effects of sirolimus on three different cell in vitro models, cultured in physiological conditions mimicking sirolimus-eluted stent, in order to clarify the effectiveness of sirolimus in blocking cell proliferation and survival. (eurekalert.org)
  • The aim of the present paper is to evaluate the long-term effects of sirolimus, rather than short-term cell survival, on three different cell in vitro models, cultured in Minimum Essential Medium, which simulates physiological conditions (w/o CO2 and glucose, in order to clarify the effectiveness of sirolimus in blocking cell proliferation and survival. (eurekalert.org)
  • Appropriate studies have not been performed on the relationship of age to the effects of sirolimus in children younger than 13 years of age or in children considered to be at high immunologic risk for prevention of kidney transplant rejection, and in children for treatment of lymphangioleiomyomatosis. (drugs.com)
  • Grapefruits and grapefruit juice may increase the effects of sirolimus by increasing the amount of this medicine in your body. (transplantliving.org)
  • The anti-proliferative effects of sirolimus may have a role in treating cancer. (wikidoc.org)
  • If they do occur, the side effects of Sirolimus are most likely to be minor and temporary. (internationaldrugmart.com)
  • It is pertinent to note that side effects of Sirolimus cannot be anticipated. (internationaldrugmart.com)
  • If any side effects of Sirolimus develop or change in intensity, the doctor should be informed as soon as possible. (internationaldrugmart.com)
  • Common side effects of sirolimus include high blood pressure, pain, diarrhea and headache. (rxwiki.com)
  • Sirolimus is the mTOR inhibitor that has been proven to be effective in reducing cyst growth both in animal models. (clinicaltrials.gov)
  • Sirolimus is designed to block a protein called mTOR (a protein that is thought to cause cancer cells to grow) inside the cancer cell. (knowcancer.com)
  • An mTOR inhibitor, sirolimus is approved to help prevent organ rejection in transplant recipients, but may have anticancer effects as well. (oncologynurseadvisor.com)
  • We report a series of eight cases of severe, sustained, unilateral and bilateral lymphoedema in patients receiving sirolimus for post-transplant immunosuppression, classify their lymphoscintigraphy findings and propose a mechanism of aetiology based on the interaction of mTOR with key mediators of lymphangiogenesis. (lymphedemapeople.com)
  • Sirolimus can also be used alone, or in conjunction with a calcineurin inhibitor (such as tacrolimus), and/or mycophenolate mofetil, to provide steroid-free immunosuppression regimens. (wikipedia.org)
  • This review summarizes the pharmacokinetics in children and youths of 2 commonly used immunosuppressive drugs, mycophenolate mofetil (MMF) and sirolimus (Sir), as presented at the IATDMCT 2007 conference. (nih.gov)
  • This prospective study included six patients at high risk for graft rejection who were treated with oral mycophenolate mofetil in combination with sirolimus for one year after penetrating keratoplasty. (aao.org)
  • Rabbit anti-thymocyte globulin (rATG), sirolimus, and mycophenolate mofetil (MMF) are all designed to prevent GVHD. (bioportfolio.com)
  • The purpose of this study is to determine whether immunosuppression by tacrolimus, mycophenolate mofetil, and prednisone compared to conversion to sirolimus, mycophenolate mofetil, and pre. (bioportfolio.com)
  • Your doctor will probably adjust your dose of sirolimus during your treatment, usually not more than once every 7 to 14 days. (medlineplus.gov)
  • Contact your doctor if ulcers occur as your dose of sirolimus may need to be reduced. (transplant.bc.ca)
  • What if you miss a dose of Sirolimus? (internationaldrugmart.com)
  • Beginning 3-7 days after the last dose of sirolimus, patients undergo surgery. (cancer.gov)
  • Take your dose of Sirolimus the same way, either with or without food. (rxwiki.com)
  • The original dose of sirolimus was not tolerated, so the dose was decreased. (physiciansweekly.com)
  • Sirolimus is indicated for the prevention of organ transplant rejection and for the treatment of lymphangioleiomyomatosis (LAM). (wikipedia.org)
  • In 2009, the FDA notified healthcare professionals that a clinical trial conducted by Wyeth showed an increased mortality in stable liver transplant patients after switching from a calcineurin inhibitor-based immunosuppressive regimen to sirolimus. (wikipedia.org)
  • The sirolimus test is used to monitor the level of the drug over time in kidney transplant recipients who are taking the drug to prevent organ rejection. (labcorp.com)
  • Monitoring is necessary as long as the transplant recipient takes sirolimus. (labcorp.com)
  • Only physicians experienced in immunosuppressive therapy and management of renal transplant patients should prescribe sirolimus for prophylaxis of organ rejection in patients receiving renal transplants, and they should have complete information requisite for the followup of the patient. (drugs.com)
  • Cases of bronchial anastomotic dehiscence, most fatal, have been reported in de novo lung transplant patients when sirolimus was used as part of an immunosuppressive regimen. (drugs.com)
  • You should not use sirolimus if you have ever had a lung transplant or liver transplant. (cigna.com)
  • Sirolimus can lower blood cells that help fight infection, and may lead to serious conditions including cancer, severe brain infection causing disability or death, or a viral infection causing kidney transplant failure. (cigna.com)
  • You should not use this medicine if you are allergic to sirolimus, or if you have ever had a lung transplant or liver transplant. (cigna.com)
  • We report the first case of an islet transplant recipient with sirolimus-induced interstitial pneumonitis. (diabetesjournals.org)
  • We conclude that sirolimus-induced pneumonitis can occur at low trough levels and should be considered in the differential diagnosis of an islet transplant recipient presenting with similar symptoms. (diabetesjournals.org)
  • Singer SJ, Tiernan R, Sullivan EJ: Interstitial pneumonitis associated with sirolimus therapy in renal-transplant recipients. (diabetesjournals.org)
  • Transplant patients maintained on calcineurin inhibitors long-term tend to develop impaired kidney function or even chronic renal failure, and this can be prevented by use of sirolimus instead. (wikidoc.org)
  • Sirolimus is FDA approved and commercially available as an anti-rejection drug for kidney transplant recipients. (knowcancer.com)
  • Sirolimus medication is a new immunosuppressant drug originally approved for use in kidney transplant recipients. (chp.edu)
  • Sirolimus is used with other medicines to prevent organ rejection after a kidney transplant. (everydayhealth.com)
  • Sirolimus is FDA approved and commercially available for the treatment of patients with a kidney transplant. (knowcancer.com)
  • Sirolimus is used to prevent rejection of a kidney transplant. (internationaldrugmart.com)
  • Monitoring of immunosuppressive drugs such as everolimus and sirolimus is important in allograft rejection prevention in transplant patients. (degruyter.com)
  • A total of 39 sirolimus and 44 everolimus paired fingerprick DBS and whole blood (WB) samples were obtained from 60 adult transplant patients for method comparison using Passing-Bablok regression. (degruyter.com)
  • You will continue to receive sirolimus until 90 days after the transplant. (bioportfolio.com)
  • Available by prescription only, sirolimus is an immunosuppressant used to prevent organ rejection after a kidney transplant. (emedtv.com)
  • Sirolimus prevents organ rejection in those patients who have received a kidney transplant. (rxwiki.com)
  • Sirolimus is a prescription medicine used to prevent organ rejection in people 13 years of age and older who have received a kidney transplant. (rxwiki.com)
  • Histological spectrum of pulmonary manifestations in kidney transplant recipients on sirolimus inclusive immunosuppressive regimens. (pneumotox.com)
  • Sirolimus-associated diffuse alveolar hemorrhage in a renal transplant recipient on long-term anticoagulation. (pneumotox.com)
  • Brief communication: sirolimus-associated pneumonitis: 24 cases in renal transplant recipients. (pneumotox.com)
  • Characteristics of sirolimus-associated interstitial pneumonitis in renal transplant patients. (pneumotox.com)
  • In-segment restenosis was identified on follow-up angiography in 16.5 percent of the patients in the paclitaxel-stent group and 6.9 percent of the patients in the sirolimus-stent group (P=0.03). (nih.gov)
  • In patients with diabetes mellitus and coronary artery disease, use of the sirolimus-eluting stent is associated with a decrease in the extent of late luminal loss, as compared with use of the paclitaxel-eluting stent, suggesting a reduced risk of restenosis. (nih.gov)
  • Sirolimus and its analogues are drugs that are commonly used to prevent restenosis. (medgadget.com)
  • New data from a Spanish study presented at the 2005 American Heart Association Scientific Sessions found that patients with bifurcation lesions fared significantly better when treated with the CYPHER® Sirolimus-eluting Coronary Stent compared with the Taxus stent in the areas of late loss, re-treatment (total lesion revascularization or TLR) and re-blockage (restenosis). (eurekalert.org)
  • Preliminary reports of studies involving simple coronary lesions indicate that a sirolimus-eluting stent significantly reduces the risk of restenosis after percutaneous coronary revascularization. (nih.gov)
  • In this randomized clinical trial involving patients with complex coronary lesions, the use of a sirolimus-eluting stent had a consistent treatment effect, reducing the rates of restenosis and associated clinical events in all subgroups analyzed. (nih.gov)
  • Sirolimus for the prevention of in-stent restenosis in a coronary artery. (nih.gov)
  • The goal of the trial was to evaluate the use of oral sirolimus for prevention of recurrent restenosis in patients with in-stent restenosis compared with placebo. (acc.org)
  • Treatment with oral sirolimus will reduce the occurrence of recurrent restenosis. (acc.org)
  • Patients with in-stent restenosis on diagnostic angiography were randomized to usual-dose sirolimus (n=99), high-dose sirolimus (n=99), or placebo (n=102). (acc.org)
  • Among patients with in-stent restenosis, treatment with high-dose oral sirolimus was associated with a lower rate of the primary endpoint of angiographic restenosis at six-month follow-up compared with placebo, but there was no treatment effect observed with usual-dose oral sirolimus compared with placebo. (acc.org)
  • No benefit of oral sirolimus was reported in an earlier small (n=22), nonrandomized pilot study of patients at high risk for restenosis, but treatment with study drug was not administered until after the angioplasty. (acc.org)
  • Randomized, double-blind, placebo-controlled trial of oral sirolimus for restenosis prevention in patients with in-stent restenosis: the Oral Sirolimus to Inhibit Recurrent In-stent Stenosis (OSIRIS) trial. (acc.org)
  • The sirolimus-eluting stent (SES) (Cypher, Cordis, Johnson and Johnson Corp, Miami, Florida) markedly decreases in-stent restenosis in elective patients with relatively simple coronary lesions ( 9,10 ). (onlinejacc.org)
  • After discontinuation of sirolimus, the decline in lung function resumed in the sirolimus group and paralleled that in the placebo group. (nih.gov)
  • A significant difference between SIR-G and CONT-G was observed at 4 weeks (-1.50 ± 5.0 vs -0.19 ± 0.4, P = 0.008) and lost significance 1 month after sirolimus discontinuation (-1.73 ± 4.3 vs -0.01 ± 0.7, P = 0.0975). (scielo.br)
  • A continuous fall in MMP-9 concentration was observed in SIR-G, with the greatest reduction at 4 weeks (-352.9 ± 455 vs +395.2 ± 377, P = 0.0004), while a positive variation was noted 4 weeks after sirolimus discontinuation (227 ± 708 vs 406.2 ± 472.1, P = 0.0958). (scielo.br)
  • SIR-G exhibited a higher increase in P-selectin after sirolimus discontinuation at week 8 (46.1 ± 67.9 vs 5.8 ± 23.7, P = 0.0025). (scielo.br)
  • After sirolimus discontinuation the generalized lymphedema started to improve and three months later all the symptoms had disappeared. (lymphedemapeople.com)
  • Comparison of sirolimus eluting stent with bioresorbable polymer to everolimus eluting stent with permanent polymer in bifurcation lesions: Results from CENTURY II trial. (terumo-europe.com)
  • For both sirolimus and everolimus, Passing-Bablok regression showed no differences between WB and DBS with slopes of 0.86 (95% CI slope, 0.72-1.02) and 0.96 (95% CI 0.84-1.06), respectively. (degruyter.com)
  • For both sirolimus and everolimus, limits of analytical acceptance were met (76.9% and 81.8%, respectively), but limits or clinical relevance were not met (77.3% and 61.5%, respectively). (degruyter.com)
  • Because pre-defined limits of clinical relevance were not met, this DBS sampling method for sirolimus and everolimus cannot replace WB sampling in our center at this time. (degruyter.com)
  • Sirolimus dosage is available as a solution in a concentration of one mg/ml, either in multi-dose amber glass bottles or as liquid-filled, unit dose pouches. (chp.edu)
  • What is the recommended dosage of Sirolimus? (internationaldrugmart.com)
  • The dosage of Sirolimus prescribed to each patient will vary. (internationaldrugmart.com)
  • Your healthcare provider may need to adjust your sirolimus dosage , especially when you first start or stop taking a CYP 3A4 inducer. (emedtv.com)
  • Do not stop taking sirolimus without talking to your doctor. (medlineplus.gov)
  • Therefore, it is very important that an effective form of birth control be used before starting sirolimus therapy, during sirolimus therapy, and for 12 weeks after sirolimus therapy has stopped. (transplantliving.org)
  • To avoid the potential deleterous effect on acidosis of the chronic use of three nucleoside reverse transcriptase inhibitors, stavudine was changed to raltegravir, 400 mg twice daily (July 2007) and 2 weeks after sirolimus substituted cyclosporin. (lww.com)
  • There was no difference in mean GFR measured by iothalamate clearance between the tacrolimus and sirolimus groups at 1 year (61 ± 19 mL/min vs. 63 ± 18 mL/min, p = 0.57) or 2 years (61 ± 17 mL/min vs. 61 ± 19 mL/min, p = 0.84). (wiley.com)
  • We found the following: (i) No additive reduction in function and viability in islets existed when tacrolimus and sirolimus were combined compared to the single drug. (hindawi.com)
  • Although human islets are prone to direct toxic effect of tacrolimus and sirolimus, we found no additive effects of the drug combination. (hindawi.com)
  • Short-term exposure of glucocorticoids could effectively reduce the proinflammatory response in human islets induced by the combination of tacrolimus and sirolimus. (hindawi.com)
  • The common immunosuppressive protocols used in clinical islet transplantation include induction therapy with either ATG or IL-2 receptor monoclonal antibody, followed by maintenance treatment including that of tacrolimus and sirolimus [ 1 ]. (hindawi.com)
  • To address these issues, a large-scale, multicenter registry of patients undergoing sirolimus-eluting stent (SES) implantation was designed with prospective data collection on the status of antiplatelet therapy during follow-up. (ahajournals.org)
  • Objectives This study was designed to compare the clinical and angiographic outcomes of sirolimus-eluting stent (SES) and bare metal stent (BMS) implantation for unprotected left main coronary artery (LMCA) stenosis. (onlinejacc.org)
  • Long-term, follow-up data presented today suggest that patients who received the CYPHER Sirolimus-eluting Coronary Stent for blockage of a bare metal stent were significantly less likely to need another procedure (target lesion revascularization or TLR) at three years compared to patients who received brachytherapy. (webwire.com)
  • The safety and efficacy of sirolimus treatment of LAM were investigated in clinical trials that compared sirolimus treatment with a placebo group in 89 patients for 12 months. (wikipedia.org)
  • The aim of this study will be to evaluate the efficacy of sirolimus associated with tacrolimus in elderly kid. (bioportfolio.com)
  • Several studies have been performed to evaluate the efficacy of sirolimus in some solid tumors, and encouraging results are obtained. (clinicaltrials.gov)
  • Although this effect has long been considered an overdose hazard, "We wanted to see if grapefruit juice can be used in a controlled fashion to increase the availability and efficacy of sirolimus," explained Cohen in the statement. (oncologynurseadvisor.com)
  • To expand the limited longterm data on sirolimus treatment in patients with lupus nephritis (LN). Our pilot short-term data suggested efficacy of sirolimus treatment in these patients. (jrheum.org)
  • Objectives This first-in-human multicenter study sought to examine prospectively the safety and efficacy of a new, cobalt chromium thin-strut, coronary absorbable polymer-coated, sirolimus-eluting stent. (onlinejacc.org)
  • Tell your doctor if you have ever had any unusual or allergic reaction to sirolimus or any other medicines. (drugs.com)
  • Sirolimus is an immunosuppressant drug used to prevent the body from rejecting a transplanted organ. (transplantliving.org)
  • According to researchers working at a Boston women's hospital an immunosuppressant drug called Sirolimus can help with mesothelioma treatment . (bloggernews.net)
  • Sirolimus ( INN ) is a relatively new immunosuppressant drug used to prevent rejection in organ transplantation , and is especially useful in kidney transplants. (wikidoc.org)
  • Healing Achilles--sirolimus versus paclitaxel. (nih.gov)
  • The study compared central subfield thickness data of patients who received monotherapy sirolimus versus those who continued with their current anti-VEGF regimen. (eyetube.net)
  • Greater M2 formation after apical versus basolateral dosing (1.6-fold) was explained by higher intracellular content of sirolimus after apical dosing. (aspetjournals.org)
  • In the first study , investigators used open label sirolimus versus standard care in 100 patients with ADPKD and mean GFR of 70 ml / min, (stage 2 chronic kidney disease). (ukidney.com)
  • A number of clinical studies have tested oral sirolimus to prevent or to treat ISR. (scielo.br)
  • The aim of the present study was to characterize the systemic response of biomarkers known to be involved in the vascular response to coronary stenting and determine if oral sirolimus has any effect on the behavior of these biomarkers. (scielo.br)
  • The sirolimus-treated group (SIR-G) comprised 11 patients treated with oral sirolimus one day before and 28 days after stenting and who had been enrolled in a previous study (13). (scielo.br)
  • Target-lesion revascularization was performed in 12.0 percent of the patients in the paclitaxel-stent group and 6.4 percent of the patients in the sirolimus-stent group (P=0.13). (nih.gov)
  • The following doses can be started and tacrolimus continued at half the current dose until sirolimus levels are therapeutic. (edren.org)
  • Consuming 8 ounces of grapefruit juice increases sirolimus levels by 350%, allowing persons with cancer to take less toxic doses of the drug. (oncologynurseadvisor.com)
  • The trials employed an adaptive escalation design to find the doses of oral, weekly sirolimus alone or in combination with either the antifungal agent ketoconazole or grapefruit juice that would achieve similar blood concentrations as temsirolimus, the intravenously administered and approved prodrug of sirolimus. (oncologynurseadvisor.com)
  • Optimal sirolimus doses for the other two groups, however, were much lower: Persons who took ketoconazole plus sirolimus needed only 16 mg per week of the latter to maintain the same blood levels of the drug. (oncologynurseadvisor.com)
  • The degree of change in the laboratory values was more directly associated with whole blood trough drug concentrations than with doses of sirolimus. (ovid.com)
  • There was no linear relationship between increasing sirolimus doses and positive vascular remodeling, suggesting this vascular event may be related to the presence of a synthetic polymer. (scielo.br)
  • Sirolimus lowers your body's immune system. (cigna.com)
  • Sirolimus weakens your body's immune system, to help keep it from 'rejecting' a transplanted organ such as a kidney. (everydayhealth.com)
  • SPC Changes Section 4.5 Interaction with other medicinal products and other forms of interaction has been updated to include potential interactions with CYP3A4 inhibitors, which may decrease the metabolism of sirolimus and increase sirolimus blood levels. (medworm.com)
  • The sirolimus is formulated in a polymer coating that affords controlled release through the healing period following coronary intervention. (wikipedia.org)
  • This first randomized clinical study of a polymer-coated zotarolimus-eluting stent (Resolute Onyx) that utilizes a novel thin-strutted metallic platform allowing for better x-ray visibility was shown to be non-inferior to an ultrathin-strutted bioresorbable polymer-coated sirolimus-eluting stent (Orsiro) that uses a cobalt-chromium strut platform. (news-medical.net)
  • Micell Technologies (Durham, NC) is releasing its flagship product, the MiStent Sirolimus Eluting Absorbable Polymer Coronary Stent System, in the European market. (medgadget.com)
  • The MiStent SES includes a proprietary stent coating that contains crystalline drug (sirolimus) and an absorbable polymer. (medgadget.com)
  • and group 3, VESTAsync TM (2.9 µg sirolimus/mm, polymer-free sirolimus-eluting stent). (scielo.br)
  • Presentation on the design of Combo - a stent eluting Sirolimus from a biodegradable polymer matrix in combination with an anti-CD34 antibody coating on its luminal surface. (bcis.org.uk)
  • Conclusions At 18 months of follow-up, this absorbable polymer-coated, cobalt chromium sirolimus-eluting stent was associated with a low and stable in-stent LLL, complete strut coverage, and no stent thrombosis. (onlinejacc.org)
  • Sirolimus seems to block the proliferation and the migration of vascular smooth muscle cells, but we lack information concerning the effects on other cells composing atherosclerotic plaques. (eurekalert.org)
  • As compared with the placebo group, the sirolimus group had improvement from baseline to 12 months in measures of forced vital capacity, functional residual capacity, serum vascular endothelial growth factor D (VEGF-D), and quality of life and functional performance. (nih.gov)
  • These particles are conglomerations of sirolimus molecules, which get embedded into the vascular tissue. (medgadget.com)
  • BRIDGEWATER, N.J., June 15, 2011 /PRNewswire-FirstCall/ -- Cordis Corporation, a worldwide leader in the development and manufacture of interventional vascular technology, today announced it will no longer pursue the development of the NEVO™ Sirolimus-Eluting Coronary Stent in order to focus on other cardiovascular therapies where significant patient need exists. (mdtmag.com)
  • At 1 year, chronicity using the Banff schema showed no difference in interstitial, tubular or glomerular changes, but fewer chronic vascular changes in the sirolimus group. (wiley.com)
  • Three-year clinical and two-year multimodality imaging outcomes of a thin-strut sirolimus-eluting bioresorbable vascular scaffold: MeRes-1 trial. (prnewswire.co.uk)
  • 2. Abizaid A. MeRes-1 Extend study: Imaging and two-year clinical outcomes of thin strut sirolimus-eluting bioresorbable vascular scaffold in patients with coronary artery disease. (prnewswire.co.uk)
  • Cordis Corporation has entered into an exclusive worldwide license with Wyeth for the localized delivery of sirolimus in certain fields of use, including delivery via vascular stenting. (bio-medicine.org)
  • Sirolimus is used in combination with other medications to prevent rejection of kidney transplants. (medlineplus.gov)
  • MOUNTAIN VIEW, CA , Nov. 01, 2016 (GLOBE NEWSWIRE) -- Amaranth Medical , a privately held medical device company, announced the initiation of a clinical study of the Company's latest-generation MAGNITUDE™ sirolimus-eluting bioresorbable scaffold (BRS) scaffold, which has a strut thickness in the sub-100-micron range. (cnbc.com)
  • Based on clinical experience and literature, the expected median survival period of patients with advanced pancreatic cancer after second-line resistance or postoperative recurrence was about 3 months, and the median survival period of such patients was expected to be extended to 6 months after the treatment with sirolimus. (clinicaltrials.gov)
  • More recently, sirolimus has been used to prevent ISR with a coated stent design with good clinical and angiographic results (11). (scielo.br)
  • As Cohen and colleagues reported in Clinical Cancer Research , the optimal cancer-fighting dose for those taking sirolimus alone was found to be about 90 mg per week. (oncologynurseadvisor.com)
  • The incidence of clinical acute rejection was 10% in the tacrolimus group and 13% in the sirolimus group (p = 0.58). (wiley.com)
  • Sirolimus (SRL) seems to impair renal recovery from ischemic injury in animal models and delayed graft function after clinical renal transplantation. (ovid.com)
  • MIAMI LAKES, Fla., June 4, 2007 /PRNewswire via COMTEX News Network/ -- An analysis of data from the Western Denmark Heart Registry found that patients who received the CYPHER(R) Sirolimus-eluting Coronary Stent to open a clogged artery were less likely to need another procedure at that same lesion site (a clinical event called target lesion revascularization or TLR) than patients who received a Taxus Stent. (bio-medicine.org)
  • The aim of this study was to evaluate the clinical and angiographic outcome of sirolimus-eluting stent (SES) for the treatment of very long lesions in real world clinical practice. (koreamed.org)
  • Sirolimus may cause serious side effects or death in patients who have had liver or lung transplants. (medlineplus.gov)
  • A series of 32 recipients of liver, kidney, or pancreas transplants who were treated with sirolimus and low-dose tacrolimus experienced a low rate of rejection and excellent graft function without drug-related toxic effects. (uwo.ca)
  • Sirolimus-tacrolimus Combination Immunosuppression" by Vivian C. McAlister, Zuhua Gao et al. (uwo.ca)
  • The chief advantage sirolimus has over calcineurin inhibitors is its low toxicity toward kidneys. (wikipedia.org)
  • The chief advantage sirolimus has over calcineurin inhibitors is that it is not toxic to kidneys. (wikidoc.org)
  • Many other medications may change the blood levels of sirolimus in your body. (nephcure.org)
  • A recent research letter regarding the use of sirolimus therapy for cutaneous and gastrointestinal telangiectasia (1) omitted the names of 2 authors. (annals.org)
  • Patients receive sirolimus orally (PO) once daily (QD) for 5-7 days. (cancer.gov)
  • In addition, patients will receive sirolimus orally beginning on day 5 through day 180 followed by a taper to approximately day 210 if there is no evidence of GVHD and their graft is doing well. (aamds.org)
  • Amaranth Medical , a medical device company developing next-generation bioresorbable scaffolds for the interventional cardiology market, presented nine-month follow-up results from the company's RENASCENT-II study of the APTITUDE® sirolimus-eluting bioresorbable scaffold (BRS) on Tuesday, May 16th during the Evolving BRS Technology session. (venturebeat.com)
  • The SIRIUS-DIRECT trial: a multi-center study of direct stenting using the sirolimus-eluting stent in patients with de novo native coronary artery lesions. (acc.org)
  • The LEADERS CTO sub-study compared the long-term results in CTO and non-CTO lesions of a Biolimus A9 (TM)-eluting stent (BES) with a sirolimus-eluting stent (SES). (uni-muenchen.de)
  • Our observations indicate that an immunosuppressive regimen including sirolimus is advantageous for the management of kidney allograft recipients in the short term. (hindawi.com)
  • Combining sirolimus with an angiotensin-converting enzyme (ACE) inhibitor may increase your risk for a serious allergic reaction known as angioedema. (emedtv.com)
  • On 28 May 2015, the FDA approved sirolimus to treat lymphangioleiomyomatosis (LAM), a rare, progressive lung disease that primarily affects women of childbearing age. (wikipedia.org)
  • Successful sirolimus treatment of lymphangioleiomyomatosis in a hepatitis B virus carrier. (springer.com)
  • Sirolimus is also used to treat lymphangioleiomyomatosis, a rare lung disease that affects predominantly women of childbearing age. (drugs.com)
  • Sirolimus is also given without other medicines to treat a rare lung disorder called lymphangioleiomyomatosis (lim-FAN-gee-oh-LYE-oh-MYE-oh-ma-TOE-sis). (cigna.com)
  • Sirolimus inhibits the response to interleukin-2 (IL-2) and thereby blocks activation of T- and B-cells . (wikidoc.org)
  • Sirolimus inhibits the lymphocytes from multiplying in response to these molecules. (chp.edu)
  • Grapefruit juice inhibits intestinal P450 enzymes that break down sirolimus as well as several other drugs. (oncologynurseadvisor.com)
  • Sirolimus, a novel immunosuppressant that inhibits cytokine-driven cell proliferation and maturation, prolongs allograft survival in animal models. (ovid.com)
  • Sirolimus is an immunosuppressant agent with anti-proliferative, anti-migratory and anti-inflammatory properties (9) and is FDA-approved for the prophylaxis of renal transplantation rejection in the United States (10). (scielo.br)
  • This study shows that a CNI-free regimen using sirolimus-MMF-prednisone produces similar acute rejection rates, graft survival and renal function 1-2 years after transplantation compared to tacrolimus-MMF-prednisone. (wiley.com)
  • This will be a phase I dose escalation study of the combination of sirolimus (2 mg adjusted to keep trough levels between 5-15 ng/ml) and hydroxychloroquine (200 mg or 400 mg) taken orally daily. (clinicaltrials.gov)
  • Sirolimus was administered orally daily after an initial loading dose, and pemetrexed was given intravenously on day 1 of every 21-day cycle. (unl.edu)
  • Thus, combining sirolimus with one of these drugs may decrease the level of sirolimus in your body, potentially making it less effective. (emedtv.com)
  • Thus, combining sirolimus with one of these drugs may increase the level of sirolimus in your body, potentially increasing your risk for side effects. (emedtv.com)
  • We conducted a two-stage trial of sirolimus involving 89 patients with LAM who had moderate lung impairment--a 12-month randomized, double-blind comparison of sirolimus with placebo, followed by a 12-month observation period. (nih.gov)
  • tell your doctor and pharmacist if you are allergic to sirolimus, any other medications, or any of the ingredients in sirolimus tablets or solution. (medlineplus.gov)
  • There are some medications that can interact with sirolimus and change its effectiveness. (chp.edu)
  • Grapefruit may interact with sirolimus and lead to unwanted side effects. (everydayhealth.com)
  • What other drugs could interact with Sirolimus? (internationaldrugmart.com)
  • It may be noted that drugs other than those listed above may also interact with Sirolimus. (internationaldrugmart.com)
  • Drugs that inhibit or accelerate the metabolism of sirolimus may affect blood levels. (labcorp.com)
  • Islets exposed to the combination of sirolimus and tacrolimus were treated with or without methylprednisolone (1000 μ g/L) and the expression of the proinflammatory cytokines was investigated. (hindawi.com)
  • Hi Keith, There has been a lot of information released lately about the combination of Sirolimus and MMF from medical journals/conferences etc. (kidneypatientguide.org.uk)
  • Treatment with sirolimus must be monitored because the range in which the drug is effective but not toxic is very narrow. (labcorp.com)
  • Treatment with sirolimus may also increase the chance of getting other infections. (transplantliving.org)
  • Your doctor should do blood tests to check your lipids during treatment with sirolimus. (rxwiki.com)
  • During treatment with sirolimus, your blood levels of cholesterol and triglycerides may remain high even if you follow your prescribed treatment plan. (rxwiki.com)