Effects of immunosuppressive therapy on wound healing

Bootun, Roshan

doi:10.1111/j.1742-481x.2012.00950.x

Cited by 113 publications

(90 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The adverse event of a subchorionic hematoma that occurred during pregnancy is a frequent finding on routine obstetric sonography and is most likely not a consequence of the transplanted uterus per se or the limited venous outflow. 9 The lack of a scientifically sound basis and the need to stop immunosuppressive therapy as soon as possible in view of renal dysfunction prompted us to anticipate the embryo transfer. 6,7 The established recommendation has been to wait at least 1 year after transplantation before attempting pregnancy.…”

Section: This Is the First Birth From A Uterus Transplant Recipient Imentioning

confidence: 99%

First live birth after uterus transplantation in the United States

Testa

McKenna

Gunby

et al. 2018

American Journal of Transplantation

192

153

View full text Add to dashboard Cite

Uterus transplantation has proven to be a successful treatment for women with absolute uterine infertility, caused either by the absence of a uterus or the presence of a nonfunctioning uterus. We report the first birth of a healthy child following uterus transplantation in the United States, from a recipient of a uterus allograft procured from an altruistic living donor. Two major modifications from the previously reported live births characterized this uterus transplant. First, the transplanted uterus relied upon and sustained the pregnancy while having only the utero-ovarian vein as venous outflow. The implication is a significantly simplified living donor surgery that paves the way for minimally invasive laparoscopic or robot-assisted techniques for the donor hysterectomy. Second, the time from transplantation to embryo transfer was significantly shortened from prior protocols, allowing for an overall shorter exposure to immunosuppression by the recipient and lowering the risk for potential adverse effects from these medications.

show abstract

Section: This Is the First Birth From A Uterus Transplant Recipient Imentioning

confidence: 99%

First live birth after uterus transplantation in the United States

Testa

McKenna

Gunby

et al. 2018

American Journal of Transplantation

192

153

View full text Add to dashboard Cite

show abstract

“…38,39 Our laboratory and others have previously demonstrated the efficacy of rapamycin in suppressing PTLD B cell lymphoma xenografts in immunodeficient mice. [41][42][43][44] On the other hand, one of the potential benefits of utilizing mTOR inhibitors for PTLD is their dual antineoplastic and antirejection properties. Here, we demonstrate using a mixed effect model that while rapamycin alone had a sizeable effect on tumor growth when compared with mice receiving vehicle control, adding a second agent (CAL-101 or MK-2206) had a significant effect on further suppressing tumor growth.…”

Section: Treatment Of Ebv-associated Ptld Remains a Clinical Challengmentioning

confidence: 99%

Dual blockade of the PI3K/Akt/mTOR pathway inhibits posttransplant Epstein-Barr virus B cell lymphomas and promotes allograft survival

Sang

McPherson

Ivison

et al. 2019

American Journal of Transplantation

View full text Add to dashboard Cite

Abbreviations: 4EBP, 4E-binding protein; DMSO, dimethyl sulfoxide; EBV, Epstein-Barr virus; ERK, extracellular signal-regulated kinase; IC 50 , half maximal Inhibitory concentration; LI, Loewe index; LMP1, latent membrane protein 1; MAPK, mitogen-activated protein kinase; mTORC, mammalian target of rapamycin complex; mTOR, mammalian target of rapamycin; NOD-SCID, Non-obese diabetic/severe combined immunodeficiency; PI3K, Phospho-inositide 3-kinase; PTLD, posttransplant lymphoproliferative disorder; RI, reduction of immunosuppression; SEM, standard error of the mean; STAT, signal transducer and activator of transcription. Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation that often manifests as Epstein-Barr virus (EBV)-associated B cell lymphomas. Current treatments for PTLD have limited efficacy and can be associated with graft rejection or systemic toxicities. The mTOR inhibitor, rapamycin, suppresses tumor growth of EBV+ B cell lymphoma cells in vitro and in vivo; however, the efficacy is limited and clinical benefits of mTOR inhibitors for PTLD are variable. Here, we show constitutive activation of multiple nodes within the PI3K/Akt/mTOR pathway in EBV+ PTLD-derived cell lines. Inhibition of either PI3K or Akt, with specific inhibitors CAL-101 and MK-2206, respectively, diminished growth of EBV+ B cell lines from PTLD patients in a dose-dependent manner. Importantly, rapamycin combined with CAL-101 or MK-2206 had a synergistic effect in suppressing cell growth as determined by IC 50 isobolographic analysis and Loewe indices. Moreover, these combinations were significantly more effective than rapamycin alone in inhibiting tumor xenograft growth in NOD-SCID mice. Finally, both CAL-101 and MK-2206 also prolonged survival of heterotopic cardiac allografts in C57BL/6 mice. Thus, combination therapy with rapamycin and a PI3K inhibitor, or an Akt inhibitor, can be an efficacious treatment for EBV-associated PTLD, while simultaneously promoting allograft survival. K E Y W O R D S basic (laboratory) research/science, immunosuppressant-mechanistic target of rapamycin (mTOR), immunosuppression/immune modulation, infection and infectious agents-viral: Epstein-Barr Virus (EBV), infectious disease, posttransplant lymphoproliferative disorder (PTLD)

show abstract

“…An explanation is that tacrolimus has a progressive effect impairing T-cell division, while additionally enhancing T-regulatory cells proliferation, which modulates the inflammatory response and promote the wound-healing process. 1, 29–32 The use of different scoring systems to assess CFS in published studies makes comparisons difficult. However, patients treated with tacrolimus in this study experienced more reduction in CFS than the reported in studies using tacrolimus 0.02% or 0.03%, or cyclosporine 0.05% or 1%, to treat ocular GVHD.…”

Section: Discussionmentioning

confidence: 99%

A Clinical Trial Comparing the Safety and Efficacy of Topical Tacrolimus versus Methylprednisolone in Ocular Graft-versus-Host Disease

et al. 2016

View full text Add to dashboard Cite

Purpose To evaluate the safety and efficacy of topical tacrolimus 0.05% vs. topical methylprednisolone 0.5% in patients with ocular graft-versus-host disease (GVHD). Design Phase I/II, prospective, randomized, double-masked clinical trial. Subjects Eighty eyes from 40 patients diagnosed with chronic ocular GVHD were enrolled. Methods Forty patients with ocular GVHD were randomized; 24 patients were treated with topical tacrolimus 0.05% and 16 patients with topical methylprednisolone 0.5% twice a day for 10 weeks, in addition to continuing their baseline treatment regimen. Main Outcome Measures Safety was evaluated based on occurrence of adverse events. Tolerability was assessed based on subjects’ reports of discomfort after drop instillation. Intraocular pressure (IOP) was monitored. The main efficacy endpoints were: corneal fluorescein staining (CFS), tear break-up time (TBUT), Schirmer test, and expression of the ocular surface inflammatory markers human leukocyte antigen-DR (HLA-DR) and intercellular adhesion molecule-1 (ICAM-1). Symptoms were evaluated using the Ocular Surface Disease Index (OSDI). Results After 10 weeks of treatment, no major adverse events occurred in either treatment group, and there was no significant difference in the composite tolerability scores between the two groups (P=0.06). However, burning sensation was more pronounced with tacrolimus (P=0.002). Topical tacrolimus was more effective than methylprednisolone in reducing the CFS score at week 10 (55% vs. 23% reduction, respectively; P=0.01), and achieved significant improvement in TBUT when compared to baseline (P<0.001). OSDI score reduction achieved statistical significance with tacrolimus (27% reduction; P=0.02) but was marginal with methylprednisolone (32% reduction; P=0.06). ICAM-1 expression by ocular surface epithelium decreased significantly in both groups (tacrolimus P=0.003; methylprednisolone P=0.008), while HLA-DR expression significantly decreased only in the tacrolimus group (P=0.03). Schirmer test scores did not change significantly in either group during the study; IOP increased significantly with methylprednisolone at week 10 (P=0.04). Conclusions Topical tacrolimus 0.05% is safe, generally well tolerated and effective for the treatment of ocular GVHD, without the hypertensive effects of topical corticosteroids.

show abstract

Effects of immunosuppressive therapy on wound healing

Cited by 113 publications

References 35 publications

First live birth after uterus transplantation in the United States

First live birth after uterus transplantation in the United States

Dual blockade of the PI3K/Akt/mTOR pathway inhibits posttransplant Epstein-Barr virus B cell lymphomas and promotes allograft survival

A Clinical Trial Comparing the Safety and Efficacy of Topical Tacrolimus versus Methylprednisolone in Ocular Graft-versus-Host Disease

Contact Info

Product

Resources

About