Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Posttransplant lymphoproliferative disease (PTLD) is a rare but clinically important disorder due to its increasing incidence and its impact on renal function and the life of the patient. Between 1979 and 2005, this center performed 1614 kidney transplants, and 23 patients had PTLD. We undertook a retrospective study, analyzing risk factors, presentation, and evolution of the disorder. The most common clinical presentation was fever and adenopathy. All cases except one received calcineurin inhibitors, and nine were treated with monoclonal or polyclonal antibodies. Serology for Epstein Barr virus (EBV) was negative in nine patients at the time of transplant, and in five it became positive on diagnosis of PTLD. The predominant disorder was non-Hodgkin's lymphoma (NHL), either polymorphous (n = 11) or monomorphous (n = 7). The base therapy consisted of reducing or suspending calcineurin inhibitors and the addition of sirolimus and antivirals. Three patients received rituximab, and five chemotherapy. The disease progressed in 36% of the polymorphous NHL, in 67% of the monomorphous, and in 100% of the Hodgkin's lymphoma, whereas 10 patients had remission. Renal function worsened on diagnosis in eight patients, and the graft was infiltrated in five (confirmed histologically). Five patients lost the graft and 12 died; six due to infection and five due to PTLD. Survival was worse in the patients aged over 55 years. We conclude that in most cases EBV is positive on diagnosis of the PTLD, an age older than 55 years affords a poor prognosis, and lymphocyte infiltration of the graft is common, as is worsening renal function.
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PMID:Posttransplant lymphoproliferative disease: a series of 23 cases. 1709 63

B-lymphoid tumor cells are often less sensitive than their normal counterparts or insensitive to transforming growth factor beta1 (TGFb) effects. We studied the apoptotic effect of exogenous TGFb in B-lymphoma cells, focusing on the activity and the role of Smad and protein phosphatase/kinase signals. Recombinant TGFb treatment and Smad4 siRNA transfection were used in HT58 B-NHL lymphoma cells in vitro. Gene expression and apoptosis were detected by RT-PCR, Western blot analysis and flow cytometry. The role of MEK1 kinase and PP2A activity--measured with a phosphatase assay--were assessed with the help of specific inhibitors. Smad4 siRNA treatment completely abolished TGFb-induced early gene upregulation, indicating the absence of the rapid activation of Smad signaling. Moreover, functional inhibition of Smad4 had no influence on TGFb-induced apoptosis, but it was dependent on PP2A phosphatase activation, ERK1/2 and JNK inactivation in lymphoma cells. The results prove that exogenous TGFb uses Smad4-independent, alternative (PP2A/PP2A-like dependent) signaling pathways for apoptosis induction in lymphoma cells. Further studies are needed to clarify the possible role and involvement of Smad4-independent effects of TGFb in normal and malignant lymphoid cells and in cells of the tumor microenvironment.
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PMID:Smad4-independent, PP2A-dependent apoptotic effect of exogenous transforming growth factor beta 1 in lymphoma cells. 1764 25

Non-Hodgkin lymphoma (NHL) incidence is greatly increased after kidney transplantation. NHL risk was investigated in a nationwide cohort of 8164 kidney transplant recipients registered on the Australia and New Zealand Dialysis and Transplant Registry. NHL diagnoses were ascertained using linkage with national cancer registry records. Multivariate Poisson regression was used to compute incidence rate ratios (IRRs) with 95% confidence intervals (CIs) comparing risk by transplant function, and risk factors for early (< 2 years) and late (>/= 2 years) NHL during the first transplantation. NHL occurred in 133 patients. Incidence was strikingly lower after transplant failure and cessation of immunosuppression than during transplant function (IRR, 0.25; 95% CI, 0.08-0.80; P = .019). Early NHL (n = 27) was associated with Epstein-Barr virus (EBV) seronegativity at transplantation (IRR, 4.66; 95% CI, 2.10-10.36, P < .001) and receipt of T cell-depleting antibodies (IRR, 2.39; 95% CI, 1.08-5.30; P = .031). Late NHL (n = 79) was associated with increasing year of age (IRR, 1.02; 95% CI, 1.01-1.04; P = .006), increasing time since transplantation (P < .001), and current use of calcineurin inhibitors (IRR, 3.13; 95% CI, 1.53-6.39; P = .002). These findings support 2 mechanisms of lymphomagenesis, one predominantly of primary EBV infection in the context of intense immunosuppression, and another of dysregulated lymphoid proliferation in a prolonged immunosuppressed state.
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PMID:Immunosuppression and other risk factors for early and late non-Hodgkin lymphoma after kidney transplantation. 1944 60