Remission of late-onset post-heart transplantation lymphoproliferative disorder following treatment with rituximab and modified mini-CHOP chemotherapy: A case report.

Post-transplant lymphoproliferative disorder (PTLD) is one of the most frequent secondary malignancies that can follow immunosuppressive therapy for solid organ transplantation, and may result in severe morbidities and even mortality. A middle-aged Han Chinese patient, prescribed with immunosuppressive cyclosporine and prednisone, developed PTLD that manifested as a painless cervical lymph node enlargement, 12 years following heart transplantation. Histology revealed monomorphic B-cell PTLD (diffuse large-cell lymphoma); as a result the immunosuppressive regimen of the patient was changed to tacrolimus and mycophenolate mofetil. In addition, the patient was changed to 6-cycle rituximab with a modified mini-CHOP (R-mini-CHOP) regimen for induction, and 8-cycle quarterly rituximab treatment and maintenance therapy. R-mini-CHOP therapy was well tolerated, and no allograft rejection occurred. The patient exhibited clinical remission as demonstrated by the results of the positron emission tomography-computed tomography at the 5-year follow-up visit following R-mini-CHOP therapy. In conclusion, R-mini-CHOP therapy following reduced immunosuppression is effective and safe for the treatment of late-onset PTLD following heart transplantation.

Expression of Chemokine XCL2 and CX3CL1 in Lung Cancer.

BACKGROUND Chemokines are a family of small proteins secreted by cells with chemotactic activity, and they play important roles in cell adhesion. However, the expression of chemokine XCL2 and CX3CL1 in lung cancers in different pathological stages remains unclear. MATERIAL AND METHODS XCL2 and CX3CL1 expression in lung cancers and adjacent non-cancerous tissues was detected by quantitative PCR and ELISA. The relative expression of both chemokines in lung cancers in different pathological stages was compared by immunohistochemical assay. RESULTS The relative expression level of XCL2 and CX3CL1 in lung cancer was significantly higher compared with adjacent normal tissues (P<0.001). The expression level of both chemokines was significantly increased with higher pathological stages, as indicated by immunohistochemical assay (P<0.05 or P <0.001). Their expression level in cancers with higher numbers of metastatic lymph nodes was also significantly increased compared with cancers with lower numbers of metastatic lymph nodes (P<0.05 or P<0.001). CONCLUSIONS The expression of XCL2 and CX3CL1 increases with increasing degree of malignancy, indicating that both chemokines might be important targets in gene therapy for lung cancer.

MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins.

OBJECTIVE: MicroRNA have recently been identified as regulators that modulate target gene expression and are involved in shaping the immune response. This study was undertaken to investigate the contribution of microRNA-146a (miR-146a), which was identified in the pilot expression profiling step, to the pathogenesis of systemic lupus erythematosus (SLE). METHODS: TaqMan microRNA assays of peripheral blood leukocytes were used for comparison of expression levels of microRNA between SLE patients and controls. Transfection and stimulation of cultured cells were conducted to determine the biologic function of miR-146a. Bioinformatics prediction and validation by reporter gene assay and Western blotting were performed to identify miR-146a targets. RESULTS: Profiling of 156 miRNA in SLE patients revealed the differential expression of multiple microRNA, including miR-146a, a negative regulator of innate immunity. Further analysis showed that underexpression of miR-146a negatively correlated with clinical disease activity and with interferon (IFN) scores in patients with SLE. Of note, overexpression of miR-146a reduced, while inhibition of endogenous miR-146a increased, the induction of type I IFNs in peripheral blood mononuclear cells (PBMCs). Furthermore, miR-146a directly repressed the transactivation downstream of type I IFN. At the molecular level, miR-146a could target IFN regulatory factor 5 and STAT-1. More importantly, introduction of miR-146a into the patients' PBMCs alleviated the coordinate activation of the type I IFN pathway. CONCLUSION: The microRNA miR-146a is a negative regulator of the IFN pathway. Underexpression of miR-146a contributes to alterations in the type I IFN pathway in lupus patients by targeting the key signaling proteins. The findings provide potential novel strategies for therapeutic intervention.

[Follow-up of twelve cases of heart transplantation].

OBJECTIVE: To observe the effects of heart transplantation. METHODS: Twelve patients undergoing orthotopic heart transplantation, one of which underwent combined heart and kidney transplantation (HKT), from June 1997 to June 2002 were followed up to observe the complications, work ability, life quality and psychic status. RESULTS: One of the 12 patients died of acute rejection and one died of acute renal failure during perioperative period. Ten cases (83.3%) survived the operation. Then one of the 10 patients died of acute rejection due to stopping Cellcept 7 months after operation; and the other 9 patients had lived well for 1 to 9 years, of which one recipient undergoing HKT survived for nearly 3 years. One year after operation the 9 patients showed class I heart function (NYHA), and all resumed their original work. One patient suffered from schizophrenia 1 week after operation. After the operation every year all cases were to receive coronary angiography with the results showing thinner coronary artery and less lateral branches, and myocardium, emission computed tomography (ECT) scanning that revealed local ischemia in anterior or posterior myocardium in 2 cases 4 and 5 years after respectively, however, no symptom of coronary artery disease was seen in all patients. Two cases, including the one receiving HKT, had symptoms of diabetes mellitus. Two patients thoracotomy during the perioperative period because of cardiac tamponade or too much blood drainage. All cases suffered from right heart failure, mouth ulcer and hypertension due to taking CsA and they had to take antihypertension drug to control their blood pressure. No malignant tumor had been found. CONCLUSION: Heart transplantation is an effective treatment for end-stage dilated cardiomyopathy. But many complications may follow. Some of them may endanger patients' life, and others may affect the quality of life. To trace the patients closely and deal with various complications in time will improve the effect of cardiac transplantation.