Hemophagocytic lymphohistiocytosis after autologous stem cell transplantation in angioimmunoblastic T-cell lymphoma: A case report.

BACKGROUND: Angioimmunoblastic T-cell lymphoma (AITL), a unique subtype of peripheral T-cell lymphoma, has relatively poor outcomes. High-dose chemotherapy with autologous stem cell transplantation (ASCT) can achieve complete remission and improve outcomes. Unfortunately, subsequent T-cell lymphoma-triggered hemophagocytic lymphohistiocytosis (HLH) has a worse prognosis than B-cell lymphoma-triggered HLH. CASE SUMMARY: We here report a 50-year-old woman with AITL who achieved a favorable outcome after developing HLH 2 mo after receiving high-dose chemotherapy/ ASCT. The patient was initially admitted to our hospital because of multiple enlarged lymph nodes. The final pathologic diagnosis, made on biopsy of a left axillary lymph node was AITL (Stage IV, Group A). Four cycles of the following chemotherapy regimen were administered: Cyclophosphamide 1.3 g, doxorubicin 86 mg, and vincristine 2 mg on day 1; prednisone 100 mg on days 1-5; and lenalidomide 25 mg on days 1-14. The interval between each cycle was 21 d. The patient received a conditioning regimen (busulfan, cyclophosphamide, and etoposide) followed by peripheral blood stem cell infusion. Unfortunately, she developed sustained fever and a low platelet count 17 d after ACST, leading to a diagnosis of HLH after ASCT. During treatment, she experienced thrombocytopenia and Pneumocystis carinii pneumonia. The patient was successfully treated with etoposide and glucocorticoids. CONCLUSION: It is possible that development of HLH is related to immune reconstitution after ASCT.

The expression of epidermal growth factor-like domain 7 regulated by oxygen tension via hypoxia inducible factor (HIF)-1α activity.

OBJECTIVE: Hypoxia inducible factor-1α (HIF-1α) regulates many genes involved in angiogenesis during embryonic development. Epidermal growth factor-like domain 7 (Egfl7) is a specific marker for human arterial endothelial cells that are in an activated state of proliferation, migration, and remodeling. This study evaluates the intricate relationship between HIF-1α and Egfl7 under both hyperoxia and hypoxia states. METHODS: The neonatal mice were exposed to either hyperoxia or hypoxia in order to detect the pulmonary and cardiac Egfl7 messenger RNA (mRNA) or protein expression regulated by oxygen tension in vivo by reverse transcriptase polymerase chain reaction or immunohistochemistry staining. Egfl7 expression in HIF-1α null pulmonary endothelial cells in hypoxia conditions and effects of overexpression or knockdown of HIF-1α on Egfl7 expression in human umbilical vein endothelial cells would be clarified in vitro by reverse transcriptase polymerase chain reaction and Western blot, respectively. RESULTS: Hyperoxia exposure significantly reduced Egfl7 expression in neonatal mice lungs by 36% compared with age-matched normoxia control mice (P < 0.05, n = 6). The pulmonary Egfl7 transcription levels were increased by 1.7- and 1.9-fold in 24 hours and by day 8 in hypoxia groups compared with the normoxia control values (P < 0.05, n = 6). The cardiac Egfl7 mRNA expression was significantly increased by 4.5-fold in the day 8 group compared with the normoxia control values (P < 0.05, n = 6). The expression of Egfl7 decreased significantly in the HIF-1α(-/-) endothelial cells (ECs), which was only 26% of wild-type HIF-1α(+/+) ECs (P < 0.05, n = 3). Hypoxia caused a mild but significant increase of Egfl7 expression in HIF-1α(+/+) ECs (P < 0.05). In vitro, overexpression of HIF-1α enhanced Egfl7 expression, whereas knockdown of HIF-1α reduced Egfl7 expression. CONCLUSIONS: Overexpression of HIF-1α enhanced Egfl7 expression, whereas knockdown of HIF-1α reduced Egfl7 expression. Egfl7 could be a HIF-1α responsive gene regulated by oxygen tension.

Association of lipoprotein-associated phospholipase A2 with characteristics of vulnerable coronary atherosclerotic plaques.

PURPOSE: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory enzyme expressed in atherosclerotic plaques. We investigated the association of circulating Lp-PLA2 with characteristics of vulnerable coronary atherosclerotic plaques. MATERIALS AND METHODS: We recruited 113 patients with either unstable angina (UA, n=59) and stable angina (SA, n=54) by coronary angiography. Thirty-six healthy subjects served as controls. Intravascular ultrasound (IVUS) was used to evaluate the characteristics of coronary atherosclerotic plaque, and serum Lp-PLA2 concentration was measured as well. RESULTS: Lp-PLA2 concentration was significantly higher in both UA and SA patients [(396±36) µg/L and (321±39) µg/L, respectively] compared with the controls [(127 ± 49) µg/L, p<0.01], and higher in UA than SA group. IVUS findings showed that remodeling index (RI) (0.91 ± 0.15 vs. 0.85 ± 0.11, p=0.005) and eccentricity index (EI) (0.73 ± 0.16 vs. 0.65 ± 0.22, p=0.039) were larger in UA than in SA group, and fibrous caps were thicker in SA than UA group [(0.91 ± 0.23) mm vs. (0.63 ± 0.21) mm, p=0.032]. Moreover, Lp-PLA2 correlated positively with EI (r=0.439, p<0.01) and RI (r=0.592, p<0.05) in UA group. There was an inverse relationship between Lp-PLA2 and fibrous cap thickness in both UA (r=-0.587, p<0.001) and SA (r=-0.318, p<0.05) groups. The independent risk factors in UA group were Lp-PLA2 (OR=1.055, 95% CI: 1.03-1.08, p=0.013), LDL-cholesterol (OR=0.032, 95% CI: 0.00-0.05, p=0.041) and fibrous cap thickness (OR=0.008, 95% CI: 0.00-0.45, p=0.019). Lp-PLA2 was strongly associated with both EI and fibrous cap thickness in both groups. CONCLUSION: Serum level of Lp-PLA2 is associated with both eccentricity index and fibrous cap thickness in both UA and SA groups. Elevated levels of circulating Lp-PLA2 might to be a strong risk factor and more serious for unstable angina than stable angina.

[siRNA inhibits efgl7 expression in human endothelial cell line HUVEC].

OBJECTIVE: To evaluate the effects of small interference RNA (siRNA) on epidermal growth factor-like domain 7 (egfl7) gene expression in human endothelial cell line HUVEC. METHODS: siRNA targeting egfl7 (siRNA1, siRNA2, siRNA3 and siRNA4) was constructed through online design of Amnion company and transfected into human endothelial cell line HUVEC with lipofectamine. The nontransfected cells and cells treated with control siRNA were taken as controls. At 24, 48 and 72 hours post various interventions, cell viability was determined by MTS method as well as LDH and ATP releasing tests. egfl7 expressions at protein and mRNA levels were detected by Western blot and RT-PCR respectively. RESULTS: Cell survival rate, LDH and ATP release were significantly reduced in siRNA treated cells compared to control cells (P < 0.05). Similarly, egfl7 expression at protein and mRNA levels was also significantly reduced in siRNA treated cells (P < 0.01), especially in siRNA1 treated cells. CONCLUSION: siRNA inhibited egfl7 gene expression and cell survival in HUVEC.