干扰素在恶性淋巴瘤自体移植后早期干预的应用

目的:观察非霍奇金淋巴瘤（non-Hodgkin's lymphoma，NHL）患者自体造血干细胞移植（autologous hematopoietic stem cell transplantation，ASCT）术后应用重组人α-2b干扰素（α-2b IFN）进行早期干预治疗的临床疗效。方法:选取18例行ASCT的NHL患者为研究对象，移植前疾病评估均未达到完全缓解（complete remission，CR），试验组血象恢复后给予IFN 3 000 000 U次/隔日干预治疗，3个月后停用；对照组未行干扰素干预治疗，分析总体疗效及两组对比的生存情况。结果:随访中位时间为34（10~50）个月，患者中位生存时间为37（31~45）个月，3年总体无进展生存（progressive free survival，PFS）、总生存（overall survivial，OS）分别为54.7%、66.8%。ASCT后试验组1年内无疾病复发，2年内复发率为12.5%；对照组1年内复发率为20%，2年内复发率为30%。结论:NHL患者在ASCT后给予重组人α-2b IFN早期干预治疗，患者耐受性好，可能降低移植后早期复发率。     

Basiliximab treatment of severe GVHD induced by donor lymphocyte infusion with interferon‐a

The development of acute graft‐versus‐host‐disease (GVHD) in recipients of donor lymphocyte infusion (DLI) is not rare and the complication is quite often fatal. We describe a severe skin GVHD patient who responded well to basiliximab. A 20‐year‐old male who received a hematopoietic stem cell transplantation at his age of 18. His fusion gene Aml1/Eto remained positive, so he was administered with DLI combined with interferon‐a (IFN‐a). Forty days after the therapy, he presented with severe skin rashes with multiple mucous membrane involvement. The skin and mucous lesions recovered after basiliximab treatment. So far, severe type of erythema multiforme in GVHD patients after DLI with IFN‐a injection is firstly reported here, together with a new alternative therapy.     

IFN-γ通过诱导上皮间质转化增强人乳头状甲状腺癌细胞株的侵袭转移能力

目的:观察IFN-γ对人乳头状甲状腺癌细胞株TPC-1侵袭和转移能力的影响，并探讨上皮间质转化过程（EMT）在其中的作用。方法:采用划痕愈合实验和Transwell侵袭实验检测IFN-γ对TPC-1侵袭转移能力的影响；实时定量PCR和Western检测EMT标志物E-cadherin，N-cadherin，Vimentin的mRNA水平及蛋白水平变化；免疫荧光检测上述标志物的定位表达。结果:划痕愈合实验和Transwell侵袭实验结果显示:IFN-γ增强了TPC-1的侵袭转移能力（P＜0.05）,实时定量PCR结果显示EMT的上皮标志物E-cadherin的mRNA表达水平明显下降，间质标志物Vimentin的mRNA表达上调，而N-cadherin的mRNA未见明显变化。Western结果显示E-cadherin在IFN-γ作用下表达下调；N-cadherin与Vimenin表达上升；免疫荧光结果与Western结果一致。结论:INF-γ可以通过诱导EMT，促进TPC-1侵袭转移，提示炎性介质IFN-γ可能参与人乳头状甲状腺癌的侵袭转移。     

PARP7 negatively regulates the type I interferon response in cancer cells and its inhibition triggers antitumor immunity

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Toll‐IL1 receptor‐mediated innate immune responses vary across HBV genotype and predict treatment response to pegylated‐IFN in HBeAg‐positive CHB patients

Patients with hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B (CHB) have suppressed TLR2 expression, function and cytokine production. The aim of this study was to explore the importance of hepatitis B virus (HBV) genotype in innate immune responses and investigate whether Toll‐like receptor (TLR) expression/function has potential roles as predictive biomarkers of successful therapy with pegylated interferon (Peg‐IFN) therapy of HBeAg seroconversion in HBeAg‐positive patients. We showed that as early as 4 weeks after initiation of Peg‐IFN, future HBeAg seroconverters had significantly elevated levels of TLR2 expression on monocytes. TLR2‐associated IL‐6 production at baseline and week 4 of therapy and TLR4 IL‐6 production at week 4 were also markedly elevated in HBeAg seroconverters. HBV genotype also influenced treatment response, with genotypes A and B more likely to seroconvert than D. We were able to demonstrate that these differences were due in part to the interaction of the specific HBeAg proteins with TLR pathway adaptor molecules, and these interactions were genotype dependent. HBeAg‐mediated modulation of TLR signalling was also observed in Huh7 cells, following stimulation with Pam3Cys. Importantly, the addition of IFN‐α to TLR2‐stimulated cells cotransfected with an HBeAg expression plasmid reversed HBeAg‐mediated suppression of hepatocytes. These findings demonstrate that patients with an activated inflammatory response are much more likely to respond to IFN therapy, with TLR responses showing promise as potential biomarkers of HBeAg seroconversion in this setting. Furthermore, our findings suggest there is differential genotype‐specific HBeAg suppression of innate signalling pathways which may account for some of the clinical differences observed across the CHB spectrum.     

聚乙二醇干扰素α联合利巴韦林治疗难治性慢性丙型肝炎过程中血常规变化与疗效的相关性

目的观察难治性慢性丙型肝炎标准治疗过程中血常规的变化与抗病毒疗效的关系。方法收集2011年9月-2012年12月于首都医科大学附属北京佑安医院就诊的难治性慢性丙型肝炎初治患者63例,给予聚乙二醇干扰素α-2a(180μg/周)联合利巴韦林治疗48周,分别在基线、治疗4、12、24、48周和随访24周时进行HCV RNA及血常规的检测,分析血常规与疗效的相关性。根据是否获得持续病毒学应答(SVR),分为SVR组和n SVR组。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验;采用简单线性相关分析法进行相关性分析。结果 63例患者有3例失访,余下60例均完成抗病毒治疗和24周随访,其中46例获得SVR,SVR率为76.7%;SVR组患者治疗4、12、24周时的淋巴细胞计数(LYPH)、白细胞计数(WBC)及中性粒细胞计数(NUET)均低于n SVR组,并且在12周时差异均有统计学意义(t值分别为3.398、2.766、2.037,P值均0.05),在24周时两组WBC及NUET差异亦均有统计学意义(t值分别为2.559、2.151,P值均0.05);此外SVR组患者在治疗4周时上述3项指标较基线的下降幅度均大于n SVR组,其中LYPH下降幅度在两组间差异有统计学意义(t=2.26,P=0.03)。LYPH、WBC、NUET在治疗4、12周时与HCV RNA的下降幅度呈正相关(r值分别为0.36、0.45、0.37、0.47、0.61、0.33,P值均0.05)。结论血常规中LYPH、WBC及NEUT的变化及下降幅度在一定程度上可作为难治性慢性丙型肝炎抗病毒疗效的预测指标。