Cyclic changes in gene expression induced by Peg-interferon alfa-2b plus ribavirin in peripheral blood monocytes (PBMC) of hepatitis C patients during the first 10 weeks of treatment.
Cyclic changes in gene expression induced by Peg-interferon alfa-2b plus ribavirin in peripheral blood monocytes (PBMC) of hepatitis C patients during the first 10 weeks of treatment.
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DOI：
10.1186/1479-5876-6-66
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发表时间：
2008-11-05
影响因子：
7.4
通讯作者：
Kwo, Paul
中科院分区：
文献类型：
--
作者：
Taylor, Milton W.;Tsukahara, Takuma;McClintick, Jeanette N.;Edenberg, Howard J.;Kwo, Paul
这项研究确定了丙型肝炎病毒患者在接受聚乙二醇化干扰素-α2b(PEGINTRON™)和利巴韦林(按重量给药)治疗的前10周内的基因表达动力学，并将其与最近完成的给予聚乙二醇化干扰素-α2a(PEGASYS™)和利巴韦林的病毒C研究进行了比较。分别于治疗前(第1天)、治疗后第3、6、10、13、27、42和70天从20例初治患者的外周血单核细胞(PBMC)中提取RNA。在第3天(290个探针)和第10天(255个探针)，许多基因的表达差异显著(p≤0.001，至少变化了1.5倍)，但在第6天(165d)和第13天(142d)，许多基因的表达有所下降。在整个试验期间，大多数基因继续上调。第二组基因，包括CXCL10、CMKLR1(趋化因子受体1)、TRAIL、IL1Rα以及与补体和脂质代谢相关的基因，在治疗早期被瞬时诱导。CDKN1C(细胞周期蛋白激酶抑制因子1)在早期被诱导，但在后期被抑制。后期诱导的基因主要与血液化学和氧气运输有关。到10周时，11例患者对治疗呈阳性反应，最终持续病毒应答(SVR)为35%。基因诱导或减少的水平与以前报道的派罗欣/利巴韦林治疗非常相似。对派格列酮/利巴韦林的反应与报告的派格西司/利巴韦林相似，尽管给药量有所不同。我们没有检测到对治疗有反应的患者和无反应的患者在基因组水平上的重大差异，可能是因为能力有限。基因诱导以循环方式发生，在注射干扰素后立即达到顶峰，并在两次给药之间下降。我们的数据表明，在治疗早期每周给药一次以上可能是可取的，以保持通过基因表达衡量的高水平反应。
This study determined the kinetics of gene expression during the first 10 weeks of therapy with Pegylated-interferon-alfa2b (PegIntron™) and ribavirin (administered by weight) in HCV patients and compared it with the recently completed Virahep C study in which Peginterferon-alfa2a (Pegasys™) and ribavirin were administered. RNA was isolated from peripheral blood monocytes (PBMC) from twenty treatment-naïve patients just before treatment (day 1) and at days 3, 6, 10, 13, 27, 42 and 70 days after treatment. Gene expression at each time was measured using Affymetrix microarrays and compared to that of day 1. The expression of many genes differed significantly (p ≤ 0.001 and changed at least 1.5-fold) at days 3 (290 probes) and 10 (255 probes), but the number dropped at days 6 (165) and 13 (142). Most genes continued to be up regulated throughout the trial period. A second group of genes, including CXCL10, CMKLR1 (chemokine receptor 1), TRAIL, IL1Rα and genes associated with complement and lipid metabolism, was transiently induced early in treatment. CDKN1C (cyclin kinase inhibitor 1) was induced early but repressed at later times. Genes induced at later times were mostly related to blood chemistry and oxygen transport. By week 10, 11 of the patients demonstrated a positive response to therapy, and the final sustained viral response (SVR) was 35%. The levels of gene induction or decrease was very similar to that previously reported with Pegasys/ribavirin treatment. The response to Pegintron/ribavirin was similar to that reported for Pegasys/ribavirin despite some differences in the amount administered. We did not detect major differences at the genomic level between patients responding to treatment or non-responders, perhaps because of limited power. Gene induction occurred in a cyclic fashion, peaking right after administration of interferon and declining between administrations of the drug. Our data suggest that more than once a week dosing might be desirable early during treatment to maintain high levels of response as measured by gene expression.
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影响因子：
3.7
作者：
Brodsky LI;Wahed AS;Li J;Tavis JE;Tsukahara T;Taylor MW
通讯作者：
Taylor MW
影响因子：
6.7
作者：
Glue, P;Fang, JWS;Jacobs, S
通讯作者：
Jacobs, S
影响因子：
6.8
作者：
Kozlowski, A;Charles, SA;Harris, JM
通讯作者：
Harris, JM
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
3.5
作者：
Kim, SH;Cohen, B;Rubinstein, M
通讯作者：
Rubinstein, M