|本期目录/Table of Contents|

[1]张荣芳,钱磊,常明杰,等.血清HBV RNA在慢性乙型肝炎抗病毒治疗过程中的动态变化及其临床意义[J].天津医科大学学报,2021,27(05):520-523.
 ZHANG Rong-fang,QIAN Lei,CHANG Ming-jie,et al.Dynamic changes and clinical significance of serum HBV RNA in patients with chronic hepatitis B during antiviral therapy[J].Journal of Tianjin Medical University,2021,27(05):520-523.
点击复制

血清HBV RNA在慢性乙型肝炎抗病毒治疗过程中的动态变化及其临床意义(PDF)
分享到:

《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
27卷
期数:
2021年05期
页码:
520-523
栏目:
临床医学
出版日期:
2021-09-10

文章信息/Info

Title:
Dynamic changes and clinical significance of serum HBV RNA in patients with chronic hepatitis B during antiviral therapy
文章编号:
1006-8147(2021)05-0520-04
作者:
张荣芳1钱磊1常明杰1付兵利2郭利敏3
(1.中国人民解放军陆军第八十三集团军医院检验科,新乡453000;2.北京市朝阳区桓兴肿瘤医院检验科,北京 100020;3.新乡市中心医院检验科,新乡453000)
Author(s):
ZHANG Rong-fang1QIAN Lei1CHANG Ming-jie1FU Bing-li2GUO Li-min3
(1.Department of Clinical Laboratory,83rd Army Group Military Hospital,The People′s Liberation Army of China,Xinxiang 453000,China; 2. Department of Clinical Laboratory,Huanxing Cancer Hospital,Chaoyang District of Beijing,Beijing 100020,China; 3.Departme
关键词:
乙型肝炎病毒抗病毒治疗HBV RNA共价闭合环状DNA
Keywords:
HBVantiviral therapyHBV RNAcovalently closed circular DNA
分类号:
R512.6+2
DOI:
-
文献标志码:
A
摘要:
目的:探讨血清HBV RNA在慢性乙型肝炎(CHB)抗病毒治疗过程中的动态变化及其临床意义。方法:慢性乙型肝炎患者62例采用恩替卡韦抗病毒治疗,分别在第0、7、14、30天以及第2、3、6、9、12个月来本院进行随访,TaqMan探针法定量检测HBV RNA水平,采用实时荧光定量PCR法进行HBV DNA水平检测,采用化学发光法进行HBsAg和HBeAg检测,采用酶法进行ALT及AST检测。结果:血清HBV RNA水平随着治疗时间的延长呈下降趋势,治疗3个月后下降速度趋缓,从9个月后变化不大。血清HBV RNA水平从0 d到6个月间,各个相邻监测点间变化均有统计学意义(均P<0.05),在治疗6~12个月两个时间点间差异无统计学意义(P>0.05)。HBeAg(+)患者基线血清HBV RNA与HBV DNA(rs =0.68,P<0.05)、HbsAg(rs =0.64,P<0.05)、HBeAg(rs=0.77,P<0.05)均强相关。在治疗前6个月各时间点,HBV RNA与HBV DNA呈强相关(rs>0.5,P<0.05)。HBV RNA与HBsAg在治疗前3个月呈强相关(rs>0.5,P<0.05),治疗6~9个月时为弱相关(rs=0.23,P=0.31;rs=0.28,P=0.23)。HBV RNA与HBeAg水平在各治疗时间点均为强相关(rs>0.5,P<0.05)。HBeAg(-)患者在治疗30 d时血清HBV RNA与HBV DNA 呈正相关(rs=0.62,P<0.05),在治疗14 d时HBV RNA与HBsAg水平呈正相关(rs=0.60,P<0.05)。结论:抗病毒治疗时,慢性乙型肝炎患者血清HBV RNA水平随着治疗时间的延长呈下降趋势。患者血清HBV RNA水平与血清HBV DNA、HBsAg、HBeAg在治疗前和治疗初期有明显相关性,随着治疗时间延长,其相关性逐渐减弱。
Abstract:
Objective: To investigate the dynamic changes and clinical significance of serum HBV RNA in patients with chronic hepatitis B(CHB) during antiviral therapy. Methods: A total of 62 patients with chronic hepatitis B were treated with Entecavir,the patients were followed up at 0,7,14,30 days and 2,3,6,9,12 months. Quantitative detection of HBV RNA was conducted by TaqMan probe,HBV DNA level was detected by real-time fluorescent quantitative PCR,HBsAg and HBeAg were detected by chemiluminescence,ALT and AST were detected by enzymatic. Results: The serum HBV RNA level showed a downward trend with the extension of treatment time,and the decline rate slowed down after 3 months of treatment,and there was little change after 9 months. The changes of serum HBV RNA between the adjacent monitoring points were all statistically significant(all P<0.05) from 0 day to 6 months. There was no significant difference between the two time points of 6-12 months(P>0.05).Serum HBV RNA in patients with HBeAg(+) was strongly correlated with HBV DNA(rs =0.68,P<0.05),HbsAg(rs =0.64,P<0.05),HbeAg(rs =0.77,P<0.05) in the cardinal line. There was a strong correlation between HBV RNA and HBV DNA during 6 months of treatment(rs > 0.50,P<0.05). The correlation between HBV RNA and HBsAg was strong during 3 months treatment(rs >0.50,P<0.05),and it was weak from 6 to 9 months during treatment(rs =0.23,P=0.31;rs =0.28,P=0.23). The correlation between HBV RNA and HBeAg level was strong at each treatment time point(rs > 0.50,P<0.05). The correlation between serum HBV RNA and HBV DNA in HbeAg(-) patients at 30 days of treatment was positive(rs =0.62,P<0.05),and the correlation between HBV RNA and HBsAg level at 14 days of treatment was positive(rs =0.60,P<0.05). Conclusion: During antiviral treatment,the serum HBV RNA level of patients with chronic hepatitis B decreases with the extension of treatment time. There is a significant correlation between serum HBV RNA level and serum HBV DNA,HBsAg,HBeAg before and at the beginning of treatment. With the extension of treatment time,the correlation is gradually weakened.

参考文献/References:

[1] KIM E S,SCOTT L J. Palbociclib:a review in HR-positive,HER2-negative, advanced or metastatic breast cancer[J]. Target Oncol,2017,12(3):373
[2] FINN R S,MARTIN M,RUGO H S,et al. Palbociclib and Letrozole in advanced breast cancer[J]. N Engl J Med,2016,375(20):1925
[3] CRISTOFANILLI M,TURNER N C,Bondarenko I,et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive,HER2-negative metastatic breast cancer that progressed on previous endocrine therapy(PALOMA-3):final analysis of the multicentre,double-blind,phase 3 randomised controlled trial[J]. Lancet Oncol,2016,17(4):425
[4] SPRING L M,WANDER S A,ANDRE F,et al. Cyclin-dependent kinase 4 and 6 inhibitors for hormone receptor-positive breast cancer:past,present,and future[J]. Lancet,2020,395(10226):817
[5] GELBERT L M,CAI S,LIN X,et al. Preclinical characterization of the CDK4/6 inhibitor LY2835219:in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine[J]. Invest New Drugs,2014,32(5):825
[6] CALDON C E,SERGIO C M,SCH?譈TTE J,et al. Estrogen regulation of cyclin E2 requires cyclin D1 but not c-Myc[J]. Mol Cell Biol,2009, 29(17):4623
[7] PANDEY K,AN H J,KIM S K,et al. Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer:a review[J]. Int J Cancer,2019,145(5):1179
[8] BUTT A J,MCNEIL C M,MUSGROVE E A,et al. Downstream targets of growth factor and oestrogen signalling and endocrine resistance:the potential roles of c-Myc, cyclin D1 and cyclin E[J]. Endocr Relat Cancer,2005,12(1 Suppl):S47
[9] VIJAYARAGHAVAN S,DOOSTAN I,CAREY JPW,et al. Abstract 2060:Characterizing acquired resistance to palbociclib in breast cancer[J]. Cancer Res,2017,77(13 Suppl):DIO:10.1158/1538-7445.AM2017-2060
[10] MAO P,KUSIEL J,COHEN O, et al. Abstract PD4-01:The role of FGF/FGFR axis in resistance to SERDs and CDK4/6 inhibitors in ER+ breast cancer[J]. Cancer Res,2018,78(4 Suppl):DOI:10.1158/1538-7445.SABCS17-PD4-01
[11] HERRERA-ABREU M T,PALAFOX M,ASGHAR U,et al. Early adaptation and acquired resistance to CDK4/6 inhibition in estrogen receptor-positive breast cancer[J]. Cancer Res,2016,76(8):2301
[12] MICHALOGLOU C,CRAFTER C,SIERSBAEK R,et al. Combined inhibition of mTOR and CDK4/6 is required for optimal blockade of E2F function and long-term growth inhibition in estrogen receptor-positive breast cancer[J]. Mol Cancer Ther,2018,17(5):908
[13] JANSEN V M,BHOLA N E,BAUER J A,et al. Kinome-wide RNA interference screen reveals a role for PDK1 in acquired resistance to CDK4/6 inhibition in ER-positive breast cancer[J]. Cancer Res,2017,77(9):2488
[14] MERENBAKH-LAMIN K,BEN-BARUCH N,YEHESKEL A,et al. D538G mutation in estrogen receptor-α:a novel mechanism for acquired endocrine resistance in breast cancer[J]. Cancer Res,2013, 73(23):6856
[15] BARDIA A,HURVITZ S. Targeted therapy for premenopausal women with HR(+),HER2(-)advanced breast cancer:focus on special considerations and latest advances[J]. Clin Cancer Res,2018,24(21):5206
[16] GYANCHANDANI R,KOTA K J,JONNALAGADDA A R,et al. Detection of ESR1 mutations in circulating cell-free DNA from patients with metastatic breast cancer treated with palbociclib and letrozole[J]. Oncotarget,2017,8(40):66901
[17] SCHAER D A,BECKMANN R P,DEMPSEY J A,et al. The CDK4/6 inhibitor abemaciclib induces a T cell inflamed tumor microenvironment and enhances the efficacy of PD-L1 checkpoint blockade[J]. Cell Rep,2018,22(11):2978
[18] O′LEARY B,CUTTS R J,LIU Y,et al. The genetic landscape and clonal evolution of breast cancer resistance to Palbociclib plus Fulvestrant in the PALOMA-3 trial[J]. Cancer Discov,2018,8(11):1390
[19] HAFNER M,MILLS C E,SUBRAMANIAN K,et al. Multiomics profiling establishes the polypharmacology of FDA-approved CDK4/6 inhibitors and the potential for differential clinical activity[J]. Cell Chem Biol,2019,26(8):1067
[20] WANDER S A,ZANGARDI M,NIEMIERKO A,et al. A multicenter analysis of abemaciclib after progression on palbociclib in patients(pts) with hormone receptor-positive(HR+)/HER2- metastatic breast cancer (MBC)[J]. J Clin Oncol,2019,37(15 suppl):1057
[21] FORMISANO L,LU Y,SERVETTO A,et al. Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer[J]. Nat Commun,2019,10(1):1373
[22] MILLER T W,HENNESSY B T,González-Angulo A M,et al. Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer[J]. J Clin Invest,2010,120(7):2406
[23] ANDR?魪 F,CIRUELOS E,RUBOVSZKY G,et al. Alpelisib for PIK3CA-mutated,hormone receptor-positive advanced breast cancer[J]. N Engl J Med,2019,380(20):1929
[24] COSTA C,WANG Y,LY A,et al. PTEN loss mediates clinical cross-resistance to CDK4/6 and PI3Kα inhibitors in breast cancer[J]. Cancer Discov,2020,10(1):72
[25] 黄元夕. 2020年美国临床肿瘤学会年会乳腺癌内分泌治疗重要内容解读[J]. 医学研究杂志,2020,49(10):7
[26] JURIC D,ISMAIL-KHAN R,CAMPONE M,et al. Abstract P3-14-01:Phase Ib/II study of ribociclib and alpelisib and letrozole in ER+,HER2-breast cancer:safety,preliminary efficacy and molecular analysis[J]. Cancer Res,2016,76(4 Suppl):DOI:10.1158/1538-7445.SABCS15-P3-14-01
[27] JONES R H,CASBARD A,CARUCCI M,et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic,oestrogen receptor-positive breast cancer (FAKTION):a multicentre,randomised,controlled,phase 2 trial[J]. Lancet Oncol,2020,21(3):345
[28] PATEL H K,TAO N,LEE K M,et al. Elacestrant(RAD1901) exhibits anti-tumor activity in multiple ER+ breast cancer models resistant to CDK4/6 inhibitors[J]. Breast Cancer Res,2019,21(1):146
[29] DENG J,WANG E S,JENKINS R W,et al. CDK4/6 inhibition augments antitumor immunity by enhancing T-cell activation[J]. Cancer Discov,2018,8(2):216 [1] KIM E S,SCOTT L J. Palbociclib:a review in HR-positive,HER2-negative, advanced or metastatic breast cancer[J]. Target Oncol,2017,12(3):373
[2] FINN R S,MARTIN M,RUGO H S,et al. Palbociclib and Letrozole in advanced breast cancer[J]. N Engl J Med,2016,375(20):1925
[3] CRISTOFANILLI M,TURNER N C,Bondarenko I,et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive,HER2-negative metastatic breast cancer that progressed on previous endocrine therapy(PALOMA-3):final analysis of the multicentre,double-blind,phase 3 randomised controlled trial[J]. Lancet Oncol,2016,17(4):425
[4] SPRING L M,WANDER S A,ANDRE F,et al. Cyclin-dependent kinase 4 and 6 inhibitors for hormone receptor-positive breast cancer:past,present,and future[J]. Lancet,2020,395(10226):817
[5] GELBERT L M,CAI S,LIN X,et al. Preclinical characterization of the CDK4/6 inhibitor LY2835219:in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine[J]. Invest New Drugs,2014,32(5):825
[6] CALDON C E,SERGIO C M,SCH?譈TTE J,et al. Estrogen regulation of cyclin E2 requires cyclin D1 but not c-Myc[J]. Mol Cell Biol,2009, 29(17):4623
[7] PANDEY K,AN H J,KIM S K,et al. Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer:a review[J]. Int J Cancer,2019,145(5):1179
[8] BUTT A J,MCNEIL C M,MUSGROVE E A,et al. Downstream targets of growth factor and oestrogen signalling and endocrine resistance:the potential roles of c-Myc, cyclin D1 and cyclin E[J]. Endocr Relat Cancer,2005,12(1 Suppl):S47
[9] VIJAYARAGHAVAN S,DOOSTAN I,CAREY JPW,et al. Abstract 2060:Characterizing acquired resistance to palbociclib in breast cancer[J]. Cancer Res,2017,77(13 Suppl):DIO:10.1158/1538-7445.AM2017-2060
[10] MAO P,KUSIEL J,COHEN O, et al. Abstract PD4-01:The role of FGF/FGFR axis in resistance to SERDs and CDK4/6 inhibitors in ER+ breast cancer[J]. Cancer Res,2018,78(4 Suppl):DOI:10.1158/1538-7445.SABCS17-PD4-01
[11] HERRERA-ABREU M T,PALAFOX M,ASGHAR U,et al. Early adaptation and acquired resistance to CDK4/6 inhibition in estrogen receptor-positive breast cancer[J]. Cancer Res,2016,76(8):2301
[12] MICHALOGLOU C,CRAFTER C,SIERSBAEK R,et al. Combined inhibition of mTOR and CDK4/6 is required for optimal blockade of E2F function and long-term growth inhibition in estrogen receptor-positive breast cancer[J]. Mol Cancer Ther,2018,17(5):908
[13] JANSEN V M,BHOLA N E,BAUER J A,et al. Kinome-wide RNA interference screen reveals a role for PDK1 in acquired resistance to CDK4/6 inhibition in ER-positive breast cancer[J]. Cancer Res,2017,77(9):2488
[14] MERENBAKH-LAMIN K,BEN-BARUCH N,YEHESKEL A,et al. D538G mutation in estrogen receptor-α:a novel mechanism for acquired endocrine resistance in breast cancer[J]. Cancer Res,2013, 73(23):6856
[15] BARDIA A,HURVITZ S. Targeted therapy for premenopausal women with HR(+),HER2(-)advanced breast cancer:focus on special considerations and latest advances[J]. Clin Cancer Res,2018,24(21):5206
[16] GYANCHANDANI R,KOTA K J,JONNALAGADDA A R,et al. Detection of ESR1 mutations in circulating cell-free DNA from patients with metastatic breast cancer treated with palbociclib and letrozole[J]. Oncotarget,2017,8(40):66901
[17] SCHAER D A,BECKMANN R P,DEMPSEY J A,et al. The CDK4/6 inhibitor abemaciclib induces a T cell inflamed tumor microenvironment and enhances the efficacy of PD-L1 checkpoint blockade[J]. Cell Rep,2018,22(11):2978
[18] O′LEARY B,CUTTS R J,LIU Y,et al. The genetic landscape and clonal evolution of breast cancer resistance to Palbociclib plus Fulvestrant in the PALOMA-3 trial[J]. Cancer Discov,2018,8(11):1390
[19] HAFNER M,MILLS C E,SUBRAMANIAN K,et al. Multiomics profiling establishes the polypharmacology of FDA-approved CDK4/6 inhibitors and the potential for differential clinical activity[J]. Cell Chem Biol,2019,26(8):1067
[20] WANDER S A,ZANGARDI M,NIEMIERKO A,et al. A multicenter analysis of abemaciclib after progression on palbociclib in patients(pts) with hormone receptor-positive(HR+)/HER2- metastatic breast cancer (MBC)[J]. J Clin Oncol,2019,37(15 suppl):1057
[21] FORMISANO L,LU Y,SERVETTO A,et al. Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer[J]. Nat Commun,2019,10(1):1373
[22] MILLER T W,HENNESSY B T,González-Angulo A M,et al. Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer[J]. J Clin Invest,2010,120(7):2406
[23] ANDR?魪 F,CIRUELOS E,RUBOVSZKY G,et al. Alpelisib for PIK3CA-mutated,hormone receptor-positive advanced breast cancer[J]. N Engl J Med,2019,380(20):1929
[24] COSTA C,WANG Y,LY A,et al. PTEN loss mediates clinical cross-resistance to CDK4/6 and PI3Kα inhibitors in breast cancer[J]. Cancer Discov,2020,10(1):72
[25] 黄元夕. 2020年美国临床肿瘤学会年会乳腺癌内分泌治疗重要内容解读[J]. 医学研究杂志,2020,49(10):7
[26] JURIC D,ISMAIL-KHAN R,CAMPONE M,et al. Abstract P3-14-01:Phase Ib/II study of ribociclib and alpelisib and letrozole in ER+,HER2-breast cancer:safety,preliminary efficacy and molecular analysis[J]. Cancer Res,2016,76(4 Suppl):DOI:10.1158/1538-7445.SABCS15-P3-14-01
[27] JONES R H,CASBARD A,CARUCCI M,et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic,oestrogen receptor-positive breast cancer (FAKTION):a multicentre,randomised,controlled,phase 2 trial[J]. Lancet Oncol,2020,21(3):345
[28] PATEL H K,TAO N,LEE K M,et al. Elacestrant(RAD1901) exhibits anti-tumor activity in multiple ER+ breast cancer models resistant to CDK4/6 inhibitors[J]. Breast Cancer Res,2019,21(1):146
[29] DENG J,WANG E S,JENKINS R W,et al. CDK4/6 inhibition augments antitumor immunity by enhancing T-cell activation[J]. Cancer Discov,2018,8(2):216 [1] KIM E S,SCOTT L J. Palbociclib:a review in HR-positive,HER2-negative, advanced or metastatic breast cancer[J]. Target Oncol,2017,12(3):373
[2] FINN R S,MARTIN M,RUGO H S,et al. Palbociclib and Letrozole in advanced breast cancer[J]. N Engl J Med,2016,375(20):1925
[3] CRISTOFANILLI M,TURNER N C,Bondarenko I,et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive,HER2-negative metastatic breast cancer that progressed on previous endocrine therapy(PALOMA-3):final analysis of the multicentre,double-blind,phase 3 randomised controlled trial[J]. Lancet Oncol,2016,17(4):425
[4] SPRING L M,WANDER S A,ANDRE F,et al. Cyclin-dependent kinase 4 and 6 inhibitors for hormone receptor-positive breast cancer:past,present,and future[J]. Lancet,2020,395(10226):817
[5] GELBERT L M,CAI S,LIN X,et al. Preclinical characterization of the CDK4/6 inhibitor LY2835219:in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine[J]. Invest New Drugs,2014,32(5):825
[6] CALDON C E,SERGIO C M,SCH?譈TTE J,et al. Estrogen regulation of cyclin E2 requires cyclin D1 but not c-Myc[J]. Mol Cell Biol,2009, 29(17):4623
[7] PANDEY K,AN H J,KIM S K,et al. Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer:a review[J]. Int J Cancer,2019,145(5):1179
[8] BUTT A J,MCNEIL C M,MUSGROVE E A,et al. Downstream targets of growth factor and oestrogen signalling and endocrine resistance:the potential roles of c-Myc, cyclin D1 and cyclin E[J]. Endocr Relat Cancer,2005,12(1 Suppl):S47
[9] VIJAYARAGHAVAN S,DOOSTAN I,CAREY JPW,et al. Abstract 2060:Characterizing acquired resistance to palbociclib in breast cancer[J]. Cancer Res,2017,77(13 Suppl):DIO:10.1158/1538-7445.AM2017-2060
[10] MAO P,KUSIEL J,COHEN O, et al. Abstract PD4-01:The role of FGF/FGFR axis in resistance to SERDs and CDK4/6 inhibitors in ER+ breast cancer[J]. Cancer Res,2018,78(4 Suppl):DOI:10.1158/1538-7445.SABCS17-PD4-01
[11] HERRERA-ABREU M T,PALAFOX M,ASGHAR U,et al. Early adaptation and acquired resistance to CDK4/6 inhibition in estrogen receptor-positive breast cancer[J]. Cancer Res,2016,76(8):2301
[12] MICHALOGLOU C,CRAFTER C,SIERSBAEK R,et al. Combined inhibition of mTOR and CDK4/6 is required for optimal blockade of E2F function and long-term growth inhibition in estrogen receptor-positive breast cancer[J]. Mol Cancer Ther,2018,17(5):908
[13] JANSEN V M,BHOLA N E,BAUER J A,et al. Kinome-wide RNA interference screen reveals a role for PDK1 in acquired resistance to CDK4/6 inhibition in ER-positive breast cancer[J]. Cancer Res,2017,77(9):2488
[14] MERENBAKH-LAMIN K,BEN-BARUCH N,YEHESKEL A,et al. D538G mutation in estrogen receptor-α:a novel mechanism for acquired endocrine resistance in breast cancer[J]. Cancer Res,2013, 73(23):6856
[15] BARDIA A,HURVITZ S. Targeted therapy for premenopausal women with HR(+),HER2(-)advanced breast cancer:focus on special considerations and latest advances[J]. Clin Cancer Res,2018,24(21):5206
[16] GYANCHANDANI R,KOTA K J,JONNALAGADDA A R,et al. Detection of ESR1 mutations in circulating cell-free DNA from patients with metastatic breast cancer treated with palbociclib and letrozole[J]. Oncotarget,2017,8(40):66901
[17] SCHAER D A,BECKMANN R P,DEMPSEY J A,et al. The CDK4/6 inhibitor abemaciclib induces a T cell inflamed tumor microenvironment and enhances the efficacy of PD-L1 checkpoint blockade[J]. Cell Rep,2018,22(11):2978
[18] O′LEARY B,CUTTS R J,LIU Y,et al. The genetic landscape and clonal evolution of breast cancer resistance to Palbociclib plus Fulvestrant in the PALOMA-3 trial[J]. Cancer Discov,2018,8(11):1390
[19] HAFNER M,MILLS C E,SUBRAMANIAN K,et al. Multiomics profiling establishes the polypharmacology of FDA-approved CDK4/6 inhibitors and the potential for differential clinical activity[J]. Cell Chem Biol,2019,26(8):1067
[20] WANDER S A,ZANGARDI M,NIEMIERKO A,et al. A multicenter analysis of abemaciclib after progression on palbociclib in patients(pts) with hormone receptor-positive(HR+)/HER2- metastatic breast cancer (MBC)[J]. J Clin Oncol,2019,37(15 suppl):1057
[21] FORMISANO L,LU Y,SERVETTO A,et al. Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer[J]. Nat Commun,2019,10(1):1373
[22] MILLER T W,HENNESSY B T,González-Angulo A M,et al. Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer[J]. J Clin Invest,2010,120(7):2406
[23] ANDR?魪 F,CIRUELOS E,RUBOVSZKY G,et al. Alpelisib for PIK3CA-mutated,hormone receptor-positive advanced breast cancer[J]. N Engl J Med,2019,380(20):1929
[24] COSTA C,WANG Y,LY A,et al. PTEN loss mediates clinical cross-resistance to CDK4/6 and PI3Kα inhibitors in breast cancer[J]. Cancer Discov,2020,10(1):72
[25] 黄元夕. 2020年美国临床肿瘤学会年会乳腺癌内分泌治疗重要内容解读[J]. 医学研究杂志,2020,49(10):7
[26] JURIC D,ISMAIL-KHAN R,CAMPONE M,et al. Abstract P3-14-01:Phase Ib/II study of ribociclib and alpelisib and letrozole in ER+,HER2-breast cancer:safety,preliminary efficacy and molecular analysis[J]. Cancer Res,2016,76(4 Suppl):DOI:10.1158/1538-7445.SABCS15-P3-14-01
[27] JONES R H,CASBARD A,CARUCCI M,et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic,oestrogen receptor-positive breast cancer (FAKTION):a multicentre,randomised,controlled,phase 2 trial[J]. Lancet Oncol,2020,21(3):345
[28] PATEL H K,TAO N,LEE K M,et al. Elacestrant(RAD1901) exhibits anti-tumor activity in multiple ER+ breast cancer models resistant to CDK4/6 inhibitors[J]. Breast Cancer Res,2019,21(1):146
[29] DENG J,WANG E S,JENKINS R W,et al. CDK4/6 inhibition augments antitumor immunity by enhancing T-cell activation[J]. Cancer Discov,2018,8(2):216 [1] KIM E S,SCOTT L J. Palbociclib:a review in HR-positive,HER2-negative, advanced or metastatic breast cancer[J]. Target Oncol,2017,12(3):373
[2] FINN R S,MARTIN M,RUGO H S,et al. Palbociclib and Letrozole in advanced breast cancer[J]. N Engl J Med,2016,375(20):1925
[3] CRISTOFANILLI M,TURNER N C,Bondarenko I,et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive,HER2-negative metastatic breast cancer that progressed on previous endocrine therapy(PALOMA-3):final analysis of the multicentre,double-blind,phase 3 randomised controlled trial[J]. Lancet Oncol,2016,17(4):425
[4] SPRING L M,WANDER S A,ANDRE F,et al. Cyclin-dependent kinase 4 and 6 inhibitors for hormone receptor-positive breast cancer:past,present,and future[J]. Lancet,2020,395(10226):817
[5] GELBERT L M,CAI S,LIN X,et al. Preclinical characterization of the CDK4/6 inhibitor LY2835219:in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine[J]. Invest New Drugs,2014,32(5):825
[6] CALDON C E,SERGIO C M,SCH?譈TTE J,et al. Estrogen regulation of cyclin E2 requires cyclin D1 but not c-Myc[J]. Mol Cell Biol,2009, 29(17):4623
[7] PANDEY K,AN H J,KIM S K,et al. Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer:a review[J]. Int J Cancer,2019,145(5):1179
[8] BUTT A J,MCNEIL C M,MUSGROVE E A,et al. Downstream targets of growth factor and oestrogen signalling and endocrine resistance:the potential roles of c-Myc, cyclin D1 and cyclin E[J]. Endocr Relat Cancer,2005,12(1 Suppl):S47
[9] VIJAYARAGHAVAN S,DOOSTAN I,CAREY JPW,et al. Abstract 2060:Characterizing acquired resistance to palbociclib in breast cancer[J]. Cancer Res,2017,77(13 Suppl):DIO:10.1158/1538-7445.AM2017-2060
[10] MAO P,KUSIEL J,COHEN O, et al. Abstract PD4-01:The role of FGF/FGFR axis in resistance to SERDs and CDK4/6 inhibitors in ER+ breast cancer[J]. Cancer Res,2018,78(4 Suppl):DOI:10.1158/1538-7445.SABCS17-PD4-01
[11] HERRERA-ABREU M T,PALAFOX M,ASGHAR U,et al. Early adaptation and acquired resistance to CDK4/6 inhibition in estrogen receptor-positive breast cancer[J]. Cancer Res,2016,76(8):2301
[12] MICHALOGLOU C,CRAFTER C,SIERSBAEK R,et al. Combined inhibition of mTOR and CDK4/6 is required for optimal blockade of E2F function and long-term growth inhibition in estrogen receptor-positive breast cancer[J]. Mol Cancer Ther,2018,17(5):908
[13] JANSEN V M,BHOLA N E,BAUER J A,et al. Kinome-wide RNA interference screen reveals a role for PDK1 in acquired resistance to CDK4/6 inhibition in ER-positive breast cancer[J]. Cancer Res,2017,77(9):2488
[14] MERENBAKH-LAMIN K,BEN-BARUCH N,YEHESKEL A,et al. D538G mutation in estrogen receptor-α:a novel mechanism for acquired endocrine resistance in breast cancer[J]. Cancer Res,2013, 73(23):6856
[15] BARDIA A,HURVITZ S. Targeted therapy for premenopausal women with HR(+),HER2(-)advanced breast cancer:focus on special considerations and latest advances[J]. Clin Cancer Res,2018,24(21):5206
[16] GYANCHANDANI R,KOTA K J,JONNALAGADDA A R,et al. Detection of ESR1 mutations in circulating cell-free DNA from patients with metastatic breast cancer treated with palbociclib and letrozole[J]. Oncotarget,2017,8(40):66901
[17] SCHAER D A,BECKMANN R P,DEMPSEY J A,et al. The CDK4/6 inhibitor abemaciclib induces a T cell inflamed tumor microenvironment and enhances the efficacy of PD-L1 checkpoint blockade[J]. Cell Rep,2018,22(11):2978
[18] O′LEARY B,CUTTS R J,LIU Y,et al. The genetic landscape and clonal evolution of breast cancer resistance to Palbociclib plus Fulvestrant in the PALOMA-3 trial[J]. Cancer Discov,2018,8(11):1390
[19] HAFNER M,MILLS C E,SUBRAMANIAN K,et al. Multiomics profiling establishes the polypharmacology of FDA-approved CDK4/6 inhibitors and the potential for differential clinical activity[J]. Cell Chem Biol,2019,26(8):1067
[20] WANDER S A,ZANGARDI M,NIEMIERKO A,et al. A multicenter analysis of abemaciclib after progression on palbociclib in patients(pts) with hormone receptor-positive(HR+)/HER2- metastatic breast cancer (MBC)[J]. J Clin Oncol,2019,37(15 suppl):1057
[21] FORMISANO L,LU Y,SERVETTO A,et al. Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer[J]. Nat Commun,2019,10(1):1373
[22] MILLER T W,HENNESSY B T,González-Angulo A M,et al. Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer[J]. J Clin Invest,2010,120(7):2406
[23] ANDR?魪 F,CIRUELOS E,RUBOVSZKY G,et al. Alpelisib for PIK3CA-mutated,hormone receptor-positive advanced breast cancer[J]. N Engl J Med,2019,380(20):1929
[24] COSTA C,WANG Y,LY A,et al. PTEN loss mediates clinical cross-resistance to CDK4/6 and PI3Kα inhibitors in breast cancer[J]. Cancer Discov,2020,10(1):72
[25] 黄元夕. 2020年美国临床肿瘤学会年会乳腺癌内分泌治疗重要内容解读[J]. 医学研究杂志,2020,49(10):7
[26] JURIC D,ISMAIL-KHAN R,CAMPONE M,et al. Abstract P3-14-01:Phase Ib/II study of ribociclib and alpelisib and letrozole in ER+,HER2-breast cancer:safety,preliminary efficacy and molecular analysis[J]. Cancer Res,2016,76(4 Suppl):DOI:10.1158/1538-7445.SABCS15-P3-14-01
[27] JONES R H,CASBARD A,CARUCCI M,et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic,oestrogen receptor-positive breast cancer (FAKTION):a multicentre,randomised,controlled,phase 2 trial[J]. Lancet Oncol,2020,21(3):345
[28] PATEL H K,TAO N,LEE K M,et al. Elacestrant(RAD1901) exhibits anti-tumor activity in multiple ER+ breast cancer models resistant to CDK4/6 inhibitors[J]. Breast Cancer Res,2019,21(1):146
[29] DENG J,WANG E S,JENKINS R W,et al. CDK4/6 inhibition augments antitumor immunity by enhancing T-cell activation[J]. Cancer Discov,2018,8(2):216

相似文献/References:

[1]申晓敏,王春妍,程晓静.FibroTest与肝纤维化4项指标评价慢性乙型肝炎纤维化的研究[J].天津医科大学学报,2015,21(06):507.
 SHEN Xiao-min,WANG Chun-yan,CHENG Xiao-jing.Diagnostic value of FibroTest combined with four serum liver fibrosis biomarkers for liver fibrosis in patients with chronic hepatitis B[J].Journal of Tianjin Medical University,2015,21(05):507.
[2]程婷婷,王凤梅,朱争艳,等.HBV慢性感染者肝脏组织中CD4+T、CD8+T和FoxP3+Tregs细胞的表达水平[J].天津医科大学学报,2016,22(02):129.
 CHENG Ting-ting,WANG Feng-mei,ZHU Zheng-yan,et al.Level of CD4+T、CD8+T and FoxP3+Tregs in the liver tissues of patients with chronic HBV infection[J].Journal of Tianjin Medical University,2016,22(05):129.
[3]杨 柳,王绕绕,尹明丽,等.自体特异性免疫效应淋巴细胞抑制转HBV基因小鼠HBV复制的研究[J].天津医科大学学报,2017,23(01):11.
 YANG Liu,WANG Rao-rao,YIN Ming-li,et al.Study on effect of autologous specific immune effective cells on inhibiting HBV replication in HBV transgenic mice[J].Journal of Tianjin Medical University,2017,23(05):11.
[4]胡善雷,李广明,任 娜,等.GP73在HBV相关性肝病中的水平及意义[J].天津医科大学学报,2019,25(06):615.
 HU Shan-lei,LI Guang-ming,REN Na,et al.The level and significance of GP73 in HBV related liver diseases[J].Journal of Tianjin Medical University,2019,25(05):615.
[5]谢永丽,汤华.YTHDF1对HBV蛋白表达和HBsAg和HBeAg抗原分泌的作用[J].天津医科大学学报,2021,27(05):461.
 XIE Yong-li,TANG Hua.Role of YTHDF1 on HBV protein expression and secretion of HBsAg and HBeAg antigens[J].Journal of Tianjin Medical University,2021,27(05):461.

备注/Memo

备注/Memo:
作者简介 张荣芳(1982-),女,主管技师,硕士,研究方向:病原生物学;通信作者:钱磊,E-mail:112690653@qq.com。
更新日期/Last Update: 2021-09-01