Changes of activated circulating endothelial cells and survivin in patients with non-small cell lung cancer after antiangiogenesis therapy

( views:77, downloads:0 )
Author:
WANG Jing(Tianjin Lung Cancer Center,Key Laboratory of Cancer Prevention and Therapy,Department of Thoracic Oncology Cancer Hospital of Tianjin Medical University,Tianjin 300060,China)
HUANG Chun(Tianjin Lung Cancer Center,Key Laboratory of Cancer Prevention and Therapy,Department of Thoracic Oncology Cancer Hospital of Tianjin Medical University,Tianjin 300060,China)
WEI Xi-yin(Central Laboratory Cancer Hospital of Tianjin Medical University,Tianjin 300060,China)
QI Da-liang(Department of Thoracic Surgery Cancer Hospital of Tianjin Medical University,Tianjin 300060,China)
GONG Li-qun(Department of Thoracic Surgery Cancer Hospital of Tianjin Medical University,Tianjin 300060,China)
MU Hai-yu(Department of Oncology,Medical College Hospital of Chinese People's Armed Police Force,Tianjin 300162,China)
YAO Qiang(Department of Oncology,People's Hospital of Tianjin,Tianjin 300121)
LI Kai(Tianjin Lung Cancer Center,Key Laboratory of Cancer Prevention and Therapy,Department of Thoracic Oncology Cancer Hospital of Tianjin Medical University,Tianjin 300060,China)
Journal Title:
CHINESE MEDICAL JOURNAL
Issue:
Volume 121, Issue 22, 2008
DOI:
Key Word:
Endostar;activated circulating endothelial cells;survivin;non-small cell lung cancer

Abstract: Background Although antiangiogenesis therapy plays an important role in anti-neoplastic treatment with its recognized efficacy and slight adverse effect,there is no prospective clinical trial to define ideal markers for predicting efficacy of antiangiogenic therapy.This study was undertaken to investigate the changes of activated circulating endothelial cells (aCECs) and survMn after anti-angiogenesis therapy and their significance in predicting the efficacy of the therapy.Methods Patients of non-small cell lung cancer (NSCLC) treated with chemotherapy with or without Endostar were observed.The amount of activated CECs was detected by flow cytometry,and the expression of survivin mRNA was determined by real-time polymerase chain reaction (PCR).Results After treatment,the amount of activated CECs decreased significantly in clinical benefit cases (P=-0.021 in chemotherapy alone,P=0.001 in chemotherapy plus Endostar),increased in disease progressive cases (P=-0.015 in chemotherapy alone,but P=0.293 in chemotherapy with Endotatar).After therapy,the expression of survivin mRNA decreased in clinical benefit cases (P=0.001) and increased in disease progressive cases (P=0.018).A positive correlation was found between activated CECs and survivin in the chemotherapy group pre- and post-therapy (P=0.001 and 0.021,respectively),but only in the chemotherapy with Endostar group pre-therapy (P=0.030) rather than post-therapy.A positive correlation was found between the decreased activated CECs after therapy and time to progression (TTP) (r=0.322,P=0.012);a negative correlation was found between the amount of survivin mRNA in serum post-therapy and TTP(r= -0.291,P=0.048).Conclusions Activated CECs and survMn may be ideal markers forecasting efficacy and prognosis of NSCLC.The former can reflect more sensitively antiangiogenic efficacy and the latter is more sensitive to shrinkage or swelling of tumors.Their combination can evaluate more accurately the efficacy of antiangiogenic therapy of NSCLC.

  • [1]Fürstenberger G,von Moos R,Lucas R,Thürlimann B,Senn HJ,Hamacher J,et al.Circulating endothelial cells and angiogenic serum factors during neoadjuvant chemotherapy of primary breast cancer.Br J Cancer 2006;94:524-531.
  • [2]Mancuso P,Burlini A,Pruneri G,Goldhirsch A,Martinelli G,Bertolini F.Resting and activated endothelial cells are increased in the peripheral blood of cancer patients.Blood 2001;97:3658 -3661.
  • [3]Gui C,Wang JA,He AN,Chen TL,Liu XB,Luo RH,et al.Expression of heregulin and ErbB receptors in mesenchymal stem cells.Chin Med J 2008;121:155-160.
  • [4]Xu TM,Xin Y,Cui MH,Jiang X,Gu LP.Inhibitory effect of ginsenoside Rg3 combined with cyclophosphamide on growth and angiogenesis of ovarian cancer.Chin Med J 2007;120:584-588.
  • [5]Zhang MZ,Qiao YH,Nesland JM,Suo ZH.Expression of seprase in effusions from patients with epithelial ovarian carcinoma.Chin Med J 2007;120:663-668.
  • [6]Wang JW,Sun Y,Liu YY,Yn QT,Zhang YP,Li K,et al.Results of randomized,multicenter,double-blind phase Ⅲ trial of re-endostatin (YH-16) in treatment of advanced non-small cell lung cancer patients.Chin J Lung Cancer (Chin) 2005;8:283-290.
  • [7]Huang C,Li K,Wei XY,Niu RF,Sun Y,Wang JW,et al.Circulating endothelial cells in the peripheral blood of advanced NSCLC patients.Chin J Oncol (Chin) 2006;28:780-783.
  • [8]Delorme B,Basire A,Gentile C,Sabatier F,Monsonis F,Desouches C,et al.Presence of endothelial progenitor cells,distinct from mature endothelial cells,within human CD146+ blood cells.Thromb Haemost 2005;94:1270-1279.
  • [9]Fürstenberger G,von Moos R,Senn HJ,Boneberg EM.Real-time PCR of CD146 mRNA in peripheral blood enables the relative quantification of circulating endothelial cells and is an indicator of angiogenesis.Br J Cancer 2005;93:793-798.
  • [10]Knstiansen G,Yu Y,Schluns K,Sers C,Dietel M,Petersen I.Expression of the cell adhesion molecule CD146/MCAM in non-small cell lung cancer.Anal Cell Pathol 2003;25:77-81.
  • [11]Allanore Y,Batteux F,Avouac J,Assous N,Weill B,Kahan A,et al.Levels of circulating endothelial progenitor cells in systemic sclerosis.Clin Exp Rheumatol 2007;25:60-66.
  • [12]Untergasser G,Koeck R,Wolf D,Rumpold H,Ott H,Debbage P,et al.CD34+/CD133-circulating endothelial precursor cells (CEP):characterization,senescence and in vivo application.Exp Gerontol 2006;41:600-608.
  • [13]Timmermans F,Van Hauwermeiren F,De Smedt M,Raedt R,Plasschaert F,De Buyzere ML,et al.Endothelial outgrowth cells are not derived from CD133+ cells or CD45+ hematopoietic precursors.Arterioscler Thromb Vasc Biol 2007;27:1572-1579.
  • [14]Bartmann C,Rohde E,Schallmoser K,Pürsmer P,Lanzer G,Linkesch W,et al.Two steps to functional mesenchymal stromal cells for clinical application.Transfusion 2007;47:1426-1435.
  • [15]Shetty P,Bharucha K,Tanavde V.Human umbilical cord blood serum can replace fetal bovine serum in the culture of mesenchymal stem cells.Cell Biol Int 2007;31:293-298.
  • [16]Yamazaki K.An ultrastructural and immunohistochemical study of elastofibroma:CD 34,MEF-2,prominin 2 (CD133),and factor XIIIa-positive proliferating fibroblastic strornal cells connected by Cx43-type gap junctions.Ultrastruct Pathol 2007;31:209-219.
  • [17]Fukuda S,Pelus LM.Survivin,a cancer target with an emerging role in normal adult tissues.Mol Cancer Ther 2006;5:1087-1098.
  • [18]Hoffmann AC,Warnecke-Eberz U,Luebke T,Prenzel K,Metzger R,Heitmann M,et al.Survivin mRNA in peripheral blood is frequently detected and significantly decreased following resection of gastrointestinal cancers.J Surg Oncol 2007;95:51-54.
  • [19]Wang G J,Sui XX,Simosa HF,Jain MK,Altieri DC,Conte MS.Regulation of vein graft hyperplasia by survivin,an inhibitor of apoptosis protein.Arterioscler Thromb Vasc Biol 2005;25:2081-2087.
  • [20]Coma S,Noe V,Lavarino C,Adán J,Rivas M,López-Matas M,et al.Use of siRNAs and antisense oligonucleotides against survivin RNA to inhibit steps leading to tumor angiogenesis.Oligonucleotides 2004;14:100-113.
  • [21]Sarela AI,Macadam RC,Farmery SM,Markham AF,Guillou PJ.Expression of the antiapoptosis gene,Survivin,predicts death from recurrent colorectal carcinoma.Gut 2000;46:645-650.
WanfangData CO.,Ltd All Rights Reserved
About WanfangData | Contact US
Healthcare Department, Fuxing Road NO.15, Haidian District Beijing, 100038 P.R.China
Tel:+86-010-58882616 Fax:+86-010-58882615 Email:yiyao@wanfangdata.com.cn