活血化瘀疗法干预肿瘤微环境与血管新生的研究进展
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摘要
近年来随着对肿瘤微环境研究的不断深入,人类对恶性肿瘤有了更进一步的认识。在临床中恶性肿瘤患者常可见到血瘀症候,并且活血化瘀法是中医治疗恶性肿瘤行之有效的方法,肿瘤微环境中血管生成理论又与中医学中的"血瘀证"、"活血化瘀法"有着诸多联系,本文就对这方面的研究进展作一综述。
In recent years,with the study of tumor microenvironment,people's understanding of malignant tumors goes deeper. The blood stasis syndrome is often seen in the patients with malignant tumor,and the method of activiting blood circulation and removing blood stasis are the effective methods for the treatment of malignant tumor. The theory of angiogenesis in the tumor microenvironment has many connections with the "blood stasis syndrome" and "blood circulation to remove blood stasis" in traditional Chinese medicine. This article reviews the progress in this field.
In recent years,with the study of tumor microenvironment,people's understanding of malignant tumors goes deeper. The blood stasis syndrome is often seen in the patients with malignant tumor,and the method of activiting blood circulation and removing blood stasis are the effective methods for the treatment of malignant tumor. The theory of angiogenesis in the tumor microenvironment has many connections with the "blood stasis syndrome" and "blood circulation to remove blood stasis" in traditional Chinese medicine. This article reviews the progress in this field.
引文
[1] 吴菲,林国桢,张晋昕.我国恶性肿瘤发病现状及趋势[J].中国肿瘤,2012,21(2):81～85
[2] Veena V S,George P S,Jayasree K,et al.Lung cancer is one of the leading cause of cancer related deaths for people of both sexes worldwide and sputum cytology has been accepted as one of the best non-invasive method for lung cancer diagnosis,but this method is not accepted as a screening techn[J].Proc.int.j.sci.res.publ,2013,2(12):1～6
[3] Amin P M,Ahmadreza B,Alireza A,et al.Iranian regional cancer incidence is misclassified in neighborhood’s provinces:[J].Gastroenterol Hepatol Bed Bench,2016,9(2):75～77
[4] Mo Z B,Huang Y Z,Zhou Y L.Analysis of death of malignant tumor in Jiangmen urban district from 2006 to 2008.[J].Journal of Tropical Medicine,2010
[5] 陈万青,孙可欣,郑荣寿,等.2014年中国分地区恶性肿瘤发病和死亡分析[J].中国肿瘤,2018,27(01):1～14
[6] Cecchi M,Vaiani M,Ceroti M,et al.A retrospective observational analysis to evaluate the off-label use of bevacizumab alone or with irinotecan in recurrent glioblastoma[J].International Journal of Clinical Pharmacy,2013,35(3):483～7
[7] Dorff T B,Longmate J A,Pal S K,et al.Bevacizumab alone or in combination with TRC105 for patients with refractory metastatic renal cell cancer.[J].Cancer,2017,123(23)
[8] Shu Z,Mao X,Wang H,et al.Efficacy and safety of bevacizumab plus erlotinib versus bevacizumab or erlotinib alone in the treatment of non-small-cell lung cancer: a systematic review and meta-analysis[J].Bmj Open,2016,6(6):e011714
[9] Schlumberger M,Tahara M,Wirth L J,et al.Lenvatinib versus placebo in radioiodine-refractory thyroid cancer[J].New England Journal of Medicine,2015,372(7):621～30
[10] Yamamoto Y,Matsui J,Matsushima T,et al.Lenvatinib,an angiogenesis inhibitor targeting VEGFR/FGFR,shows broad antitumor activity in human tumor xenograft models associated with microvessel density and pericyte coverage.[J].Vascular Cell,2014,6(1):18
[11] Stjepanovic N,Capdevila J.Multikinase inhibitors in the treatment of thyroid cancer: specific role of lenvatinib[J].Biologics Targets & Therapy,2014,8(8):129～39
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[13] 杜钢军,时小燕.治疗癌症的新途径:靶向肿瘤微环境[J].国际药学研究杂志,2011,38(05):336～340
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[30] Porta C,Kumar B S,Larghi P,et al.Tumor Promotion by Tumor-Associated Macrophages[J].Oxygen Transport to Tissue XXXIII,2007,604(604):67～86
[31] Torisu H,Ono M,Kiryu H,et al.Macrophage infiltration correlates with tumor stage and angiogenesis in human malignant melanoma: possible involvement of TNF alpha and IL-1alpha[J].Int J Cancer,2000,85(2),182～188
[32] 李琳.肥大细胞与食管鳞状上皮增生、癌变及血管生成关系的研究[D].汕头大学,2012
[33] 刘天聪,王欢,吕昌龙.肿瘤相关中性粒细胞对肿瘤生长的双重作用[J].微生物学免疫学进展,2013,41(2):61～64
[34] 齐元富,钱伯文,陈伟.41例胃癌患者血瘀证研究及活血化瘀治疗作用的观察[J].陕西中医,1996(1):12～12
[35] 卢尔夫,李彬先.恶性肿瘤患者血液流变指标检测分析[J].中国血液流变学杂志,1999,9(4):256～257
[36] 王安璐.陈可冀院士血瘀证辨治方法的临床评价研究[D].北京中医药大学,2016
[37] Delcombel R,Janssen L,Vassy R,et al.New prospects in the roles of the C-terminal domains of VEGF-A and their cooperation for ligand binding,cellular signaling and vessels formation.[J].Angiogenesis,2013,16(2):353～371
[38] Bry M,Kivel R,Lepp nen V M,et al.Vascular endothelial growth factor-B in physiology and disease.[J].Physiological Reviews,2014,94(3):779～794
[39] Xia H,Shen J,Chen S,et al.Overexpression of VEGF-C correlates with a poor prognosis in esophageal cancer patients[J].Cancer Biomarkers,2016,17(2):165
[40] Krishnan J,Kirkin V,Steffen A,et al.Differential in Vivo and in Vitro Expression of Vascular Endothelial Growth Factor (VEGF)-C and VEGF-D in Tumors and Its Relationship to Lymphatic Metastasis in Immunocompetent Rats[J].Cancer Research,2003,63(3):713～22
[41] Iyer S,Leonidas D D,Swaminathan G J,et al.The crystal structure of human placenta growth factor-1 (PlGF-1),an angiogenic protein,at 2.0 A resolution[J].Journal of Biological Chemistry,2001,276(15):12153～61
[42] Luo H L.The progress in research on vascular endothelial growth factor[J].Journal of Gansu Agricultural University,2001
[43] Siveen K S,Prabhu K,Krishnankutty R,et al.Vascular Endothelial Growth Factor (VEGF) Signaling in Tumour Vascularization: Potential and Challenges[J].Current Vascular Pharmacology,2017,15(4):-
[44] 张前,牛欣,闫妍,等.羟基红花黄色素A抑制新生血管形成的机制研究[J].北京中医药大学学报,2004(03):25～29
[45] 杨振江,赵霞,邹映珍,等.瘀毒清抗B16黑色素瘤血管生成的研究[J].医学研究通讯,2004(02):14～17
[46] 郑振茹,王亚珍,吕品田,等.赤芍总苷对人黑色素瘤细胞A375 血管生成因子VEGF 和Ang-2 的影响[J].医学动物防制,2011,27(12) : 1095～1097
[47] Oppenheim J,Fujiwara H.The role of cyt okines in cancer.Cyt okine Grow th Fact or Rew,1996;7(3):279 ～ 88
[48] Suyama K,Shapiro I,Guttman M,et al.A signaling pathway leading to metastasis is controlled by N-cadherin and the FGF receptor[J].Cancer Cell,2002,2(4):301～314
[49] 张培红,刘京芳,马学伟,等.活血化瘀方对乳腺增生病患者血管内皮生长因子及碱性成纤维细胞生长因子的影响[J].河北中医,2011,33(12):1786～1787
[50] Rey S,Semenza G L.Hypoxia-inducible factor-1-dependent mechanisms of vascularization and vascular remodelling.[J].Cardiovascular Research,2010,86(2):236
[51] 任为民.川芎嗪对肺癌细胞在乏氧微环境下粘附、侵袭和转移能力改变影响的研究[D].中国中医科学院中国中医研究院,2011
[52] 王兆朋,张维东,武利存,等.蝎毒多肽提取物抑制肝癌H22细胞化疗期间再增殖实验研究[J].中国中药杂志,2010,35(01):108～113
[53] 冯俭,谢萍,秦银花,等.丹参联合5-Fu对小鼠Lewis肺癌中HIF-1α、VEGF和MVD表达的影响[J].华西药学杂志,2014,29(01):42～44
[54] 郑昱婧,宋淑亮,梁浩,等.中药多糖在抗肿瘤免疫中的研究进展[J].生命的化学,2016,36(05):601～606
[55] 杜钢军,林海红,许启泰,等.阳和汤对乌拉坦诱导小鼠肺癌的动态影响[J].时珍国医国药,2008,19(5) :1151～1153
[56] 沈洪,刘增巍,朱萱萱,等.莪术对SGC7901 胃癌细胞COX-1、COX-2、VEGF 和PGE2表达的影响[J].世界华人消化杂志,2006,14(16) : 1548～1553
[57] 张莹,朱萱萱,王海丹.三棱莪术组方对人胃癌细胞SGC-7901移植瘤裸鼠血清COX-2、VEGF和bFGF含量的影响[J].中华中医药学刊,2016,34(05):1196～1199
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[2] Veena V S,George P S,Jayasree K,et al.Lung cancer is one of the leading cause of cancer related deaths for people of both sexes worldwide and sputum cytology has been accepted as one of the best non-invasive method for lung cancer diagnosis,but this method is not accepted as a screening techn[J].Proc.int.j.sci.res.publ,2013,2(12):1～6
[3] Amin P M,Ahmadreza B,Alireza A,et al.Iranian regional cancer incidence is misclassified in neighborhood’s provinces:[J].Gastroenterol Hepatol Bed Bench,2016,9(2):75～77
[4] Mo Z B,Huang Y Z,Zhou Y L.Analysis of death of malignant tumor in Jiangmen urban district from 2006 to 2008.[J].Journal of Tropical Medicine,2010
[5] 陈万青,孙可欣,郑荣寿,等.2014年中国分地区恶性肿瘤发病和死亡分析[J].中国肿瘤,2018,27(01):1～14
[6] Cecchi M,Vaiani M,Ceroti M,et al.A retrospective observational analysis to evaluate the off-label use of bevacizumab alone or with irinotecan in recurrent glioblastoma[J].International Journal of Clinical Pharmacy,2013,35(3):483～7
[7] Dorff T B,Longmate J A,Pal S K,et al.Bevacizumab alone or in combination with TRC105 for patients with refractory metastatic renal cell cancer.[J].Cancer,2017,123(23)
[8] Shu Z,Mao X,Wang H,et al.Efficacy and safety of bevacizumab plus erlotinib versus bevacizumab or erlotinib alone in the treatment of non-small-cell lung cancer: a systematic review and meta-analysis[J].Bmj Open,2016,6(6):e011714
[9] Schlumberger M,Tahara M,Wirth L J,et al.Lenvatinib versus placebo in radioiodine-refractory thyroid cancer[J].New England Journal of Medicine,2015,372(7):621～30
[10] Yamamoto Y,Matsui J,Matsushima T,et al.Lenvatinib,an angiogenesis inhibitor targeting VEGFR/FGFR,shows broad antitumor activity in human tumor xenograft models associated with microvessel density and pericyte coverage.[J].Vascular Cell,2014,6(1):18
[11] Stjepanovic N,Capdevila J.Multikinase inhibitors in the treatment of thyroid cancer: specific role of lenvatinib[J].Biologics Targets & Therapy,2014,8(8):129～39
[12] Allen M,Louise Jones J.Jekyll and hyde: the role of the microenvironment on the progression of cancer[J].J Pathol,2011,223(2):162～176
[13] 杜钢军,时小燕.治疗癌症的新途径:靶向肿瘤微环境[J].国际药学研究杂志,2011,38(05):336～340
[14] Fidler I J.The pathogenesis of cancer metastasis:the seed and soil hypothesis revisited.Nat Rev Cancer,2003,3(6):453～458
[15] Noonan E M M.The tumor microenvironment: biology of a complex cellular and tissue society.[J].The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR),[and] Section of the Society of.,2010,54(3):244
[15] Bahrami A,Khazaei M,Hassanian S M,et al.Targeting the tumor microenvironment as a potential therapeutic approach in colorectal cancer: Rational and progress[J].Journal of Cellular Physiology,2018,233(4)
[16] Ribatti D.Tumor Microenvironment[J].2016
[17] Mlecnik B,Bindea G,Kirilovsky A,et al.The tumor microenvironment and Immunoscore are critical determinants of dissemination to distant metastasis.[J].Science Translational Medicine,2016,8(327):327ra26
[18] Munn D H,Mellor A L.IDO in the Tumor Microenvironment: Inflammation,Counter-regulation and Tolerance[J].Trends in Immunology,2016,37(3):193
[19] Bussard K M,Mutkus L,Stumpf K,et al.Tumor-associated stromal cells as key contributors to the tumor microenvironment[J].Breast Cancer Research,2016,18(1):84
[20] Folkman J.Tumor Angiogenesis: from Bench to Bedside[J].2008
[21] Hanahan D,Folkman J.Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis.[J].Cell,1996,86(3):353～64
[22] Bergers G,Benjamin LE.Tumorigenesis and the angiogenic switch[J]Nat Rev Cancer,2003,3(6):401～410
[23] Risau W.Mechanisms of angiogenesis.[J].Nature,1997,386(6626):671～4
[24] 许成云,倪庆桂,张陆勇.肿瘤微环境与肿瘤血管新生[J].中国医疗前沿,2009,04(5):21～23
[25] Thiery J P,Sleeman J P.Complex networks orchestrate epithelial-mesenchymal transitions.[J].Nat Rev Mol Cell Biol,2006,7(2):131～142
[26] Fukumura D,Xu L,Chen Y,et al.Hypoxia and acidosis independentlyup-regulate vascular endothelial growth factor transcription in brain tumors in vivo.Cancer Res 2001;61:6020–6024
[27] Allen M,Jones J L.Jekyll and Hyde: the role of the microenvironment on the progression of cancer[J].Journal of Pathology,2011,223(2):162～176
[28] Karin M,Greten F R.Karin M,Greten FRNF-B: linking inflammation and immunity to cancer development and progression.Nat Rev Immunol 10: 749～759[J].Nature Reviews Immunology,2005,5(10):749～759
[29] Laoui D,Overmeire E V,Baetselier P D,et al.Functional Relationship between Tumor-Associated Macrophages and Macrophage Colony-Stimulating Factor as Contributors to Cancer Progression[J].Frontiers in Immunology,2014,5(5):489
[30] Porta C,Kumar B S,Larghi P,et al.Tumor Promotion by Tumor-Associated Macrophages[J].Oxygen Transport to Tissue XXXIII,2007,604(604):67～86
[31] Torisu H,Ono M,Kiryu H,et al.Macrophage infiltration correlates with tumor stage and angiogenesis in human malignant melanoma: possible involvement of TNF alpha and IL-1alpha[J].Int J Cancer,2000,85(2),182～188
[32] 李琳.肥大细胞与食管鳞状上皮增生、癌变及血管生成关系的研究[D].汕头大学,2012
[33] 刘天聪,王欢,吕昌龙.肿瘤相关中性粒细胞对肿瘤生长的双重作用[J].微生物学免疫学进展,2013,41(2):61～64
[34] 齐元富,钱伯文,陈伟.41例胃癌患者血瘀证研究及活血化瘀治疗作用的观察[J].陕西中医,1996(1):12～12
[35] 卢尔夫,李彬先.恶性肿瘤患者血液流变指标检测分析[J].中国血液流变学杂志,1999,9(4):256～257
[36] 王安璐.陈可冀院士血瘀证辨治方法的临床评价研究[D].北京中医药大学,2016
[37] Delcombel R,Janssen L,Vassy R,et al.New prospects in the roles of the C-terminal domains of VEGF-A and their cooperation for ligand binding,cellular signaling and vessels formation.[J].Angiogenesis,2013,16(2):353～371
[38] Bry M,Kivel R,Lepp nen V M,et al.Vascular endothelial growth factor-B in physiology and disease.[J].Physiological Reviews,2014,94(3):779～794
[39] Xia H,Shen J,Chen S,et al.Overexpression of VEGF-C correlates with a poor prognosis in esophageal cancer patients[J].Cancer Biomarkers,2016,17(2):165
[40] Krishnan J,Kirkin V,Steffen A,et al.Differential in Vivo and in Vitro Expression of Vascular Endothelial Growth Factor (VEGF)-C and VEGF-D in Tumors and Its Relationship to Lymphatic Metastasis in Immunocompetent Rats[J].Cancer Research,2003,63(3):713～22
[41] Iyer S,Leonidas D D,Swaminathan G J,et al.The crystal structure of human placenta growth factor-1 (PlGF-1),an angiogenic protein,at 2.0 A resolution[J].Journal of Biological Chemistry,2001,276(15):12153～61
[42] Luo H L.The progress in research on vascular endothelial growth factor[J].Journal of Gansu Agricultural University,2001
[43] Siveen K S,Prabhu K,Krishnankutty R,et al.Vascular Endothelial Growth Factor (VEGF) Signaling in Tumour Vascularization: Potential and Challenges[J].Current Vascular Pharmacology,2017,15(4):-
[44] 张前,牛欣,闫妍,等.羟基红花黄色素A抑制新生血管形成的机制研究[J].北京中医药大学学报,2004(03):25～29
[45] 杨振江,赵霞,邹映珍,等.瘀毒清抗B16黑色素瘤血管生成的研究[J].医学研究通讯,2004(02):14～17
[46] 郑振茹,王亚珍,吕品田,等.赤芍总苷对人黑色素瘤细胞A375 血管生成因子VEGF 和Ang-2 的影响[J].医学动物防制,2011,27(12) : 1095～1097
[47] Oppenheim J,Fujiwara H.The role of cyt okines in cancer.Cyt okine Grow th Fact or Rew,1996;7(3):279 ～ 88
[48] Suyama K,Shapiro I,Guttman M,et al.A signaling pathway leading to metastasis is controlled by N-cadherin and the FGF receptor[J].Cancer Cell,2002,2(4):301～314
[49] 张培红,刘京芳,马学伟,等.活血化瘀方对乳腺增生病患者血管内皮生长因子及碱性成纤维细胞生长因子的影响[J].河北中医,2011,33(12):1786～1787
[50] Rey S,Semenza G L.Hypoxia-inducible factor-1-dependent mechanisms of vascularization and vascular remodelling.[J].Cardiovascular Research,2010,86(2):236
[51] 任为民.川芎嗪对肺癌细胞在乏氧微环境下粘附、侵袭和转移能力改变影响的研究[D].中国中医科学院中国中医研究院,2011
[52] 王兆朋,张维东,武利存,等.蝎毒多肽提取物抑制肝癌H22细胞化疗期间再增殖实验研究[J].中国中药杂志,2010,35(01):108～113
[53] 冯俭,谢萍,秦银花,等.丹参联合5-Fu对小鼠Lewis肺癌中HIF-1α、VEGF和MVD表达的影响[J].华西药学杂志,2014,29(01):42～44
[54] 郑昱婧,宋淑亮,梁浩,等.中药多糖在抗肿瘤免疫中的研究进展[J].生命的化学,2016,36(05):601～606
[55] 杜钢军,林海红,许启泰,等.阳和汤对乌拉坦诱导小鼠肺癌的动态影响[J].时珍国医国药,2008,19(5) :1151～1153
[56] 沈洪,刘增巍,朱萱萱,等.莪术对SGC7901 胃癌细胞COX-1、COX-2、VEGF 和PGE2表达的影响[J].世界华人消化杂志,2006,14(16) : 1548～1553
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