苏木提取物的免疫抑制及抗肿瘤作用机制研究
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摘要
肿瘤是机体在各种致瘤因素的作用下,局部组织的细胞在基因水平上失去对其生长的正常调控,导致克隆性异常增生或凋亡不足而形成的新生物,这种新生物往往形成局部肿块。肿瘤不管是良性还是恶性,也不管是上皮组织来源还是间叶组织来源,本质上都表现为细胞失去控制的异常增殖,这种异常生长的能力除了表现为肿瘤本身的持续生长之外,在恶性肿瘤还表现为对邻近正常组织的侵犯以及经血管、淋巴管和体腔转移到身体其它部位,而这往往是肿瘤致死的原因。
祖国传统医学关于肿瘤发生的病机,历代医家的论述主要包括正气内虚、血瘀痰凝、邪毒内攻等。根据肿瘤患者病理性肿块、疼痛、出血、舌质瘀紫或有瘀点瘀斑,以及晚期面色黧黑、肌肤甲错等临床表现,认为血瘀症与肿瘤关系密切。
近年来,随着分子生物学理论不断深入研究,中医药治疗肿瘤方面的研究进展取得了较为长足的进步,使我们对中药在抑制肿瘤生长,提高机体免疫功能,防止肿瘤转移的分子机制有了初步的认识。中医药对肿瘤的影响也从最初的免疫功能调节研究,发展到了今天的抗肿瘤血管生成研究,诱导细胞凋亡,抑制端粒酶活性等研究。苏木(Caesalpinia Sappan L,CAE)为豆科云实属植物的干燥心材。有行血祛瘀,消肿止痛之功效,中医临床常用于经痛、风湿痛、跌打瘀痛等症。临床上也用于肿瘤的治疗,现代药理学研究表明其具有抗肿瘤、免疫抑制等作用。但其具体的抗癌机制目前仍未知。为此我们用现代医学测试技术,测定苏木醇提取物免疫抑制与对抗肿瘤的作用机制。
本研究的第一部分主要观察苏木不同提取物对小鼠胸腺组织、外周T细胞增殖和产生INF-γ的影响。通过制备苏木不同提取物分别给予灌胃小鼠,取小鼠胸腺称重计算胸腺指数;采用MTT法测定小鼠脾T细胞的增殖能力;用双抗体夹心ELISA法测定T细胞培养上清中产生INF-γ的含量。结果发现苏木不同提取物不仅对胸腺重量具有明显的抑制作用,而且还对T细胞的增殖和产生INF-γ的能力具有明显的抑制作用。其中苏木醇提取物和正丁醇提取物对T细胞的抑制作用较强。
鉴于醇类提取物作用较强,在研究的第二部分主要观察苏木醇提物对人肺癌A549细胞的细胞毒作用和诱导凋亡作用。将苏木醇提物按不同浓度分别同人肺癌A549细胞共同培养,MTT法检测对细胞增殖作用的影响,光学显微镜、细胞膜磷脂酰丝氨酸外翻分析、细胞周期分析观察不同浓度苏木醇提物对人肺癌A549细胞的细胞毒和调亡作用。发现苏木醇提物对人肺癌A549细胞有抑制作用,并呈浓度依赖性;苏木醇提物在诱导细胞发生凋亡外还存在其它形式的细胞死亡方式并对细胞各期均有影响。
经过第二部分体外抗肿瘤实验后,进行体内抗瘤实验。第三部分研究主要观察苏木醇提物对H22腹水瘤细胞抑瘤作用,通过皮下接种H22腹水瘤细胞的方法建立荷瘤惺竽Ｐ?用苏木醇提物灌胃处理,观察各组荷瘤小鼠的肿瘤生长情况,采用缺口末端标记法测定肿瘤细胞凋亡指数,免疫组织化学方法测定凋亡蛋白Bcl-2、Bax的表达情况。发现苏木醇提物可抑制H22移植瘤生长,促进瘤体细胞凋亡,降低瘤体细胞Bcl-2/Bax比值;其机制与通过调控凋亡相关蛋白Bcl-2、Bax的表达诱导肿瘤细胞凋亡有关。
With the effects of various tumorigenic factors, cells of local tissues will lose control on their growth in the level of genes, which leads to clonal hyperplasia or insufficient apoptosis and results in a neoformation called tumor, often existing in the form of local mass. Whether the tumor is benign or malignant, or has its origins in epithelial tissue or mesenchymal tissue, it manifests abnormal proliferation of cells losing control. This abnormal growing ability can not only be seen from tumor's continuous growth but also from aggression to its adjacent normal tissues and transfer to other parts through blood vessels, lymphatic vessels and body cavity especially for malignant tumor, which is always the cause of death.
In traditional Chinese medicine, physicians in past dynasties regarded that the pathogenesis of tumor mainly contained insufficient healthy qi, blood stasis and phlegm stagnation and invasion of pathogenic toxins etc. They thought tumor is closely related with blood stasis syndrome based on the clinical manifestations of tumor patients such as pathologic tumor mass, pain, hemorrhage, purple tongue with stasis or ecchymosis or blood spots, swarthy complexion and scaly skin in the advanced stage.
In recent years, with constant study on molecular biology theory, the study of treating tumor with traditional Chinese medicine has made great progress, giving us a preliminary understanding of the molecule mechanism of inhibiting tumor growth, enhancing immunity and preventing the transfer of tumor with Chinese herbs. The study of traditional Chinese medicine's effects on tumor has developed from the preliminary study on immune function regulation to the current anti-tumor angiogenesis research and apoptosis induction and telomerase activity inhibition research.
Hematoxylon (Caesalpinia Sappan L, CAE) is the dry heartwood of Leguminosae Caesalpinia which has the effect of promoting blood flow to eliminate stasis and dissolving the swelling to kill the pain. Caesalpinia Sappan L is used to treat dysmenorrheal, rheumatic pain and traumatic injuries and pains etc in Chinese medicine. It can also be used to treat tumor, as the modern pharmacological research shows that it has anti-tumor and immunosuppressive functions, although its specific anti-tumor mechanism is still unknown. Therefore, we can use modern medical testing technology to study the anti-tumor and immunosuppressive mechanism of Hematoxylin alcohol extracts.
In the first part, the main purpose is to observe the effect of different extracts of Hematoxylon in mouse thymus, peripheral T cell proliferation and INF-γgeneration. Different extracts prepared from Caesalpinia Sappan L were lavaged to the mice in order to count thymus index by taking out their thymus, to calculate the proliferation capacity of spleen T cells by using MTT method, to measure the INF-γcontent generated by T cell culture supernatant by using double-antibody sandwich ELISA method. The results showed that different extracts of Hematoxylon not only had remarkable inhibition effect in thymus weight but also in T cell's proliferation and INF-γgeneration abilities. Hematoxylin alcohol and n-butanol extracts had stronger inhibiting effects on T cells.
Given the strong effects of alcohol extract, in the second part of the study, the main purpose is to observe Hematoxylin alcoholl extract's cytotoxicity and apoptosis inducing effects on A549 cell of lung caner. Hematoxylin alcoholl extracts with different concentration were co-cultured with lung cancer A549 cells in order to observe effects on cell proliferation by using MTT method, study the effects on cytotoxicity and apoptosis of lung cancer A549 cells using optical microscope, phosphatidylserine ecstrophy analysis and cell period analysis. The results showed that Hematoxylin alcohol extracts had inhibiting effects on human lung cancer A549 cells in a dose-dependent manner; besides the cell apoptosis induced by these extracts, there existed other forms of cell death and affected cells in every period.
Following the second part of anti-tumor experiment outside, here comes the internal one. The third part is mainly to observe the extract's anti-tumor effect on H22 ascites tumor cells. Tumor-bearing rat model was built by subcutaneous inoculation of H22 ascites tumor cells and lavaged with Hematoxylin alcohol extracts in order to observe the tumor growth conditionsmof tumor-bearing mice in each group, measure the tumor cell apoptotic index by using the nick end labeling method and apoptotic protein Bcl-2, Bax expression by using immunohistochemical technology. The results showed that Hematoxylin alcohol extract can inhibit the H22 transplantation tumor growth, facilitate tumor cell apoptosis, reduce Bcl-2/Bax ratio of tumor cells and the mechanism was related with the induction of tumor cell apoptosis by regulating the expression of apoptosis-related protein Bcl-2/Bax.
祖国传统医学关于肿瘤发生的病机,历代医家的论述主要包括正气内虚、血瘀痰凝、邪毒内攻等。根据肿瘤患者病理性肿块、疼痛、出血、舌质瘀紫或有瘀点瘀斑,以及晚期面色黧黑、肌肤甲错等临床表现,认为血瘀症与肿瘤关系密切。
近年来,随着分子生物学理论不断深入研究,中医药治疗肿瘤方面的研究进展取得了较为长足的进步,使我们对中药在抑制肿瘤生长,提高机体免疫功能,防止肿瘤转移的分子机制有了初步的认识。中医药对肿瘤的影响也从最初的免疫功能调节研究,发展到了今天的抗肿瘤血管生成研究,诱导细胞凋亡,抑制端粒酶活性等研究。苏木(Caesalpinia Sappan L,CAE)为豆科云实属植物的干燥心材。有行血祛瘀,消肿止痛之功效,中医临床常用于经痛、风湿痛、跌打瘀痛等症。临床上也用于肿瘤的治疗,现代药理学研究表明其具有抗肿瘤、免疫抑制等作用。但其具体的抗癌机制目前仍未知。为此我们用现代医学测试技术,测定苏木醇提取物免疫抑制与对抗肿瘤的作用机制。
本研究的第一部分主要观察苏木不同提取物对小鼠胸腺组织、外周T细胞增殖和产生INF-γ的影响。通过制备苏木不同提取物分别给予灌胃小鼠,取小鼠胸腺称重计算胸腺指数;采用MTT法测定小鼠脾T细胞的增殖能力;用双抗体夹心ELISA法测定T细胞培养上清中产生INF-γ的含量。结果发现苏木不同提取物不仅对胸腺重量具有明显的抑制作用,而且还对T细胞的增殖和产生INF-γ的能力具有明显的抑制作用。其中苏木醇提取物和正丁醇提取物对T细胞的抑制作用较强。
鉴于醇类提取物作用较强,在研究的第二部分主要观察苏木醇提物对人肺癌A549细胞的细胞毒作用和诱导凋亡作用。将苏木醇提物按不同浓度分别同人肺癌A549细胞共同培养,MTT法检测对细胞增殖作用的影响,光学显微镜、细胞膜磷脂酰丝氨酸外翻分析、细胞周期分析观察不同浓度苏木醇提物对人肺癌A549细胞的细胞毒和调亡作用。发现苏木醇提物对人肺癌A549细胞有抑制作用,并呈浓度依赖性;苏木醇提物在诱导细胞发生凋亡外还存在其它形式的细胞死亡方式并对细胞各期均有影响。
经过第二部分体外抗肿瘤实验后,进行体内抗瘤实验。第三部分研究主要观察苏木醇提物对H22腹水瘤细胞抑瘤作用,通过皮下接种H22腹水瘤细胞的方法建立荷瘤惺竽Ｐ?用苏木醇提物灌胃处理,观察各组荷瘤小鼠的肿瘤生长情况,采用缺口末端标记法测定肿瘤细胞凋亡指数,免疫组织化学方法测定凋亡蛋白Bcl-2、Bax的表达情况。发现苏木醇提物可抑制H22移植瘤生长,促进瘤体细胞凋亡,降低瘤体细胞Bcl-2/Bax比值;其机制与通过调控凋亡相关蛋白Bcl-2、Bax的表达诱导肿瘤细胞凋亡有关。
With the effects of various tumorigenic factors, cells of local tissues will lose control on their growth in the level of genes, which leads to clonal hyperplasia or insufficient apoptosis and results in a neoformation called tumor, often existing in the form of local mass. Whether the tumor is benign or malignant, or has its origins in epithelial tissue or mesenchymal tissue, it manifests abnormal proliferation of cells losing control. This abnormal growing ability can not only be seen from tumor's continuous growth but also from aggression to its adjacent normal tissues and transfer to other parts through blood vessels, lymphatic vessels and body cavity especially for malignant tumor, which is always the cause of death.
In traditional Chinese medicine, physicians in past dynasties regarded that the pathogenesis of tumor mainly contained insufficient healthy qi, blood stasis and phlegm stagnation and invasion of pathogenic toxins etc. They thought tumor is closely related with blood stasis syndrome based on the clinical manifestations of tumor patients such as pathologic tumor mass, pain, hemorrhage, purple tongue with stasis or ecchymosis or blood spots, swarthy complexion and scaly skin in the advanced stage.
In recent years, with constant study on molecular biology theory, the study of treating tumor with traditional Chinese medicine has made great progress, giving us a preliminary understanding of the molecule mechanism of inhibiting tumor growth, enhancing immunity and preventing the transfer of tumor with Chinese herbs. The study of traditional Chinese medicine's effects on tumor has developed from the preliminary study on immune function regulation to the current anti-tumor angiogenesis research and apoptosis induction and telomerase activity inhibition research.
Hematoxylon (Caesalpinia Sappan L, CAE) is the dry heartwood of Leguminosae Caesalpinia which has the effect of promoting blood flow to eliminate stasis and dissolving the swelling to kill the pain. Caesalpinia Sappan L is used to treat dysmenorrheal, rheumatic pain and traumatic injuries and pains etc in Chinese medicine. It can also be used to treat tumor, as the modern pharmacological research shows that it has anti-tumor and immunosuppressive functions, although its specific anti-tumor mechanism is still unknown. Therefore, we can use modern medical testing technology to study the anti-tumor and immunosuppressive mechanism of Hematoxylin alcohol extracts.
In the first part, the main purpose is to observe the effect of different extracts of Hematoxylon in mouse thymus, peripheral T cell proliferation and INF-γgeneration. Different extracts prepared from Caesalpinia Sappan L were lavaged to the mice in order to count thymus index by taking out their thymus, to calculate the proliferation capacity of spleen T cells by using MTT method, to measure the INF-γcontent generated by T cell culture supernatant by using double-antibody sandwich ELISA method. The results showed that different extracts of Hematoxylon not only had remarkable inhibition effect in thymus weight but also in T cell's proliferation and INF-γgeneration abilities. Hematoxylin alcohol and n-butanol extracts had stronger inhibiting effects on T cells.
Given the strong effects of alcohol extract, in the second part of the study, the main purpose is to observe Hematoxylin alcoholl extract's cytotoxicity and apoptosis inducing effects on A549 cell of lung caner. Hematoxylin alcoholl extracts with different concentration were co-cultured with lung cancer A549 cells in order to observe effects on cell proliferation by using MTT method, study the effects on cytotoxicity and apoptosis of lung cancer A549 cells using optical microscope, phosphatidylserine ecstrophy analysis and cell period analysis. The results showed that Hematoxylin alcohol extracts had inhibiting effects on human lung cancer A549 cells in a dose-dependent manner; besides the cell apoptosis induced by these extracts, there existed other forms of cell death and affected cells in every period.
Following the second part of anti-tumor experiment outside, here comes the internal one. The third part is mainly to observe the extract's anti-tumor effect on H22 ascites tumor cells. Tumor-bearing rat model was built by subcutaneous inoculation of H22 ascites tumor cells and lavaged with Hematoxylin alcohol extracts in order to observe the tumor growth conditionsmof tumor-bearing mice in each group, measure the tumor cell apoptotic index by using the nick end labeling method and apoptotic protein Bcl-2, Bax expression by using immunohistochemical technology. The results showed that Hematoxylin alcohol extract can inhibit the H22 transplantation tumor growth, facilitate tumor cell apoptosis, reduce Bcl-2/Bax ratio of tumor cells and the mechanism was related with the induction of tumor cell apoptosis by regulating the expression of apoptosis-related protein Bcl-2/Bax.
引文
[1]王栋,陈超,周珏.苏木的临床药理及化学成分研究进展.中医药信息,2003,20(3):15-16.
[2]Masahiro N,Seiji N.Protosappanins E-1 and E-2,stereoisomeric dibenzoxocins combined with Brazilin from Sappan Lignum.Chem Pharm Bull,1990,38(6):1490-1494.
[3]Mai Thanh Thi N,Suresh A,Yasuhiro T,et al.Neo sappanone A,axanthine oxidase(XO)inhibitory dimericmet hanodibenzoxocinone with a new carbon skeleton from Caesalpinia sappan.Tetrahedron Lett,2004,45(46):8519-8522.
[4]Ou YB,Ke CQ,He ZS,et al.Brazilide A,a novel lactone with anunprecedented skeleton from Caesalpinia sappan.Tetrahedron Lett,2002,43(9):1731-1733.
[5]Michio N,Hiroyuki N,Mariko N,et al.Homoisoflavonoids and Related compounds.Ⅲ.Phenolic Constituent s of Caesalpinia japonica SIEB.et ZUCC.Chem Pharm Bull,1987,35(9):3568-3575.
[6]郭荣辉,张红良,李晖.吸光光度法测定苏木中总酚含量.理化检测—化学分册,2004,40(4):213-215.
[7]Yan XL,Wang W,Xing DM,et al.Development and optimization of amethod for the analysis of Brazilein by HPLC with electrochemical detection.J of Chromatography,2005,1077(1):44-48.
[8]于波,侯静波,吕航,等.苏木有效成分对大鼠免疫活性细胞的影响.中国急救医学,2002,22(4):87.
[9]周亚滨,李天发,关振中,等,苏木对大鼠同种异位心脏移植急性排斥反应的影响.中医药学报,2000,28(1):67-68.
[10]侯静波,于波,吕航,等.苏木水提物抗心脏移植急性排斥反应的实验研究.中国急救医学,2002,22(3):125-126.
[11]侯静波,于俊民,鄂明艳,等.苏木醇提取物对心脏移植后外周血部分辅助性T淋巴细胞因子水平的影响.中华心血管病杂志,2003,31(3):212-215.
[12]于波,侯静波,吕航,苏木提取物对心脏移植大鼠T淋巴细胞亚群的免疫抑制和对心肌的保护作用.中国地方病学杂志,2004,23(6):539-542.
[13]崔丽丽,于波.苏木水提取物的抗急性排斥与Th1/Th2免疫偏移作用.中国胸心血管外科临床杂志,2006,13(4):255-259.
[14]李述峰,侯静波,吴健,等.苏木水提物对心脏异位移植大鼠血清IL-4和IL-10的影响.中 国地方病学杂志,2006,25(5):511-513.
[15]崔丽丽,于波.苏木醇提取物对心脏移植急性排斥反应的抑制作用及机制.浙江临床医学,2006,8(11):1126-1127.
[16]金鹏,周亚滨,宋琦,等.苏木有效成分免疫抑制作用的实验研究.中药材,2007,30(2):196-200.
[17]彭新,王红炜,徐江雁,等.苏木提取物对SD/Wistar大鼠皮肤移植的影响.中华中医药杂志,2006,21(9):564-565.
[18]Shrishailappa B,Sudheer M,Rammanoharsingh RS,et al.Antioxidant activity of Caesalpinia sappan heartwood.BiolPharm Bull,2003,26(11):1534-1537.
[19]Niranjan RVL,Ravikanth V,Jansi Lakshmi V,et al.Inhibitoryactivity of homoisoflavonoids from Caesalpinia sappan against Beauveria bassiana.Fitoterapia,2003,74(6):600-602.
[20]任连生,张蕻.洋苏木素体内外抗肿瘤作用研究.山西医药杂志,1994,23(5):169.
[21]Ryang OS,Seon KD,Seon LI,et al.Anticomplementary activity of constituent s from the heartwood of Caesalpinia sappan.PlantaMed,1998,64(5):456-458.
[22]王三龙,蔡兵,崔承彬等.中药苏木提取物诱导k562细胞凋亡的研究.癌症,2001,20(12):1376-1379.
[23]徐建国,郭素堂,乔丽娟等.苏木提取液抑制肿瘤作用的研究.肿瘤研究与临床,2006,11(18):726-728.
[24]乔丽娟,徐建国,郭文杰.苏木抗癌有效成分抗移植性肝癌H22的实验研究.海南医学2001:12(7):51-52.
[25]乔丽娟,田艳伟,苏木抗癌有效成份作用荷瘤小鼠TSGF的观察.山西职工医学院学报,2001,11(2):5-6.
[26]乔丽娟,徐建国,马克荣.苏木抗癌有效成分对HL-60细胞的增殖抑制.海南医学,2001,12(3):55.
[27]EC Kim,YS Hwang,HJ Lee,SK Lee,et al.Caesalpinia sappan induces cell death by increasing the expression of P53 and P21 WAf1/CIP1 in head and neck cancer cells.Am J Chin Med,2005,33(3):405-414.
[28]郑虎占,董泽宏,余靖,等.中药现代研究与应用[M].北京:学苑出版社.1999.2261
[29]山口琢儿.苏木的活性成分研究.国外医学中医中药分册.1991.13(2):58
[30]郑虎占.董泽宏.佘靖等.中药现代研究与应用.北京.学苑出版社.1999.1:2261-2267
[31]Chiaki Fuke.Johji Yamahara.Takashi Shimokawa et al Two aromatic compounds related to brazilin from CaesalPinia Sappan.Phytochemistry.1985.24(10):2403-2405
[32]中国科学院上海有机化学研究所中药有效成分数据库.
[33]Masahiro Nagai.Seiji Nagumo.Shu-mei Lee et al.Protosappanin A,a Novel Biphenyl compound from Sappan Lignum.Chem Pharm Bull.1986.34(1):1-6
[34]Masahiro Nagai.Seiji Nagumo.ProtosappaninsE-landE-2,Stereoisomeric Dibenzoxocins combined with Brazilin from Sappan Lignum.Chem Pharm Bull.1990.38(6):1490
[35]YS Chang,ER Woo.Korean medicinal plants inhibiting to human immuno- deficiency virus type 1(HIV-1) fusion.Phytother Res,2003,17(4):426-429.
[36]MS Zheng;YZ Zhang.Anti-HBsAg herbs employing ELISA technique.Chung His I Chieh Ho Tsa Chih,1990,10(9):560-562.
[37]NI Baek,SG Jeon,EM Ahn,et al.Anticonvulsant compounds from thewood of Caesalpinia sappan L..Arch Pharmacal Res,2000,23(4):344-348.
[38]KH Lee,HJ Lee,HI Park,et al.Screening of prolyl endopeptidase inhibitors fromnatural products.Yakhak Hoechi,1997,41(2):153-160.
[39]BH Lee,BW Choi,GS Ryu,et al.Screening of the inhibitors from medicinal plants.Saengyak Hakhoechi,1997,28(4):167-173.
[40]YW Xie,DS Ming,HX Xu,et al.Vaso relaxing effeets of Caesalpinia sappan.Involvement of endogenous nitric oxide.Life Sci,2000,67(15):1913-1918.
[41]IM Shih,HS Chiang,LL Yang,et al.Antimotility effeets of Chinese herbal- medicines on human sperm.J Formos Med Assoc,1990,89(6):466-469.
[42]梁书评,周淑艳.蒙药苏木治疗痛经60例.中国民族医药杂志,2003,12(4):27-28.
[43]韩艳,郑世成,张根印.透骨苏木公英汤外用治疗膝关节非感染性滑膜炎26例.陕西中医学院学报,2006,29(1):38
[1]肖崇厚《中药化学》第2版,上海:上海科学技术出版社,1994
[2]匡海学《中药化学》第3版,北京:中国中医药出版社,2004
[3]金竹萍.超临界流体萃取技术的应用及研究进展[J].山西化工,2007,27(2):42.
[4]曹茂堂.超临界萃取技术在医药领域中的应用[J].时珍国医国药,2003,14(12):784-785.
[5]郭章华,周敏华.超临界萃取技术在医药领域中的应用[J].国际医药卫生导报,2003,9(2-3):82-83.
[6]陈磊,刘晔,康鲁平,等.超临界萃取技术在中草药研究中的应用[J].药学实践杂志,2004,(4):193-196.
[7]周庆华,范卓文,杨波.超临界萃取技术在中药中的应用[J].中医药信息,2002,19(6):18-19.
[8]马海乐,王超,刘伟平.葛根总黄酮微波辅助萃取技术[J].江苏大学学报(自然科学版),2005,26(2):98.
[9]王白军,王国卫,齐誉.白芥子中总黄酮的微波提取与含量测定[J].时珍国医国药,2005,16(6):512.
[10]曾里,夏之宁.超声波和微波对中药提取的促进和影响[J].化学研究与应用,2002,14(3):245.
[11]朱凯,朱新宝.超临界CO2萃取八角茴香精油的研究[J].生物质化学工程,2007,1:28.
[12]宋应华,郁威,王远明.超临界CO2萃取川芎挥发油过程研究[J].中成药,2005,27(9):1007.
[13]唐庆峰,吴振廷,金涛,等.地鳖虫活性物质的超临界CO2萃取及其药效[J].昆虫知识,2006,43(3):375.
[14]刘莉,徐新刚,陈飞龙,等.超临界CO2萃取云南红豆杉枝叶中紫杉醇的研究[J].中成药,2006,28(4):480.
[15]蔡庆群,黄耀海,席萍,等.藿香正气方超临界萃取物质谱及薄层色谱分析[J].现代食品与药品杂志,2006,16(3):32.
[16]Quan Cem,Li shufen,Tian Song Jiang,et al Supercritical Fluid Extraction and clean up of organochlorine Pesticides in Ginseng[J].The journal of Supercritical Fluids,2004,31(2):149.
[17]王玉华,容蓉,魏英勤,等.四物汤及单药材超临界萃取物的质量控制和稳定性研究[J].世界科学技术——中医药现代化,2005,7(2):50.
[18]郑颖,张红,宋其生,等.芪灵益肝煎及其CO2超临界萃取液对肝癌细胞株H22端粒酶反转录亚单位表达的影响[J].中国临床药学杂志,2005,14(3):180.
[19]罗兰,朱丹妮,严永清.当归芍药散精简方CO2超临界萃取部位化学成分研究[J].中成药,2005,27(11):1251.
[20]葛发欢.再论中药现化代与超临界二氧化碳萃取技术[J].中药材,2003,26(5):373.
[21]陈晓东.对二氧化碳超临界萃取运用在中药提取上的看法[J].医药工程设计杂志,2004,25(3):1.
[22]张代佳,刘传斌,修志龙.微波技术在植物细胞内有效成分提取中的应用[J].中草药,2000,31(9):.
[23]魏亚冉.油桃果皮红色素的微波提取工艺及特性研究[J].中国食品添加剂,2007,1:76.
[24]马海乐,王超,刘伟平.葛根总黄酮微波辅助萃取技术[J].江苏大学学报(自然科学版),2005,26(2):98.
[25]王晓燕,黄敏仁,韩正敏.微波辅助提取石蒜属植物忽地笑中加兰他敏的研究[J].南京中医药大学学报,2005,21(6):374.
[26]郝金玉,韩伟,施超欧,等.黄花蒿中青蒿素的微波辅助提取[J].中国医药工业杂志,2002,33(8):385.
[27]韩伟,郝金玉,薛伯勇,等.微波辅助提取青蒿素的研究[J].中成药,2002,24(2):83
[28]Young J C.Microwave-Assisted Extraction of the Fungal metaboliteer Gosterol and Total Faritty Acids[J].Journal of Agriculture and chemistry,1995,43:2904.
[29]DabiritM,Salimi S,GhassempourA,et al Optimization of Microwave-Assisted Extraction for Alizarin and Purpurin in Rubiaceae Plants and its Comparison with Conventional Extraction Methods[J].J Sep 2005,28(4):387-396.
[30]Jones N M,et al Comparison of Methods for Extraction of Tabacco Alkaloids[J].JAOAC Int,2001,84(2):309.
[31]Brachet A,et al Focused Microwave assisted Extraction of Cocaine and Benzoy lecgonine from Caca Leaves[J].Phytochem Ana,2002,13(3):162.
[32]Then M,et al Effect of Sample Handing on Alkaloid and Mineral Content of Aqueous Extracts of Great Celandine[J].ChromatogrA,2000,889:69.
[33]史小萌.超声法提取银鹊树种皮总黄酮的工艺研究[J].西北林学院学报,2007,22(2):148.
[34]胡斌杰,陈金锋,王宫南.超声波法与传统热水法提取灵芝多糖的比较研究[J].食品工业科技,2007,28(2):190-192.
[35]郭孝武.超声提取与碱性浸泡法对小檗碱成分提出率的影响[J].陕西师范大学学报,1997,259(1):47.
[36]郭孝武.超声提取对黄连素提出率的影响[J].中国中药杂志,1995,20(11):673.
[37]Schinor EC,Salvad MJ,Turatti CI,Comparison of Classical and Ultra-Sound -Assisted Extractions of Steroids and Triterpenoids from Three Chrestaspp[J].Ultrasonics Sono-chemistry,2005,12:301.
[38]白中明.工业化超声波中药提取装备研究[J].中草药,2005,36(8):1274.
[39]王成东.超声波应用于中药提取生产的体会及前景分析[J].机电信息,2004,(18):31.
[40]薛伟明,张效林,刘袖洞,等.酶一膜法药用植物有效成分提取分离过程应用研究[J].西北大学学报(自然科学版),1997,27(6):494-498.
[41]薛伟明,张效林,亢茂德,等.红花黄色素的酶法提取应用研究[J].化学工程,1999,27(1):42-44,50.
[42]王廉,张效林,薛伟明,等.侧柏叶有效成分提取过程研究[J].化学工程,1998,26(3):21-24.
[43]刘佳佳,赵国玲,章晓骅,等.金银花绿原酸酶法提取新工艺研究[J].中成药,2002,24(6):416-418.
[44]杨军宜,尹蓉丽,杨胜,等.纤维素酶在三七提取工业中的应用[J].中国中医药科技,2001,8(5):F003-F003.
[45]王晓,张红侠,王其亮,等.酶法提取山楂叶中总黄酮的研究[J].工艺技术,2002,23(3):37-39.
[46]董海丽,纵伟.酶法提取姜黄素的研究[J].纯碱工业,2000,6:55-56,60.
[47]纵伟.酶法提取银杏叶中总黄酮的研究[J].山西食品工业,2000,1:13-15.
[48]李兆龙,虞杏英.用树脂法和酶法从银杏叶中提取黄酮类化合物的专利介绍[J].中成药,1994,16(10):52.
[49]侯嵘桥,孟宪纾,徐育新.以酶解法从中药及药渣制备β-葡萄糖的研究[J].沈阳药学院学报,1994,11(4):289.
[50]王兴文.水提三七总苷[J].云南中医学院学报,2001,24(3):1-3
[51]李道荣,李魁,段雪梅,蒲黄花粉多糖提取工艺研究[J].郑州工程学院学报,2002,23(4):55-57,63
[52]傅博强,谢明勇,周鹏,等.纤维素酶法提取茶多糖[J].无锡轻工大学学报,2002,21(4):362-366.
[53]李元波,殷辉安,唐明林,等.复合酶解法提取三七皂苷的实验研究[J].天然产物研究与开发,2005,17(4):488.
[54]闫巧娟,韩鲁佳,江正强.纤维素酶法提取黄芪多糖[J].中草药,2005,36(12):1804.
[55]许明淑,邢新会,罗明芳,等.银杏叶黄酮的酶法强化提取工艺条件研究[J].中国实验方剂学杂志,2006,12(4):2.
[56]余冬生,卫纪章.酶法提取香菇多糖[J].江苏食品与发酵,2001,(4):10,11.
[57]沈爱英,谷文英.复合酶法提取姬松茸子实体多糖的研究[J].食用菌,2001:23(3):7-9.
[58]陈哲超,林宇野,谢必峰,等.复合酶解法提取香菇多糖蛋白的研究[J].生物工程进展,1995,15(1):47-50.
[59]孙兴权,付蕾,曹云龙,等.林蛙多糖(TCPS)提取工艺的初步研究[J].吉林农业大学学报,2001,23(4):108-110.
[60]马田田.纤维素酶用于中药提取的初步研究[J].中草药,1994,25(3):123,139.
[61]马桔云.纤维素酶在黄连提取工艺中的应用[J].中草药,2000,31(2):103.
[62]马桔云.纤维素酶用于中药穿心莲提取的初步研究[J].黑龙江医药,2000,31(2):103.
[63]韩颂,李晓晖.纤维素酶在黄芩提取工艺中应用的初步探索[J].黑龙江医药,1997,10(6):339-340
[64]林翠英,周晶,赵晶,等.芦丁超声提取新技术的再探索[J].中草药,1999,30(5):350.
[65]张兆旺,孙秀梅.半仿生提取法的特点与应用[J].提取技术与工艺,2000,2(1):35.
[66]周庆华,范卓文,杨波.超临界萃取技术在中药中的应用[J].中医药信息,2002,19(6):18-191.
[67]孙秀梅,张兆旺,丁菊英,等.寒痛定泡腾冲剂4种提取方法的比较[J].中国中药杂志,1006,21(3):159-161.
[68]孙秀梅,张兆旺,卢连华,等.黄连解毒颗粒2剂4种提取方法的成分比较[J].中国中药杂志,1996,21(8):474.
[69]孙秀梅,张兆旺,郭婕,等.芍甘止痛颗粒剂4利提取方法的成分比较[J].中成药,1996,18(11):34.
[70]张兆旺,孙秀梅.半仿生提取法的特点与应用[J].世界科学技术—中药现代化,2000,2(1):35.
[71]孙秀梅,张兆旺,张学兰,等.四神茶剂4种提取方法的成分比较[J].中国中药杂志,1997,22(6):349-351.
[72]贺立中,徐德云,黄泽华,等.采用超滤技术制备伸筋草注射液的中试生产研究.中成药,2002,24(2):137-9.
[73]张忠义,雷正杰,黄昌全,等.超临界CO2—分子蒸馏制备大蒜注射液.中国医院药学杂志,2002,22(101:581-2.
[74]张宇,曹玉娥,李殿奎.应用超滤技术制备四逆汤口服液的研究.佳木斯医学院学报, 1992,15(2):30-2.
[75]刘洪谦,屈凌波,贾金付.生脉饮口服液超滤技术研究.中草药,1996,27(4):209-11.
[76]朱献镭.连续动态逆流提取工艺流程及预浸器的设计[J].轻工机械,2005,(4):127.
[77]斯黎明.逆流动态中药提取工艺[J].医药工程设计,2003,24(4):23.
[1]曾益新,《肿瘤学》第2版,北京:人民卫生出版社,2003
[2]刘复生,《中国肿瘤病理学分类》,北京:科学技术文献出版社,2001
[3]贾英杰.中医药“立体疗法”治疗恶性肿瘤新理念.开卷有益:求医问药,2007,(10):12-13.
[4]McCann J,Ames BN.Detection of carcinogens as mutagens in the Salmonella/microsome test:assay of 300 chemicals:discussion.Proc Natl Acad Sci U S A.1976,73(3):950-4.
[5]Ames BN.Identifying environmental chemicals causing mutations and cancer.Science,1979,204(4393):587-93.
[6]Ames BN,Magaw R,Gold LS.Ranking possible carcinogenic hazards.Science.1987,17(4799):271-80.
[7]Ames BN.What are the major carcinogens in the etiology of human cancer?Environmental pollution,natural carcinogens,and the causes of human cancer:six errors.Important Adv Oncol.1989:237-47.
[8]Ames BN,Gold LS,Willett WC.The causes and prevention of cancer.Proc Natl Acad Sci U S A.1995,92(12):5258-65.
[9]Katsusaburo Yamagiwa.CA Cancer J Clin.1977,27(3):172-3.
[10]Henschen F.Yamagiwa's tar cancer and its historical significance.From Percival Pott to Katsusaburo Yamagiwa.Gann.1968,59:447-51.
[11]BERENBLUM I.A speculative review:the probable nature of promoting action and its significance in the understanding of the mechanism of carcinogenesis.Cancer Res.1954 Aug:14(7):471-7.
[12]Berenblum I.A re-evaluation of the concept of cocarciongenesis.Prog Exp Tumor Res.1969:11:21-30.
[13]Berenblum I.Established principles and unresolved problems in carcinogenesis.J Natl Cancer Inst.1978 Apr:60(4):723-6.
[14]Berenblum I,Armuth V.Two independent aspects of tumor promotion.Biochim Biophys Acta.1981,651(1):51-63.
[15]Stockwell S.Classics in oncology:Isaac Berenblum,M.D.CA Cancer J Clin.1981,31(4):239-53.
[16]Knudson AG Jr.Mutation and cancer:statistical study of retinoblastoma.Proc Natl Acad Sci USA.1971,68(4):820-3.
[17]Knudson AG Two genetic hits (more or less)to cancer.Nat Rev Cancer.2001,l(2):157-62.
[18]Burnet FM.The concept of immunological surveillance.Prog Exp Tumor Res.1970:13:1-27.
[19]Burnet FM.Immunological surveillance in neoplasia.Transplant Rev.1971:7:3-25.
[20]Lanier LL.A renaissance for the tumor immunosurveillance hypothesis.Nat Med.2001,7(11):1178-80.
[21]Dunn GP,Bruce AT,Dceda H,Old LJ,Schreiber RD.Cancer immunoediting:from immunosurveillance to tumor escape.Nat Immunol.2002,3(ll):991-8.
[22]Ochsenbein AF.Principles of tumor immunosurveillance and implications for immunotherapy.Cancer Gene Ther.2002,9(12):1043-55.
[23]Boon T,van Baren N.Immunosurveillance against cancer and immunotherapy—synergy or antagonism? N Engl J Med.2003,348(3):252-4.
[24]Dunn GP,Old LJ,Schreiber RD.The immunobiology of cancer immunosurveillance and immunoediting.Immunity.2004,21(2):137-48.
[25]Qin Z,Blankenstein T.A cancer immunosurveillance controversy.Nat Immunol.2004,5(1):3-5.
[26]Ichim CV.Revisiting immunosurveillance and immunostimulation:Implications for cancer immunotherapy.J Transl Med.2005,3(1):8.
[27]Klein G,Klein E.Surveillance against tumors~is it mainly immunological? Immunol Lett.2005,100(1):29-33.
[28]Zirvogel L,Tesniere A,Kroemer G Cancer despite immunosurveillance:immunoselection and immunosubversion.Nat Rev hnmunol.2006,6(l0):715-27.
[29]Smyth MJ,Dunn GP,Schreiber RD.Cancer immunosurveillance and immunoediting:the roles of immunity in suppressing tumor development and shaping tumor immunogenicity.Adv Immunol.2006:90:1-50.
[30]Prehn RT.An adaptive immune reaction may be necessary for cancer development-Theor Biol Med Model.2006,3:3(1):6
[31]Bishop JM.Molecular themes in oncogenesis.Cell,1991,64:235-248.
[32]Lengauer C,Kinzler KW,Vogelstein B.Genetic instabilities in human cancers.Nature,1998,396:643-649.
[33]Mao L,Sidransky D Cancer screening based on genetic alterations in human tumors.Cancer Res 1994,54:1939s-1940s.
[34]Sidransky D.Molecular markers in cancer:can we make better predictions? Int J Cancer 1995,64:1-2.
[35]Renan MJ.How many mutations are required for tumorigenesis? Implications from human cancer data.Mol Carcinog1993,7:139-146.
[36]Loeb KR,Loeb LA Significance of multiple mutations in cancer.Carcinogenesis 2000,21:379-385.
[37]Cohen AM,Minsky BD,Schilsky RL.Cancer of the colon.In:VT DeVita,S Hellman,SA Rosenberg(eds):Cancer:Principles and Practice of Oncology,5th ed.Lippincott-Raven,Philadelphia1997,1144-1197.
[38]Weinberg RA.The action of oncogenes in the cytoplasm and nucleus.Science.1985230(4727):770-6.
[39]Land H,Chen AC,Morgenstem JP,Parada LF,Weinberg RA.Behavior of myc and ras oncogenes in transformation of rat embryo fibroblasts.Mol Cell Biol.1986,6:1917-25.
[40]Friend SH,Bemards R,Rogelj S,Weinberg RA,Rapaport JM,Albert DM,Dryja TP.A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma.Nature.1986,323(6089):643-6.
[41]Weinberg RA.Oncogenes,antioncogenes,and the molecular bases of multistep carcinogenesis.Cancer Res.1989,49(14):3713-21.
[42]Shigeta T,Takagi M,Delia D,Chessa L,Iwata S,Kanke Y,Asada M,Eguchi M,Mizutani S Defective control of apoptosis and mitotic spindle checkpoint in heterozygous carriers of ATM mutations.Cancer Res 1999,59:2602-2607.
[43]Lipkin SM,Wang V,Jacoby R,Banerjee-Basu S,Baxevanis AD,Lynch HT,Elliott RM,Collins FS MLH3:a DNA mismatch repair gene associated with mammalian microsatellite instability.Nat Genet 2000,24:27-35.
[44]Chang CL,Marra G,Chauhan DP,Ha HT,Chang DK,Ricciardiello L,Randolph A,Carethers JM,Boland CR Oxidative stress inactivates the human DNA mismatch repair system.Am J Physiol Cell Physiol 2002283:C148-154.
[45]孟灵源.中医药治疗恶性肿瘤的思路探讨.中医药管理杂志,2007,15(8):625-627.
[46]潘国凤,朱晓新,张晓东.肿瘤系统生物学的发展与中医药的现代化[J].中华中医药杂志,2007,22(10):698-701.
[47]徐振晔,郑展.试论中医阴阳平衡法治疗恶性肿瘤.上海中医药杂志,2007,41(4):37-39.
[48]苏婉,徐振晔.肿瘤靶向治疗与中药多靶点效应的研究进展[J].上海中医药杂 志,2007,41(9):87-88.
[49]王笑民,郁仁存,胡玉芳等.益气活血法对癌症血癖证影响的临床与实验研究.实用中西医结合杂志,1996,9(5):315
[50]王禹堂,王笑民,郁仁存等.癌症患者的血癖证研究.中国中医药学报,1996,11(6):57
[51]傅乃武,范贤俊,王永泉等.丹参对实验性肿瘤生长和转移的影响及其作用原理的初步探讨.中华肿瘤杂志,1981,3(3):165-167
[52]刘明章,黄贻建,肖伟琪.丹参酮n-A磺酸钠对Lewis癌无促进生长与转移作用.中国药理学报,1991,12(6):534-537
[53]徐德成,张培宇.活血化癖强度与气血双亏型胃癌转移率相关性机理探讨中医杂志.1998,39(3):156-157
[54]张俊.顾王荣老中医辨治肝癌的经验.新中医,1999,31(1):8-9
[55]翁维良.20种活血药对血液粘滞性作用的比较观察中医杂志,1984,25(2):69-71
[56]王涛,杨华山.菝葜乙酸乙酯提取物抗癌机制研究肿瘤基础与临床[J].2004,20(2):129-131
[57]付丽华,胡玉红,孙盛梅,卢北燕.白藜芦醇抗肿瘤作用的研究进展[J].黑龙江医药科学,2006,29(6):98-100
[58]曹文涛.白藜芦醇抗肿瘤血管生成机制[J].国际肿瘤学杂志,2006,3(12):918.921
[59]伍石华.白杨素的抗肿瘤作用及机理研究[J].湖南师范大学学报(医学版),2006,3(4):78-81
[60]韩玉萍,洪行球.姜黄色素抗肿瘤作用的研究[J].中国实用医药杂志,2007,2(1):96-97
[61]符矗,龚涛,刘振谧,张志荣.姜黄素衍生物在体外的抗肿瘤试验[J].华西药学杂志,2006,21(6):552-553
[62]官杰,罗晓庆,王琪,李殿俊.壳寡糖抑制肿瘤的实验研究[J]冲国免疫马玲娣,张彦,文世宏,和於娟,刘小珊,康格菲,蒋纪恺.苦参碱抗肿瘤作用及其机制的初步研究[J].中国免疫学杂志,2007,23(5):434-437
[63]李建军,雷林生,余传林,朱正光,马安德.灵芝多糖抗肿瘤作用的免疫学相关性研究[J].中药材,2007,30(1):71.73
[64]张健英,毕建成,楚健子.灵芝在预防肿瘤化疗患者白细胞减少中的作用[J].中国中医药信息杂志,2007,13(11):63
[65]蒋国松.茉莉素抗肿瘤作用及其机制研究进展[J].国际肿瘤学杂志,2007,34(3):167-170
[66]J本艳,段大航,李坦.蒲公英对消化系统作用及抗肿瘤研究现状[J].吉林中医药,2006,26(12):72-73
[67]李世辉,潘岐.青蒿素及其衍生物抗肿瘤机制研究进展[J].中成药,2007,29(4):561-562
[68]余艳秋.蚯蚓提取物抗肿瘤作用的研究进展[J].临床肿瘤学杂志,2007,12(3):232·234
[69]黄松音.去甲斑蝥素抗肿瘤作用基础与临床研究进展[J].国际检验医学杂志,2007,28(3):235.237
[70]郭风,于广久.人参皂甙Rh2诱导肿瘤细胞凋亡的研究进展[J].锦州医学院学 报,2007,27(5):52-54
[71]杨全,张卉,王琦,王文全.桑黄胞外多糖抗肿瘤活性的研究[J].北京中医药大学学报表,2007,301 3):188-190
[72]徐建国,郭素堂,乔丽娟,张少云,史天良,刘维兰,郑启英.苏木提取液抑制肿瘤作用的研究[J].肿瘤研究与临床,2006,18(11):726-727
[73]张维东,张月英,王朝霞,王兆明,贾青.蝎毒多肽提取物对肿瘤生长和细胞免疫功能的影响[J].山东大学学报(医学版),2007,45(3):286-289
[74]林梅,裴军昌,张东生,时军.雄黄抗癌作用的研究发展[J].中国实用医药杂志,2007,2(13):1-4
[75]李翠玲,张玲,顾洪涛,王军,毛海婷,杨尚军,温培娥.淫羊藿苷体内抑瘤作用及其机～J[J].中国肿瘤生物治疗杂志,2007,14(2):137-142
[76]曲萌,董志恒,盖晓东,毕胜利,王冰梅.银耳多糖对小鼠移植性肝癌治疗作用及机制的实验研究[J].中国老年学杂志,2006,26(12):1662.1665
[77]单保恩,付小梅,华正祥,李巧霞,梁文杰,刘冀琴,张华,刘刚参.中药五加皮提取成分抗肿瘤活性作用机理研究[J].中国中西医结合杂志,2005,25(9):825-828
[78]李劲,林奕,陈闻纳,赖惠萍.中药紫草对离体人乳头瘤病毒DNA作用的实验研究[J].成都中医药大学学报,2006,29(4):52-54
[79]郭志军.香菇多糖抗肿瘤应用研究概况[J].中医药导报,2007,13(1):78-80
[80]常垄,范延英,任青华,李强.中药三龙丹的药效学研究[J].中国实用医学,2007,1(5):29-30
[81]韦良宏,陈海东,林瑶光.参芪扶正注射液对老年中晚期恶性肿瘤病人生活质量的影响[J].广西医学,2007,299(1):85-86
[82]孙艳,孙艳影,蒋丽艳.冬虫夏草制剂对恶性肿瘤患者化疗后T细胞亚群的影响[J].齐齐哈尔医学院学报,2006,27(17):2063-2064
[83]张广信,李岑,马秋波,辛雨玲.扶正降逆颗粒治疗恶性肿瘤化疗所致毒副作用临床观察[J].河北中医药,2007,29(1):24-25
[84]邓毅丰,谢湘林,张大方.扶正消积胶囊对荷瘤动物免疫功能的影响[J].长春中医药大学学报,2007,23(1):19-20
[85]嫒媛,贾彤,张广美.扶正消瘤颗粒对环磷酰胺处理后小鼠骨髓及免疫功能的影响[J].中国中医药科技.2006,13(6):402
[86]魏光敏.岩舒联合化疗治疗中晚期恶性肿瘤疗效观察[J].中国误诊学杂志,2007,7(3):488-489
[87]高宏,殷东风,张宁苏.济川煎加味治疗肿瘤病人便秘的临床观察[J].辽宁中医杂志,2007,34(5):612-613
[88]徐杰军,王蕾.加昧逍遥散改善肿瘤化疗毒副反应128例临床观察[J].西部医学,2007,19(3):428-430
[89]陈衍智,李萍萍,杨华.酸枣仁汤加味治疗肿瘤患者失眠症54例体会[J].中医药临床杂志,2007,19(1):3
[90]韩旭.消肿散癃汤治疗癌性疼痛99例[J].新中医,2007,39(4):85-86
[91]翁德新.血府逐瘀汤联合5—氟尿嘧啶治疗小鼠移植性肿瘤的实验研究[J].现代中西医结合杂志,2007,16(3):311-312
[92]张学民,钱钢,陈洁.自拟健脾补肾方治疗肿瘤相关性贫血疗效观察[J].江西中医药,2007,38(292):25-26
[93]赵晓珍,徐振晔,方肇勤.中医药治疗肿瘤的不同治法与基因组学结合研究应用的探讨[J].山西中医,2007,23(2):1-2
[94]杨杰,高锋,孙洋,丁维俊,王米渠.中药抗癌的分子药效探讨[J].中华中医药学刊,2007,25(3):577-579
[95]徐伟,孙维峰,汪立新.中药抗化疗呕吐作用机制的实验研究进展[J].中国中西医结合消化杂志,2007,15(1):65
[96]徐霞飞,陆茵冲药抗肿瘤血管生成研究进展[J].现代中药研究与实践.2007,21(1):61-64
[97]蔡宇,冯笑珍.中药逆转肿瘤多药耐药研究现状[J].现代医院.2007,7(1):4-6
[98]李杰.试谈中药十八反,十九畏对药组方对各种肿瘤的特殊疗效[J].医药世界,2007,(2):5-6
[1]乔丽娟,田艳伟等.苏木抗癌有效成分作用荷瘤小鼠TSGF的观察.山西职工医学院学报,2001,11(2):5-7.
[2]徐慧,周志华,杨俊山.苏木化学成分的研究.中国中药杂志,1994,19(8):485.
[3]杨广文,程秀珍,马俊英.苏木煎液的抗癌作用研究.山西临床医药杂志,1999,8(2):92-93.
[4]杨锋,樊良卿,沈翔,等,八味活血化瘀中药对小鼠细胞免疫调节作用的量效关系研究[J]中国实验临床免疫学杂志,1997,9(1):49-52
[5]于波,侯静波,吕航,等.苏木有效成分对大鼠免疫活性细胞的影响[J]中国急救医学,2002,22(4):187-189
[6]刘昱霞,王淑玲等,中药提取方法概论[J],中国药业.2008,17(16)2-3
[7]于波,侯静波,吕航,等.苏木提取物对心脏移植大鼠T淋巴细胞亚群的免疫抑制和对心肌的保护作用.[J]中国地方病学杂志,2004,23:539-542.
[1]张民庆,龚惠明,丁冠民,等.抗肿瘤中药的临床应用.北京,人民卫生出版社,1998.271-272
[2]杨锋,戴关海,沈翔,等.苏木对体外人淋巴细胞增殖的抑制作用.上海免疫学杂志,1997,17(4):212-215
[3]Tao L,Zhou L,Zheng L,Yao M.Elemene displays anti-cancer ability on laryngeal cancer cells in vitro and in vivo.Cancer Chemother Pharmacol.2006,58:24-34.
[4]花文峰,蔡绍晖.β-榄香烯抗肿瘤作用的基础与临床研究冲药材,2006,29(1):93-97.
[5]Meijer L,Borgne A,Mulner O,et al.Biochemical and cellular effects of roscovitine,apotent and selective inhibitor of the cyclin-dependent kinases cdc2,cdk2 and cdk5.Eur J Biochem 1997,243(1-2):527-536.
[1]俞顺章.原发性肝癌流行病学研究进展[J].实用肿瘤杂志,1998,13(3):130
[2]吴孟超.原发性肝癌外科综合治疗的现状和展望[J].中华外科杂志,2004,42(1):13-15
[3]邹移海,徐志伟,苏钢强.实验动物学[M].北京:科学出版社,2004:154
[4]苗明三.实验动物与动物实验方法[M].上海:上海科学技术出版社,2005:67
[5]张绪慧,陈达理,罗荣城.鳖甲煎丸对H22荷瘤小鼠的抑瘤作用及对增殖核抗原表达的影响[J].南方医科大学学报,2006,26(12):1791-1793
[6]陈奇.中药药理研究方法学[M].北京:人民卫生出版社,1993
[7]陈清勇,吴玉泉,何永生,等.复方抗瘤冲剂抑制小鼠肉瘤S180的生长及对p53和增殖细胞核抗原表达的影响[J].解放军医学杂志,2001,26(11):853-855.
[8]水若鸿,等.套细胞淋巴瘤石蜡包埋组织中细胞周期蛋白D1和t(11;14)易位检测的临床病理意义[J].中华病理学杂志,2003,8,32:337-341.
[9]杜标炎,等.六味地黄丸对小鼠移植性肝癌自杀基因治疗增效作用的病理学研究[J].广州中医药大学学报,2007,24(5):386-391.
[10]许良中,杨文涛.免疫组织化学反应结果的判断标准[J].中国癌症杂志,1996,6(4):229-231
[11]周振华,宋明志,于尔辛等.健脾理气方对小鼠HAC肝癌细胞凋亡和bax基因蛋白表达影响的实验研究[J].中国中西医结合脾胃杂志,2000,8(2):78-82
[12]刘文兰,张颖.细胞凋亡检测方法[J].解剖科学进展,1999,5(4):330-332
[13]赵利红,崔利德,李陈莉.细胞凋亡的检测方法[J],河北医药,2005,27(10),783-785
[14]Lipponen P,Aaltomaa S,Apoptosis in bladder cancer as related to standard prognostic factors and prognosis[J].Pathol,994,173:333
[15]Lipponen P,Aaltomaa S,Kosma VA,Apoptosis in breast cancer as related histopathological characteristics and prognosis,Eta J Cancer,1994,30A:2068
[16]Brambilla E,Negoescu A,Gazzeri S,et al.Apoptosis related factors p53,Bcl-2,and Bax in neuroendocrine lung tumors[J].Am J Pathol,1996,149(6):1941-1952
[17]Schulte HR,Bursch W,Kranpp GB,et al.Cell proliferation and apoptosis in normal liver and preneoplastic foc[J].Environ Health Perspect,1993,101(5);87-90
[18]刘明华,卿晨,刘吉开,等.伍氏百叶散对荷瘤小鼠肿瘤生长及免疫功能的影响[J].中国新药杂志,2006,15(3):201-204
[19]Inik Chang,Sunshin Kim,Ja Young Kim,et al.Nuclear Factor β Protects Pancreaticβ-Cells From Tumor Necrosis Factor-α-Mediated Apoptosis[J].Diabetes,2003,52(5):1169-1175
[20]Weiqin Jiang,Zongjian Zhu,Neehar Bhatia,et al.Mechanisms of Energy Restriction:Effects of Corticosterone on Cell Growth,Cell Cycle Mzchinery,and Apoptosis[J].Cancer Research,2002,62(15):5280-5287
[21]龚守良.细胞凋亡分子机理的研究现状[J].中国实验诊断学,2000,4(3):147-148
[22]Adams JM,Cory S.The bcl-2 protein family:arbiters of cell survival[J].Science,1998,281(5381):1322-1326
[23]Humlova Z.Protooncogene Bcl-2 in process ofapoptosis[J].Sb Lek,2002,103:419-425
[2]Masahiro N,Seiji N.Protosappanins E-1 and E-2,stereoisomeric dibenzoxocins combined with Brazilin from Sappan Lignum.Chem Pharm Bull,1990,38(6):1490-1494.
[3]Mai Thanh Thi N,Suresh A,Yasuhiro T,et al.Neo sappanone A,axanthine oxidase(XO)inhibitory dimericmet hanodibenzoxocinone with a new carbon skeleton from Caesalpinia sappan.Tetrahedron Lett,2004,45(46):8519-8522.
[4]Ou YB,Ke CQ,He ZS,et al.Brazilide A,a novel lactone with anunprecedented skeleton from Caesalpinia sappan.Tetrahedron Lett,2002,43(9):1731-1733.
[5]Michio N,Hiroyuki N,Mariko N,et al.Homoisoflavonoids and Related compounds.Ⅲ.Phenolic Constituent s of Caesalpinia japonica SIEB.et ZUCC.Chem Pharm Bull,1987,35(9):3568-3575.
[6]郭荣辉,张红良,李晖.吸光光度法测定苏木中总酚含量.理化检测—化学分册,2004,40(4):213-215.
[7]Yan XL,Wang W,Xing DM,et al.Development and optimization of amethod for the analysis of Brazilein by HPLC with electrochemical detection.J of Chromatography,2005,1077(1):44-48.
[8]于波,侯静波,吕航,等.苏木有效成分对大鼠免疫活性细胞的影响.中国急救医学,2002,22(4):87.
[9]周亚滨,李天发,关振中,等,苏木对大鼠同种异位心脏移植急性排斥反应的影响.中医药学报,2000,28(1):67-68.
[10]侯静波,于波,吕航,等.苏木水提物抗心脏移植急性排斥反应的实验研究.中国急救医学,2002,22(3):125-126.
[11]侯静波,于俊民,鄂明艳,等.苏木醇提取物对心脏移植后外周血部分辅助性T淋巴细胞因子水平的影响.中华心血管病杂志,2003,31(3):212-215.
[12]于波,侯静波,吕航,苏木提取物对心脏移植大鼠T淋巴细胞亚群的免疫抑制和对心肌的保护作用.中国地方病学杂志,2004,23(6):539-542.
[13]崔丽丽,于波.苏木水提取物的抗急性排斥与Th1/Th2免疫偏移作用.中国胸心血管外科临床杂志,2006,13(4):255-259.
[14]李述峰,侯静波,吴健,等.苏木水提物对心脏异位移植大鼠血清IL-4和IL-10的影响.中 国地方病学杂志,2006,25(5):511-513.
[15]崔丽丽,于波.苏木醇提取物对心脏移植急性排斥反应的抑制作用及机制.浙江临床医学,2006,8(11):1126-1127.
[16]金鹏,周亚滨,宋琦,等.苏木有效成分免疫抑制作用的实验研究.中药材,2007,30(2):196-200.
[17]彭新,王红炜,徐江雁,等.苏木提取物对SD/Wistar大鼠皮肤移植的影响.中华中医药杂志,2006,21(9):564-565.
[18]Shrishailappa B,Sudheer M,Rammanoharsingh RS,et al.Antioxidant activity of Caesalpinia sappan heartwood.BiolPharm Bull,2003,26(11):1534-1537.
[19]Niranjan RVL,Ravikanth V,Jansi Lakshmi V,et al.Inhibitoryactivity of homoisoflavonoids from Caesalpinia sappan against Beauveria bassiana.Fitoterapia,2003,74(6):600-602.
[20]任连生,张蕻.洋苏木素体内外抗肿瘤作用研究.山西医药杂志,1994,23(5):169.
[21]Ryang OS,Seon KD,Seon LI,et al.Anticomplementary activity of constituent s from the heartwood of Caesalpinia sappan.PlantaMed,1998,64(5):456-458.
[22]王三龙,蔡兵,崔承彬等.中药苏木提取物诱导k562细胞凋亡的研究.癌症,2001,20(12):1376-1379.
[23]徐建国,郭素堂,乔丽娟等.苏木提取液抑制肿瘤作用的研究.肿瘤研究与临床,2006,11(18):726-728.
[24]乔丽娟,徐建国,郭文杰.苏木抗癌有效成分抗移植性肝癌H22的实验研究.海南医学2001:12(7):51-52.
[25]乔丽娟,田艳伟,苏木抗癌有效成份作用荷瘤小鼠TSGF的观察.山西职工医学院学报,2001,11(2):5-6.
[26]乔丽娟,徐建国,马克荣.苏木抗癌有效成分对HL-60细胞的增殖抑制.海南医学,2001,12(3):55.
[27]EC Kim,YS Hwang,HJ Lee,SK Lee,et al.Caesalpinia sappan induces cell death by increasing the expression of P53 and P21 WAf1/CIP1 in head and neck cancer cells.Am J Chin Med,2005,33(3):405-414.
[28]郑虎占,董泽宏,余靖,等.中药现代研究与应用[M].北京:学苑出版社.1999.2261
[29]山口琢儿.苏木的活性成分研究.国外医学中医中药分册.1991.13(2):58
[30]郑虎占.董泽宏.佘靖等.中药现代研究与应用.北京.学苑出版社.1999.1:2261-2267
[31]Chiaki Fuke.Johji Yamahara.Takashi Shimokawa et al Two aromatic compounds related to brazilin from CaesalPinia Sappan.Phytochemistry.1985.24(10):2403-2405
[32]中国科学院上海有机化学研究所中药有效成分数据库.
[33]Masahiro Nagai.Seiji Nagumo.Shu-mei Lee et al.Protosappanin A,a Novel Biphenyl compound from Sappan Lignum.Chem Pharm Bull.1986.34(1):1-6
[34]Masahiro Nagai.Seiji Nagumo.ProtosappaninsE-landE-2,Stereoisomeric Dibenzoxocins combined with Brazilin from Sappan Lignum.Chem Pharm Bull.1990.38(6):1490
[35]YS Chang,ER Woo.Korean medicinal plants inhibiting to human immuno- deficiency virus type 1(HIV-1) fusion.Phytother Res,2003,17(4):426-429.
[36]MS Zheng;YZ Zhang.Anti-HBsAg herbs employing ELISA technique.Chung His I Chieh Ho Tsa Chih,1990,10(9):560-562.
[37]NI Baek,SG Jeon,EM Ahn,et al.Anticonvulsant compounds from thewood of Caesalpinia sappan L..Arch Pharmacal Res,2000,23(4):344-348.
[38]KH Lee,HJ Lee,HI Park,et al.Screening of prolyl endopeptidase inhibitors fromnatural products.Yakhak Hoechi,1997,41(2):153-160.
[39]BH Lee,BW Choi,GS Ryu,et al.Screening of the inhibitors from medicinal plants.Saengyak Hakhoechi,1997,28(4):167-173.
[40]YW Xie,DS Ming,HX Xu,et al.Vaso relaxing effeets of Caesalpinia sappan.Involvement of endogenous nitric oxide.Life Sci,2000,67(15):1913-1918.
[41]IM Shih,HS Chiang,LL Yang,et al.Antimotility effeets of Chinese herbal- medicines on human sperm.J Formos Med Assoc,1990,89(6):466-469.
[42]梁书评,周淑艳.蒙药苏木治疗痛经60例.中国民族医药杂志,2003,12(4):27-28.
[43]韩艳,郑世成,张根印.透骨苏木公英汤外用治疗膝关节非感染性滑膜炎26例.陕西中医学院学报,2006,29(1):38
[1]肖崇厚《中药化学》第2版,上海:上海科学技术出版社,1994
[2]匡海学《中药化学》第3版,北京:中国中医药出版社,2004
[3]金竹萍.超临界流体萃取技术的应用及研究进展[J].山西化工,2007,27(2):42.
[4]曹茂堂.超临界萃取技术在医药领域中的应用[J].时珍国医国药,2003,14(12):784-785.
[5]郭章华,周敏华.超临界萃取技术在医药领域中的应用[J].国际医药卫生导报,2003,9(2-3):82-83.
[6]陈磊,刘晔,康鲁平,等.超临界萃取技术在中草药研究中的应用[J].药学实践杂志,2004,(4):193-196.
[7]周庆华,范卓文,杨波.超临界萃取技术在中药中的应用[J].中医药信息,2002,19(6):18-19.
[8]马海乐,王超,刘伟平.葛根总黄酮微波辅助萃取技术[J].江苏大学学报(自然科学版),2005,26(2):98.
[9]王白军,王国卫,齐誉.白芥子中总黄酮的微波提取与含量测定[J].时珍国医国药,2005,16(6):512.
[10]曾里,夏之宁.超声波和微波对中药提取的促进和影响[J].化学研究与应用,2002,14(3):245.
[11]朱凯,朱新宝.超临界CO2萃取八角茴香精油的研究[J].生物质化学工程,2007,1:28.
[12]宋应华,郁威,王远明.超临界CO2萃取川芎挥发油过程研究[J].中成药,2005,27(9):1007.
[13]唐庆峰,吴振廷,金涛,等.地鳖虫活性物质的超临界CO2萃取及其药效[J].昆虫知识,2006,43(3):375.
[14]刘莉,徐新刚,陈飞龙,等.超临界CO2萃取云南红豆杉枝叶中紫杉醇的研究[J].中成药,2006,28(4):480.
[15]蔡庆群,黄耀海,席萍,等.藿香正气方超临界萃取物质谱及薄层色谱分析[J].现代食品与药品杂志,2006,16(3):32.
[16]Quan Cem,Li shufen,Tian Song Jiang,et al Supercritical Fluid Extraction and clean up of organochlorine Pesticides in Ginseng[J].The journal of Supercritical Fluids,2004,31(2):149.
[17]王玉华,容蓉,魏英勤,等.四物汤及单药材超临界萃取物的质量控制和稳定性研究[J].世界科学技术——中医药现代化,2005,7(2):50.
[18]郑颖,张红,宋其生,等.芪灵益肝煎及其CO2超临界萃取液对肝癌细胞株H22端粒酶反转录亚单位表达的影响[J].中国临床药学杂志,2005,14(3):180.
[19]罗兰,朱丹妮,严永清.当归芍药散精简方CO2超临界萃取部位化学成分研究[J].中成药,2005,27(11):1251.
[20]葛发欢.再论中药现化代与超临界二氧化碳萃取技术[J].中药材,2003,26(5):373.
[21]陈晓东.对二氧化碳超临界萃取运用在中药提取上的看法[J].医药工程设计杂志,2004,25(3):1.
[22]张代佳,刘传斌,修志龙.微波技术在植物细胞内有效成分提取中的应用[J].中草药,2000,31(9):.
[23]魏亚冉.油桃果皮红色素的微波提取工艺及特性研究[J].中国食品添加剂,2007,1:76.
[24]马海乐,王超,刘伟平.葛根总黄酮微波辅助萃取技术[J].江苏大学学报(自然科学版),2005,26(2):98.
[25]王晓燕,黄敏仁,韩正敏.微波辅助提取石蒜属植物忽地笑中加兰他敏的研究[J].南京中医药大学学报,2005,21(6):374.
[26]郝金玉,韩伟,施超欧,等.黄花蒿中青蒿素的微波辅助提取[J].中国医药工业杂志,2002,33(8):385.
[27]韩伟,郝金玉,薛伯勇,等.微波辅助提取青蒿素的研究[J].中成药,2002,24(2):83
[28]Young J C.Microwave-Assisted Extraction of the Fungal metaboliteer Gosterol and Total Faritty Acids[J].Journal of Agriculture and chemistry,1995,43:2904.
[29]DabiritM,Salimi S,GhassempourA,et al Optimization of Microwave-Assisted Extraction for Alizarin and Purpurin in Rubiaceae Plants and its Comparison with Conventional Extraction Methods[J].J Sep 2005,28(4):387-396.
[30]Jones N M,et al Comparison of Methods for Extraction of Tabacco Alkaloids[J].JAOAC Int,2001,84(2):309.
[31]Brachet A,et al Focused Microwave assisted Extraction of Cocaine and Benzoy lecgonine from Caca Leaves[J].Phytochem Ana,2002,13(3):162.
[32]Then M,et al Effect of Sample Handing on Alkaloid and Mineral Content of Aqueous Extracts of Great Celandine[J].ChromatogrA,2000,889:69.
[33]史小萌.超声法提取银鹊树种皮总黄酮的工艺研究[J].西北林学院学报,2007,22(2):148.
[34]胡斌杰,陈金锋,王宫南.超声波法与传统热水法提取灵芝多糖的比较研究[J].食品工业科技,2007,28(2):190-192.
[35]郭孝武.超声提取与碱性浸泡法对小檗碱成分提出率的影响[J].陕西师范大学学报,1997,259(1):47.
[36]郭孝武.超声提取对黄连素提出率的影响[J].中国中药杂志,1995,20(11):673.
[37]Schinor EC,Salvad MJ,Turatti CI,Comparison of Classical and Ultra-Sound -Assisted Extractions of Steroids and Triterpenoids from Three Chrestaspp[J].Ultrasonics Sono-chemistry,2005,12:301.
[38]白中明.工业化超声波中药提取装备研究[J].中草药,2005,36(8):1274.
[39]王成东.超声波应用于中药提取生产的体会及前景分析[J].机电信息,2004,(18):31.
[40]薛伟明,张效林,刘袖洞,等.酶一膜法药用植物有效成分提取分离过程应用研究[J].西北大学学报(自然科学版),1997,27(6):494-498.
[41]薛伟明,张效林,亢茂德,等.红花黄色素的酶法提取应用研究[J].化学工程,1999,27(1):42-44,50.
[42]王廉,张效林,薛伟明,等.侧柏叶有效成分提取过程研究[J].化学工程,1998,26(3):21-24.
[43]刘佳佳,赵国玲,章晓骅,等.金银花绿原酸酶法提取新工艺研究[J].中成药,2002,24(6):416-418.
[44]杨军宜,尹蓉丽,杨胜,等.纤维素酶在三七提取工业中的应用[J].中国中医药科技,2001,8(5):F003-F003.
[45]王晓,张红侠,王其亮,等.酶法提取山楂叶中总黄酮的研究[J].工艺技术,2002,23(3):37-39.
[46]董海丽,纵伟.酶法提取姜黄素的研究[J].纯碱工业,2000,6:55-56,60.
[47]纵伟.酶法提取银杏叶中总黄酮的研究[J].山西食品工业,2000,1:13-15.
[48]李兆龙,虞杏英.用树脂法和酶法从银杏叶中提取黄酮类化合物的专利介绍[J].中成药,1994,16(10):52.
[49]侯嵘桥,孟宪纾,徐育新.以酶解法从中药及药渣制备β-葡萄糖的研究[J].沈阳药学院学报,1994,11(4):289.
[50]王兴文.水提三七总苷[J].云南中医学院学报,2001,24(3):1-3
[51]李道荣,李魁,段雪梅,蒲黄花粉多糖提取工艺研究[J].郑州工程学院学报,2002,23(4):55-57,63
[52]傅博强,谢明勇,周鹏,等.纤维素酶法提取茶多糖[J].无锡轻工大学学报,2002,21(4):362-366.
[53]李元波,殷辉安,唐明林,等.复合酶解法提取三七皂苷的实验研究[J].天然产物研究与开发,2005,17(4):488.
[54]闫巧娟,韩鲁佳,江正强.纤维素酶法提取黄芪多糖[J].中草药,2005,36(12):1804.
[55]许明淑,邢新会,罗明芳,等.银杏叶黄酮的酶法强化提取工艺条件研究[J].中国实验方剂学杂志,2006,12(4):2.
[56]余冬生,卫纪章.酶法提取香菇多糖[J].江苏食品与发酵,2001,(4):10,11.
[57]沈爱英,谷文英.复合酶法提取姬松茸子实体多糖的研究[J].食用菌,2001:23(3):7-9.
[58]陈哲超,林宇野,谢必峰,等.复合酶解法提取香菇多糖蛋白的研究[J].生物工程进展,1995,15(1):47-50.
[59]孙兴权,付蕾,曹云龙,等.林蛙多糖(TCPS)提取工艺的初步研究[J].吉林农业大学学报,2001,23(4):108-110.
[60]马田田.纤维素酶用于中药提取的初步研究[J].中草药,1994,25(3):123,139.
[61]马桔云.纤维素酶在黄连提取工艺中的应用[J].中草药,2000,31(2):103.
[62]马桔云.纤维素酶用于中药穿心莲提取的初步研究[J].黑龙江医药,2000,31(2):103.
[63]韩颂,李晓晖.纤维素酶在黄芩提取工艺中应用的初步探索[J].黑龙江医药,1997,10(6):339-340
[64]林翠英,周晶,赵晶,等.芦丁超声提取新技术的再探索[J].中草药,1999,30(5):350.
[65]张兆旺,孙秀梅.半仿生提取法的特点与应用[J].提取技术与工艺,2000,2(1):35.
[66]周庆华,范卓文,杨波.超临界萃取技术在中药中的应用[J].中医药信息,2002,19(6):18-191.
[67]孙秀梅,张兆旺,丁菊英,等.寒痛定泡腾冲剂4种提取方法的比较[J].中国中药杂志,1006,21(3):159-161.
[68]孙秀梅,张兆旺,卢连华,等.黄连解毒颗粒2剂4种提取方法的成分比较[J].中国中药杂志,1996,21(8):474.
[69]孙秀梅,张兆旺,郭婕,等.芍甘止痛颗粒剂4利提取方法的成分比较[J].中成药,1996,18(11):34.
[70]张兆旺,孙秀梅.半仿生提取法的特点与应用[J].世界科学技术—中药现代化,2000,2(1):35.
[71]孙秀梅,张兆旺,张学兰,等.四神茶剂4种提取方法的成分比较[J].中国中药杂志,1997,22(6):349-351.
[72]贺立中,徐德云,黄泽华,等.采用超滤技术制备伸筋草注射液的中试生产研究.中成药,2002,24(2):137-9.
[73]张忠义,雷正杰,黄昌全,等.超临界CO2—分子蒸馏制备大蒜注射液.中国医院药学杂志,2002,22(101:581-2.
[74]张宇,曹玉娥,李殿奎.应用超滤技术制备四逆汤口服液的研究.佳木斯医学院学报, 1992,15(2):30-2.
[75]刘洪谦,屈凌波,贾金付.生脉饮口服液超滤技术研究.中草药,1996,27(4):209-11.
[76]朱献镭.连续动态逆流提取工艺流程及预浸器的设计[J].轻工机械,2005,(4):127.
[77]斯黎明.逆流动态中药提取工艺[J].医药工程设计,2003,24(4):23.
[1]曾益新,《肿瘤学》第2版,北京:人民卫生出版社,2003
[2]刘复生,《中国肿瘤病理学分类》,北京:科学技术文献出版社,2001
[3]贾英杰.中医药“立体疗法”治疗恶性肿瘤新理念.开卷有益:求医问药,2007,(10):12-13.
[4]McCann J,Ames BN.Detection of carcinogens as mutagens in the Salmonella/microsome test:assay of 300 chemicals:discussion.Proc Natl Acad Sci U S A.1976,73(3):950-4.
[5]Ames BN.Identifying environmental chemicals causing mutations and cancer.Science,1979,204(4393):587-93.
[6]Ames BN,Magaw R,Gold LS.Ranking possible carcinogenic hazards.Science.1987,17(4799):271-80.
[7]Ames BN.What are the major carcinogens in the etiology of human cancer?Environmental pollution,natural carcinogens,and the causes of human cancer:six errors.Important Adv Oncol.1989:237-47.
[8]Ames BN,Gold LS,Willett WC.The causes and prevention of cancer.Proc Natl Acad Sci U S A.1995,92(12):5258-65.
[9]Katsusaburo Yamagiwa.CA Cancer J Clin.1977,27(3):172-3.
[10]Henschen F.Yamagiwa's tar cancer and its historical significance.From Percival Pott to Katsusaburo Yamagiwa.Gann.1968,59:447-51.
[11]BERENBLUM I.A speculative review:the probable nature of promoting action and its significance in the understanding of the mechanism of carcinogenesis.Cancer Res.1954 Aug:14(7):471-7.
[12]Berenblum I.A re-evaluation of the concept of cocarciongenesis.Prog Exp Tumor Res.1969:11:21-30.
[13]Berenblum I.Established principles and unresolved problems in carcinogenesis.J Natl Cancer Inst.1978 Apr:60(4):723-6.
[14]Berenblum I,Armuth V.Two independent aspects of tumor promotion.Biochim Biophys Acta.1981,651(1):51-63.
[15]Stockwell S.Classics in oncology:Isaac Berenblum,M.D.CA Cancer J Clin.1981,31(4):239-53.
[16]Knudson AG Jr.Mutation and cancer:statistical study of retinoblastoma.Proc Natl Acad Sci USA.1971,68(4):820-3.
[17]Knudson AG Two genetic hits (more or less)to cancer.Nat Rev Cancer.2001,l(2):157-62.
[18]Burnet FM.The concept of immunological surveillance.Prog Exp Tumor Res.1970:13:1-27.
[19]Burnet FM.Immunological surveillance in neoplasia.Transplant Rev.1971:7:3-25.
[20]Lanier LL.A renaissance for the tumor immunosurveillance hypothesis.Nat Med.2001,7(11):1178-80.
[21]Dunn GP,Bruce AT,Dceda H,Old LJ,Schreiber RD.Cancer immunoediting:from immunosurveillance to tumor escape.Nat Immunol.2002,3(ll):991-8.
[22]Ochsenbein AF.Principles of tumor immunosurveillance and implications for immunotherapy.Cancer Gene Ther.2002,9(12):1043-55.
[23]Boon T,van Baren N.Immunosurveillance against cancer and immunotherapy—synergy or antagonism? N Engl J Med.2003,348(3):252-4.
[24]Dunn GP,Old LJ,Schreiber RD.The immunobiology of cancer immunosurveillance and immunoediting.Immunity.2004,21(2):137-48.
[25]Qin Z,Blankenstein T.A cancer immunosurveillance controversy.Nat Immunol.2004,5(1):3-5.
[26]Ichim CV.Revisiting immunosurveillance and immunostimulation:Implications for cancer immunotherapy.J Transl Med.2005,3(1):8.
[27]Klein G,Klein E.Surveillance against tumors~is it mainly immunological? Immunol Lett.2005,100(1):29-33.
[28]Zirvogel L,Tesniere A,Kroemer G Cancer despite immunosurveillance:immunoselection and immunosubversion.Nat Rev hnmunol.2006,6(l0):715-27.
[29]Smyth MJ,Dunn GP,Schreiber RD.Cancer immunosurveillance and immunoediting:the roles of immunity in suppressing tumor development and shaping tumor immunogenicity.Adv Immunol.2006:90:1-50.
[30]Prehn RT.An adaptive immune reaction may be necessary for cancer development-Theor Biol Med Model.2006,3:3(1):6
[31]Bishop JM.Molecular themes in oncogenesis.Cell,1991,64:235-248.
[32]Lengauer C,Kinzler KW,Vogelstein B.Genetic instabilities in human cancers.Nature,1998,396:643-649.
[33]Mao L,Sidransky D Cancer screening based on genetic alterations in human tumors.Cancer Res 1994,54:1939s-1940s.
[34]Sidransky D.Molecular markers in cancer:can we make better predictions? Int J Cancer 1995,64:1-2.
[35]Renan MJ.How many mutations are required for tumorigenesis? Implications from human cancer data.Mol Carcinog1993,7:139-146.
[36]Loeb KR,Loeb LA Significance of multiple mutations in cancer.Carcinogenesis 2000,21:379-385.
[37]Cohen AM,Minsky BD,Schilsky RL.Cancer of the colon.In:VT DeVita,S Hellman,SA Rosenberg(eds):Cancer:Principles and Practice of Oncology,5th ed.Lippincott-Raven,Philadelphia1997,1144-1197.
[38]Weinberg RA.The action of oncogenes in the cytoplasm and nucleus.Science.1985230(4727):770-6.
[39]Land H,Chen AC,Morgenstem JP,Parada LF,Weinberg RA.Behavior of myc and ras oncogenes in transformation of rat embryo fibroblasts.Mol Cell Biol.1986,6:1917-25.
[40]Friend SH,Bemards R,Rogelj S,Weinberg RA,Rapaport JM,Albert DM,Dryja TP.A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma.Nature.1986,323(6089):643-6.
[41]Weinberg RA.Oncogenes,antioncogenes,and the molecular bases of multistep carcinogenesis.Cancer Res.1989,49(14):3713-21.
[42]Shigeta T,Takagi M,Delia D,Chessa L,Iwata S,Kanke Y,Asada M,Eguchi M,Mizutani S Defective control of apoptosis and mitotic spindle checkpoint in heterozygous carriers of ATM mutations.Cancer Res 1999,59:2602-2607.
[43]Lipkin SM,Wang V,Jacoby R,Banerjee-Basu S,Baxevanis AD,Lynch HT,Elliott RM,Collins FS MLH3:a DNA mismatch repair gene associated with mammalian microsatellite instability.Nat Genet 2000,24:27-35.
[44]Chang CL,Marra G,Chauhan DP,Ha HT,Chang DK,Ricciardiello L,Randolph A,Carethers JM,Boland CR Oxidative stress inactivates the human DNA mismatch repair system.Am J Physiol Cell Physiol 2002283:C148-154.
[45]孟灵源.中医药治疗恶性肿瘤的思路探讨.中医药管理杂志,2007,15(8):625-627.
[46]潘国凤,朱晓新,张晓东.肿瘤系统生物学的发展与中医药的现代化[J].中华中医药杂志,2007,22(10):698-701.
[47]徐振晔,郑展.试论中医阴阳平衡法治疗恶性肿瘤.上海中医药杂志,2007,41(4):37-39.
[48]苏婉,徐振晔.肿瘤靶向治疗与中药多靶点效应的研究进展[J].上海中医药杂 志,2007,41(9):87-88.
[49]王笑民,郁仁存,胡玉芳等.益气活血法对癌症血癖证影响的临床与实验研究.实用中西医结合杂志,1996,9(5):315
[50]王禹堂,王笑民,郁仁存等.癌症患者的血癖证研究.中国中医药学报,1996,11(6):57
[51]傅乃武,范贤俊,王永泉等.丹参对实验性肿瘤生长和转移的影响及其作用原理的初步探讨.中华肿瘤杂志,1981,3(3):165-167
[52]刘明章,黄贻建,肖伟琪.丹参酮n-A磺酸钠对Lewis癌无促进生长与转移作用.中国药理学报,1991,12(6):534-537
[53]徐德成,张培宇.活血化癖强度与气血双亏型胃癌转移率相关性机理探讨中医杂志.1998,39(3):156-157
[54]张俊.顾王荣老中医辨治肝癌的经验.新中医,1999,31(1):8-9
[55]翁维良.20种活血药对血液粘滞性作用的比较观察中医杂志,1984,25(2):69-71
[56]王涛,杨华山.菝葜乙酸乙酯提取物抗癌机制研究肿瘤基础与临床[J].2004,20(2):129-131
[57]付丽华,胡玉红,孙盛梅,卢北燕.白藜芦醇抗肿瘤作用的研究进展[J].黑龙江医药科学,2006,29(6):98-100
[58]曹文涛.白藜芦醇抗肿瘤血管生成机制[J].国际肿瘤学杂志,2006,3(12):918.921
[59]伍石华.白杨素的抗肿瘤作用及机理研究[J].湖南师范大学学报(医学版),2006,3(4):78-81
[60]韩玉萍,洪行球.姜黄色素抗肿瘤作用的研究[J].中国实用医药杂志,2007,2(1):96-97
[61]符矗,龚涛,刘振谧,张志荣.姜黄素衍生物在体外的抗肿瘤试验[J].华西药学杂志,2006,21(6):552-553
[62]官杰,罗晓庆,王琪,李殿俊.壳寡糖抑制肿瘤的实验研究[J]冲国免疫马玲娣,张彦,文世宏,和於娟,刘小珊,康格菲,蒋纪恺.苦参碱抗肿瘤作用及其机制的初步研究[J].中国免疫学杂志,2007,23(5):434-437
[63]李建军,雷林生,余传林,朱正光,马安德.灵芝多糖抗肿瘤作用的免疫学相关性研究[J].中药材,2007,30(1):71.73
[64]张健英,毕建成,楚健子.灵芝在预防肿瘤化疗患者白细胞减少中的作用[J].中国中医药信息杂志,2007,13(11):63
[65]蒋国松.茉莉素抗肿瘤作用及其机制研究进展[J].国际肿瘤学杂志,2007,34(3):167-170
[66]J本艳,段大航,李坦.蒲公英对消化系统作用及抗肿瘤研究现状[J].吉林中医药,2006,26(12):72-73
[67]李世辉,潘岐.青蒿素及其衍生物抗肿瘤机制研究进展[J].中成药,2007,29(4):561-562
[68]余艳秋.蚯蚓提取物抗肿瘤作用的研究进展[J].临床肿瘤学杂志,2007,12(3):232·234
[69]黄松音.去甲斑蝥素抗肿瘤作用基础与临床研究进展[J].国际检验医学杂志,2007,28(3):235.237
[70]郭风,于广久.人参皂甙Rh2诱导肿瘤细胞凋亡的研究进展[J].锦州医学院学 报,2007,27(5):52-54
[71]杨全,张卉,王琦,王文全.桑黄胞外多糖抗肿瘤活性的研究[J].北京中医药大学学报表,2007,301 3):188-190
[72]徐建国,郭素堂,乔丽娟,张少云,史天良,刘维兰,郑启英.苏木提取液抑制肿瘤作用的研究[J].肿瘤研究与临床,2006,18(11):726-727
[73]张维东,张月英,王朝霞,王兆明,贾青.蝎毒多肽提取物对肿瘤生长和细胞免疫功能的影响[J].山东大学学报(医学版),2007,45(3):286-289
[74]林梅,裴军昌,张东生,时军.雄黄抗癌作用的研究发展[J].中国实用医药杂志,2007,2(13):1-4
[75]李翠玲,张玲,顾洪涛,王军,毛海婷,杨尚军,温培娥.淫羊藿苷体内抑瘤作用及其机～J[J].中国肿瘤生物治疗杂志,2007,14(2):137-142
[76]曲萌,董志恒,盖晓东,毕胜利,王冰梅.银耳多糖对小鼠移植性肝癌治疗作用及机制的实验研究[J].中国老年学杂志,2006,26(12):1662.1665
[77]单保恩,付小梅,华正祥,李巧霞,梁文杰,刘冀琴,张华,刘刚参.中药五加皮提取成分抗肿瘤活性作用机理研究[J].中国中西医结合杂志,2005,25(9):825-828
[78]李劲,林奕,陈闻纳,赖惠萍.中药紫草对离体人乳头瘤病毒DNA作用的实验研究[J].成都中医药大学学报,2006,29(4):52-54
[79]郭志军.香菇多糖抗肿瘤应用研究概况[J].中医药导报,2007,13(1):78-80
[80]常垄,范延英,任青华,李强.中药三龙丹的药效学研究[J].中国实用医学,2007,1(5):29-30
[81]韦良宏,陈海东,林瑶光.参芪扶正注射液对老年中晚期恶性肿瘤病人生活质量的影响[J].广西医学,2007,299(1):85-86
[82]孙艳,孙艳影,蒋丽艳.冬虫夏草制剂对恶性肿瘤患者化疗后T细胞亚群的影响[J].齐齐哈尔医学院学报,2006,27(17):2063-2064
[83]张广信,李岑,马秋波,辛雨玲.扶正降逆颗粒治疗恶性肿瘤化疗所致毒副作用临床观察[J].河北中医药,2007,29(1):24-25
[84]邓毅丰,谢湘林,张大方.扶正消积胶囊对荷瘤动物免疫功能的影响[J].长春中医药大学学报,2007,23(1):19-20
[85]嫒媛,贾彤,张广美.扶正消瘤颗粒对环磷酰胺处理后小鼠骨髓及免疫功能的影响[J].中国中医药科技.2006,13(6):402
[86]魏光敏.岩舒联合化疗治疗中晚期恶性肿瘤疗效观察[J].中国误诊学杂志,2007,7(3):488-489
[87]高宏,殷东风,张宁苏.济川煎加味治疗肿瘤病人便秘的临床观察[J].辽宁中医杂志,2007,34(5):612-613
[88]徐杰军,王蕾.加昧逍遥散改善肿瘤化疗毒副反应128例临床观察[J].西部医学,2007,19(3):428-430
[89]陈衍智,李萍萍,杨华.酸枣仁汤加味治疗肿瘤患者失眠症54例体会[J].中医药临床杂志,2007,19(1):3
[90]韩旭.消肿散癃汤治疗癌性疼痛99例[J].新中医,2007,39(4):85-86
[91]翁德新.血府逐瘀汤联合5—氟尿嘧啶治疗小鼠移植性肿瘤的实验研究[J].现代中西医结合杂志,2007,16(3):311-312
[92]张学民,钱钢,陈洁.自拟健脾补肾方治疗肿瘤相关性贫血疗效观察[J].江西中医药,2007,38(292):25-26
[93]赵晓珍,徐振晔,方肇勤.中医药治疗肿瘤的不同治法与基因组学结合研究应用的探讨[J].山西中医,2007,23(2):1-2
[94]杨杰,高锋,孙洋,丁维俊,王米渠.中药抗癌的分子药效探讨[J].中华中医药学刊,2007,25(3):577-579
[95]徐伟,孙维峰,汪立新.中药抗化疗呕吐作用机制的实验研究进展[J].中国中西医结合消化杂志,2007,15(1):65
[96]徐霞飞,陆茵冲药抗肿瘤血管生成研究进展[J].现代中药研究与实践.2007,21(1):61-64
[97]蔡宇,冯笑珍.中药逆转肿瘤多药耐药研究现状[J].现代医院.2007,7(1):4-6
[98]李杰.试谈中药十八反,十九畏对药组方对各种肿瘤的特殊疗效[J].医药世界,2007,(2):5-6
[1]乔丽娟,田艳伟等.苏木抗癌有效成分作用荷瘤小鼠TSGF的观察.山西职工医学院学报,2001,11(2):5-7.
[2]徐慧,周志华,杨俊山.苏木化学成分的研究.中国中药杂志,1994,19(8):485.
[3]杨广文,程秀珍,马俊英.苏木煎液的抗癌作用研究.山西临床医药杂志,1999,8(2):92-93.
[4]杨锋,樊良卿,沈翔,等,八味活血化瘀中药对小鼠细胞免疫调节作用的量效关系研究[J]中国实验临床免疫学杂志,1997,9(1):49-52
[5]于波,侯静波,吕航,等.苏木有效成分对大鼠免疫活性细胞的影响[J]中国急救医学,2002,22(4):187-189
[6]刘昱霞,王淑玲等,中药提取方法概论[J],中国药业.2008,17(16)2-3
[7]于波,侯静波,吕航,等.苏木提取物对心脏移植大鼠T淋巴细胞亚群的免疫抑制和对心肌的保护作用.[J]中国地方病学杂志,2004,23:539-542.
[1]张民庆,龚惠明,丁冠民,等.抗肿瘤中药的临床应用.北京,人民卫生出版社,1998.271-272
[2]杨锋,戴关海,沈翔,等.苏木对体外人淋巴细胞增殖的抑制作用.上海免疫学杂志,1997,17(4):212-215
[3]Tao L,Zhou L,Zheng L,Yao M.Elemene displays anti-cancer ability on laryngeal cancer cells in vitro and in vivo.Cancer Chemother Pharmacol.2006,58:24-34.
[4]花文峰,蔡绍晖.β-榄香烯抗肿瘤作用的基础与临床研究冲药材,2006,29(1):93-97.
[5]Meijer L,Borgne A,Mulner O,et al.Biochemical and cellular effects of roscovitine,apotent and selective inhibitor of the cyclin-dependent kinases cdc2,cdk2 and cdk5.Eur J Biochem 1997,243(1-2):527-536.
[1]俞顺章.原发性肝癌流行病学研究进展[J].实用肿瘤杂志,1998,13(3):130
[2]吴孟超.原发性肝癌外科综合治疗的现状和展望[J].中华外科杂志,2004,42(1):13-15
[3]邹移海,徐志伟,苏钢强.实验动物学[M].北京:科学出版社,2004:154
[4]苗明三.实验动物与动物实验方法[M].上海:上海科学技术出版社,2005:67
[5]张绪慧,陈达理,罗荣城.鳖甲煎丸对H22荷瘤小鼠的抑瘤作用及对增殖核抗原表达的影响[J].南方医科大学学报,2006,26(12):1791-1793
[6]陈奇.中药药理研究方法学[M].北京:人民卫生出版社,1993
[7]陈清勇,吴玉泉,何永生,等.复方抗瘤冲剂抑制小鼠肉瘤S180的生长及对p53和增殖细胞核抗原表达的影响[J].解放军医学杂志,2001,26(11):853-855.
[8]水若鸿,等.套细胞淋巴瘤石蜡包埋组织中细胞周期蛋白D1和t(11;14)易位检测的临床病理意义[J].中华病理学杂志,2003,8,32:337-341.
[9]杜标炎,等.六味地黄丸对小鼠移植性肝癌自杀基因治疗增效作用的病理学研究[J].广州中医药大学学报,2007,24(5):386-391.
[10]许良中,杨文涛.免疫组织化学反应结果的判断标准[J].中国癌症杂志,1996,6(4):229-231
[11]周振华,宋明志,于尔辛等.健脾理气方对小鼠HAC肝癌细胞凋亡和bax基因蛋白表达影响的实验研究[J].中国中西医结合脾胃杂志,2000,8(2):78-82
[12]刘文兰,张颖.细胞凋亡检测方法[J].解剖科学进展,1999,5(4):330-332
[13]赵利红,崔利德,李陈莉.细胞凋亡的检测方法[J],河北医药,2005,27(10),783-785
[14]Lipponen P,Aaltomaa S,Apoptosis in bladder cancer as related to standard prognostic factors and prognosis[J].Pathol,994,173:333
[15]Lipponen P,Aaltomaa S,Kosma VA,Apoptosis in breast cancer as related histopathological characteristics and prognosis,Eta J Cancer,1994,30A:2068
[16]Brambilla E,Negoescu A,Gazzeri S,et al.Apoptosis related factors p53,Bcl-2,and Bax in neuroendocrine lung tumors[J].Am J Pathol,1996,149(6):1941-1952
[17]Schulte HR,Bursch W,Kranpp GB,et al.Cell proliferation and apoptosis in normal liver and preneoplastic foc[J].Environ Health Perspect,1993,101(5);87-90
[18]刘明华,卿晨,刘吉开,等.伍氏百叶散对荷瘤小鼠肿瘤生长及免疫功能的影响[J].中国新药杂志,2006,15(3):201-204
[19]Inik Chang,Sunshin Kim,Ja Young Kim,et al.Nuclear Factor β Protects Pancreaticβ-Cells From Tumor Necrosis Factor-α-Mediated Apoptosis[J].Diabetes,2003,52(5):1169-1175
[20]Weiqin Jiang,Zongjian Zhu,Neehar Bhatia,et al.Mechanisms of Energy Restriction:Effects of Corticosterone on Cell Growth,Cell Cycle Mzchinery,and Apoptosis[J].Cancer Research,2002,62(15):5280-5287
[21]龚守良.细胞凋亡分子机理的研究现状[J].中国实验诊断学,2000,4(3):147-148
[22]Adams JM,Cory S.The bcl-2 protein family:arbiters of cell survival[J].Science,1998,281(5381):1322-1326
[23]Humlova Z.Protooncogene Bcl-2 in process ofapoptosis[J].Sb Lek,2002,103:419-425