异常黑胆质成熟剂总黄酮抗肿瘤及逆转肿瘤细胞耐药性机制研究
|
摘要
肿瘤是严重威胁人类健康的一类疾病。寻找有效的抗肿瘤药物与方法,彻底攻克肿瘤是世界医学界的重要研究课题。肿瘤治疗强调综合治疗,因中医中药的应用可使患者症状改善显著,全身状态保持较好,病情发展较慢,肿瘤亦可缩小或带瘤长期生存,故其在中晚期肿瘤的综合治疗中占有重要地位[1]。肿瘤化疗过程中,出现多药耐药(Multidrug resistance MDR)是化疗失败的主要原因之一。当今抗肿瘤药物发展战略的重点之一是从天然药物中寻找活性成分,而我国有丰富的中药材资源以及数千年的中医药理论与实践经验,对中药抗肿瘤作用的研究与开发前景良好。目前已筛选出一些具有抗肿瘤作用的天然中药及单体,如苦参碱、三羟异黄酮、白藜芦醇、紫杉醇等,其中一些已广泛地应用于临床,显示出良好的效果。同样,天然药物中寻找逆转肿瘤耐药性、增加化疗药物作用、有效低毒的逆转剂,长期以来一直是医学界关注的的热点。维吾尔医学认为,异常黑胆质作为胆液质、血液质、粘液质、黑胆质被“燃烧”,继而“沉淀”的最终病理产物或表现形式,经常导致肿瘤等难治性疾病。临床大部分肿瘤患者也表现为异常黑胆质性[2]。我区名老维医巴黑.玉素甫和吐尔逊·托乎提阿吉等多年来根据维医理论和临床治疗原则将维医异常黑胆质成熟剂应用于癌症患者的治疗,取得良好的疗效,被患者誉为“神医”。
肿瘤的维医异常黑胆质成熟剂治疗有良好效果,其促使我们,采用现代科学技术对异常黑胆质成熟剂的抗肿瘤作用进行深入研究,揭示其作用机理。十几年来,哈木拉提教授为首的课题组采用现代科学技术对异常黑胆质成熟剂作用机理进行了较深入的研究。动物实验研究表明,该复方能够促进免疫细胞的生长和增殖,提高机体的免疫功能,增强免疫器官中抗氧化酶的活性,增强机体的抗癌能力[3-8]。研究发现,异常黑胆质成熟剂具有明显的抗氧化应激对淋巴细胞DNA的损伤作用及减轻氧化造成的淋巴细胞毒性,能上调淋巴细胞Bcl-2蛋白的表达水平,能显著抑制氧化应激诱导的淋巴细胞的凋亡,能明显降低氧化诱导对淋巴细胞NF-κB的激活作用,同时异常黑胆质成熟剂本身也能激活淋巴细胞的NF-κB作用。异常黑胆质成熟剂中可能存在作用于细胞增殖凋亡信号传导通路和影响相关基因表达调节的活性成份,这些仅在已发生癌变的细胞中发挥着诱导细胞凋亡、上调抑癌基因表达和下调凋亡抑制基因的作用,而且在正常细胞中发挥着抗氧化应激对细胞DNA的损伤作用及减轻氧化造成的细胞毒性,通过上调淋巴细胞Bcl-2蛋白的表达水平,抑制氧化应激诱导的淋巴细胞的凋亡、降低氧化诱导对淋巴细胞NF-κB的激活作用,从而预防细胞发生癌变[9-13]。通过动物实验[14]观察受照射小鼠体重、脾脏指数、骨髓功能和SOD等指标的变化,发现辐射后各组小鼠体质量均下降;异常黑胆质成熟剂干预各组脾脏指数明显低于对照,各组异常黑胆质成熟剂干预后受照射小鼠的SOD值、白细胞数、红细胞数和30d生存率均有明显的升高。认为在活体组织中异常黑胆质成熟剂对辐射有确切的保护作用。
同时,以往工作中,发现异常黑胆质成熟剂对HepG2(人肝癌细胞)[15]、Hela(人宫颈癌细胞)[16]、T淋巴瘤细胞[17]、乳腺癌细胞[18]体外具有抗癌作用,已初步确定异常黑胆质成熟剂总黄酮是异常黑胆质成熟剂重要的抗癌活性成分。我们应用运用体外细胞培养技术,研究异常黑胆质成熟剂总黄酮对结肠癌细胞增殖、凋亡、分化的影响;运用动物实验来研究总黄酮对结肠癌癌前期病变的预防和抑制作用;以进一步明确抗癌谱的同时探讨异常黑胆质成熟剂总黄酮逆转肿瘤细胞耐药性的作用机制,主要内容如下:
1.异常黑胆质成熟剂总黄酮对人结肠癌细胞株(Caco-2)生长、凋亡及DNA链断裂的影响
本研究中以人结肠癌细胞株(Caco-2)等作为研究抗癌活性的体外细胞模型,采用体外细胞培养技术、琼脂糖凝胶电泳技术、流式细胞术研究异常黑胆质成熟剂总黄酮对癌细胞体外生长和凋亡调控的影响,从而探讨异常黑胆质成熟剂总黄酮诱导细胞凋亡的作用机理。探索维吾尔医异常黑胆质成熟剂总黄酮的抗肿瘤作用机理。
MTT实验结果表明,异常黑胆质成熟剂总黄酮不同作用时间对Caco-2细胞抑制作用的IC50分别为5.99mg/ml(48h)及3.02mg/ml(72h)。异常黑胆质成熟剂总黄酮与Caco-2细胞共同培育48h后,对Caco-2细胞DNA链断裂的作用有所不同。当样品浓度在0.5～5.0mg/ml时,总黄酮对DNA没有产生明显的影响,即凝胶图谱上没有出现明显的“梯子”样DNA条带。但在7.5mg/ml浓度时,对Caco-2细胞DNA链产生明显的作用,出现了较明显的“梯子”样DNA条带。流式细胞术观察表明,当Caco-2细胞与异常黑胆质成熟剂总黄酮共同培养48小时后,与空白对照组比较,表现出浓度依赖性得阻滞细胞周期,使细胞滞留于sub-G1期,癌细胞凋亡率逐渐提高(P<0.05),尤其是当浓度为7.5mg/ml时,明显提高Caco-2细胞在sub-G1期的百分比。
2.异常黑胆质成熟剂总黄酮对1,2-二甲肼(DMH)诱导的大鼠结肠异常隐窝灶的影响
1,2-二甲肼(1,2-dimethylhydrazine,DMH)诱导的大鼠结肠癌前期病变是一个长期、多因素共同参与的过程,其引起的细胞动力学、组织病理学变化和肿瘤形成的分子机制的改变等方面均与人类的结肠癌前期的形成过程比较近似,是研究结肠癌形成的一个良好模型。实验结果表明,不同剂量的异常黑胆质成熟剂总黄酮预防组和抑制组可以明显抑制DMH诱发的大鼠体重减轻的趋势,明显抑制DMH诱发的大鼠ACF、AC总数及其多样性,明显抑制由DMH攻击引起的大鼠免疫器官重量减轻,提高DMH诱发大鼠免疫器官(胸腺及脾脏)指数。本研究发现异常黑胆质成熟剂总黄酮抑制DMH诱发的大鼠结肠癌癌前期病变的作用,这与其抑制ACF形成有关,而且证实了异常黑胆质成熟剂总黄酮具有较强的体内预防及抑制肿瘤形成作用。
3.异常黑胆质成熟剂总黄酮对人肝癌耐药细胞株Bel/Fu逆转肿瘤多药耐药机制的研究
我们应用MTT实验方法测定Bel/Fu的IC50、耐药细胞集落实验观察异常黑胆质成熟剂总黄酮对耐药细胞株Bel/Fu(肝癌耐药细胞)逆转作用,同时观察异常黑胆质成熟剂总黄酮和氟尿嘧啶协同效果。FCM(流式细胞技术)观察细胞周期改变和凋亡。免疫组织化学法(S-P)法检测细胞P糖蛋白的表达。逆转录PCR法检测细胞内MDR1、GSTπ、TopoⅡ、凋亡基因mRNA的表达。研究异常黑胆质成熟剂总黄酮对人肝癌细胞株Bel/Fu逆转多药耐药作用机制。
异常黑胆质成熟剂总黄酮对肝癌耐药细胞Bel/Fu的IC50是2000.68μg/ml,用药安全范围很大。异常黑胆质成熟剂总黄酮在390μg/ml浓度时对细胞无明显的杀伤作用,但与抗癌药物5-Fu合用时,合并用药组的细胞毒性作用与单独用5-Fu抗癌药物的相比有显著性差异(P<0.01),表明异常黑胆质成熟剂总黄酮与抗癌药物有协同作用,逆转倍数为7.8。随异常黑胆质成熟剂总黄酮浓度的加大集落逐渐变小、集落形成率减少,390μg/ml时表现为极小的集落,集落形成率仅为3.5%、细胞形状不规则有中毒颗粒,460μg/ml基本无集落形成。免疫组织化学法(S-P)实验证实,异常黑胆质成熟剂总黄酮抑制P-gp的表达。因此我们认为异常黑胆质成熟剂总黄酮很可能是通过抑制P-170糖蛋白的作用而升高耐药细胞内药物浓度,达到增敏目的。
实验还发现异常黑胆质成熟剂总黄酮对MDR1/mRNA和P-gp的表达有明显的抑制作用。对MRP、GSTπ和TopoⅡ基因表达进行了同步观察,发现异常黑胆质成熟剂总黄酮同样可以升高的TopoⅡαmRNA水平,提示异常黑胆质成熟剂总黄酮也是TopoⅡα耐药逆转剂。流式细胞技术观察结果,异常黑胆质成熟剂总黄酮以不同的浓度作用于Bel/Fu细胞48h后,对细胞周期产生不同的影响。在2.5、5.0和7.5mg/ml时,凋亡细胞所特有的sub-G1期的百分比分别为0.9%、4.0%、7.8%,在2.5及7.5mg/ml时分别与空白对照组(0.4%)比较具有显著性差异(P<0.05),同时我们发现异常黑胆质成熟剂总黄酮对Bel/Fu细胞凋亡(sub-G1)的诱导作用具有明显的浓度依赖性。异常黑胆质成熟剂总黄酮逆转作用提高抑癌基因p53及促凋亡基因p21、Bax mRNA表达、抑制抗凋亡基因Bcl-2 mRNA表达等有关。
4.结论
4.1由维吾尔医复方衍生的异常黑胆质成熟剂总黄酮不仅具有体内外抗肿瘤作用,而且具有体外逆转肿瘤细胞多药耐药性之功效。
4.2异常黑胆质成熟剂总黄酮对结肠癌细胞(Caco-2)体外抗癌作用可能主要通过诱导癌细胞凋亡等途径来实现。即引起癌细胞DNA链断裂,诱导细胞凋亡,癌细胞滞留于sub-G1期,使癌细胞凋亡率逐渐增高。
4.3异常黑胆质成熟剂总黄酮抑制DMH诱发的大鼠结肠ACF形成,具有预防和抑制肿瘤发生作用。其部分机理在于提高使用DMH诱发的异常隐窝大鼠的胸腺指数达正常水平,抑制DMH诱发的异常隐窝大鼠体重的减轻,提高DMH诱发的异常隐窝大鼠免疫器官指数。
4.4异常黑胆质成熟剂总黄酮对肝癌耐药细胞(Bel/Fu)具有逆转多药耐药MDR的作用,其机制可能与抑制Bel/Fu细胞的MDR1/mRNA,降低Pgp的表达和功能,升高TopoⅡα的mRNA水平有关。
4.5异常黑胆质成熟剂总黄酮抑制肿瘤耐药细胞耐药集落形成、减少集落形成率、增加细胞中毒现象,从而抑制耐药细胞的生长。
4.6异常黑胆质成熟剂总黄酮可能通过肿瘤耐药细胞滞留在sub-G1期,提高抑癌基因p53及促凋亡基因p21、Bax mRNA表达、抑制抗凋亡基因Bcl-2 mRNA表达等作用来诱导肿瘤耐药细胞凋亡。
A large numer of anticancer agents, including alkylating agents, antitumor antibioltics, antimetabolites, and various other agents such as platinum derivatives, procarbazine, and emetine, have been tried, alone and in a variety of combinations and by different routes of administration, to treat carcinoma, but the predictable response rate has always been less than 20%. Additionally, drug toxicity is frequent. Current trials are investigateing the use of plant derivatives , much attention has been paid to Chinese herd, because it has little toxicity, not susceptible to get drug resistance, has multimeans in antitumor.
Multidrug resistance (MDR) is the protection of tumor cell population against numerous drugs differing in structure and mechanisms of influence on the cells. MDR is also one of the major causes of failure of chemotherapy of human maligancies. It is related to many active mechanisms. Often several different mechanisms are switched on in the cells, but usually one major mechanism is operating. The active mechanisms read as follows: a) activation of transmembrane proteins effluxing different chemical substances from the cells (P-glycoprotein is the most known efflux pump); b) activation of the enzymes of glutathione detoxification system; alteration of the genes and the proteins involved into the control of apoptosis (especially P53 and Bcl-2); changes of activity and quantity of topoisomerases. The tumor cell MDR and looking for little toxic and more effective chemotherapy drug has long been an interesting subject.
Uighur medicine considers that Abnormal Savda is a pathological production resulted from the combustion of different body fluids known as Savda, Sapra, Belghem and Kan. It is main leading cause of cancers, and about 90% of caners attribute to Abnormal Savda in clinical reports. Bahki Yusup and Tursun Tohti Haji, two of the famous Uighur Doctor,according to the traditional therapy, have applied the ASMq-TF for treatment of cancers, which demonstrated remarkable clinical results, there by gaining the honor of“highly skilled doctor”by the local people.
To date, the anticancer effects of ASMq-TF have only been little studied and its potential mechanism of action is still unclear, so a possible anticancer effect of Munziq of Abnoraml Savda clearly warrants further investigation.
In the present study, we used human clone cells and Caco-2 to examine the anticancer effects of ASMq-TF, and also examine in vivo by used 1,2-dimethylhydrazine (DMH) induced rat colon carcinogenesis.We used Reversal of resistance to 5-Fu in human hepatocarcinoma cell line BEL /Fu toexamine reversal effects of ASMq-TF.
Part1 The effect of Abnormal Savda Munziq Total Flavonoids on the proliferation, apop- tosis in Caco-2
Colon cancer cells line of Caco-2 was cultured by cell culture technique. The effect of ASMq-TF, on the proliferation of Caco-2 cells after exposure to different concentration and different time was evaluated by MTT. Apoptosis rate was determined by using flow cytometry, DNA fragmentation assay. The study the effects of Abnormal Savda Munziq on the proliferation, apoptosis and correlative gene expression in cancer cells line of Caco-2.
The results of MTT assay demonstrated that water soluble of ASMq-TF ethanol extract showed different effects on Caco-2 cell grows at 48h and72h incubation. The IC50, they were IC50 5.99mg/ml(48h)and 3.02mg/ml(72h). DNA fragmentation observed by gel electrophoresis showed that there were no significant DNA ladders in Caco-2 after treatment with different water soluble of ASMq-TF 0.5~5.0mg/ml , and seems to be no detectable difference between control cultures. But ethyl acetate extract induced the typical pattern of DNA ladders in Caco-2 cells at 7.5mg/ml. To study the acting mechanism of the fractions of ASMq-TF ethanol extract, flow cytometry was used to detect the cell cycle distribution of Caco-2 cells after 48h treatment with each fraction, respectively. The percentage of HepG2 cells in phase sub-G1 was most high concentration of 7.5mg/ml.
Part2 Effects of Abnormal Savda Munziq Total Flavonoids on DMH induced colon carcinogenesis
In vivo experiment was designed to assess the potential preventive and curative effect of ASMq-TF on 1,2-dimethylhydrazine (DMH) induced rat colon carcinogenesis. Obserb number of aberrant crypt foci (ACF) and aberrant crypt (AC) and crypt multiplicity. The study on the preventive and treatment effects of Abnormal Savda Munziq on colon carcinogenesis.
The results showed that all doses (400, 800 and 1600 mg/kg b. w.) of ASMq-TF ethanol extract in the pre-treatment group as well as in the treatment group significantly reduced the number of aberrant crypt foci (ACF), aberrant crypt (AC) and crypt multiplicity (P<0.05), the organ relative weights in pre-treatment and treatment groups were regained by ASMq-TF ethanol extract administration when compared to negative control group (P<0.05). These findings suggested that ASMq-TF ethanol extract had a chemoprotective effects on DMH-induced colon carcinogenesis, by suppressing the development of preneoplastic lesions, and probably exert protection against the initiation and promotion steps of colon carcinogenesis.
Part3 Reversal mechanism of resistance to 5-Fu in human hepatocar- cinoma cell line BEL/Fu by Abnormal Savda Munziq Total Flavonoids
A drug-resistant hepatocarcinoma cell line BEL/Fu was used in this study. The aim of this study was to observe the reversal effect of 5-Fu resistance and its potential mechanism in hepatocarcinoma cell line BEL/Fu by Abnormal Savda Munziq.
Sentivity to 5-Fu of BEL-/Fu cells was assessed by MTT assay. The reversal action of ASMq-TF, IC50 value and synergic action of vincristine and ASMq-TF were determined by MTT assay. The reversal action of ASMq-TF was also observed by clone forming text. MDR1 expression of Pgp was examined by immunochemical assay and determination of gene expression of MDR1 ,MRP, glutathione S-transferase(GSTpi) and topoisomeraseⅡαof Bel-7402 cell line were investigated using reverse transcription polymerase chain reaction (RT-PCR). Expression of bcl-2 protein and percentage of cell apoptosis was detected by flow cytometry. MDR1 expression of Pgp was examined by immunochemical assay.
The reversal effect of ASMq-TF was evaluated using Bel/Fu cell line with innate resistance in this study. The IC50 value of ASMq-TF crude extract was 2000.68μg/ml. ASMq-TF at 390μg/ml concentration was no toxic but had a toxic effect on Bel/Fucell line with 5-FU. The cytotoxicity of 390μg/ml ASMq-TF and 5-FU to Bel/Fu cellline was more remarkable than only with 5-FU (P<0.01). The fold reversal of ASMq-TF combining with 5-FU was 7.8.While ASMq-TF concentrations lower than 390μg/ml had less toxic, it had no synergetic effect with 5-FU. ASMq-TF concentrations higher than 400μg/ml were not suitable due to cytotoxicitiy to tumor cells .The reversal effect of ASMq-TF was confirmed by clone forming text. The inhibited effect of ASMq-TF on Bel/Fu cell line correlated well with ASMq-TF concentration. However, Bel/Fu cell line treated with 5-FU and ASMq-TF showed significantly inhibited effect as comparing with ASMq-TF treatment. Bel/Fu cells treated with 390μg/ml ASMq-TF,The clone forming size is much smaller and the clone forming rate was only 3.5%. At same time, the irregular shaped cells, intracellular toxic granules, very loosely arranged cell and bizarre cells were observed. There was not clone forming and a few of dispersed cells in cells treated with 460μg/ml ASMq-TF .
Human Pgp is coded by gene MDR1 and related to MDR of tumor cells. ASMq-TF has been found to downed-regulat MDR1/Pgp gene and proteinexpression. And simultaneously it could up-regulate TopoⅡαmRNA.Taken together, the present study suggested that the apoptosis triggered by ASMq-TF total flavonoids was mediated through DNA fragmentation, cell cycle arrest at sub-G1, up-regulation of p53, p21 and Bax gene expression, down-regulation of Bcl-2 gene expression in concentration- dependent manner. We concluded that the anticancer properties of ASMq-TF was possibly mediated through multiple pathways, suggesting multiple ingredients, rather than single component The acting ingredients in ASMq-TF that exerted the anticancer effect may include total flavonoids which are abundant in ASMq-TF.
肿瘤的维医异常黑胆质成熟剂治疗有良好效果,其促使我们,采用现代科学技术对异常黑胆质成熟剂的抗肿瘤作用进行深入研究,揭示其作用机理。十几年来,哈木拉提教授为首的课题组采用现代科学技术对异常黑胆质成熟剂作用机理进行了较深入的研究。动物实验研究表明,该复方能够促进免疫细胞的生长和增殖,提高机体的免疫功能,增强免疫器官中抗氧化酶的活性,增强机体的抗癌能力[3-8]。研究发现,异常黑胆质成熟剂具有明显的抗氧化应激对淋巴细胞DNA的损伤作用及减轻氧化造成的淋巴细胞毒性,能上调淋巴细胞Bcl-2蛋白的表达水平,能显著抑制氧化应激诱导的淋巴细胞的凋亡,能明显降低氧化诱导对淋巴细胞NF-κB的激活作用,同时异常黑胆质成熟剂本身也能激活淋巴细胞的NF-κB作用。异常黑胆质成熟剂中可能存在作用于细胞增殖凋亡信号传导通路和影响相关基因表达调节的活性成份,这些仅在已发生癌变的细胞中发挥着诱导细胞凋亡、上调抑癌基因表达和下调凋亡抑制基因的作用,而且在正常细胞中发挥着抗氧化应激对细胞DNA的损伤作用及减轻氧化造成的细胞毒性,通过上调淋巴细胞Bcl-2蛋白的表达水平,抑制氧化应激诱导的淋巴细胞的凋亡、降低氧化诱导对淋巴细胞NF-κB的激活作用,从而预防细胞发生癌变[9-13]。通过动物实验[14]观察受照射小鼠体重、脾脏指数、骨髓功能和SOD等指标的变化,发现辐射后各组小鼠体质量均下降;异常黑胆质成熟剂干预各组脾脏指数明显低于对照,各组异常黑胆质成熟剂干预后受照射小鼠的SOD值、白细胞数、红细胞数和30d生存率均有明显的升高。认为在活体组织中异常黑胆质成熟剂对辐射有确切的保护作用。
同时,以往工作中,发现异常黑胆质成熟剂对HepG2(人肝癌细胞)[15]、Hela(人宫颈癌细胞)[16]、T淋巴瘤细胞[17]、乳腺癌细胞[18]体外具有抗癌作用,已初步确定异常黑胆质成熟剂总黄酮是异常黑胆质成熟剂重要的抗癌活性成分。我们应用运用体外细胞培养技术,研究异常黑胆质成熟剂总黄酮对结肠癌细胞增殖、凋亡、分化的影响;运用动物实验来研究总黄酮对结肠癌癌前期病变的预防和抑制作用;以进一步明确抗癌谱的同时探讨异常黑胆质成熟剂总黄酮逆转肿瘤细胞耐药性的作用机制,主要内容如下:
1.异常黑胆质成熟剂总黄酮对人结肠癌细胞株(Caco-2)生长、凋亡及DNA链断裂的影响
本研究中以人结肠癌细胞株(Caco-2)等作为研究抗癌活性的体外细胞模型,采用体外细胞培养技术、琼脂糖凝胶电泳技术、流式细胞术研究异常黑胆质成熟剂总黄酮对癌细胞体外生长和凋亡调控的影响,从而探讨异常黑胆质成熟剂总黄酮诱导细胞凋亡的作用机理。探索维吾尔医异常黑胆质成熟剂总黄酮的抗肿瘤作用机理。
MTT实验结果表明,异常黑胆质成熟剂总黄酮不同作用时间对Caco-2细胞抑制作用的IC50分别为5.99mg/ml(48h)及3.02mg/ml(72h)。异常黑胆质成熟剂总黄酮与Caco-2细胞共同培育48h后,对Caco-2细胞DNA链断裂的作用有所不同。当样品浓度在0.5～5.0mg/ml时,总黄酮对DNA没有产生明显的影响,即凝胶图谱上没有出现明显的“梯子”样DNA条带。但在7.5mg/ml浓度时,对Caco-2细胞DNA链产生明显的作用,出现了较明显的“梯子”样DNA条带。流式细胞术观察表明,当Caco-2细胞与异常黑胆质成熟剂总黄酮共同培养48小时后,与空白对照组比较,表现出浓度依赖性得阻滞细胞周期,使细胞滞留于sub-G1期,癌细胞凋亡率逐渐提高(P<0.05),尤其是当浓度为7.5mg/ml时,明显提高Caco-2细胞在sub-G1期的百分比。
2.异常黑胆质成熟剂总黄酮对1,2-二甲肼(DMH)诱导的大鼠结肠异常隐窝灶的影响
1,2-二甲肼(1,2-dimethylhydrazine,DMH)诱导的大鼠结肠癌前期病变是一个长期、多因素共同参与的过程,其引起的细胞动力学、组织病理学变化和肿瘤形成的分子机制的改变等方面均与人类的结肠癌前期的形成过程比较近似,是研究结肠癌形成的一个良好模型。实验结果表明,不同剂量的异常黑胆质成熟剂总黄酮预防组和抑制组可以明显抑制DMH诱发的大鼠体重减轻的趋势,明显抑制DMH诱发的大鼠ACF、AC总数及其多样性,明显抑制由DMH攻击引起的大鼠免疫器官重量减轻,提高DMH诱发大鼠免疫器官(胸腺及脾脏)指数。本研究发现异常黑胆质成熟剂总黄酮抑制DMH诱发的大鼠结肠癌癌前期病变的作用,这与其抑制ACF形成有关,而且证实了异常黑胆质成熟剂总黄酮具有较强的体内预防及抑制肿瘤形成作用。
3.异常黑胆质成熟剂总黄酮对人肝癌耐药细胞株Bel/Fu逆转肿瘤多药耐药机制的研究
我们应用MTT实验方法测定Bel/Fu的IC50、耐药细胞集落实验观察异常黑胆质成熟剂总黄酮对耐药细胞株Bel/Fu(肝癌耐药细胞)逆转作用,同时观察异常黑胆质成熟剂总黄酮和氟尿嘧啶协同效果。FCM(流式细胞技术)观察细胞周期改变和凋亡。免疫组织化学法(S-P)法检测细胞P糖蛋白的表达。逆转录PCR法检测细胞内MDR1、GSTπ、TopoⅡ、凋亡基因mRNA的表达。研究异常黑胆质成熟剂总黄酮对人肝癌细胞株Bel/Fu逆转多药耐药作用机制。
异常黑胆质成熟剂总黄酮对肝癌耐药细胞Bel/Fu的IC50是2000.68μg/ml,用药安全范围很大。异常黑胆质成熟剂总黄酮在390μg/ml浓度时对细胞无明显的杀伤作用,但与抗癌药物5-Fu合用时,合并用药组的细胞毒性作用与单独用5-Fu抗癌药物的相比有显著性差异(P<0.01),表明异常黑胆质成熟剂总黄酮与抗癌药物有协同作用,逆转倍数为7.8。随异常黑胆质成熟剂总黄酮浓度的加大集落逐渐变小、集落形成率减少,390μg/ml时表现为极小的集落,集落形成率仅为3.5%、细胞形状不规则有中毒颗粒,460μg/ml基本无集落形成。免疫组织化学法(S-P)实验证实,异常黑胆质成熟剂总黄酮抑制P-gp的表达。因此我们认为异常黑胆质成熟剂总黄酮很可能是通过抑制P-170糖蛋白的作用而升高耐药细胞内药物浓度,达到增敏目的。
实验还发现异常黑胆质成熟剂总黄酮对MDR1/mRNA和P-gp的表达有明显的抑制作用。对MRP、GSTπ和TopoⅡ基因表达进行了同步观察,发现异常黑胆质成熟剂总黄酮同样可以升高的TopoⅡαmRNA水平,提示异常黑胆质成熟剂总黄酮也是TopoⅡα耐药逆转剂。流式细胞技术观察结果,异常黑胆质成熟剂总黄酮以不同的浓度作用于Bel/Fu细胞48h后,对细胞周期产生不同的影响。在2.5、5.0和7.5mg/ml时,凋亡细胞所特有的sub-G1期的百分比分别为0.9%、4.0%、7.8%,在2.5及7.5mg/ml时分别与空白对照组(0.4%)比较具有显著性差异(P<0.05),同时我们发现异常黑胆质成熟剂总黄酮对Bel/Fu细胞凋亡(sub-G1)的诱导作用具有明显的浓度依赖性。异常黑胆质成熟剂总黄酮逆转作用提高抑癌基因p53及促凋亡基因p21、Bax mRNA表达、抑制抗凋亡基因Bcl-2 mRNA表达等有关。
4.结论
4.1由维吾尔医复方衍生的异常黑胆质成熟剂总黄酮不仅具有体内外抗肿瘤作用,而且具有体外逆转肿瘤细胞多药耐药性之功效。
4.2异常黑胆质成熟剂总黄酮对结肠癌细胞(Caco-2)体外抗癌作用可能主要通过诱导癌细胞凋亡等途径来实现。即引起癌细胞DNA链断裂,诱导细胞凋亡,癌细胞滞留于sub-G1期,使癌细胞凋亡率逐渐增高。
4.3异常黑胆质成熟剂总黄酮抑制DMH诱发的大鼠结肠ACF形成,具有预防和抑制肿瘤发生作用。其部分机理在于提高使用DMH诱发的异常隐窝大鼠的胸腺指数达正常水平,抑制DMH诱发的异常隐窝大鼠体重的减轻,提高DMH诱发的异常隐窝大鼠免疫器官指数。
4.4异常黑胆质成熟剂总黄酮对肝癌耐药细胞(Bel/Fu)具有逆转多药耐药MDR的作用,其机制可能与抑制Bel/Fu细胞的MDR1/mRNA,降低Pgp的表达和功能,升高TopoⅡα的mRNA水平有关。
4.5异常黑胆质成熟剂总黄酮抑制肿瘤耐药细胞耐药集落形成、减少集落形成率、增加细胞中毒现象,从而抑制耐药细胞的生长。
4.6异常黑胆质成熟剂总黄酮可能通过肿瘤耐药细胞滞留在sub-G1期,提高抑癌基因p53及促凋亡基因p21、Bax mRNA表达、抑制抗凋亡基因Bcl-2 mRNA表达等作用来诱导肿瘤耐药细胞凋亡。
A large numer of anticancer agents, including alkylating agents, antitumor antibioltics, antimetabolites, and various other agents such as platinum derivatives, procarbazine, and emetine, have been tried, alone and in a variety of combinations and by different routes of administration, to treat carcinoma, but the predictable response rate has always been less than 20%. Additionally, drug toxicity is frequent. Current trials are investigateing the use of plant derivatives , much attention has been paid to Chinese herd, because it has little toxicity, not susceptible to get drug resistance, has multimeans in antitumor.
Multidrug resistance (MDR) is the protection of tumor cell population against numerous drugs differing in structure and mechanisms of influence on the cells. MDR is also one of the major causes of failure of chemotherapy of human maligancies. It is related to many active mechanisms. Often several different mechanisms are switched on in the cells, but usually one major mechanism is operating. The active mechanisms read as follows: a) activation of transmembrane proteins effluxing different chemical substances from the cells (P-glycoprotein is the most known efflux pump); b) activation of the enzymes of glutathione detoxification system; alteration of the genes and the proteins involved into the control of apoptosis (especially P53 and Bcl-2); changes of activity and quantity of topoisomerases. The tumor cell MDR and looking for little toxic and more effective chemotherapy drug has long been an interesting subject.
Uighur medicine considers that Abnormal Savda is a pathological production resulted from the combustion of different body fluids known as Savda, Sapra, Belghem and Kan. It is main leading cause of cancers, and about 90% of caners attribute to Abnormal Savda in clinical reports. Bahki Yusup and Tursun Tohti Haji, two of the famous Uighur Doctor,according to the traditional therapy, have applied the ASMq-TF for treatment of cancers, which demonstrated remarkable clinical results, there by gaining the honor of“highly skilled doctor”by the local people.
To date, the anticancer effects of ASMq-TF have only been little studied and its potential mechanism of action is still unclear, so a possible anticancer effect of Munziq of Abnoraml Savda clearly warrants further investigation.
In the present study, we used human clone cells and Caco-2 to examine the anticancer effects of ASMq-TF, and also examine in vivo by used 1,2-dimethylhydrazine (DMH) induced rat colon carcinogenesis.We used Reversal of resistance to 5-Fu in human hepatocarcinoma cell line BEL /Fu toexamine reversal effects of ASMq-TF.
Part1 The effect of Abnormal Savda Munziq Total Flavonoids on the proliferation, apop- tosis in Caco-2
Colon cancer cells line of Caco-2 was cultured by cell culture technique. The effect of ASMq-TF, on the proliferation of Caco-2 cells after exposure to different concentration and different time was evaluated by MTT. Apoptosis rate was determined by using flow cytometry, DNA fragmentation assay. The study the effects of Abnormal Savda Munziq on the proliferation, apoptosis and correlative gene expression in cancer cells line of Caco-2.
The results of MTT assay demonstrated that water soluble of ASMq-TF ethanol extract showed different effects on Caco-2 cell grows at 48h and72h incubation. The IC50, they were IC50 5.99mg/ml(48h)and 3.02mg/ml(72h). DNA fragmentation observed by gel electrophoresis showed that there were no significant DNA ladders in Caco-2 after treatment with different water soluble of ASMq-TF 0.5~5.0mg/ml , and seems to be no detectable difference between control cultures. But ethyl acetate extract induced the typical pattern of DNA ladders in Caco-2 cells at 7.5mg/ml. To study the acting mechanism of the fractions of ASMq-TF ethanol extract, flow cytometry was used to detect the cell cycle distribution of Caco-2 cells after 48h treatment with each fraction, respectively. The percentage of HepG2 cells in phase sub-G1 was most high concentration of 7.5mg/ml.
Part2 Effects of Abnormal Savda Munziq Total Flavonoids on DMH induced colon carcinogenesis
In vivo experiment was designed to assess the potential preventive and curative effect of ASMq-TF on 1,2-dimethylhydrazine (DMH) induced rat colon carcinogenesis. Obserb number of aberrant crypt foci (ACF) and aberrant crypt (AC) and crypt multiplicity. The study on the preventive and treatment effects of Abnormal Savda Munziq on colon carcinogenesis.
The results showed that all doses (400, 800 and 1600 mg/kg b. w.) of ASMq-TF ethanol extract in the pre-treatment group as well as in the treatment group significantly reduced the number of aberrant crypt foci (ACF), aberrant crypt (AC) and crypt multiplicity (P<0.05), the organ relative weights in pre-treatment and treatment groups were regained by ASMq-TF ethanol extract administration when compared to negative control group (P<0.05). These findings suggested that ASMq-TF ethanol extract had a chemoprotective effects on DMH-induced colon carcinogenesis, by suppressing the development of preneoplastic lesions, and probably exert protection against the initiation and promotion steps of colon carcinogenesis.
Part3 Reversal mechanism of resistance to 5-Fu in human hepatocar- cinoma cell line BEL/Fu by Abnormal Savda Munziq Total Flavonoids
A drug-resistant hepatocarcinoma cell line BEL/Fu was used in this study. The aim of this study was to observe the reversal effect of 5-Fu resistance and its potential mechanism in hepatocarcinoma cell line BEL/Fu by Abnormal Savda Munziq.
Sentivity to 5-Fu of BEL-/Fu cells was assessed by MTT assay. The reversal action of ASMq-TF, IC50 value and synergic action of vincristine and ASMq-TF were determined by MTT assay. The reversal action of ASMq-TF was also observed by clone forming text. MDR1 expression of Pgp was examined by immunochemical assay and determination of gene expression of MDR1 ,MRP, glutathione S-transferase(GSTpi) and topoisomeraseⅡαof Bel-7402 cell line were investigated using reverse transcription polymerase chain reaction (RT-PCR). Expression of bcl-2 protein and percentage of cell apoptosis was detected by flow cytometry. MDR1 expression of Pgp was examined by immunochemical assay.
The reversal effect of ASMq-TF was evaluated using Bel/Fu cell line with innate resistance in this study. The IC50 value of ASMq-TF crude extract was 2000.68μg/ml. ASMq-TF at 390μg/ml concentration was no toxic but had a toxic effect on Bel/Fucell line with 5-FU. The cytotoxicity of 390μg/ml ASMq-TF and 5-FU to Bel/Fu cellline was more remarkable than only with 5-FU (P<0.01). The fold reversal of ASMq-TF combining with 5-FU was 7.8.While ASMq-TF concentrations lower than 390μg/ml had less toxic, it had no synergetic effect with 5-FU. ASMq-TF concentrations higher than 400μg/ml were not suitable due to cytotoxicitiy to tumor cells .The reversal effect of ASMq-TF was confirmed by clone forming text. The inhibited effect of ASMq-TF on Bel/Fu cell line correlated well with ASMq-TF concentration. However, Bel/Fu cell line treated with 5-FU and ASMq-TF showed significantly inhibited effect as comparing with ASMq-TF treatment. Bel/Fu cells treated with 390μg/ml ASMq-TF,The clone forming size is much smaller and the clone forming rate was only 3.5%. At same time, the irregular shaped cells, intracellular toxic granules, very loosely arranged cell and bizarre cells were observed. There was not clone forming and a few of dispersed cells in cells treated with 460μg/ml ASMq-TF .
Human Pgp is coded by gene MDR1 and related to MDR of tumor cells. ASMq-TF has been found to downed-regulat MDR1/Pgp gene and proteinexpression. And simultaneously it could up-regulate TopoⅡαmRNA.Taken together, the present study suggested that the apoptosis triggered by ASMq-TF total flavonoids was mediated through DNA fragmentation, cell cycle arrest at sub-G1, up-regulation of p53, p21 and Bax gene expression, down-regulation of Bcl-2 gene expression in concentration- dependent manner. We concluded that the anticancer properties of ASMq-TF was possibly mediated through multiple pathways, suggesting multiple ingredients, rather than single component The acting ingredients in ASMq-TF that exerted the anticancer effect may include total flavonoids which are abundant in ASMq-TF.
引文
[1]孙燕.肿瘤综合治疗.载张天泽,徐光炜主编.肿瘤学.第二版.天津科学技术出版社, 2005. 825-840.
[2]巴黑.玉素甫.肿瘤患者的维医异常体液分型.维吾尔医药, 2004,(4):23-7
[3]阿不都热依木,哈木拉提,阿布都艾尼.维吾尔医成熟剂和清除剂抗活性氧的作用研究[J].中国民族医药杂志,2000;6 (3):30-2
[4]阿不都热依木,哈木拉提,阿布都艾尼.异常黑胆质成熟剂和清除剂抗氧化作用的ESR研究[J].中药新药与临床药理,2001,12 (6):420-2
[5]阿布都艾尼,阿不都热依木,哈木拉提.异常黑胆质成熟剂和清除剂对OH.引发的DNA损伤的保护作用[J].中药药理与临床,2000,16 (3):34-6
[6]哈木拉提.吾甫尔.维吾尔医气质?体液论及其现代研究[M], 2003,98-99
[7] Halmurat U, Abdiryim Y, Anwar U, Moore N. Uighur traditional medicine syndrome of Abnormal Savda in men is associated with oxidative stress, which can be improved by Munziq and Mushil of Abnormal Savda. Therapie 2004;59 (4):483-4
[8] Abdiryim Y, Halmurat U, Anwar U, Moore N. Protective effects of Munziq and Mushil of abnormal Savda to mitochondrial oxidative damage. Fundam Clin Pharmacol 2004;18 (4):471-6
[9]哈木拉提,李林,陈艳.异常黑胆质成熟剂与清除剂对氧化损伤的淋巴细胞p53蛋白表达的影响[J].新疆医科大学学报,2005,28 (4):287-289
[10]李林,姬艳丽,陈艳.异常黑胆质成熟剂与清除剂对H2O2诱导的淋巴细胞毒性的影响[J].新疆医科大学学报,2005,28 (4):290-292
[11]姬艳丽,李林,武贵臻.异常黑胆质成熟剂与清除剂对H2O2诱导的淋巴细胞凋亡的影响[J].新疆医科大学学报,2005,28 (4):293-296
[12]李林,哈木拉提.异常黑胆质成熟剂和清除剂对氧化应激的基因调控?细胞损伤和凋亡的研究.新疆医科大学博士学位论文,2004
[13]陈艳,李林,武贵臻.异常黑胆质成熟剂与清除剂对H2O2诱导的淋巴细胞NF-κB的影响[J].新疆医科大学学报,2005,28 (4):296-299
[14]张莉,哈木拉提·吾甫尔,张仑.异常黑胆质成熟剂提取物对小鼠辐射的防护作用中南大学学报(医学版) 2007,32(1):73
[15]阿不都热依木.玉苏甫,哈木拉提.吾甫尔,吐尔洪.卡迪尔.异常黑胆质成熟剂醇提物诱导HepG2细胞凋亡机制的研究.中成药2006,28(7):1008
[16]古扎丽努尔.异常黑胆质成熟剂Hela细胞凋亡机制的研究.博士后课题内容2007.(内部资料).
[17]艾斯卡尔·依米提,哈木拉提·吾甫尔,布再娜甫·伊力哈木.维吾尔医成熟及清除剂诱导T淋巴瘤细胞凋亡的研究[J].中药药理与临床.2000;16(2):34
[18]刘跃民.维药没食子提取物诱导乳腺癌细胞Bcap-37凋亡的实验研究[J].中国中药信息杂志.2006;11,31-33
[19] Schottenfeld D, Beebe-Dimmer JL. ADVANCES IN CANCER EPIDEMIOLOGY: Understanding Causal Mechanisms and the Evidence for Implementing Interventions. Annu Rev Public Health 2005;26:37-60
[20] Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55 (2):74-108
[21] Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ. Cancer statistics, 2005. CA Cancer J Clin 2005;55 (1):10-30
[22] Yang L, Parkin DM, Li LD, Chen YD, Bray F. Estimation and projection of the national profile of cancer mortality in China: 1991-2005. Br J Cancer 2004;90 (11):2157-66
[23] Yang L, Parkin DM, Ferlay J, Li L, Chen Y. Estimates of cancer incidence in China for 2000 and projections for 2005. Cancer Epidemiol Biomarkers Prev 2005;14 (1):243-50
[24] Yang L, Parkin DM, Li L, Chen Y. A comparison of the sources of cancer mortality in China. Cancer Causes Control 2004;15 (7):681-7
[25] Pao W, Wang TY, Riely GJ, et al. KRAS mutation and primary resistance of lung adenocarcinoma to gefitinib or erlotinib. PLOS, 2005, 2(1): 57-61
[26] Camp ER, Summy J, Bauer T, et al. Molecular mechanisms of resistance to therapies targeting the epidermal growth factor receptor. Clin Cancer Res, 2005, 11: 397-405
[27] Learn CA, Hartzell TL, Wikstrand CJ, et al. Resistance to tyrosine kinase inhibition by mutant epidermal growth factor receptor variant III contributes to the neoplastic phenotype of glioblastoma multiforme. Clin Cancer Res, 2004,10:3216-3224
[28] Kokubo Y, Gemma A, Noro R, et al. Reduction of PTEN protein and loss of epidermal growth factor receptor gene mutation in lung cancer with natural resistance to gefitinib(Iressa). Br J Cancer ,2005,92: 1711-1719
[29]谭永苏.抗肿瘤药物研究与开发.北京.现代生物技术与药物科技出版中心.2004.118
[30] SchefferGL, SchroeijersAB, IzquerdoMA, et al. Lung resistance-related protein/ major vault protein and vaults in multi drug resistant cancer[J]. Curr Opin Oncol,2000, 12(6):550-556
[31] Jung CK, Lee KY, Kim Y, et al. Epstein-Barr virus infection drug resistance and prognosis in Korean T- and NK-cell lymphomas [J].Pathol Int,2001,51(5): 355-363
[32] Filipts M, Jaeger U, Simonitisch I. Clinical relevance of the lung resistance protein in diffuse large B-cell lymphomas [J]. Clin Cancer Res,2000,6(9): 3417-3423
[33] Syahruddin E, Oguri T, Takahashi T, et al. Differential expression of DNA topoismerase 22 and 11 genes between small cell and non small cell lung cancer [J]. Jpn J Cancer Res,1998,89(8): 787-795
[34] Wuchter C,Leonid K,Ruppert V,Schrappe M,Buchner T,Schoch C,Haferlach T , Harbott J,Ratei R, Dorken B,Ludwig WD. Clinical significance of P-glycoprotein expression and function for response to induction chemotherapy, relapse rate and overall survival in acute leukemia. Haematologica,2000;85:711-721
[35] DeGeorge JJ, Ahn CH, Andrews PA, et al. Regulatory considerations for preclinical development of anticancer drugs.Cancer Chemother Pharmacol, 1998;41:173-185
[36] Nkopolou L, Lazaris AC, Karvantzas N, et al. DNA topoisomerase 11-alpha immunoreactivity as a marker of tumor aggressiveness in invasive breastcancer[J]. Pathobiology, 2001, 32(2): 137-143
[37] Dingemans AC, van Ark-Otte J , Span S, et al. TopoisomeraseⅡalpha and other drug resistance markers in advanced non small cell lung cancer[J]. Lung Cancer, 2001, 32(2):117-128
[38] Dingemans AC, Witlox MA , Stallaert RA, et al. Expression of DNA topoisomerase 11 alpha and topoisomeraseⅡbeta genes predicts survival and response to chemotherapy in patients with small cell lung cancer[J]. Clin Cancer Res, 1999, 5(8): 2048-2058
[39] Ferreira CG, Tolis C, Span SW, et al. Drug-induced apoptosis in lung cancer cells is not mediated by the Fas/FasL(CD95/APO1)signaling pathway[J].Clin Cancer Res,2000,6(1):203-212
[40] Schmidt P, Thiele M, Rudroff C, et al.Detection ofrumor cells in peritoneallavage from patients with gastrointestinal cancer by multiplex reverse transcriptase PCR[J].Hepatogatogastroenterology,2001,48(42):1675
[41] Nakanishi H, Kodera Y, Yamamura Y, et al. Rapid quantitative detection of carcinoembryonic antigen-expressing free tumor cells in the peritoneal cavity of gastric-cancer patients with real-time RT-PCR in the lightcycler[J]. Int J Cancer ,2000,89(5):411
[42] Huang P,Olive PL,Durand RE. Use of the comet assay for assessment of drug resistance and its modulation in vivo.Br J Cancer, 1998;77:412-416
[43] Ramachandran C,Melnick SJ. Multidrug resistance in human tumors molecular diagnosis and clinical significance. Mol Diagn, 1999;4:81-94
[44]刘忠民,寿楠海,姜希宏.多药耐药相关蛋白在大肠癌中的表达及其临床意义[J].世界华人消化杂志, 1999;7:1000-1001
[45] Zhang LJ, Chen KN, Xu GW, Xing HP, Shi XT. Congenital expression of mdr-1 gene in tissues of carcinoma and its relation with atho morphology and prognosis. World J Gastroenterol, 1999;5:53-56
[46]俞丽芬,吴云林,章永平.鸦胆子油乳剂对人胃腺癌长春新碱耐药细胞株MKN28/VCR的逆转作用[J].世界华人消化杂志,2001;9:376-378
[47] Kodera Y, Nakanishi H, Ito S, et al. Quantitative detection of disseminated free cancer cells in peritoneal washes with real-time reverse transcriptase–polymerase chain reaction:a sensitive predictor of outcome for patients with gastric carcinoma[J].Ann Surg,2002,235(4):499
[48] Nishida S, Kitamura K, Ichikawa D, er al. Molecular detection of disseminated cancer cells in the peripheral blood of patients with gastric cancer[J].Anticancer Res ,2000,20(3B):2155
[49] Jiang Z, Liu L, Fang W, Shou WZ, Zhang DS, Dai MM. Local radiative treatment of hepatocellular cancer with phosphorus-32 glass microspheres to enhance the efficacy of hepatic artery chemoembolism and possibly related with MDR expressed P-glycoprotein. World J Gastroenterol , 2000;6(Suppl 3):59
[50] Jiang JF, Liu WJ, Ding J. Regulation of telomerase activity in camptot hecin - induced apoptosis of human leukemia HL-60 cells. Acta Pharmacol Sin ,2000;21:759-764
[51] Volm M. Multidrug resistance and its reversal. Anticancer Res,1998;18: 2905-2917
[52] Johnstone RW,Ruefli AA,Tainton KM,Smyth MJ. A role for P-glycoprotein in regulating cell death. Leuk Lymphoma,2000;38:1-11
[53] Walther W,Stein U,Fichtner I,Alexander M,Shoemaker RH,Schlag PM. Mdr1promoter driven tumor necrosis factor alpha expression for a chemotherapy controllable combined in vivo gene therapy and chemotherapy of tumors. Cancer Gene Ther,2000;7:893-900
[54] Savas B, Arslan G, Gelen T, Karpuzoglu G, Ozkaynak C. Multidrug resist ant malignant melanoma with intracranial metastasis responding to immunotherapy. Anticancer Res, 1998;19:4413-4420
[55] Guo YS,Jin GF,Houston CW,Thompson JC,Townsend CM Jr. Insulin like growth factorⅠpromotes multidrug resistance in MCLM colon cancer cells. J Cell Physiol,1998;175:141-148
[56]廖海涛,刘立义等.P-gp,p53过表达与胃癌及乳腺癌转移的关系[J].中华肿瘤杂志, 2003,17(2):132
[57]易永芬,于冬青,林晓,等.三种耐药蛋白在胃癌中的表达及意义[J].实用肿瘤杂志, 2003,18(3):185-187
[58]陈毅,吴云林.逆转MDR1基因相关的消化系统肿瘤多药耐药[J].国外医学.消化系疾病分册2003,11(5): 77-79
[59]陈立军,宋廷惠,汲言山,等.定量检测多药耐药基因在胃癌?大肠癌组织中的表达及其临床意义[J].肿瘤研究与临床,1997;9:10-13
[60]刘冀龙,董新舒,刘忠臣.应用RT-PCR方法定量分析大肠癌患者多药耐药基因表达水平及其临床意义[J].中国肿瘤临床, 1999;26:39-41
[61]姚学清,卿三华.多药耐药基因在进展期大肠癌中检测及意义[J].世界华人消化杂志, 1999;7:535-536
[62]姚学清,林锋.肿瘤多药耐药和进展期大肠癌耐药细胞株建立研究进展[J].世界华人消化杂志, 2003;11(9):1433-1435
[63]王百林,陈孝平,翟淑萍.多药耐药相关蛋白基因在原发性肝细胞癌中的表达[J]. 2006年4月23日.来源:健康中国论坛
[64]刘忠民,寿楠海.肠道肿瘤多药耐药相关蛋白和肺耐药蛋白表达的临床意义[J].世界华人消化杂志, 1999;7:95
[65]陈昊,蒋芹,张连云,王燕青.肺癌组织中P170?P190?TOPOⅡ?GSTπ的表达及意义[J].中华中西医杂志.2003,14(2)108-120
[66]吴书庆,邹正辉,李建勇,等.乳腺癌耐药蛋白在急性白血病中的表达及其临床意义[J].中华现代中西医杂志2004,2(1):124-135
[67] Plouzek CA, Ciolino HP, Clarke R, et al.Inhibition of P-glycoprotein activity and reversal of multidrug resistance in vitro rosemary extract. Eur J Cancer 1999; 35:1541-5
[68] Tito Fojo,Susan Bate. Strategies for reversing drug resistance. Oncogene.2003,22, 7512–75239
[69] David J. Samson, Jerome Seidenfeld, Kathleen Ziegler, and Naomi Aronson. Chemotherapy Sensitivity and Resistance Assays:A Systematic Review. J Clin Oncol 2004,22:3618-3630
[70]李贺,熊茂明,孟翔凌,等.三氧化二砷逆转肝癌细胞株HepG2/ADM多药耐药的作用[J],世界华人消化杂志2006; 14(27): 2691-2694
[71]王秀丽,孔力,赵瑾瑶,等.三氧化二砷逆转人乳腺癌CF-7/ADM细胞耐药的机制研究[J].中华肿瘤杂志2002; 24: 339-343
[72]韩冰,石玉枝,霍建民.三氧化二砷对肺腺癌细胞凋亡及肺耐药蛋白基因多药耐药蛋白基因表达的影响[J].中国实用内科杂志2005; 25: 243-244
[73]史立军,闫彬彬,李双星,等. As2O3对胰腺癌细胞株的抑制作用及其机制的初步探讨[J].中国病理生理杂志2005; 21: 1572-1574
[74]何景利,王贵英,单宝恩.三氧化二砷联合顺铂对人结肠癌细胞株colon26抑制作用机理的研究[J].中国肿瘤临床2005; 32: 1125-1128
[75]刘连新,朱安龙,陈炜,等.三氧化二砷对原发性肝癌的作用及其机理研究[J].中华外科杂志2005; 43: 33-36
[76]李英,徐功立,李颖,张楠.鸦胆子油乳诱导白血病U937细胞凋亡的实验研究[J].中华血液学杂志.2004,25(6):381-382
[77]刘悦,王禾,符庆吉,等.鸦胆子油乳诱导膀胱癌BIU287细胞凋亡的研究[J].中国中西医结合外科杂志.2001,7(2):76-78
[78]马力,张月宁.鸦胆子油乳诱导肝癌细胞凋亡基对相关基因表达的影响[J].世界华人消化杂志.2004,12(3):559-562
[79]李贵海,孙付军,王宁,等.苦参碱干预获得性多药耐药小鼠S180肿瘤细胞相关生物因子P170过度表达与细胞凋亡的相关性.中药材, 2005,28(4):310-312
[80]李芮,杜健鹏,候仰韶,等.复方苦参注射液对SGC-7901,HepG2和BEL-7402肿瘤细胞作用的实验研究[J].肿瘤研究和临床.2006,18(1):8-10
[81]高船舟,杨佩满,吕广艳,曲淑贤1.20 (R)2人参皂甙Rg3逆转K562/ ADM细胞MDR及诱导其凋亡的研究[J],解剖科学进展.(2002)01-0031-35
[82]郝立宏,赵瑾瑶,杨佩满.川芎嗪与B-榄香烯联合应用诱导K562/ADM细胞凋亡及逆转其的实验研究[J].中国肿瘤临床.2005,32(1):25-28
[83]阿吉.阿不力米提.玉素甫主编.维吾尔医学基础理论.卫生厅人民出版社,1988
[84]哈木拉提.吾甫尔.维吾尔医气质?体液论及其现代研究[M], 2003,34-38
[85]哈木拉提.吾甫尔.维吾尔医气质?体液论及其现代研究[M], 2003,78-79
[86]哈木拉提.吾甫尔.维吾尔医气质?体液论及其现代研究[M], 2003,93-94
[87]阿吉.阿布里米提.玉素甫.维吾尔医学基础理论.乌鲁木齐:新疆科技卫生出版社, 1988
[88]易沙克江.马合穆德.中国医学百科全书维吾尔医学分卷:新疆人民卫生出版社,1988
[89]阿布都克力木.吐尔逊.肿瘤发病机制的维医理论探讨.维吾尔医专科学校学报,2003,(2):36-8
[90]阿不都热依木,哈木拉提.异常黑胆质成熟清除剂消除自由基及对OH.引发的DNA损伤的保护作用.新疆医科大学硕士学位论文,1999
[91]艾斯卡尔,哈木拉提,伊里哈木江.维医成熟剂和清除剂诱导T淋巴瘤细胞调亡的研究[J].中药药理与临床,2000,16 (2):33-4
[92]哈木拉提,艾斯卡尔,伊里哈木江.异常黑胆质成熟剂与清除剂对人Hela细胞调亡基因表达的影响[J].细胞与分子免疫学杂志,2001;17 (2):109-11
[93] Abdiryim Y, Halmurat U, Umar A, Moore N. Cytotoxicity of Abnormal Savda Munziq aqueous extract in human hepatoma (HepG2) cells. Fundam Clin Pharmacol 2005;19(3):1-6
[94] Abdiryim Y, Halmurat U, Umar A, Moore N. Cytotoxicity of Abnormal Savda Munziq: Inhibition of cell growth and DNA, protein synthesis in HepG2 cells. 10th International Congress of Toxicology, July 2004, Tempere, Finland. Toxicology and Applied Pharmacology 2004; 197(3): 309
[95] Inhibition of cell growth and cellular protein, DNA and RNA synthesis in human hepatoma (HepG2) cells by ethanol extract of Abnormal Savda Munziq. Journal of Ethnopharmacology (in press)
[96] Halmurat U, Abdiryim Y, Umar A, Moore N. Uighur traditional medicine syndrome of Abnormal Savda in man is associated with oxidative stress, which can be improved by Munziq and Mushil of Abnormal Savda. 15th International Congress of Clinical Pharmacology and Theripeutic. 2004, Australia
[97]贺慧颖,吴秉铨.分子病理学在肿瘤分子靶向治疗中的应用.2005年CSCO会议录.2005,546-550
[98] McPherson K,Steel CM,Dixon JM.ABC of breast diseases.Breast cancer epidemiology, riskfactors, and genetics[J].BMJ,2000,3(7):624-628
[99]李连弟,饶克勤,张思维,等.中国12市县1993-1997年肿瘤发病和死亡登记资料统计分析[J].中国肿瘤,2002,11(9):497-507
[100]周岱翰.临床中医肿瘤学[M].北京:人民卫生出版社, 2003,150-151
[101]肖立峰,张天虹,刘江涛,等.中药薏苡仁酯作用喉癌Hepg-2细胞的体外作用[J].哈尔滨医科大学学报,2004,38(3):252-262
[102]林芳,钱之玉,薛红卫,等.青蒿素和青蒿琥酯对人乳腺癌MCF-7细胞的体外抑制作用比较研究[J].中草药,2003,34(4):164-1661
[103]陈俊霞,夏俊,刘基巍,等.人参皂甙Rg3诱导乳腺癌细胞系MCF-7凋亡的实验研究[J].癌变畸变突变,2005,17(4):213-216
[104]张莹,张起辉,吴立军,等.吴茱萸碱诱导人宫颈癌HeLa细胞凋亡过程中非caspase调控因素[J].中国药理学通报,2004, 20(1) :61-64
[105]阿不都热依木,哈木拉提.异常黑胆质成熟剂及其有效组分的抗癌活性研究.新疆医科大学博士学位论文,2005
[106] Lopez-Hoyos M, Carrio R, Merino J, Merino R. Regulation of B cell apoptosis by Bcl-2 and Bcl-XL and its role in the development of autoimmune diseases (Review). Int J Mol Med 1998;1 (2):475-83
[107] Califice S, Waltregny D, Castronovo V, van den Brule F. [Prostate carcinoma cell lines and apoptosis: a review]. Rev Med Liege 2004;59 (12):704-10
[108] Longuet M, Serduc R, Riva C. Implication of bax in apoptosis depends on microtubule network mobility. Int J Oncol 2004;25 (2):309-17
[109] Laux MT, Aregullin M, Berry JP, Flanders JA, Rodriguez E. Identification of a p53-dependent pathway in the induction of apoptosis of human breast cancer cells by the natural product, resveratrol. J Altern Complement Med 2004;10 (2):235-9
[110] Kulcsar G. Apoptosis of tumor cells induced by substances of the circulatory system. Cancer Biother Radiopharm 1997;12(1):19-26
[111] Kulcsar G. Synergistic potentiating effect of D(+)-mannose, orotic, and hippuric acid sodium salt on selective toxicity of a mixture of 13 substances of the circulatory system in culture for various tumor cell lines. Cancer Detect Prev 2000;24(5):485-95
[112] Liu SL, Shi DY, Shen ZH, Wu YD. Effects of glutamine on tumor growth and apoptosis of hepatoma cells. Acta Pharmacol Sin 2000;21(7):668-72
[113] Daniele B, Perrone F, Gallo C, Pignata S, De Martino S, De Vivo R, Barletta E, Tambaro R, Abbiati R, D'Agostino L. Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: a double blind, placebo controlled, randomised trial. Gut 2001;48(1):28-33
[114] Obrador E, Carretero J, Esteve JM, Pellicer JA, Pascual A, Petschen I, Estrela JM. Glutamine potentiates TNF-alpha-induced tumor cytotoxicity. Free Radic BiolMed 2001;31 (5):642-50
[115] Carretero J, Obrador E, Pellicer JA, Pascual A, Estrela JM. Mitochondrial glutathione depletion by glutamine in growing tumor cells. Free Radic Biol Med 2000;29 (9):913-23
[116] Bounous G. Whey protein concentrate (WPC) and glutathione modulation in cancer treatment. Anticancer Res 2000;20 (6C):4785-92
[117] Asea A, Ara G, Teicher BA, Stevenson MA, Calderwood SK. Effects of the flavonoid drug quercetin on the response of human prostate tumours to hyperthermia in vitro and in vivo. Int J Hyperthermia 2001;17 (4):347-56
[118] Polkowski K, Mazurek AP. Biological properties of genistein. A review of in vitro and in vivo data. Acta Pol Pharm 2000;57 (2):135-55
[119] Polkowski K, Skierski JS, Mazurek AP. Anticancer activity of genistein-piperazine complex. In vitro study with HL-60 cells. Acta Pol Pharm 2000;57 (3):223-32
[120] Siess MH, Le Bon AM, Canivenc-Lavier MC, Suschetet M. Mechanisms involved in the chemoprevention of flavonoids. Biofactors 2000;12 (1-4):193-9
[121] Spinozzi F, Pagliacci MC, Migliorati G, Moraca R, Grignani F, Riccardi C, Nicoletti I. The natural tyrosine kinase inhibitor genistein produces cell cycle arrest and apoptosis in Jurkat T-leukemia cells. Leuk Res 1994;18 (6):431-9
[122] Theodorescu D, Laderoute KR, Calaoagan JM, Guilding KM. Inhibition of human bladder cancer cell motility by genistein is dependent on epidermal growth factor receptor but not p21ras gene expression. Int J Cancer 1998;78 (6):775-82
[123] Ren W, Qiao Z, Wang H, Zhu L, Zhang L. Flavonoids: promising anticancer agents. Med Res Rev 2003;23 (4):519-34.
[124]塘翔,许实波(导师)?黄酮类化合物DO1抗肿瘤的药理作用研究?中山大学硕士学位论文,2003?
[125] Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, van Norren K, van Leeuwen PA. Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr 2001;74 (4):418-25.
[126] Young M, Plosker GL. Paclitaxel: a pharmacoeconomic review of its use in the treatment of ovarian cancer. Pharmacoeconomics 2001;19 (12):1227-59.
[127] Yao LH, Jiang YM, Shi J, Tomas-Barberan FA, Datta N, Singanusong R, Chen SS. Flavonoids in food and their health benefits. Plant Foods Hum Nutr 2004;59 (3):113-22.
[128] Firenzuoli F, Gori L, Crupi A, Neri D. [Flavonoids: risks or therapeuticopportunities?]. Recenti Prog Med 2004;95 (7-8):345-51.
[129] Chen CH, Huang LL, Huang CC, Lin CC, Lee Y, Lu FJ. Baicalein, a novel apoptotic agent for hepatoma cell lines: a potential medicine for hepatoma. Nutr Cancer 2000;38 (2):287-95.
[130] Csokay B, Prajda N, Weber G, Olah E. Molecular mechanisms in the antiproliferative action of quercetin. Life Sci 1997;60 (24):2157-63.
[131] Brownson DM, Azios NG, Fuqua BK, Dharmawardhane SF, Mabry TJ. Flavonoid effects relevant to cancer. J Nutr 2002;132 (11 Suppl):3482S-9S.
[132] Brusselmans K, Vrolix R, Verhoeven G, Swinnen JV. Induction of cancer cell apoptosis by flavonoids is associated with their ability to inhibit fatty acid synthase activity. J Biol Chem 2005;280 (7):5636-45.
[133] Janisch KM, Milde J, Schempp H, Elstner EF. Vitamin C, vitamin E and flavonoids. Dev Ophthalmol 2005;38:59-69.
[134] Malinska D, Kiersztan A. Flavonoids--characteristics and significance for therapy]. Postepy Biochem 2004;50 (2):182-96.
[135] Manthey JA, Buslig BS, Baker ME. Flavonoids in cell function. Adv Exp Med Biol 2002;505:1-7.
[136] Wiseman S, Mulder T, Rietveld A. Tea flavonoids: bioavailability in vivo and effects on cell signaling pathways in vitro. Antioxid Redox Signal 2001;3 (6):1009-21.
[137] Williams RJ, Spencer JP, Rice-Evans C. Flavonoids: antioxidants or signalling molecules? Free Radic Biol Med 2004;36 (7):838-49.
[138] Freire R, van Vugt MA, Mamely I, Medema RH.Claspin: timing the cell cycle arrest when the genome is damaged. Cell Cycle 2006; 5: 2831-2834
[139] Owa T, Yoshino H, Yoshimatsu K, Nagasu T. Cell cycle regulation in the G1 phase: a promising target for the development of new chemotherapeutic anticancer agents. Curr Med Chem 2001; 8: 1487-503
[140]陆丽华,等.氧化苦参碱对人结肠癌细胞P21, P27, Cyclin E1及CDK2表达的影响.世界华人消化杂志2007;15(12):1353-1357
[141]余增丽,张立实,吴德生.玉米赤霉烯酮对MCF27细胞肿瘤相关基因表达的影响.毒理学杂志.2005.(19)3:175-177
[142]唐丽华,游本刚,徐向毅.珍珠菜总黄酮苷诱导HL-60细胞凋亡作用的研究.上海中医药大学学报,2007.(21)1:54-57
[143]孙震,姚辉愿.叶黄素-玉米黄素分子结构修饰对抑制肿瘤细胞增殖活性的影响.食品科学.2007;28(4):296-300
[144]毛新民,哈木拉提.吾甫尔.溃结安对维医载体溃疡性结肠炎模型的作用.毛新民论文.2004年
[145]毛新民,哈木拉提.吾甫尔.溃结安对TNBS所致溃疡性结肠炎模型的作用.毛新民论文.2004年
[146] Taupin D, Pedersen J, Familari M, Cook G, Yeoman N, Giraud AS. Augmented intestinal trefoil factor (TFF3) and loss of pS2 (TFF1) expression precedes metaplastic differentiation of gastric epithelium. Lab Invest, 2001;81:397-408
[147] Lin J, Nadroo AM, Chen W, Holzman IR, Fan QX, Babyatsky MW. Ontogeny and prenatal expression of trefoil factor 3/ITF in the human intestine. Early Hum Dev, 2003;71:103-109
[148]毛新民,哈木拉提.吾甫尔肝郁脾虚型溃疡型结肠炎大鼠的免疫学研究新疆医科大学学报,2004,27(4)367---369
[149]毛新民、哈木拉提.吾甫尔溃结安对TNBS导致实验性溃疡型结肠炎大鼠凝血的影响新疆医科大学学报,2004,27(5)
[150] Shirazi T, Longman RJ, Corfield AP, Probert CS. Mucin and inflammatory bowel disease. Postgrad Med J, 2000;76:473-478
[151]刘延泽等,天然产物研究与开发. 1995, 7(3):1
[152]宋分举武光林陈可欣天津市1981年～2000年结肠癌发病年龄趋势研究天津医科大学学报2004;10( 1)
[153]靖大道结肠癌病因学研究现状胃肠病学2001 ;6 (4)
[154]江学良,王志奎,秦成勇.中国溃疡性结肠炎的研究现状与对策.世界华人消化杂志, 2000;8(6)610-613
[155]周婷,林平,潘慧.溃疡性结肠炎发病机制及其研究进展[J].世界华人消化杂志, 2003;11(11):1782-1786
[156]徐芝勇细胞内活性氧与肿瘤生物学通报2004,39(9);24—25
[157]费立军上颌窦癌患者血小板聚集、粘附功能及血浆中八因子相关蛋白的检测中国冶金工业医学杂志2001 18( 1):55
[158]陈杰张先稳艾迪注射液对荷瘤小鼠的抗癌效应及免疫调节作用徐州医学院学报2005;25 (3)
[159]吴学勇补益类中药在肿瘤治疗中的应用中医研究1999;12(1)53-55
[160]刘景芳中医药防治恶性肿瘤的现状及展望中医药时代1995;2(4):18
[161] 1earon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell, 1990, 61: 759-767
[162]张振书马强结肠癌的流行病学胃肠病学2001,6;(4):231
[163]高玉堂我国常见恶性肿瘤的发病趋势中国肿瘤,1996,5:3-6
[164]陈渝萍曲洁新龚飞跃珠海地区结肠息肉结肠癌流行病学的相关因素分析右江医学2003年第’31卷第1期74-76
[165]李其龙俞玲玲马新源嘉善县大肠癌发病及生存率分析中国肿瘤2005 ,14( 9)
[166]张霞葛敏徐望红1972～2000)年上海市长宁区恶性肿瘤发病趋势中国肿瘤2005 ,14( 9)
[167]金凡,周淑贞,陶蓉芳等.上海市恶性肿瘤性病趋势1972～1994年.肿瘤, 1999;19:255-258
[168]戴颖秀王建华叶苗凉上海市杨浦区1992-2001年结肠癌流行特征和趋势中国肿瘤!2003;12(8):452-455
[169]郑莹,李德录,俞顺章上海市恶性肿瘤疾病负担的研究中国肿瘤2001年第10卷第4期196-199
[170] Bus PJ, Nagcgaul ID, Verspaget HW, Ismcrs CB, Geldof H, Van Krieken JH, GriffioenGMesalazine-fndueed apoptosis of colnrx:tal career; on the verge of a new cl,enwpreventive era? Aliment Phamraeol Ther, 1999, 13: 1397,-1402
[171] Reinacher-Schick A, Seideustioker F, Petrasch S, Rcise,M, Plulippou S, Theega,ten D, Preitag G, Sclbnriegel W.Mesalazine changes apoptosis anti proliferation in normal mucosa of patients with sporadic polyps of the large bowel. Eadoscopy, 2000, 32: 245-254
[172] Gasche C, Goel A, Boland CR. 5-aminosalieylic acid (5-ASA) but rot acetylsalicylic acid (aspirin) reduces the spontaneous mutation rate at a (CA)_ m,-satelite (MS)-Gastroenterology, 2001, 120:651
[173] Kaiser G(:, Yen F, Poll, DR. Mesalamine blocks tumor necrosis factor growth inhibition and unclear factor kappaB activation in mousee olnnocytcs. Castruenterolegy, 1999,116:602-609
[174] Tlmn MJ, Namboadiri MM, Heath CW Jr. Aspirin use and reduced risk of fatal colon cancer. N Fngl)Meal, 1991,325:1593-1596.
[175] Reddy BS, Hirose Y, I.ubet R, Stele V, Kellof G, Paulson S, Seibert K, Rao CV. Chemoprevention of colon cancer by spcific cyclooxygenase-2 inhibitor, celecoxib, administered during different stages of carcinogenesis. Can—Res. 2000. 60: 293-297.
[176] BirdRP.Observationandquantificationofaberrantcryptsinthemurinecolontreatedwithacoloncarcinogen:preliminaryfindings.CancerLett,1987,7:147—151
[177] McLellanEA,BirdRP.Specificitystudytoevaluateinductionofaberrantcryptsinmurinecolons.CancerRes,1988,48:6183—61866
[178] RoncucciL,MedlineA,BruceWR.Classificationofaberrantcryptfociandmicroadenomainhumancolon.CancerEpidemiolBiomarkersPrevent,1991,1:57—607
[179] WargovichMJ,ChenCD,HarrisC,etal.Inhibitionofaberrantcryptgrowthbynon-steroidalanti-inflammatoryagentsanddifferentiationagentsintheratcolon.IntJCancer,1995,60:515—5198
[180] SmithAJ,SternHS,PennerM,etal.SomaticAPCandK-rascodon12mutationsinaberrantcryptfocifromhumancolons.CancerRes,1994,54:5527—5530
[181]金松杰李玉林1,2-二甲肼诱发大鼠肠黏膜腺体癌变的组织学研究中华病理学杂志1993;22:218
[182]黄信孚大肠息肉见:郑芝田主编胃肠病学第2版,北京:人民卫生出版社1992,702-703
[183]唐伟军吴志勇喻德洪结直肠癌的实验模型中华实验外科杂志2000,17(4):380-381
[184]吴成秋,陈雯,张桥,钟小明,二甲肼诱导大鼠肠癌过程中增殖细胞核抗原的表达中国癌症杂志2000,10(6):553-556
[185]陈锋,张桥,螺旋藻对二甲肼诱导大肠变性隐窝的抑制作用〔J〕中华预防医学杂志,1995,29(1):13 17
[186] Potten C S, Owen G, Hewitt D, et al. Stimulation and inhibition of proliferation in the small intestinal crypts of the mouse after in vivo administration of growth factors. Gut, 1995, 36(6): 864-873
[187] Pinto D, Clevers H . Wnt, stem cells and cancer in the intestine. Biol Cell, 2005, 97(3): 185-196
[188] Radtke F, Clevers H. Self-renewal and cancer of the gut: two sides of a coin. Science, 2005, 307(5717): 1904-1909
[189] Glinsky G V, Beregovska O, Glinskn A B. Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. J Clin Invest, 2005, 115(6): 1503-1521
[190] Campbell F, Geraghty J M, Appleton M A, et al. Increased stem cell somatic mutation in the non-neoplastic colorectal mucosa of patients with familial adenomatous polyposis. Hum Pathol, 1998, 29(12): 1531-1535
[191] Preston S L. Bottom-up histogenesis of colorectal adenomas: origin in the monocryptal adenoma and initial expansion by crypt fission. Cancer Res, 2003, 63(13): 3819-3825
[192] Campbell F, Appleton M A, Shields C J, et al. No difference in stem cell somatic mutation between the background mucosa of right-and left-sided sporadic colorectal carcinomas. J Pathol, 1998, 186(1): 31-357
[193]李军吕愈敏.金珠,等塞来昔布对-甲基脱诱导的大鼠畸变.隐窝灶的顶防作用.中华消化杂志,zooq.,z4:m-15s.
[194] Takayama T, Katsuki S,Takahashi Y. et al. herrant crypt foci of the colon as precursors of adenoma and cancer.NEng J Med, f998,339; 1277-1284.
[195] Uchida K. 1Cado S. Ando M, et al. A mutinous histochemical study on tmalignancy of aberrant crypt foci (ACF) in rat colonJ Vet Vled Sci> zJ01,63:145-149.
[196] Tanaka T, Kohno H, Shimada k, et al. Prevention of colonic aberrant crypt foci 6y dietary feeding of garcinol in male F344 rare. Carcinogenesis, 2000, 21; 1183-1189.
[197] Pretlow TP, 0'Riordan MA, Somich GA, et al. Aberrant crypts correlate with tumor incidence in F344 rats treated with azoxyrrtethane and phytate [J]. Carcinogenesis, 1992,13(9):1509-1512
[198] Uchida K,Kado S,Ando M,et al.A mutinous histochemical study on malignancy of aberrant crypt foci in rat colon [J]. J Vet Med Sci, 2001, 63 (2):145-149
[199] Rowland IR, Rumney CJ, Coutts JT, et al. Effect of bifi- dobacterium longum and insulin on gut bacterial metabo-lism and carcinogen-induced ACF in rats [J]. Carcino-genesis, 1998, 19 ( 2 ) :281-285
[200] Tm,a T, Kohno H, Shimada R, et al. Prevention of colonic aberrant crypt foci by dietary feeding of garcinol in male F344 rats [J]. Carcinogenesis, 2000, 21(6):1183-1189
[201] End- J, Abrams K, Eklarm A, Jackson E, Mayhem J Colorectal cancer prevention in ulcerarice colitis: a c.-control sturlv. Aliment Pharmaaol Then- 2000. 14: 145-153.
[202]伊沙克江·马合穆德,主编.中国医学百科全书维吾尔医学分册[M],第一册?乌鲁木齐:新疆人民卫生出版社.1988.第一版.
[203]哈木拉提.吾甫尔.维吾尔医气质?体液论及其现代研究[M], 2003,58-60
[204]张莉,哈木拉提·吾甫尔,恶性肿瘤神经-内分泌-免疫网络紊乱的维西医研究.新疆医科大学博士论文.2006
[205] Sylvie Mazine,Khaled Meflah,Emanuelle Tavan etal. Effect of resistant starch and \or fat-soluble vitamins A and E on the initiation stage of aberrant crypts in rat colon ,NUTRITION AND CANCER ,1998,31(3):168-177
[206]戴颖秀王建华叶苗凉上海市杨浦区1992年~2001年结肠癌流行特征和趋势中国肿瘤2003 12 (8):58-60
[207]邹浩军,明亮.黄酮类化合物抗炎免疫及抗衰老药理研究进展.安徽卫生职业技术学院学报2003,3(6)
[208]许士凯,王晓东,赵军宁等天然药物抗衰老有效成分研究进展(之三)?现代中西医结合杂志2005,14(21),2773-2775
[209]魏巍.中药甙类活性成分抗辐射作用的研究?中国辐射卫生2006,15(2)251-252?
[210]努尔买买提,哈木拉提.吾甫尔等.异常黑胆质成熟剂和清除剂对小鼠神经内分泌免疫网络的调节作用.维吾尔医学及其他传统医学的研究与应用[C]?乌鲁木齐:新疆人民卫生出版社2003:11-12.
[211] Tusruo T,Lida H, Tsukagoshi S, et al. Overcoming of VCR resistance in P338leukemia in viva and vitro through enhanced cytotoxicity of VCR and VDS byverapmil[J]. Cancer Res, 1981,41:1967
[212]刘燕,潘启超.钙通道阻滞剂对长春碱类抗癌药物的体内增效作用[J].癌症,1991,10(6):466-468
[213] Smyth M J, Krasovkis E, Sutton V R et al. The Drug Efflux Protein, Additionally Protects Drug-resistant Tumor Cells from Multiple Forms of aspase-dependent Apoptosis[J]. Proc Natl Acad Sci USA, 1998,95(12):7042
[214] Bobinson L J, Roberus W K, Lamming D, et al. Human MDR1 Protein verexpression Delays the Apoptotic Cascade in Chinese Hamster Ovary ibroblasts[J]. Biochemistry, 1997,36(37):11169
[215] Kataoka S, Natio M, Tomida A, et al. Resistance to Antitumor Agent-induced Apoptosis in A Mutant of Human Myeloid Leukemia U937 Cells[J]. Exp Cell Res, 1994,215(1):199
[216]潘启超,田晖.多种中药单体逆转肿瘤多药耐药性[J].科学通报,1995,40(20): 190122
[217] Humlova Z. Protooncogene bcl-2 in process of apoptosis. Review article. Sb Lek 2002;103 (4):419-25
[218] Lopez-Hoyos M, Carrio R, Merino J, Merino R. Regulation of B cell apoptosis by Bcl-2 and Bcl-XL and its role in the development of autoimmune diseases (Review). Int J Mol Med 1998;1 (2):475-83
[219] Califice S, Waltregny D, Castronovo V, van den Brule F. [Prostate carcinoma cell lines and apoptosis: a review]. Rev Med Liege 2004;59 (12):704-10
[220] Longuet M, Serduc R, Riva C. Implication of bax in apoptosis depends on microtubule network mobility. Int J Oncol 2004;25 (2):309-17
[221] Laux MT, Aregullin M, Berry JP, Flanders JA, Rodriguez E. Identification of a p53-dependent pathway in the induction of apoptosis of human breast cancer cells by the natural product, resveratrol. J Altern Complement Med 2004;10 (2):235-9
[222] Gu J, Zhang L, Swisher SG, Liu J, Roth JA, Fang B. Induction of p53-regulated genes in lung cancer cells: implications of the mechanism for adenoviral p53-mediated apoptosis. Oncogene 2004;23(6):1300-7
[223] Kuang YF, Chen YH. Induction of apoptosis in a non-small cell human lung cancer cell line by isothiocyanates is associated with P53 and P21. Food Chem Toxicol 2004;42 (10):1711-8
[224] Gardner CR. Anticancer drug development based on modulation of the Bcl-2 family core apoptosis mechanism. Expert Rev Anticancer Ther 2004;4 (6):1157-77
[225] Jin J, Huan M, Liu GT. Studies on the resistance mechanism of a 5-fluorouracil resistant human hepatocellular carcinoma cell line Bel/5-FU. The Chi nese Young Pharmacologists Symposi um, Beiji ng ,2002:83-4
[226] Huang Y, Ibrado AM, Reed JC et al. Coexpression of severalμmolecular mechanisms of multidrug resistance and their significance for paclitaxel cytotoxicity in human AML HL260 cells.Leukemia, 1997 ;11 (2) :253-7
[227] Lehnert M. Clinical multidrug resistance in cancer :A multifactorial problem. Eur J Cancer , 1996 ;32A(6):912-20
[228] Gupta S. Molecular steps of death receptor and mitochondrial path-ways of apoptosis. L if e Sci , 2001 ;69 (25-26):2957-64
[229] Takehara T , Liu XL , Fujimoto J et al . Expression and role of Bcl-xl in human hepatocellular carcinomas. Hepatology , 2001;34(1):55-61
[230] Nita ME, Ono2Nita SK, Tsuno N et al . Bcl2X(L) antisense sensitizes human colon cancer cell line to 52fluorouracil. J pn J Cancer Res, 2000;91(8):825-32
[231] Tsuda H, Sata M, Ijuuin H et al. A novel strategy for remission induction andmaintenance in cancer therapy. Oncol Rep , 2002;9(1):65-8
[232] Stavrovskaya AA. Cellular mechanisms of multidrug resistance of tumor cells. Biochemist ry ( Mosc) , 2000;65(1):95-106
[233] Chu G. Cellular responses to cisplatin. The roles of DNA-binding proteins and DNA repair. J Biol Chem, 1994; 269(2):787-90
[234] Siess MH, Le Bon AM, Canivenc-Lavier MC, Suschetet M. Mechanisms involved in the chemoprevention of flavonoids. Biofactors 2000;12 (1-4):193-9
[235] Ford JM, Hait WN.Pharmacology of drugs that alter multidrug resistance in cancer[J].Phar.Rev, 1990,42(3):155-99
[236] TwentymanPR.Modifiers of multidrug resistance [J].BrJHaematol,1995,90:735
[237] Sikic B I. Modulation of multidrug resistance: at the threshold[J]. J ClinOncol, 1993,11:1629
[238]敖忠芳,夏薇.汉防已甲素逆转白血病细胞耐药的研究[J].中华血液学杂志, 1995,16(5):235-238
[239]李文瑜,李舜华,崔克义,等.苦参碱逆转的白血病多药耐药细胞系K562/A02对柔红霉素耐药性的研究[J].中华病理生理学杂志,1998,14(5):521-523
[240]田晖,潘启超.双苄基异喹啉生物碱蝙蝠葛碱与蝙蝠葛苏林碱逆转多药耐药性的研究[J].癌症,1996,15(6):410-413
[241] Sandler AB, Gray R, Brahmer J, et al. Randomized phase II/III trial of paclitaxel (P) plus carboplatin (C) with or without bevacizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC): An Eastern Cooperative Oncology Group (ECOG) trial– E4599. Pro Am Soc Clin Oncol, 2005,23:2s LBA4.
[242] Half E, Broaddus R, Danenberg KD, et al. HER-2 receptor expression, localization, and activation in colorectal cancer cell lines and human tumors. Int J Cancer, 2004,108:540-548.
[243] Sekharam M, Zhao H, Sun M, et al: Insulin-like growth factor 1 receptor enhances invasion and induces resistance to apoptosis of colon cancer cells through the Akt/Bcl-x(L) pathway. Cancer Res, 2003, 63: 7708-7716.
[244] Chun YJ, Park S, Yang SA, et al. Activation of Fas receptor modulates cytochrome P450 3A4 expression in human colon carcinoma cells. Toxicol Lett, 2003,146:75-81.
[245] Ohana G, Bar-Yehuda S, Arich A, et al. Inhibition of primary colon carcinoma growth and liver metastasis by the A3 adenosine receptor agonist CF101. Br JCancer, 2003,20, 89:1552-1558.
[246] Tsuda H , SataM, Ijuuin H, et al. Anovel strategy for remission induction and maintenance in cancer therapy. Oncol Rep, 2002, 9(1): 65- 68
[247] Linenberger ML, Hong T, Flowers D, et al. Multidrug– resistance phenotype and clinical responses to gemtuzumab ozogamicin . Blood, 2001, 98 (4): 988- 994
[248] Tsimberidou AM, Paterakis G. Evaluation of the clinical relevance of the expression and function of P- glycoprotein, multidrug resistance protein and lung resistance protein in patients with primary acute myelogenous leukemia. Leuk Res, 2002,26 (2):143- 154
[249] Nicholson DW, Thornberry NA. Apoptosis: Life and death decisions. Science, 2003, 299(6504): 214- 215
[250] Yu EZ, Li YY, Liu XH, et al. Antiapoptotic action of hypoxia– inducible factor- 1 alpha in human endothelial cells. Lab Invest, 2004, 84(5): 552-561
[251] Fojo T, Bates S. Strategies for reversing drug resistance. Oncogene, 2003, 22(47):7512- 7523
[252] Shangary S, Johnson DE. Recent advances in the development of anticancer agents targeting cell death inhibitors in the bcl - 2 protein family. Leukemia, 2003, 17(8): 1470- 1481
[253] Hersey P, Zhang XD. Overcoming resistance of cancer cells to apoptosis. J Cell Physiol, 2003, 196(1):9- 18
[254] Scotto KW. Transcriptional regulation of ABC drug transporters [J]. Oncogene, 2003 , 22 (47): 7496- 7511
[255] Tsuruo T, Naito M, Tomida A, et al . Molecular targeting therapy of cancer: drug resistance, apoptosis and survival signal. Cancer Sci, 2003, 94 (1): 15- 21
[256] Hwang GY, Lin Huang LM. Detection of the hepatitis B virus X protein (HBx) antigen and anti- HBx antibodies in cases of human hepatocellular carcinoma. J Clin Microbiol, 2003, 41(12):5598- 5603
[257] Ohyashiki K, Ohyashiki JD, Nishimaki J, et al. Overexpression of P21 /waf 1 leads to increased inhibition of E2F 1 phosphorylation and sensitivity to anticancer drugs in retinoblastoma negative human sarloma cells. Cancer Res, 1997; 57: 2100
[258] Tetu B, Brisson J, Plante V, et al. P53and C erbB 2 a 3 markers of resistance to adjuvant chemotherapy in breast cancer. Mod Pathol, 1998; 11(9): 823
[259] Kurt WK. Regulation genes and drug sensitivity. J Nation Cancer Institu, 1996; 88: 1255
[260] Schneider HJ, Sampson SA, Cunningham D, et al. Bcl 2 expression and response to chemotherapy in colorectal adenocarcinomas. British J Cancer, 1997; 75: 427
[261] Kuhl FS, Krajwski S, Duran GE, et al. Spontaneous overexpression of the long form of the bcl X protein in a highly resistant P338 leukaemia, British J Cancer, 1997; 75: 268
[262] Ahamed S, Nageatte IB, mizan P, et al. Mechanisms of resistance in a human cell line exposed to sequencial to poisomerase poisoning, Cancer Research, 1997; 57: 5100
[263] Hotta T, Saito Y, Mikami J, et al. Interrelationship between O 6 alkylguanine DNA alkyltransferase activity and susceptibility to chlorothylnitrosoureas in several glioma cell lines, J Neurooncol, 1993; 17:1
[264] Wu ZN, Chan CL, Eastman A, et al. Expression of human O 6 methylguanineDNA methyltransferase in a DNA exeision repair deficient Chinese hanster ovary cell line and its respons to certain alkylating agnts. Cancer Res, 1992; 52: 32
[265] Fink D, Zheng H, Nebel S, et al. In vitro and in vivo resistance to cisplatin in cells that have lost DNA mismatch repair. Cancer Res, 1997; 57: 1841
[266] Brown SJ, Kellett PJ, Lippard SJ, et al. A yeast protein that binds to platinated DNA and confer sensitivity to cisplatin. Science, 1993; 261: 603
[267] Vaisman A, Chanty SG. Induction of UV damaged recognition protein by cisplatin treatment. Bio Chemirtry, 1995; 34: 105
[268] Aliosman F, Berger MS, Raikar A, et al. Enhanced repair of a cisplatin damaged reporter chloramphenicol O acetyltransferase gene and altered activites of DNA polymeraseαandβand DNA ligase in cells of a human malignant glioma following in vivo cisplatin therepy. J Cell Biochem, 1994;54:11
[269] Dabholka M, Vionnet J, Bostick BF, et al. Messenger RNA levels of XPAC and ERCC1 in ovarian cancer tissue correlate with response to platinum based chemotherapy. J Clin Invest, 1994; 94: 703
[270]李波,李德华,苟兴华,等.反义核酸逆转人肝癌细胞株多药耐药性的效应.中华肝胆外科杂志, 2005,11(1):63-64
[271] Wu H, Hait WN, Yang JM. Small interfering RNA- induced suppression ofMDR1 (P- glycoprotein) restores sensitivity to multidrug- resistant cancer cells. CancerRes, 2003, 63(7): 1515- 1519
[272] Mohamed MM, Mohamed MA, Fikry NM. Enhancement of anti-tumor effects of 5- fluorouracil combined with ultrasound on Ehrlich ascites tumor in vivo. Ultrasound Med Biol, 2003, 29 (11): 1635- 1643
[273] Drobna Z, Stein U, Walther W, et al. Pentoxifylline influences drug transport activity of P - glycoprotein and decreases MDR1 gene expression in multidrug resistant mouse leukemic L1210 /VCR cells . Gen Physiol Biophys , 2002, 21: 103-109
[274] Powis G, Kirkpatrick L. Hypoxia inducible factor- l alpha as a cancer drug target. Mol Cancer Ther, 2004, 3(5):647-654
[275]李贵海,孙付军,王宁,等.苦参碱干预获得性多药耐药小鼠S180肿瘤细胞相关生物因子P170过度表达与细胞凋亡的相关性.中药材, 2005,28(4):310-312
[276] Holm PS, Lage H, Bergmann S, et al. Multidrug - resistant cancer cells facilitate E1 - independent adenoviral replication: impact forcancer gene therapy. Cancer Res, 2004, 64 (1): 322-328
[277] Ford JM, Hait WN.Pharmacology of drugs that alter multidrug resistance in cancer[J].Phar.Rev, 1990,42(3):155-99
[278]田晖,潘启超.双苄基异喹啉生物碱蝙蝠葛碱与蝙蝠葛苏林碱逆转多药耐药性的研究[J].癌症,1996,15(6):410-413
[279] Lin H L, Liu T Y, Wu C W, et al.Berberine modulates expression of mdr1 geneproduct and the response to digestive track cancer cells to Paclitaxel[J].Br JCancer,1999,8(13):416-422
[280] Scambia G, Ranelletti F O, Benedetti Panici P, et al. Quercetin potentiates theeffect of Adriamycin in a multidrug-resistance MCF-7 human breast-cancer cellline: P-glycopreotein as a possible terget[J]. Cancer Chemother Pharmocol, 1994,34:459-464
[281] Lin H L, Liu TY, Lui W Y, et al. Up-regulation of multidrug resistance transporter expression by berberine in human and murine hepatoma cells[J].Cancer, 1999,85(9):1937-1942
[1]杨纯正.肿瘤耐药研究的若干问题.中华医学杂志,2001 ,81(24) :1475
[2] Scaglotti G V , Novello S , Selvaggi G. Multidrug resistance in on small cell lung cancer. Ann oncol , 1999 , 5 :83
[3] Thomas H , Coley HM. Overcoming multidrug resistance in cancer : an update on the clinical strategy of inhibiting p2glycoprotein. Cancer Control ,2003 ,10(2) :159
[4] Loo TW and Clarke DM. Location of the Rhodamine-binding Site in the Human Multidrug Resistance P-glycoprotin[J].J Biol Chem, 2002,277(46):44332-44338
[5] Sonneveld P. Multidrug resistance in haematological malignancies[J]. J Intern Med, 2000, 247(5):521-534
[6] Taylor JC, Horvath AR, Higgins CF,et al.The multidrug resistance P-glycoprotein. Oligomeric state and intramolecular interactions[J]. J Biol Chem,2001,276(39): 36075-36078
[7] Schinkel AH,Kemp S,Dolle M,et al.N-Glycosylation and deletion mutants of the human MDR, P-glycoprotein [J].J Biol Chem,1993,68:7474-748
[8] Rosenberg MF, Callaghan R,Ford RC,et al.Structure of the multidrug resistance P-glycoprotein to 2.5nm resolution determined by electron microscopy and image analysis [J].J Biol Chem, 1997,272:10658-10694
[9] Sauna ZE andAmbudkar SV.Evidence for a requirement for ATP hydrolysis at tow disitinct steps during a single turnover of the catakytic cycle of human P-glycoprotein [J] . Proc Natl Acad Sci, 2000,97:2515-2520
[10] Auna ZE andAmbudkar SV.Characterization of the catalytic cycle of ATP hydrolysis by human P-glycoprotein [J].J Biol Chem, 2001,276:11653-11661
[11] Ruiz Gomez MJ, Souviron Rodriguez A , Martinez Morillo M. P-glyco-protein , a membrane pump that represents a barrier to chemotherapy in cancer patients. An Med Interna ,2002 , 19(9) :477
[12] Hoffman M M, Roepe P D. Analysis of ion transport perturbations caused by hu MDR1 protein overexpression. Biochemistry , 1997 , 36(37) :11153
[13] Shtil AA.Signal transduction pathqays and transcriptional mechanisms as targets for prevention of emergence of multidrug resistance in human cancer cells [J]. Curr Drug Targets, 2001,2(1):57-77
[14] Geoffrey Chang. Multidrug resistance ABC transporter[J]. FEBS, 2003,555: 102-105
[15] Cordon-CardoC, O’BrienJ, BocciaJ, etal. Expression if multidrug resistance gene product in human normal and tumor tissue[J].J Histochem 1990,38:1277-1287
[16] Anil K, Sood MD, Richard E,etal.Drug resistance in ovarian cancer: from the laboratory to clinic [J].Obstet Gynecol, 1998, 92:312-319
[17] Victor L.Multidrug resistance: molecular mechanisms and clinical relevance[J]. Cancer Chemoth Pharmacol 1997,40:S3-S8
[18] Nooter K. Multidrug resistance (mdr) genes in human cancer[J] .Br J Cancer 1991,63:663-669
[19] Van den Heuvel-Eibrink MM, Sonneveld P and Pieters R. The prognostic significance of membrance transport-associated multidrug resistance (MDR)proteins in leukemia[J]. Int J Clin Pharmacol Ther, 2000,38(3):94-110
[20] Cole SPC and Deeley RG. Multidrug resistance mediated by the ATP-binding cassette transporter protein MRP[J]. Bio Essays, 1998,20:931-940
[21] Rosenberg MF, Mao QC, Holzenburg A, et al. The Structure of the Multidrug +Resistance Protein1 (MRP1/ABCC1) Crystallization and Single-paritcle Analysis[J]. J Biol Chem, 2001,276(19):16076-16082
[22] Borst P,Evers R,Kool M,et al.A family of drug transporters:the multidrug resistance-associated proteins[J]. J Natl Cancer Inst, 2000,92(16):1295-1302
[23] Jedlitschky G, and Keppler D.Transport of leukotriene C4 and structurally related conjugates[J]. Vitam Horm, 2002,64:153-184
[24] Leslie EM, Deeley RG, and Cole SP. Toxicological relevance of the multidrug resistance protein 1, MRP1 (ABCC1) and related transporters [J]. Toxicology, 2001,167(1):3-23
[25] Ishikawa T, Bao JJ,Yamane Y, et al.Coordinated induction of MRP/GS-X pump andγ-glutamylcysteine synthetase by heavy metals in human leukemina cells[J]. J Biol Chem, 1996,271:14981-14988
[26] Kool M deHass M, Scheffer GL,et al .Analysis of exprssion of cMOAT(MRP2),MRP3,MRP4,and MRP5,homologues of the multidrug resistance associated protein gene(MRP) in human cancer cell line[J] .Cancer Res 1997,57: 3537-3547
[27] Abbaszadegan MR, Futscher BW, Klimecki WT, et al.Analysis of multidrug resistance–associated protein (MRP)messenger RNA in normal and malignant hematopoietic cell [J]. Cancer Res 1994,54:4676-4679
[28] Schneider E, Cowan KH, Bader H,etal .Increased expression of the multidrugresistance–associated protein gene in relapsed acute leukemia[J]. Blood 1995,85: 186-193
[29] Rappa G, Finch R A , Sartrelli A C , et al . New insights into the biolo- gy and pharmacology of the multidrug resistance protein (MRP) from gene knockout models. Biochem Pharmacol , 1999 ,58 (4) :557
[30] Benderra Z , Morjani H , Trussardi A , et al . Evidence for functionaldiscrimination between leukemic cells overexpressing multidrug resis-tance associated protein (MRP) and P2glycoprotein. Adv Exp Med Bi-ol , 1999 , 457 :151
[31] Izquiero MA, Scheffer GL, Flens MJ, etc. Broad distribution of the multidrug mresistance-related vault lung resistance protein in normal tissue and tumors[J]. Am J Pathol. 1996,148(3):877-87
[32] Broxtermans HJ, Schuurhuis GJ.Transport protein in drug resistance detection and prognostic significance in acute myeloid leukemia[J]. J Int Med 1997,740:S147-151
[33] KD Tew. Glutathione-associated enzymes in anticancer drug resistance[J]. Cancer Res, 1994, 54: 4313-4320
[34] Ban M, Takahashi Y, Takayama T, et al. Transfection of Glutathione Stransferase (GST)πantisense complementary DNA increases the sensitvity of a colon cancer cell line to adriamycin, cisplatin, melphalan, and etoposide[J]. Cancer Res, 1996, 56: 3577
[35] Pommier Y, Leteurte F, Fesen MR, et al. Cellular determinants of sensitivity and resistance to DNA topoisomerase inhibitors[J]. Cancer Invest, 1994, 12: 530–42
[36]陈中平,Areti MALAPETSA , Anne MONKS ,等.人肿瘤细胞核苷酸切除修复蛋白表达与抗癌药耐药的相关性.癌症,2002 ,21(3) :233
[37]杨晓葵,郑芳,陈建华,等.凋亡相关蛋白的表达及Caspase23活性改变与人卵巢癌细胞铂耐药的关系.癌症,2002 ,21 (12) : 1288
[38] Lebedeva I , Rando R , Ojwang J , et al . Bcl-xL in prostate cancer cells : effects of overexpression and down2regulation on chemotherapy. Caner Res , 2000 ,60 :6052
[39]王雨田,胡家潞,药立波,等. P38信号途径与胃癌细胞阿霉素耐药相关.解放军医学杂志,2001 ,26(1) :24
[40] Ohyashiki K, Ohyashiki JD, Nishimaki J, et al. Overexpression of P21/waf1 leads to increased inhibition of E2F1 phosphorylation and sensitivity to anticancer drugs in retinoblastoma negative human sarloma cells[J]. Cancer Res,1997,57: 2100
[41] Tetu B, Brisson J, Plante V, et al. P53and CerbB2 a 3 markers of resistance to adjuvant chemotherapy in breast cancer[J]. Mod Pathol, 1998, 11(9): 823
[42] Schneider HJ, Sampson SA, Cunningham D, et al. Bcl2 expression and response to chemotherapy in colorectal adenocarcinomas[J]. British J Cancer, 1997, 75: 427
[43] Kuhl FS, Krajwski S, Duran GE, et al. Spontaneous overexpression of the long form of the bclX protein in a highly resistant P338 leukaemia[J]. British JCancer, 1997, 75: 268
[44] Herr, I., Wilhelm,D., B?hler,T.,et al. JNK/SAPK activity is not sufficient for anticancer therapy-induced apoptosis involving CD95-L, TRAIL and TNF- . Int[J]. J. Cancer, 1999,80: 417-424
[45] Elliott T , Sethi T. Integrins and extracellular matrix : a novel mechanism of multidrug resistance. Expert Rev Anticancer Ther ,2002 , 2(4) :449
[46] Yang J M, Xu Z, Wu H , et al . Over expression of extracellular matrix metalloproteinase inducer in multidrug resistant cancer cells. Mol Cancer Res , 2003 , 1(6) :420
[47] Vadgama J V , Wu Y, Shen D , et al . Effect of selenium in combination with adriamycin or taxol on several different cancer cells. Anti-cancer Res , 2000 ,20 (3) :1391
[48] Epsztein S , Glickstein H , Picard V , et al . H2ferritin subunit overex pression in erythroid cells reduces the oxidative stress response and induces multidrug resistance properties. Blood ,1999 ,94 (10) :3593
[49] Robert J.Multidrug resistance in oncology :diagnostic and therapeutic approaches[J]. Eur J Clin Invest, 1999,29:536-545
[50] Naito M, Watanabe T, Tsuge H, et al. Potentiation of the reversal activity of SDZ-PSC833 on multi-drug resistance by an anti-poglycoprotein monoclonal antibody MRK-16 [J]. International J Cancer,1996,67:435-440
[51]李惠芳,孙桂香,卢微微.多药耐药基因反义寡核苷酸逆转肿瘤细胞耐药的初步研究[J].中华血液学杂志, 1997,18(2):76-79
[52]曹江,胡汛,潘锵荣,等.MDRl反义RNA表达质粒的构建及其在多药耐药细胞抗药机理研究中的应用[J].中华医学杂志,1995,75:557
[53]王宝成,郭军,顾广玉,等.切割MDR1 RNA的核酶(Ribozyme)肝癌多药耐药细胞株BEL-7402/DOX化疗耐药性的逆转作用[J].中国肿瘤生物治疗杂志,1997,4: 107
[54] Kikuchi A, Holan V,Minowada J.Effects of tumor necrosis factor alpha ,interferon alpha and interferon gamma on non lymphoid leukemia cell lines :growth inhibition ,differentiation induction and drug sensitivity modulation[J]. Cancer Immunol Immunother 1992,35:257-263
[55] BorsellinoN,CrescimannoM,FlandianC,etal.Combined activity of interleukin-1 alpha or TNF-alpha and doxorubicin on multidrug resistant cell lines evidence that TNF and DXR have synergistic antitumor and differntiation inducing effects[J]. Anticancer Res, 1994,14:2643-2648
[56] Kang Y, Perry RR.Effect of alpha interferon on Pgp expression and function and on verapmil modulation of doxorubicin resistance[J]. Cancer Res, 1994,54:2952-2958
[57] Scala S, Pacelli R, Iaffaioli RV, etal. Reversal of adriamycin resistance by recombinant alpha interferon in multidrug resistant human colon carcinoma LoVo doxorubicin cells [J]. Cancer Res, 1991,51:4898-4902
[58] Wlther W, Stein U. RNA analysis using miniprep RNA in RT-PCR[J].Bio Technique, 1994,17:674-675
[59]高贤钧.中草药钙通道阻滞剂的研究与展望[J].中西医结合杂志,1990,10(7):4721
[60]潘启超,田晖.多种中药单体逆转肿瘤多药耐药性[J].科学通报,1995,40(20): 190122
[61]李达,杨淑莲,梁冰.中医药抗白血病细胞耐药的临床研究探讨[J].中国中西医结合杂志,1995;15(10):63623
[62]陈泽涛,顾振东.中药对淋巴细胞白血病小鼠细胞膜流动的影响[J].中国中西医结合杂志,1991,11(1):39
[63]潘启超,田晖.多种中药单体逆转肿瘤多药耐药性[J].科学通报, 1995,40(2): 190122
[64]陈宝安,盛茗,程坚,等.汉防己甲素对HL-60/Adr细胞凋亡作用的实验研究[J].南京铁道医学院学报,1999,18(3):158-159
[65]梁蓉,杨平地,陈协群,等.川芎嗪(或)环孢素A对HL60/ HT细胞耐药的逆转[J ] .中华内科杂志,1999 ,38(4) :260– 261
[66]姜晓峰,甄永苏.大黄素逆转肿瘤细胞的多药耐药[J ] .国外医学·肿瘤学分册,1998 ,26(化疗分册) :42– 44
[67]王宝成,郭军,狄剑时,等.榄香稀乳剂于肿瘤多药耐药的基础研究[J ] .中国肿瘤临床,1996 ,23(2) :143– 146
[68]卢步峰,于丽敏,边春香,等.β2榄香烯吗素抗肿瘤作用的实验研究[J ] .中国组织化学与细胞化学杂志, 2000 ,19(1) :78– 81
[69]郭娟娟,潘祥林,冯长伟,等.冬凌草甲素诱导多药耐药细胞系K562/ A02凋亡?逆转耐药性的研究[J].安徽中医学院学报,2000 ,19 (3) :34– 36
[70]史曦凯,张翼军,赵春景.人参皂甙单体Rb1对多药耐药细胞系K562/ HHT的耐药逆转作用[J ] .第三军医大学学报,1999 ,21(11) :827– 826
[71]史噶凯,张冀军,赵春景.人参皂甙单体Rbl对多药耐药细胞系K562/ HHT的耐药逆转作用.第三军医大学学报, 1999 , 21 (11) :825
[72] Tian H, Pan Q C. Modulation of multidrug resistance by three bisben-zylisoquinolines in comparison with verapamil. Acta Phamacol Sin ,1997, 18(5):455
[73]李佩文,蒋礼年,陆杭双.金艾康合并化学药物治疗肿瘤临床疗效观察[J].中成药,1999 ,21(11) :575
[74]叶祖光,孙爱续,李兰芳,等.汉防己甲素对阿霉素或长春新碱耐药株人癌细胞的逆转抗药性作用[J].中国中药杂志, 1996 ,21(6) :369
[75]胡军,赵瑾瑶,杨佩满.β2榄香烯乳剂逆转多药耐药细胞株MCF27/ ADM对阿霉素耐药性研究[J].中国微生态学杂志,2002 ,14(4) :214
[76]胡凯文,郑洪霞,齐静,等.浙贝母碱逆转白血病细胞多药耐药的研究[J].中华血液学杂志,1999 ,20(12) :650
[77]李旭芬,张苏展,郑树.苦参碱对K562及其多药耐药细胞K562/VIN的细胞生物学影响[J].中国病理生理杂志, 2002 , 18(10) :1233
[78]刘叙仪,孟松浪,杨敬贤,等.中药R3(补骨脂抽提剂)对阿霉素人乳腺癌细胞MCF27adr多药耐药的逆转[J].中国肿瘤临床,1997 ,24 (5) :325
[79]杨国旺,石朝玉.中药联合化疗的抗肿瘤增效作用[J].中国实验方剂杂志, 2000,6(3) :59
[80]张慧珠,杨林,任雷鸣,等.中药活性成份逆转肿瘤细胞多药耐药作用的体外筛选[J].华北煤炭医学院学报2003;5(5):265
[81]冯正权,郭勇,朱宁希,等.复方三根制剂逆转多药耐药的实验研究[J].中国肿瘤2003;12(6):370
[82]王宝成,郭军,狄剑时,等.榄香烯乳剂与肿瘤多药耐药的基础研究[J].中国肿瘤临床1996;23(2):143
[83]胥彬,许建华.抗癌药物与肿瘤化学治疗进展.北京:科学出版社,2001,19-25
[84]梁蓉,杨平地,陈协群.川芎嗪对白血病HL260/ VCR细胞多药耐药的逆转及其机制研究[J].中华血液学杂志,1999 ,20(6) :323
[85]王金华,叶祖光,孙爱续,等.粉防己碱逆转人乳腺癌MCF27多药耐药细胞的抗凋亡作用[J].中国中药杂志,2002 ,27(1) :46
[86]孙华丽,余桂清.扶正增效方对恶性肿瘤放射增敏作用的临床和实验研究[J].中医杂志,1990 , (6) :2521
[87]李云凤,张永恒,于桂兰,等.十全大补冲剂对肿瘤化疗药物增效减毒作用的研究[J].肿瘤杂志,1996 ,1(16) :38– 39
[88]陈泽涛,顾振东.中药对淋巴细胞白血病小鼠细胞膜流动性的影响[J].中国中西医结合杂志,1991 ,11(1) :39
[89]张旋波,白绍怀,屈艺,等,中药制剂Fw132te41逆转裸鼠移植瘤多药耐药性的初步研究[J].华西医大学报,1999 ,30 (4) :360-362
[90]张代钊,于尔辛,余桂清,等.中医药对肿瘤放化疗的增敏减毒作用[J].中国中西医结合杂志,1992 ,3(2) ;135-137
[91]杨岚,杨平地,梁蓉,等.川芎嗪联合环胞霉素A逆转白血病多药耐药的研究[J].癌症,2000 ,19(4):304-306
[92]田韧,杨劲松,张保国,等.以榄香稀乳剂为调变剂联合化疗耐药胃癌临床观察[J].肿瘤防治研究,1999 ,26(3):215-216
[1]斯依提·穆哈穆德·候赛音,主编.麦合孜尼艾地维亚(草药宝库)(波斯文)[M].印度吉维力可西瓦出版社, 1988年(农历):251-292?
[2]伊沙克江·马合穆德,主编.中国医学百科全书维吾尔医学分册[M].第一册,乌鲁木齐:新疆人民卫生出版社, 1988,第一版.
[3]安尼瓦尔,阿不都热依木,哈木拉提,等.维吾尔医体液燃烧的本质[J].维吾尔医药杂志, 1998,(1):11-16.
[4]哈木拉提,安尼瓦尔,艾尼,等.异常黑胆质及其清除剂与自由基关系的研究[J].维吾尔医药杂志, 1996,(2):10-15.
[5]陈瑗,周玫主编.自由基医学[M].北京:人民军医出版社, 1991,42-53.
[6]哈木拉提,阿不都热依木,阿不都艾尼,热孜万古丽.维吾尔医成熟剂和清除剂抗活性氧的作用研究[J].中国民族医药杂志. 2000, 6 (3):31
[7]阿布力米提·玉素甫·阿吉主编.维吾尔医基础理论(维文).乌鲁木齐:新疆科技卫生出版社, 1988, 32-46.
[8]周志东,赵伟康.机体抗氧化系统研究进展[J].国外医学.老年医学分册, 1999, 20(4):172-1761
[9] Kankofer M. Antioxidative defence mechanisms against reactive oxygen species in bovine retained and not-retained placenta: activity of glutathione peroxidase, glutathione transferase, catalase and superoxide dismutase. Placenta, 2001,May, 22(5):466-4721
[10]潘华珍,冯立明,许彩民,等.丙二醛对红细胞的作用[J].生物化学与生物物理学进展, 1984,2:341
[11]Dizdaroglu M. Chemistry of free radical damage to DNA and nucleoproteins. DNA and Free Radical. London: Ellis Horwood, 1993:19~39
[12]Malins DC, Polissar NL, Gunselman SJ. Progressiol on human breast cancers to themeta staticstate is linked on OH·radical induced damage. Proc Natl Acad Sci USA, 1996, 93:2557~2563
[13]Patrizia M, Giorgio F, Stefania F, etal. Age dependent increase in Axidative damage to DNA, lipids and proteins in human skeletal muscle. Free Radic Biol Med, 1999, 26:303~317
[14]Wiseman H, Kaur H, Halliwell B. DNA damage and cancer : measurement and mechanism. Cancer Lett, 1995;93:113~120
[15]阿布都艾尼,阿不都热依木,哈木拉提.异常黑胆质成熟剂和清除剂对OH·引发的DNA损伤的保护作用[J].中药药理与临床. 2000;16(3)36
[16]阿不都热依木,哈木拉提异常黑胆质成熟剂和清除剂抗氧化作用的ESR研究中药新药与临床药理2001年第12卷第6期:422
[17]李林,姬艳丽,陈艳,武贵臻,哈木拉提·吾甫尔.异常黑胆质成熟剂与清除剂对H2O2诱导的淋巴细胞毒性的影响[J].新疆医科大学学报. 2005. , 28(4):292
[18]Barbouti A, Doulias PT, Zhu BZ, etal. Intracellulariron, but not copper, plays a critical role in hydrogen peroxide-induce DNA damage [J]. Free Radic Biol Med, 2001, 31(4):490-498.
[19]徐永俊. DNA氧化损伤生物标志物8-OH-dG的检测及其在医学上的应用[J].癌变·畸变·突变, 2002, 14(1):50253.
[20]Alicia J. Kowaltowski, Anibal E. Vercesi. Mitochondrial damage induced by conditions of oxidative stress[J]. Free Radic. Biol. Med. , 1999, (26):463-471.
[21]Turrens J. F. Superoxide production by the mitochondrial respitory chain [J]. Biosc. Rep. , 1997, (17):328.
[22]阿不都热依木,哈木拉提,斯拉甫,努尔买买提,肖开提.异常黑胆质清除剂对线粒体氧化损伤的保护作用[J].中国中医基础医学杂志. 2002, 8(7):40
[23]阿不都热依木·玉苏甫,哈木拉提·吾甫尔.异常黑胆质成熟剂水提物和醇提物对HepG2细胞m5dC及82OH2dG形成的影响[J].中国中医基础医学杂志2006, 12(10):730
[24]阿布都艾尼,阿不都热依木,哈木拉提.异常黑胆质成熟剂和清除剂对OH#引发的DNA损伤的保护作用[J].中药药理与临床, 2000, 16(3):34-36.
[25]阿不都热依木,哈木拉提,阿布都艾尼.维吾尔医成熟剂和清除剂抗活性氧的作用研究[J].中国民族医药杂志, 2000, 6(3):30-32.
[26]阿不都热依木,哈木拉提,阿布都艾尼.异常黑胆质成熟剂和清除剂抗氧化作用的ESR研究[J].中药新药与临床药理, 2001, 12(6):420-422.
[27]HalmuratU, AbdiryimY, AnwarU, MooreN. Uighur traditionalMedicine syndrome of Abnormal Savda in men is associated with Oxidative stress, which can be improved by Munziq and Mushil of Abnormal Savda [J]. Therapie, 2004, 59(4):483-484.
[28]姬艳丽,李林,武贵臻,陈艳,哈木拉提·吾甫尔.异常黑胆质成熟剂与清除剂对H2O2诱导的淋巴细胞凋亡的影响[J].新疆医科大学学报2005. , 28(4):294-298
[29]宝福凯.程序性细胞死亡的基因调控[J].生命科学, 1995, 7(5):15217.
[30]Clark AR, Purdie CA, etal. Thymocyte apoptosis induce by p53-dependent and indepandent pathway [J]. Nature, 1993, 362:849-852.
[31]Lowe SW, Schrmitt EM, Smith SW, etal. p53 is required for radiation-inducedapoptosis in mouse thymocytes [J]. Nature, 1993, 362:847-849.
[32]哈木拉提.吾甫尔,李林,陈艳,等.异常黑胆质成熟剂与清除剂对氧化损伤的淋巴细胞p53蛋白表达的影响[J].新疆医科大学学报, 2005,28(4):289
[33]Somasundaram K. Tumor suppression p53: regulation andf unction [J]. Frontiers Bioscience, 2000, 5:D424-437.
[34]Oren M. Regulation of the p53 tumer suppresspr protein [J]. Jbiol Chem, 1999, 274(51):36031-36034.
[35]Li Y, Chopp M, Zhang ZG, etal. P53–Immunore active Protein and P53 mRNA expression aftertr ansient middle cerebral artery occlusion in rats [J]. Stroke, 1994, 25(4):849-855.
[36]艾斯卡尔·依米提,哈木拉提·吾甫尔,布再娜甫·伊力哈木.维吾尔医成熟及清除剂诱导T淋巴瘤细胞凋亡的研究[J].中药药理与临床. 2000;16(2):34
[37]Perkins ND. The Rel/NF-kappaB family : friend and foe [J]. Trends Biochem Sci, 2000, 25(9):434-440.
[38]哈木拉提,阿不都热依木,阿不都艾尼.维吾尔医成熟剂和清除剂抗活性氧的作用研究[J].中国民族医药杂志, 2000, 6(3):30-32.
[39]阿不都热依木,阿不都艾尼,哈木拉提.五种维药的清除羟自由基及抗DNA损伤作用研究[J].中草药, 2001, 32(3):2362238.
[40]李林,哈木拉提,武贵臻,等.异常黑胆质成熟剂及清除剂对氧化诱导的淋巴细胞DNA损伤的保护作用[J].中华中西医杂志, 2004, 5(15):154021543.
[41]陈艳,李林,武贵臻,等.异常黑胆质成熟剂与清除剂对H2O2诱导的淋巴细胞NF2JB表达的影响.新疆医科大学学报[J]. 2005, 28(4):298
[42]Dumont A, Hehnet SP. Hofmann TG etal. Hydrogen peroxide induced apoptosis is CD95-independent, requires the release of mitochondria-derived reactive oxygen species and the activation of NF-kappaB [J]. Oncogene, 1999, 18(3):747-757.
[43]Brown JM, Wouters BG. Apoptosis, p53, and tumor cell sensitivity toAnticancer agents [J]. Cancer Res, 1999, 59(7):1391-13991
[44]Ma J, Reed KA, Gallo JM. Cells designed to deliver anticancer drugs by apoptosis [J]. Cancer Res, 2002, 62(5):1382-13871
[45]阿不都热依木·玉苏甫,哈木拉提·吾甫尔.异常黑胆质成熟剂乙酸乙酯萃取物对HepG2细胞生长和凋亡及相关基因调控的研究[J].中国药科大学学报2006, 37(2):161-164
[46]Gardner CR, Anticancer drug development based on modulation of the Bcl-a family apoptosis mechamism [J]Expert Rev anti-cancer ther, 2004, 4(6):1157-1177
[47]Brown JM, Kim BG, Apoptosis P53 and tumor cell sensitivity to anticancer agents[J]Cancer Res, 1999, 59(7):1391-1399
[48]阿不都热依木.玉苏甫1, 2,哈木拉提.吾甫尔2,吐尔洪.卡迪尔1, 3异常黑胆质成熟剂醇提物诱导HepG2细胞凋亡机制的研究中成药2006年第28卷第7期:1008
[49]Kwon KB, Kim EK, LimJG, etal. Molecular mechanisms of apoptosis induced by Scopio water extract in human hepatoma HePG2 cells[J]World J Gastroenterol, 2005, 11(7):943-947
[50]李莉. Caspase与细胞调亡[J].辽宁医学杂志, 2004, 18(3)151-153
[51]张莉,哈木拉提·吾甫尔,张仑.异常黑胆质成熟剂提取物对小鼠辐射的防护作用中南大学学报(医学版) 2007, 32(1):73
[52]哈木拉提·吾甫尔.异常黑胆质成熟剂和清除剂体内外抗氧化功能的研究[M]维吾尔医气质?体液论及其现代研究.乌鲁木齐:新疆科学技术出版社, 2003:100-115.
[53]阿依努尔·买提斯迪克,尼加提·热合曼,哈木拉提·吾甫尔等.异常黑胆质载体动物模型下丘脑-垂体-肾上腺轴形态学的观察[J].新疆医科大学学报, 2006, 28(10):907-909.
[54]阿依努尔·买提斯迪克,哈木拉提·吾甫尔.异常黑胆质载体动物模型饮食量和饮水量的观察[J].新疆中医药, 2006, 24(1):527.
[55]阿地力江·阿不力米提,胡汉华.异常黑胆质成熟剂对异常黑胆质载体动物模型下丘脑-垂体-肾上腺轴细胞超微结构的影响.国际病理科学与临床杂志[J]. 27(3):190
[2]巴黑.玉素甫.肿瘤患者的维医异常体液分型.维吾尔医药, 2004,(4):23-7
[3]阿不都热依木,哈木拉提,阿布都艾尼.维吾尔医成熟剂和清除剂抗活性氧的作用研究[J].中国民族医药杂志,2000;6 (3):30-2
[4]阿不都热依木,哈木拉提,阿布都艾尼.异常黑胆质成熟剂和清除剂抗氧化作用的ESR研究[J].中药新药与临床药理,2001,12 (6):420-2
[5]阿布都艾尼,阿不都热依木,哈木拉提.异常黑胆质成熟剂和清除剂对OH.引发的DNA损伤的保护作用[J].中药药理与临床,2000,16 (3):34-6
[6]哈木拉提.吾甫尔.维吾尔医气质?体液论及其现代研究[M], 2003,98-99
[7] Halmurat U, Abdiryim Y, Anwar U, Moore N. Uighur traditional medicine syndrome of Abnormal Savda in men is associated with oxidative stress, which can be improved by Munziq and Mushil of Abnormal Savda. Therapie 2004;59 (4):483-4
[8] Abdiryim Y, Halmurat U, Anwar U, Moore N. Protective effects of Munziq and Mushil of abnormal Savda to mitochondrial oxidative damage. Fundam Clin Pharmacol 2004;18 (4):471-6
[9]哈木拉提,李林,陈艳.异常黑胆质成熟剂与清除剂对氧化损伤的淋巴细胞p53蛋白表达的影响[J].新疆医科大学学报,2005,28 (4):287-289
[10]李林,姬艳丽,陈艳.异常黑胆质成熟剂与清除剂对H2O2诱导的淋巴细胞毒性的影响[J].新疆医科大学学报,2005,28 (4):290-292
[11]姬艳丽,李林,武贵臻.异常黑胆质成熟剂与清除剂对H2O2诱导的淋巴细胞凋亡的影响[J].新疆医科大学学报,2005,28 (4):293-296
[12]李林,哈木拉提.异常黑胆质成熟剂和清除剂对氧化应激的基因调控?细胞损伤和凋亡的研究.新疆医科大学博士学位论文,2004
[13]陈艳,李林,武贵臻.异常黑胆质成熟剂与清除剂对H2O2诱导的淋巴细胞NF-κB的影响[J].新疆医科大学学报,2005,28 (4):296-299
[14]张莉,哈木拉提·吾甫尔,张仑.异常黑胆质成熟剂提取物对小鼠辐射的防护作用中南大学学报(医学版) 2007,32(1):73
[15]阿不都热依木.玉苏甫,哈木拉提.吾甫尔,吐尔洪.卡迪尔.异常黑胆质成熟剂醇提物诱导HepG2细胞凋亡机制的研究.中成药2006,28(7):1008
[16]古扎丽努尔.异常黑胆质成熟剂Hela细胞凋亡机制的研究.博士后课题内容2007.(内部资料).
[17]艾斯卡尔·依米提,哈木拉提·吾甫尔,布再娜甫·伊力哈木.维吾尔医成熟及清除剂诱导T淋巴瘤细胞凋亡的研究[J].中药药理与临床.2000;16(2):34
[18]刘跃民.维药没食子提取物诱导乳腺癌细胞Bcap-37凋亡的实验研究[J].中国中药信息杂志.2006;11,31-33
[19] Schottenfeld D, Beebe-Dimmer JL. ADVANCES IN CANCER EPIDEMIOLOGY: Understanding Causal Mechanisms and the Evidence for Implementing Interventions. Annu Rev Public Health 2005;26:37-60
[20] Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55 (2):74-108
[21] Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ. Cancer statistics, 2005. CA Cancer J Clin 2005;55 (1):10-30
[22] Yang L, Parkin DM, Li LD, Chen YD, Bray F. Estimation and projection of the national profile of cancer mortality in China: 1991-2005. Br J Cancer 2004;90 (11):2157-66
[23] Yang L, Parkin DM, Ferlay J, Li L, Chen Y. Estimates of cancer incidence in China for 2000 and projections for 2005. Cancer Epidemiol Biomarkers Prev 2005;14 (1):243-50
[24] Yang L, Parkin DM, Li L, Chen Y. A comparison of the sources of cancer mortality in China. Cancer Causes Control 2004;15 (7):681-7
[25] Pao W, Wang TY, Riely GJ, et al. KRAS mutation and primary resistance of lung adenocarcinoma to gefitinib or erlotinib. PLOS, 2005, 2(1): 57-61
[26] Camp ER, Summy J, Bauer T, et al. Molecular mechanisms of resistance to therapies targeting the epidermal growth factor receptor. Clin Cancer Res, 2005, 11: 397-405
[27] Learn CA, Hartzell TL, Wikstrand CJ, et al. Resistance to tyrosine kinase inhibition by mutant epidermal growth factor receptor variant III contributes to the neoplastic phenotype of glioblastoma multiforme. Clin Cancer Res, 2004,10:3216-3224
[28] Kokubo Y, Gemma A, Noro R, et al. Reduction of PTEN protein and loss of epidermal growth factor receptor gene mutation in lung cancer with natural resistance to gefitinib(Iressa). Br J Cancer ,2005,92: 1711-1719
[29]谭永苏.抗肿瘤药物研究与开发.北京.现代生物技术与药物科技出版中心.2004.118
[30] SchefferGL, SchroeijersAB, IzquerdoMA, et al. Lung resistance-related protein/ major vault protein and vaults in multi drug resistant cancer[J]. Curr Opin Oncol,2000, 12(6):550-556
[31] Jung CK, Lee KY, Kim Y, et al. Epstein-Barr virus infection drug resistance and prognosis in Korean T- and NK-cell lymphomas [J].Pathol Int,2001,51(5): 355-363
[32] Filipts M, Jaeger U, Simonitisch I. Clinical relevance of the lung resistance protein in diffuse large B-cell lymphomas [J]. Clin Cancer Res,2000,6(9): 3417-3423
[33] Syahruddin E, Oguri T, Takahashi T, et al. Differential expression of DNA topoismerase 22 and 11 genes between small cell and non small cell lung cancer [J]. Jpn J Cancer Res,1998,89(8): 787-795
[34] Wuchter C,Leonid K,Ruppert V,Schrappe M,Buchner T,Schoch C,Haferlach T , Harbott J,Ratei R, Dorken B,Ludwig WD. Clinical significance of P-glycoprotein expression and function for response to induction chemotherapy, relapse rate and overall survival in acute leukemia. Haematologica,2000;85:711-721
[35] DeGeorge JJ, Ahn CH, Andrews PA, et al. Regulatory considerations for preclinical development of anticancer drugs.Cancer Chemother Pharmacol, 1998;41:173-185
[36] Nkopolou L, Lazaris AC, Karvantzas N, et al. DNA topoisomerase 11-alpha immunoreactivity as a marker of tumor aggressiveness in invasive breastcancer[J]. Pathobiology, 2001, 32(2): 137-143
[37] Dingemans AC, van Ark-Otte J , Span S, et al. TopoisomeraseⅡalpha and other drug resistance markers in advanced non small cell lung cancer[J]. Lung Cancer, 2001, 32(2):117-128
[38] Dingemans AC, Witlox MA , Stallaert RA, et al. Expression of DNA topoisomerase 11 alpha and topoisomeraseⅡbeta genes predicts survival and response to chemotherapy in patients with small cell lung cancer[J]. Clin Cancer Res, 1999, 5(8): 2048-2058
[39] Ferreira CG, Tolis C, Span SW, et al. Drug-induced apoptosis in lung cancer cells is not mediated by the Fas/FasL(CD95/APO1)signaling pathway[J].Clin Cancer Res,2000,6(1):203-212
[40] Schmidt P, Thiele M, Rudroff C, et al.Detection ofrumor cells in peritoneallavage from patients with gastrointestinal cancer by multiplex reverse transcriptase PCR[J].Hepatogatogastroenterology,2001,48(42):1675
[41] Nakanishi H, Kodera Y, Yamamura Y, et al. Rapid quantitative detection of carcinoembryonic antigen-expressing free tumor cells in the peritoneal cavity of gastric-cancer patients with real-time RT-PCR in the lightcycler[J]. Int J Cancer ,2000,89(5):411
[42] Huang P,Olive PL,Durand RE. Use of the comet assay for assessment of drug resistance and its modulation in vivo.Br J Cancer, 1998;77:412-416
[43] Ramachandran C,Melnick SJ. Multidrug resistance in human tumors molecular diagnosis and clinical significance. Mol Diagn, 1999;4:81-94
[44]刘忠民,寿楠海,姜希宏.多药耐药相关蛋白在大肠癌中的表达及其临床意义[J].世界华人消化杂志, 1999;7:1000-1001
[45] Zhang LJ, Chen KN, Xu GW, Xing HP, Shi XT. Congenital expression of mdr-1 gene in tissues of carcinoma and its relation with atho morphology and prognosis. World J Gastroenterol, 1999;5:53-56
[46]俞丽芬,吴云林,章永平.鸦胆子油乳剂对人胃腺癌长春新碱耐药细胞株MKN28/VCR的逆转作用[J].世界华人消化杂志,2001;9:376-378
[47] Kodera Y, Nakanishi H, Ito S, et al. Quantitative detection of disseminated free cancer cells in peritoneal washes with real-time reverse transcriptase–polymerase chain reaction:a sensitive predictor of outcome for patients with gastric carcinoma[J].Ann Surg,2002,235(4):499
[48] Nishida S, Kitamura K, Ichikawa D, er al. Molecular detection of disseminated cancer cells in the peripheral blood of patients with gastric cancer[J].Anticancer Res ,2000,20(3B):2155
[49] Jiang Z, Liu L, Fang W, Shou WZ, Zhang DS, Dai MM. Local radiative treatment of hepatocellular cancer with phosphorus-32 glass microspheres to enhance the efficacy of hepatic artery chemoembolism and possibly related with MDR expressed P-glycoprotein. World J Gastroenterol , 2000;6(Suppl 3):59
[50] Jiang JF, Liu WJ, Ding J. Regulation of telomerase activity in camptot hecin - induced apoptosis of human leukemia HL-60 cells. Acta Pharmacol Sin ,2000;21:759-764
[51] Volm M. Multidrug resistance and its reversal. Anticancer Res,1998;18: 2905-2917
[52] Johnstone RW,Ruefli AA,Tainton KM,Smyth MJ. A role for P-glycoprotein in regulating cell death. Leuk Lymphoma,2000;38:1-11
[53] Walther W,Stein U,Fichtner I,Alexander M,Shoemaker RH,Schlag PM. Mdr1promoter driven tumor necrosis factor alpha expression for a chemotherapy controllable combined in vivo gene therapy and chemotherapy of tumors. Cancer Gene Ther,2000;7:893-900
[54] Savas B, Arslan G, Gelen T, Karpuzoglu G, Ozkaynak C. Multidrug resist ant malignant melanoma with intracranial metastasis responding to immunotherapy. Anticancer Res, 1998;19:4413-4420
[55] Guo YS,Jin GF,Houston CW,Thompson JC,Townsend CM Jr. Insulin like growth factorⅠpromotes multidrug resistance in MCLM colon cancer cells. J Cell Physiol,1998;175:141-148
[56]廖海涛,刘立义等.P-gp,p53过表达与胃癌及乳腺癌转移的关系[J].中华肿瘤杂志, 2003,17(2):132
[57]易永芬,于冬青,林晓,等.三种耐药蛋白在胃癌中的表达及意义[J].实用肿瘤杂志, 2003,18(3):185-187
[58]陈毅,吴云林.逆转MDR1基因相关的消化系统肿瘤多药耐药[J].国外医学.消化系疾病分册2003,11(5): 77-79
[59]陈立军,宋廷惠,汲言山,等.定量检测多药耐药基因在胃癌?大肠癌组织中的表达及其临床意义[J].肿瘤研究与临床,1997;9:10-13
[60]刘冀龙,董新舒,刘忠臣.应用RT-PCR方法定量分析大肠癌患者多药耐药基因表达水平及其临床意义[J].中国肿瘤临床, 1999;26:39-41
[61]姚学清,卿三华.多药耐药基因在进展期大肠癌中检测及意义[J].世界华人消化杂志, 1999;7:535-536
[62]姚学清,林锋.肿瘤多药耐药和进展期大肠癌耐药细胞株建立研究进展[J].世界华人消化杂志, 2003;11(9):1433-1435
[63]王百林,陈孝平,翟淑萍.多药耐药相关蛋白基因在原发性肝细胞癌中的表达[J]. 2006年4月23日.来源:健康中国论坛
[64]刘忠民,寿楠海.肠道肿瘤多药耐药相关蛋白和肺耐药蛋白表达的临床意义[J].世界华人消化杂志, 1999;7:95
[65]陈昊,蒋芹,张连云,王燕青.肺癌组织中P170?P190?TOPOⅡ?GSTπ的表达及意义[J].中华中西医杂志.2003,14(2)108-120
[66]吴书庆,邹正辉,李建勇,等.乳腺癌耐药蛋白在急性白血病中的表达及其临床意义[J].中华现代中西医杂志2004,2(1):124-135
[67] Plouzek CA, Ciolino HP, Clarke R, et al.Inhibition of P-glycoprotein activity and reversal of multidrug resistance in vitro rosemary extract. Eur J Cancer 1999; 35:1541-5
[68] Tito Fojo,Susan Bate. Strategies for reversing drug resistance. Oncogene.2003,22, 7512–75239
[69] David J. Samson, Jerome Seidenfeld, Kathleen Ziegler, and Naomi Aronson. Chemotherapy Sensitivity and Resistance Assays:A Systematic Review. J Clin Oncol 2004,22:3618-3630
[70]李贺,熊茂明,孟翔凌,等.三氧化二砷逆转肝癌细胞株HepG2/ADM多药耐药的作用[J],世界华人消化杂志2006; 14(27): 2691-2694
[71]王秀丽,孔力,赵瑾瑶,等.三氧化二砷逆转人乳腺癌CF-7/ADM细胞耐药的机制研究[J].中华肿瘤杂志2002; 24: 339-343
[72]韩冰,石玉枝,霍建民.三氧化二砷对肺腺癌细胞凋亡及肺耐药蛋白基因多药耐药蛋白基因表达的影响[J].中国实用内科杂志2005; 25: 243-244
[73]史立军,闫彬彬,李双星,等. As2O3对胰腺癌细胞株的抑制作用及其机制的初步探讨[J].中国病理生理杂志2005; 21: 1572-1574
[74]何景利,王贵英,单宝恩.三氧化二砷联合顺铂对人结肠癌细胞株colon26抑制作用机理的研究[J].中国肿瘤临床2005; 32: 1125-1128
[75]刘连新,朱安龙,陈炜,等.三氧化二砷对原发性肝癌的作用及其机理研究[J].中华外科杂志2005; 43: 33-36
[76]李英,徐功立,李颖,张楠.鸦胆子油乳诱导白血病U937细胞凋亡的实验研究[J].中华血液学杂志.2004,25(6):381-382
[77]刘悦,王禾,符庆吉,等.鸦胆子油乳诱导膀胱癌BIU287细胞凋亡的研究[J].中国中西医结合外科杂志.2001,7(2):76-78
[78]马力,张月宁.鸦胆子油乳诱导肝癌细胞凋亡基对相关基因表达的影响[J].世界华人消化杂志.2004,12(3):559-562
[79]李贵海,孙付军,王宁,等.苦参碱干预获得性多药耐药小鼠S180肿瘤细胞相关生物因子P170过度表达与细胞凋亡的相关性.中药材, 2005,28(4):310-312
[80]李芮,杜健鹏,候仰韶,等.复方苦参注射液对SGC-7901,HepG2和BEL-7402肿瘤细胞作用的实验研究[J].肿瘤研究和临床.2006,18(1):8-10
[81]高船舟,杨佩满,吕广艳,曲淑贤1.20 (R)2人参皂甙Rg3逆转K562/ ADM细胞MDR及诱导其凋亡的研究[J],解剖科学进展.(2002)01-0031-35
[82]郝立宏,赵瑾瑶,杨佩满.川芎嗪与B-榄香烯联合应用诱导K562/ADM细胞凋亡及逆转其的实验研究[J].中国肿瘤临床.2005,32(1):25-28
[83]阿吉.阿不力米提.玉素甫主编.维吾尔医学基础理论.卫生厅人民出版社,1988
[84]哈木拉提.吾甫尔.维吾尔医气质?体液论及其现代研究[M], 2003,34-38
[85]哈木拉提.吾甫尔.维吾尔医气质?体液论及其现代研究[M], 2003,78-79
[86]哈木拉提.吾甫尔.维吾尔医气质?体液论及其现代研究[M], 2003,93-94
[87]阿吉.阿布里米提.玉素甫.维吾尔医学基础理论.乌鲁木齐:新疆科技卫生出版社, 1988
[88]易沙克江.马合穆德.中国医学百科全书维吾尔医学分卷:新疆人民卫生出版社,1988
[89]阿布都克力木.吐尔逊.肿瘤发病机制的维医理论探讨.维吾尔医专科学校学报,2003,(2):36-8
[90]阿不都热依木,哈木拉提.异常黑胆质成熟清除剂消除自由基及对OH.引发的DNA损伤的保护作用.新疆医科大学硕士学位论文,1999
[91]艾斯卡尔,哈木拉提,伊里哈木江.维医成熟剂和清除剂诱导T淋巴瘤细胞调亡的研究[J].中药药理与临床,2000,16 (2):33-4
[92]哈木拉提,艾斯卡尔,伊里哈木江.异常黑胆质成熟剂与清除剂对人Hela细胞调亡基因表达的影响[J].细胞与分子免疫学杂志,2001;17 (2):109-11
[93] Abdiryim Y, Halmurat U, Umar A, Moore N. Cytotoxicity of Abnormal Savda Munziq aqueous extract in human hepatoma (HepG2) cells. Fundam Clin Pharmacol 2005;19(3):1-6
[94] Abdiryim Y, Halmurat U, Umar A, Moore N. Cytotoxicity of Abnormal Savda Munziq: Inhibition of cell growth and DNA, protein synthesis in HepG2 cells. 10th International Congress of Toxicology, July 2004, Tempere, Finland. Toxicology and Applied Pharmacology 2004; 197(3): 309
[95] Inhibition of cell growth and cellular protein, DNA and RNA synthesis in human hepatoma (HepG2) cells by ethanol extract of Abnormal Savda Munziq. Journal of Ethnopharmacology (in press)
[96] Halmurat U, Abdiryim Y, Umar A, Moore N. Uighur traditional medicine syndrome of Abnormal Savda in man is associated with oxidative stress, which can be improved by Munziq and Mushil of Abnormal Savda. 15th International Congress of Clinical Pharmacology and Theripeutic. 2004, Australia
[97]贺慧颖,吴秉铨.分子病理学在肿瘤分子靶向治疗中的应用.2005年CSCO会议录.2005,546-550
[98] McPherson K,Steel CM,Dixon JM.ABC of breast diseases.Breast cancer epidemiology, riskfactors, and genetics[J].BMJ,2000,3(7):624-628
[99]李连弟,饶克勤,张思维,等.中国12市县1993-1997年肿瘤发病和死亡登记资料统计分析[J].中国肿瘤,2002,11(9):497-507
[100]周岱翰.临床中医肿瘤学[M].北京:人民卫生出版社, 2003,150-151
[101]肖立峰,张天虹,刘江涛,等.中药薏苡仁酯作用喉癌Hepg-2细胞的体外作用[J].哈尔滨医科大学学报,2004,38(3):252-262
[102]林芳,钱之玉,薛红卫,等.青蒿素和青蒿琥酯对人乳腺癌MCF-7细胞的体外抑制作用比较研究[J].中草药,2003,34(4):164-1661
[103]陈俊霞,夏俊,刘基巍,等.人参皂甙Rg3诱导乳腺癌细胞系MCF-7凋亡的实验研究[J].癌变畸变突变,2005,17(4):213-216
[104]张莹,张起辉,吴立军,等.吴茱萸碱诱导人宫颈癌HeLa细胞凋亡过程中非caspase调控因素[J].中国药理学通报,2004, 20(1) :61-64
[105]阿不都热依木,哈木拉提.异常黑胆质成熟剂及其有效组分的抗癌活性研究.新疆医科大学博士学位论文,2005
[106] Lopez-Hoyos M, Carrio R, Merino J, Merino R. Regulation of B cell apoptosis by Bcl-2 and Bcl-XL and its role in the development of autoimmune diseases (Review). Int J Mol Med 1998;1 (2):475-83
[107] Califice S, Waltregny D, Castronovo V, van den Brule F. [Prostate carcinoma cell lines and apoptosis: a review]. Rev Med Liege 2004;59 (12):704-10
[108] Longuet M, Serduc R, Riva C. Implication of bax in apoptosis depends on microtubule network mobility. Int J Oncol 2004;25 (2):309-17
[109] Laux MT, Aregullin M, Berry JP, Flanders JA, Rodriguez E. Identification of a p53-dependent pathway in the induction of apoptosis of human breast cancer cells by the natural product, resveratrol. J Altern Complement Med 2004;10 (2):235-9
[110] Kulcsar G. Apoptosis of tumor cells induced by substances of the circulatory system. Cancer Biother Radiopharm 1997;12(1):19-26
[111] Kulcsar G. Synergistic potentiating effect of D(+)-mannose, orotic, and hippuric acid sodium salt on selective toxicity of a mixture of 13 substances of the circulatory system in culture for various tumor cell lines. Cancer Detect Prev 2000;24(5):485-95
[112] Liu SL, Shi DY, Shen ZH, Wu YD. Effects of glutamine on tumor growth and apoptosis of hepatoma cells. Acta Pharmacol Sin 2000;21(7):668-72
[113] Daniele B, Perrone F, Gallo C, Pignata S, De Martino S, De Vivo R, Barletta E, Tambaro R, Abbiati R, D'Agostino L. Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: a double blind, placebo controlled, randomised trial. Gut 2001;48(1):28-33
[114] Obrador E, Carretero J, Esteve JM, Pellicer JA, Pascual A, Petschen I, Estrela JM. Glutamine potentiates TNF-alpha-induced tumor cytotoxicity. Free Radic BiolMed 2001;31 (5):642-50
[115] Carretero J, Obrador E, Pellicer JA, Pascual A, Estrela JM. Mitochondrial glutathione depletion by glutamine in growing tumor cells. Free Radic Biol Med 2000;29 (9):913-23
[116] Bounous G. Whey protein concentrate (WPC) and glutathione modulation in cancer treatment. Anticancer Res 2000;20 (6C):4785-92
[117] Asea A, Ara G, Teicher BA, Stevenson MA, Calderwood SK. Effects of the flavonoid drug quercetin on the response of human prostate tumours to hyperthermia in vitro and in vivo. Int J Hyperthermia 2001;17 (4):347-56
[118] Polkowski K, Mazurek AP. Biological properties of genistein. A review of in vitro and in vivo data. Acta Pol Pharm 2000;57 (2):135-55
[119] Polkowski K, Skierski JS, Mazurek AP. Anticancer activity of genistein-piperazine complex. In vitro study with HL-60 cells. Acta Pol Pharm 2000;57 (3):223-32
[120] Siess MH, Le Bon AM, Canivenc-Lavier MC, Suschetet M. Mechanisms involved in the chemoprevention of flavonoids. Biofactors 2000;12 (1-4):193-9
[121] Spinozzi F, Pagliacci MC, Migliorati G, Moraca R, Grignani F, Riccardi C, Nicoletti I. The natural tyrosine kinase inhibitor genistein produces cell cycle arrest and apoptosis in Jurkat T-leukemia cells. Leuk Res 1994;18 (6):431-9
[122] Theodorescu D, Laderoute KR, Calaoagan JM, Guilding KM. Inhibition of human bladder cancer cell motility by genistein is dependent on epidermal growth factor receptor but not p21ras gene expression. Int J Cancer 1998;78 (6):775-82
[123] Ren W, Qiao Z, Wang H, Zhu L, Zhang L. Flavonoids: promising anticancer agents. Med Res Rev 2003;23 (4):519-34.
[124]塘翔,许实波(导师)?黄酮类化合物DO1抗肿瘤的药理作用研究?中山大学硕士学位论文,2003?
[125] Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, van Norren K, van Leeuwen PA. Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr 2001;74 (4):418-25.
[126] Young M, Plosker GL. Paclitaxel: a pharmacoeconomic review of its use in the treatment of ovarian cancer. Pharmacoeconomics 2001;19 (12):1227-59.
[127] Yao LH, Jiang YM, Shi J, Tomas-Barberan FA, Datta N, Singanusong R, Chen SS. Flavonoids in food and their health benefits. Plant Foods Hum Nutr 2004;59 (3):113-22.
[128] Firenzuoli F, Gori L, Crupi A, Neri D. [Flavonoids: risks or therapeuticopportunities?]. Recenti Prog Med 2004;95 (7-8):345-51.
[129] Chen CH, Huang LL, Huang CC, Lin CC, Lee Y, Lu FJ. Baicalein, a novel apoptotic agent for hepatoma cell lines: a potential medicine for hepatoma. Nutr Cancer 2000;38 (2):287-95.
[130] Csokay B, Prajda N, Weber G, Olah E. Molecular mechanisms in the antiproliferative action of quercetin. Life Sci 1997;60 (24):2157-63.
[131] Brownson DM, Azios NG, Fuqua BK, Dharmawardhane SF, Mabry TJ. Flavonoid effects relevant to cancer. J Nutr 2002;132 (11 Suppl):3482S-9S.
[132] Brusselmans K, Vrolix R, Verhoeven G, Swinnen JV. Induction of cancer cell apoptosis by flavonoids is associated with their ability to inhibit fatty acid synthase activity. J Biol Chem 2005;280 (7):5636-45.
[133] Janisch KM, Milde J, Schempp H, Elstner EF. Vitamin C, vitamin E and flavonoids. Dev Ophthalmol 2005;38:59-69.
[134] Malinska D, Kiersztan A. Flavonoids--characteristics and significance for therapy]. Postepy Biochem 2004;50 (2):182-96.
[135] Manthey JA, Buslig BS, Baker ME. Flavonoids in cell function. Adv Exp Med Biol 2002;505:1-7.
[136] Wiseman S, Mulder T, Rietveld A. Tea flavonoids: bioavailability in vivo and effects on cell signaling pathways in vitro. Antioxid Redox Signal 2001;3 (6):1009-21.
[137] Williams RJ, Spencer JP, Rice-Evans C. Flavonoids: antioxidants or signalling molecules? Free Radic Biol Med 2004;36 (7):838-49.
[138] Freire R, van Vugt MA, Mamely I, Medema RH.Claspin: timing the cell cycle arrest when the genome is damaged. Cell Cycle 2006; 5: 2831-2834
[139] Owa T, Yoshino H, Yoshimatsu K, Nagasu T. Cell cycle regulation in the G1 phase: a promising target for the development of new chemotherapeutic anticancer agents. Curr Med Chem 2001; 8: 1487-503
[140]陆丽华,等.氧化苦参碱对人结肠癌细胞P21, P27, Cyclin E1及CDK2表达的影响.世界华人消化杂志2007;15(12):1353-1357
[141]余增丽,张立实,吴德生.玉米赤霉烯酮对MCF27细胞肿瘤相关基因表达的影响.毒理学杂志.2005.(19)3:175-177
[142]唐丽华,游本刚,徐向毅.珍珠菜总黄酮苷诱导HL-60细胞凋亡作用的研究.上海中医药大学学报,2007.(21)1:54-57
[143]孙震,姚辉愿.叶黄素-玉米黄素分子结构修饰对抑制肿瘤细胞增殖活性的影响.食品科学.2007;28(4):296-300
[144]毛新民,哈木拉提.吾甫尔.溃结安对维医载体溃疡性结肠炎模型的作用.毛新民论文.2004年
[145]毛新民,哈木拉提.吾甫尔.溃结安对TNBS所致溃疡性结肠炎模型的作用.毛新民论文.2004年
[146] Taupin D, Pedersen J, Familari M, Cook G, Yeoman N, Giraud AS. Augmented intestinal trefoil factor (TFF3) and loss of pS2 (TFF1) expression precedes metaplastic differentiation of gastric epithelium. Lab Invest, 2001;81:397-408
[147] Lin J, Nadroo AM, Chen W, Holzman IR, Fan QX, Babyatsky MW. Ontogeny and prenatal expression of trefoil factor 3/ITF in the human intestine. Early Hum Dev, 2003;71:103-109
[148]毛新民,哈木拉提.吾甫尔肝郁脾虚型溃疡型结肠炎大鼠的免疫学研究新疆医科大学学报,2004,27(4)367---369
[149]毛新民、哈木拉提.吾甫尔溃结安对TNBS导致实验性溃疡型结肠炎大鼠凝血的影响新疆医科大学学报,2004,27(5)
[150] Shirazi T, Longman RJ, Corfield AP, Probert CS. Mucin and inflammatory bowel disease. Postgrad Med J, 2000;76:473-478
[151]刘延泽等,天然产物研究与开发. 1995, 7(3):1
[152]宋分举武光林陈可欣天津市1981年～2000年结肠癌发病年龄趋势研究天津医科大学学报2004;10( 1)
[153]靖大道结肠癌病因学研究现状胃肠病学2001 ;6 (4)
[154]江学良,王志奎,秦成勇.中国溃疡性结肠炎的研究现状与对策.世界华人消化杂志, 2000;8(6)610-613
[155]周婷,林平,潘慧.溃疡性结肠炎发病机制及其研究进展[J].世界华人消化杂志, 2003;11(11):1782-1786
[156]徐芝勇细胞内活性氧与肿瘤生物学通报2004,39(9);24—25
[157]费立军上颌窦癌患者血小板聚集、粘附功能及血浆中八因子相关蛋白的检测中国冶金工业医学杂志2001 18( 1):55
[158]陈杰张先稳艾迪注射液对荷瘤小鼠的抗癌效应及免疫调节作用徐州医学院学报2005;25 (3)
[159]吴学勇补益类中药在肿瘤治疗中的应用中医研究1999;12(1)53-55
[160]刘景芳中医药防治恶性肿瘤的现状及展望中医药时代1995;2(4):18
[161] 1earon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell, 1990, 61: 759-767
[162]张振书马强结肠癌的流行病学胃肠病学2001,6;(4):231
[163]高玉堂我国常见恶性肿瘤的发病趋势中国肿瘤,1996,5:3-6
[164]陈渝萍曲洁新龚飞跃珠海地区结肠息肉结肠癌流行病学的相关因素分析右江医学2003年第’31卷第1期74-76
[165]李其龙俞玲玲马新源嘉善县大肠癌发病及生存率分析中国肿瘤2005 ,14( 9)
[166]张霞葛敏徐望红1972～2000)年上海市长宁区恶性肿瘤发病趋势中国肿瘤2005 ,14( 9)
[167]金凡,周淑贞,陶蓉芳等.上海市恶性肿瘤性病趋势1972～1994年.肿瘤, 1999;19:255-258
[168]戴颖秀王建华叶苗凉上海市杨浦区1992-2001年结肠癌流行特征和趋势中国肿瘤!2003;12(8):452-455
[169]郑莹,李德录,俞顺章上海市恶性肿瘤疾病负担的研究中国肿瘤2001年第10卷第4期196-199
[170] Bus PJ, Nagcgaul ID, Verspaget HW, Ismcrs CB, Geldof H, Van Krieken JH, GriffioenGMesalazine-fndueed apoptosis of colnrx:tal career; on the verge of a new cl,enwpreventive era? Aliment Phamraeol Ther, 1999, 13: 1397,-1402
[171] Reinacher-Schick A, Seideustioker F, Petrasch S, Rcise,M, Plulippou S, Theega,ten D, Preitag G, Sclbnriegel W.Mesalazine changes apoptosis anti proliferation in normal mucosa of patients with sporadic polyps of the large bowel. Eadoscopy, 2000, 32: 245-254
[172] Gasche C, Goel A, Boland CR. 5-aminosalieylic acid (5-ASA) but rot acetylsalicylic acid (aspirin) reduces the spontaneous mutation rate at a (CA)_ m,-satelite (MS)-Gastroenterology, 2001, 120:651
[173] Kaiser G(:, Yen F, Poll, DR. Mesalamine blocks tumor necrosis factor growth inhibition and unclear factor kappaB activation in mousee olnnocytcs. Castruenterolegy, 1999,116:602-609
[174] Tlmn MJ, Namboadiri MM, Heath CW Jr. Aspirin use and reduced risk of fatal colon cancer. N Fngl)Meal, 1991,325:1593-1596.
[175] Reddy BS, Hirose Y, I.ubet R, Stele V, Kellof G, Paulson S, Seibert K, Rao CV. Chemoprevention of colon cancer by spcific cyclooxygenase-2 inhibitor, celecoxib, administered during different stages of carcinogenesis. Can—Res. 2000. 60: 293-297.
[176] BirdRP.Observationandquantificationofaberrantcryptsinthemurinecolontreatedwithacoloncarcinogen:preliminaryfindings.CancerLett,1987,7:147—151
[177] McLellanEA,BirdRP.Specificitystudytoevaluateinductionofaberrantcryptsinmurinecolons.CancerRes,1988,48:6183—61866
[178] RoncucciL,MedlineA,BruceWR.Classificationofaberrantcryptfociandmicroadenomainhumancolon.CancerEpidemiolBiomarkersPrevent,1991,1:57—607
[179] WargovichMJ,ChenCD,HarrisC,etal.Inhibitionofaberrantcryptgrowthbynon-steroidalanti-inflammatoryagentsanddifferentiationagentsintheratcolon.IntJCancer,1995,60:515—5198
[180] SmithAJ,SternHS,PennerM,etal.SomaticAPCandK-rascodon12mutationsinaberrantcryptfocifromhumancolons.CancerRes,1994,54:5527—5530
[181]金松杰李玉林1,2-二甲肼诱发大鼠肠黏膜腺体癌变的组织学研究中华病理学杂志1993;22:218
[182]黄信孚大肠息肉见:郑芝田主编胃肠病学第2版,北京:人民卫生出版社1992,702-703
[183]唐伟军吴志勇喻德洪结直肠癌的实验模型中华实验外科杂志2000,17(4):380-381
[184]吴成秋,陈雯,张桥,钟小明,二甲肼诱导大鼠肠癌过程中增殖细胞核抗原的表达中国癌症杂志2000,10(6):553-556
[185]陈锋,张桥,螺旋藻对二甲肼诱导大肠变性隐窝的抑制作用〔J〕中华预防医学杂志,1995,29(1):13 17
[186] Potten C S, Owen G, Hewitt D, et al. Stimulation and inhibition of proliferation in the small intestinal crypts of the mouse after in vivo administration of growth factors. Gut, 1995, 36(6): 864-873
[187] Pinto D, Clevers H . Wnt, stem cells and cancer in the intestine. Biol Cell, 2005, 97(3): 185-196
[188] Radtke F, Clevers H. Self-renewal and cancer of the gut: two sides of a coin. Science, 2005, 307(5717): 1904-1909
[189] Glinsky G V, Beregovska O, Glinskn A B. Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. J Clin Invest, 2005, 115(6): 1503-1521
[190] Campbell F, Geraghty J M, Appleton M A, et al. Increased stem cell somatic mutation in the non-neoplastic colorectal mucosa of patients with familial adenomatous polyposis. Hum Pathol, 1998, 29(12): 1531-1535
[191] Preston S L. Bottom-up histogenesis of colorectal adenomas: origin in the monocryptal adenoma and initial expansion by crypt fission. Cancer Res, 2003, 63(13): 3819-3825
[192] Campbell F, Appleton M A, Shields C J, et al. No difference in stem cell somatic mutation between the background mucosa of right-and left-sided sporadic colorectal carcinomas. J Pathol, 1998, 186(1): 31-357
[193]李军吕愈敏.金珠,等塞来昔布对-甲基脱诱导的大鼠畸变.隐窝灶的顶防作用.中华消化杂志,zooq.,z4:m-15s.
[194] Takayama T, Katsuki S,Takahashi Y. et al. herrant crypt foci of the colon as precursors of adenoma and cancer.NEng J Med, f998,339; 1277-1284.
[195] Uchida K. 1Cado S. Ando M, et al. A mutinous histochemical study on tmalignancy of aberrant crypt foci (ACF) in rat colonJ Vet Vled Sci> zJ01,63:145-149.
[196] Tanaka T, Kohno H, Shimada k, et al. Prevention of colonic aberrant crypt foci 6y dietary feeding of garcinol in male F344 rare. Carcinogenesis, 2000, 21; 1183-1189.
[197] Pretlow TP, 0'Riordan MA, Somich GA, et al. Aberrant crypts correlate with tumor incidence in F344 rats treated with azoxyrrtethane and phytate [J]. Carcinogenesis, 1992,13(9):1509-1512
[198] Uchida K,Kado S,Ando M,et al.A mutinous histochemical study on malignancy of aberrant crypt foci in rat colon [J]. J Vet Med Sci, 2001, 63 (2):145-149
[199] Rowland IR, Rumney CJ, Coutts JT, et al. Effect of bifi- dobacterium longum and insulin on gut bacterial metabo-lism and carcinogen-induced ACF in rats [J]. Carcino-genesis, 1998, 19 ( 2 ) :281-285
[200] Tm,a T, Kohno H, Shimada R, et al. Prevention of colonic aberrant crypt foci by dietary feeding of garcinol in male F344 rats [J]. Carcinogenesis, 2000, 21(6):1183-1189
[201] End- J, Abrams K, Eklarm A, Jackson E, Mayhem J Colorectal cancer prevention in ulcerarice colitis: a c.-control sturlv. Aliment Pharmaaol Then- 2000. 14: 145-153.
[202]伊沙克江·马合穆德,主编.中国医学百科全书维吾尔医学分册[M],第一册?乌鲁木齐:新疆人民卫生出版社.1988.第一版.
[203]哈木拉提.吾甫尔.维吾尔医气质?体液论及其现代研究[M], 2003,58-60
[204]张莉,哈木拉提·吾甫尔,恶性肿瘤神经-内分泌-免疫网络紊乱的维西医研究.新疆医科大学博士论文.2006
[205] Sylvie Mazine,Khaled Meflah,Emanuelle Tavan etal. Effect of resistant starch and \or fat-soluble vitamins A and E on the initiation stage of aberrant crypts in rat colon ,NUTRITION AND CANCER ,1998,31(3):168-177
[206]戴颖秀王建华叶苗凉上海市杨浦区1992年~2001年结肠癌流行特征和趋势中国肿瘤2003 12 (8):58-60
[207]邹浩军,明亮.黄酮类化合物抗炎免疫及抗衰老药理研究进展.安徽卫生职业技术学院学报2003,3(6)
[208]许士凯,王晓东,赵军宁等天然药物抗衰老有效成分研究进展(之三)?现代中西医结合杂志2005,14(21),2773-2775
[209]魏巍.中药甙类活性成分抗辐射作用的研究?中国辐射卫生2006,15(2)251-252?
[210]努尔买买提,哈木拉提.吾甫尔等.异常黑胆质成熟剂和清除剂对小鼠神经内分泌免疫网络的调节作用.维吾尔医学及其他传统医学的研究与应用[C]?乌鲁木齐:新疆人民卫生出版社2003:11-12.
[211] Tusruo T,Lida H, Tsukagoshi S, et al. Overcoming of VCR resistance in P338leukemia in viva and vitro through enhanced cytotoxicity of VCR and VDS byverapmil[J]. Cancer Res, 1981,41:1967
[212]刘燕,潘启超.钙通道阻滞剂对长春碱类抗癌药物的体内增效作用[J].癌症,1991,10(6):466-468
[213] Smyth M J, Krasovkis E, Sutton V R et al. The Drug Efflux Protein, Additionally Protects Drug-resistant Tumor Cells from Multiple Forms of aspase-dependent Apoptosis[J]. Proc Natl Acad Sci USA, 1998,95(12):7042
[214] Bobinson L J, Roberus W K, Lamming D, et al. Human MDR1 Protein verexpression Delays the Apoptotic Cascade in Chinese Hamster Ovary ibroblasts[J]. Biochemistry, 1997,36(37):11169
[215] Kataoka S, Natio M, Tomida A, et al. Resistance to Antitumor Agent-induced Apoptosis in A Mutant of Human Myeloid Leukemia U937 Cells[J]. Exp Cell Res, 1994,215(1):199
[216]潘启超,田晖.多种中药单体逆转肿瘤多药耐药性[J].科学通报,1995,40(20): 190122
[217] Humlova Z. Protooncogene bcl-2 in process of apoptosis. Review article. Sb Lek 2002;103 (4):419-25
[218] Lopez-Hoyos M, Carrio R, Merino J, Merino R. Regulation of B cell apoptosis by Bcl-2 and Bcl-XL and its role in the development of autoimmune diseases (Review). Int J Mol Med 1998;1 (2):475-83
[219] Califice S, Waltregny D, Castronovo V, van den Brule F. [Prostate carcinoma cell lines and apoptosis: a review]. Rev Med Liege 2004;59 (12):704-10
[220] Longuet M, Serduc R, Riva C. Implication of bax in apoptosis depends on microtubule network mobility. Int J Oncol 2004;25 (2):309-17
[221] Laux MT, Aregullin M, Berry JP, Flanders JA, Rodriguez E. Identification of a p53-dependent pathway in the induction of apoptosis of human breast cancer cells by the natural product, resveratrol. J Altern Complement Med 2004;10 (2):235-9
[222] Gu J, Zhang L, Swisher SG, Liu J, Roth JA, Fang B. Induction of p53-regulated genes in lung cancer cells: implications of the mechanism for adenoviral p53-mediated apoptosis. Oncogene 2004;23(6):1300-7
[223] Kuang YF, Chen YH. Induction of apoptosis in a non-small cell human lung cancer cell line by isothiocyanates is associated with P53 and P21. Food Chem Toxicol 2004;42 (10):1711-8
[224] Gardner CR. Anticancer drug development based on modulation of the Bcl-2 family core apoptosis mechanism. Expert Rev Anticancer Ther 2004;4 (6):1157-77
[225] Jin J, Huan M, Liu GT. Studies on the resistance mechanism of a 5-fluorouracil resistant human hepatocellular carcinoma cell line Bel/5-FU. The Chi nese Young Pharmacologists Symposi um, Beiji ng ,2002:83-4
[226] Huang Y, Ibrado AM, Reed JC et al. Coexpression of severalμmolecular mechanisms of multidrug resistance and their significance for paclitaxel cytotoxicity in human AML HL260 cells.Leukemia, 1997 ;11 (2) :253-7
[227] Lehnert M. Clinical multidrug resistance in cancer :A multifactorial problem. Eur J Cancer , 1996 ;32A(6):912-20
[228] Gupta S. Molecular steps of death receptor and mitochondrial path-ways of apoptosis. L if e Sci , 2001 ;69 (25-26):2957-64
[229] Takehara T , Liu XL , Fujimoto J et al . Expression and role of Bcl-xl in human hepatocellular carcinomas. Hepatology , 2001;34(1):55-61
[230] Nita ME, Ono2Nita SK, Tsuno N et al . Bcl2X(L) antisense sensitizes human colon cancer cell line to 52fluorouracil. J pn J Cancer Res, 2000;91(8):825-32
[231] Tsuda H, Sata M, Ijuuin H et al. A novel strategy for remission induction andmaintenance in cancer therapy. Oncol Rep , 2002;9(1):65-8
[232] Stavrovskaya AA. Cellular mechanisms of multidrug resistance of tumor cells. Biochemist ry ( Mosc) , 2000;65(1):95-106
[233] Chu G. Cellular responses to cisplatin. The roles of DNA-binding proteins and DNA repair. J Biol Chem, 1994; 269(2):787-90
[234] Siess MH, Le Bon AM, Canivenc-Lavier MC, Suschetet M. Mechanisms involved in the chemoprevention of flavonoids. Biofactors 2000;12 (1-4):193-9
[235] Ford JM, Hait WN.Pharmacology of drugs that alter multidrug resistance in cancer[J].Phar.Rev, 1990,42(3):155-99
[236] TwentymanPR.Modifiers of multidrug resistance [J].BrJHaematol,1995,90:735
[237] Sikic B I. Modulation of multidrug resistance: at the threshold[J]. J ClinOncol, 1993,11:1629
[238]敖忠芳,夏薇.汉防已甲素逆转白血病细胞耐药的研究[J].中华血液学杂志, 1995,16(5):235-238
[239]李文瑜,李舜华,崔克义,等.苦参碱逆转的白血病多药耐药细胞系K562/A02对柔红霉素耐药性的研究[J].中华病理生理学杂志,1998,14(5):521-523
[240]田晖,潘启超.双苄基异喹啉生物碱蝙蝠葛碱与蝙蝠葛苏林碱逆转多药耐药性的研究[J].癌症,1996,15(6):410-413
[241] Sandler AB, Gray R, Brahmer J, et al. Randomized phase II/III trial of paclitaxel (P) plus carboplatin (C) with or without bevacizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC): An Eastern Cooperative Oncology Group (ECOG) trial– E4599. Pro Am Soc Clin Oncol, 2005,23:2s LBA4.
[242] Half E, Broaddus R, Danenberg KD, et al. HER-2 receptor expression, localization, and activation in colorectal cancer cell lines and human tumors. Int J Cancer, 2004,108:540-548.
[243] Sekharam M, Zhao H, Sun M, et al: Insulin-like growth factor 1 receptor enhances invasion and induces resistance to apoptosis of colon cancer cells through the Akt/Bcl-x(L) pathway. Cancer Res, 2003, 63: 7708-7716.
[244] Chun YJ, Park S, Yang SA, et al. Activation of Fas receptor modulates cytochrome P450 3A4 expression in human colon carcinoma cells. Toxicol Lett, 2003,146:75-81.
[245] Ohana G, Bar-Yehuda S, Arich A, et al. Inhibition of primary colon carcinoma growth and liver metastasis by the A3 adenosine receptor agonist CF101. Br JCancer, 2003,20, 89:1552-1558.
[246] Tsuda H , SataM, Ijuuin H, et al. Anovel strategy for remission induction and maintenance in cancer therapy. Oncol Rep, 2002, 9(1): 65- 68
[247] Linenberger ML, Hong T, Flowers D, et al. Multidrug– resistance phenotype and clinical responses to gemtuzumab ozogamicin . Blood, 2001, 98 (4): 988- 994
[248] Tsimberidou AM, Paterakis G. Evaluation of the clinical relevance of the expression and function of P- glycoprotein, multidrug resistance protein and lung resistance protein in patients with primary acute myelogenous leukemia. Leuk Res, 2002,26 (2):143- 154
[249] Nicholson DW, Thornberry NA. Apoptosis: Life and death decisions. Science, 2003, 299(6504): 214- 215
[250] Yu EZ, Li YY, Liu XH, et al. Antiapoptotic action of hypoxia– inducible factor- 1 alpha in human endothelial cells. Lab Invest, 2004, 84(5): 552-561
[251] Fojo T, Bates S. Strategies for reversing drug resistance. Oncogene, 2003, 22(47):7512- 7523
[252] Shangary S, Johnson DE. Recent advances in the development of anticancer agents targeting cell death inhibitors in the bcl - 2 protein family. Leukemia, 2003, 17(8): 1470- 1481
[253] Hersey P, Zhang XD. Overcoming resistance of cancer cells to apoptosis. J Cell Physiol, 2003, 196(1):9- 18
[254] Scotto KW. Transcriptional regulation of ABC drug transporters [J]. Oncogene, 2003 , 22 (47): 7496- 7511
[255] Tsuruo T, Naito M, Tomida A, et al . Molecular targeting therapy of cancer: drug resistance, apoptosis and survival signal. Cancer Sci, 2003, 94 (1): 15- 21
[256] Hwang GY, Lin Huang LM. Detection of the hepatitis B virus X protein (HBx) antigen and anti- HBx antibodies in cases of human hepatocellular carcinoma. J Clin Microbiol, 2003, 41(12):5598- 5603
[257] Ohyashiki K, Ohyashiki JD, Nishimaki J, et al. Overexpression of P21 /waf 1 leads to increased inhibition of E2F 1 phosphorylation and sensitivity to anticancer drugs in retinoblastoma negative human sarloma cells. Cancer Res, 1997; 57: 2100
[258] Tetu B, Brisson J, Plante V, et al. P53and C erbB 2 a 3 markers of resistance to adjuvant chemotherapy in breast cancer. Mod Pathol, 1998; 11(9): 823
[259] Kurt WK. Regulation genes and drug sensitivity. J Nation Cancer Institu, 1996; 88: 1255
[260] Schneider HJ, Sampson SA, Cunningham D, et al. Bcl 2 expression and response to chemotherapy in colorectal adenocarcinomas. British J Cancer, 1997; 75: 427
[261] Kuhl FS, Krajwski S, Duran GE, et al. Spontaneous overexpression of the long form of the bcl X protein in a highly resistant P338 leukaemia, British J Cancer, 1997; 75: 268
[262] Ahamed S, Nageatte IB, mizan P, et al. Mechanisms of resistance in a human cell line exposed to sequencial to poisomerase poisoning, Cancer Research, 1997; 57: 5100
[263] Hotta T, Saito Y, Mikami J, et al. Interrelationship between O 6 alkylguanine DNA alkyltransferase activity and susceptibility to chlorothylnitrosoureas in several glioma cell lines, J Neurooncol, 1993; 17:1
[264] Wu ZN, Chan CL, Eastman A, et al. Expression of human O 6 methylguanineDNA methyltransferase in a DNA exeision repair deficient Chinese hanster ovary cell line and its respons to certain alkylating agnts. Cancer Res, 1992; 52: 32
[265] Fink D, Zheng H, Nebel S, et al. In vitro and in vivo resistance to cisplatin in cells that have lost DNA mismatch repair. Cancer Res, 1997; 57: 1841
[266] Brown SJ, Kellett PJ, Lippard SJ, et al. A yeast protein that binds to platinated DNA and confer sensitivity to cisplatin. Science, 1993; 261: 603
[267] Vaisman A, Chanty SG. Induction of UV damaged recognition protein by cisplatin treatment. Bio Chemirtry, 1995; 34: 105
[268] Aliosman F, Berger MS, Raikar A, et al. Enhanced repair of a cisplatin damaged reporter chloramphenicol O acetyltransferase gene and altered activites of DNA polymeraseαandβand DNA ligase in cells of a human malignant glioma following in vivo cisplatin therepy. J Cell Biochem, 1994;54:11
[269] Dabholka M, Vionnet J, Bostick BF, et al. Messenger RNA levels of XPAC and ERCC1 in ovarian cancer tissue correlate with response to platinum based chemotherapy. J Clin Invest, 1994; 94: 703
[270]李波,李德华,苟兴华,等.反义核酸逆转人肝癌细胞株多药耐药性的效应.中华肝胆外科杂志, 2005,11(1):63-64
[271] Wu H, Hait WN, Yang JM. Small interfering RNA- induced suppression ofMDR1 (P- glycoprotein) restores sensitivity to multidrug- resistant cancer cells. CancerRes, 2003, 63(7): 1515- 1519
[272] Mohamed MM, Mohamed MA, Fikry NM. Enhancement of anti-tumor effects of 5- fluorouracil combined with ultrasound on Ehrlich ascites tumor in vivo. Ultrasound Med Biol, 2003, 29 (11): 1635- 1643
[273] Drobna Z, Stein U, Walther W, et al. Pentoxifylline influences drug transport activity of P - glycoprotein and decreases MDR1 gene expression in multidrug resistant mouse leukemic L1210 /VCR cells . Gen Physiol Biophys , 2002, 21: 103-109
[274] Powis G, Kirkpatrick L. Hypoxia inducible factor- l alpha as a cancer drug target. Mol Cancer Ther, 2004, 3(5):647-654
[275]李贵海,孙付军,王宁,等.苦参碱干预获得性多药耐药小鼠S180肿瘤细胞相关生物因子P170过度表达与细胞凋亡的相关性.中药材, 2005,28(4):310-312
[276] Holm PS, Lage H, Bergmann S, et al. Multidrug - resistant cancer cells facilitate E1 - independent adenoviral replication: impact forcancer gene therapy. Cancer Res, 2004, 64 (1): 322-328
[277] Ford JM, Hait WN.Pharmacology of drugs that alter multidrug resistance in cancer[J].Phar.Rev, 1990,42(3):155-99
[278]田晖,潘启超.双苄基异喹啉生物碱蝙蝠葛碱与蝙蝠葛苏林碱逆转多药耐药性的研究[J].癌症,1996,15(6):410-413
[279] Lin H L, Liu T Y, Wu C W, et al.Berberine modulates expression of mdr1 geneproduct and the response to digestive track cancer cells to Paclitaxel[J].Br JCancer,1999,8(13):416-422
[280] Scambia G, Ranelletti F O, Benedetti Panici P, et al. Quercetin potentiates theeffect of Adriamycin in a multidrug-resistance MCF-7 human breast-cancer cellline: P-glycopreotein as a possible terget[J]. Cancer Chemother Pharmocol, 1994,34:459-464
[281] Lin H L, Liu TY, Lui W Y, et al. Up-regulation of multidrug resistance transporter expression by berberine in human and murine hepatoma cells[J].Cancer, 1999,85(9):1937-1942
[1]杨纯正.肿瘤耐药研究的若干问题.中华医学杂志,2001 ,81(24) :1475
[2] Scaglotti G V , Novello S , Selvaggi G. Multidrug resistance in on small cell lung cancer. Ann oncol , 1999 , 5 :83
[3] Thomas H , Coley HM. Overcoming multidrug resistance in cancer : an update on the clinical strategy of inhibiting p2glycoprotein. Cancer Control ,2003 ,10(2) :159
[4] Loo TW and Clarke DM. Location of the Rhodamine-binding Site in the Human Multidrug Resistance P-glycoprotin[J].J Biol Chem, 2002,277(46):44332-44338
[5] Sonneveld P. Multidrug resistance in haematological malignancies[J]. J Intern Med, 2000, 247(5):521-534
[6] Taylor JC, Horvath AR, Higgins CF,et al.The multidrug resistance P-glycoprotein. Oligomeric state and intramolecular interactions[J]. J Biol Chem,2001,276(39): 36075-36078
[7] Schinkel AH,Kemp S,Dolle M,et al.N-Glycosylation and deletion mutants of the human MDR, P-glycoprotein [J].J Biol Chem,1993,68:7474-748
[8] Rosenberg MF, Callaghan R,Ford RC,et al.Structure of the multidrug resistance P-glycoprotein to 2.5nm resolution determined by electron microscopy and image analysis [J].J Biol Chem, 1997,272:10658-10694
[9] Sauna ZE andAmbudkar SV.Evidence for a requirement for ATP hydrolysis at tow disitinct steps during a single turnover of the catakytic cycle of human P-glycoprotein [J] . Proc Natl Acad Sci, 2000,97:2515-2520
[10] Auna ZE andAmbudkar SV.Characterization of the catalytic cycle of ATP hydrolysis by human P-glycoprotein [J].J Biol Chem, 2001,276:11653-11661
[11] Ruiz Gomez MJ, Souviron Rodriguez A , Martinez Morillo M. P-glyco-protein , a membrane pump that represents a barrier to chemotherapy in cancer patients. An Med Interna ,2002 , 19(9) :477
[12] Hoffman M M, Roepe P D. Analysis of ion transport perturbations caused by hu MDR1 protein overexpression. Biochemistry , 1997 , 36(37) :11153
[13] Shtil AA.Signal transduction pathqays and transcriptional mechanisms as targets for prevention of emergence of multidrug resistance in human cancer cells [J]. Curr Drug Targets, 2001,2(1):57-77
[14] Geoffrey Chang. Multidrug resistance ABC transporter[J]. FEBS, 2003,555: 102-105
[15] Cordon-CardoC, O’BrienJ, BocciaJ, etal. Expression if multidrug resistance gene product in human normal and tumor tissue[J].J Histochem 1990,38:1277-1287
[16] Anil K, Sood MD, Richard E,etal.Drug resistance in ovarian cancer: from the laboratory to clinic [J].Obstet Gynecol, 1998, 92:312-319
[17] Victor L.Multidrug resistance: molecular mechanisms and clinical relevance[J]. Cancer Chemoth Pharmacol 1997,40:S3-S8
[18] Nooter K. Multidrug resistance (mdr) genes in human cancer[J] .Br J Cancer 1991,63:663-669
[19] Van den Heuvel-Eibrink MM, Sonneveld P and Pieters R. The prognostic significance of membrance transport-associated multidrug resistance (MDR)proteins in leukemia[J]. Int J Clin Pharmacol Ther, 2000,38(3):94-110
[20] Cole SPC and Deeley RG. Multidrug resistance mediated by the ATP-binding cassette transporter protein MRP[J]. Bio Essays, 1998,20:931-940
[21] Rosenberg MF, Mao QC, Holzenburg A, et al. The Structure of the Multidrug +Resistance Protein1 (MRP1/ABCC1) Crystallization and Single-paritcle Analysis[J]. J Biol Chem, 2001,276(19):16076-16082
[22] Borst P,Evers R,Kool M,et al.A family of drug transporters:the multidrug resistance-associated proteins[J]. J Natl Cancer Inst, 2000,92(16):1295-1302
[23] Jedlitschky G, and Keppler D.Transport of leukotriene C4 and structurally related conjugates[J]. Vitam Horm, 2002,64:153-184
[24] Leslie EM, Deeley RG, and Cole SP. Toxicological relevance of the multidrug resistance protein 1, MRP1 (ABCC1) and related transporters [J]. Toxicology, 2001,167(1):3-23
[25] Ishikawa T, Bao JJ,Yamane Y, et al.Coordinated induction of MRP/GS-X pump andγ-glutamylcysteine synthetase by heavy metals in human leukemina cells[J]. J Biol Chem, 1996,271:14981-14988
[26] Kool M deHass M, Scheffer GL,et al .Analysis of exprssion of cMOAT(MRP2),MRP3,MRP4,and MRP5,homologues of the multidrug resistance associated protein gene(MRP) in human cancer cell line[J] .Cancer Res 1997,57: 3537-3547
[27] Abbaszadegan MR, Futscher BW, Klimecki WT, et al.Analysis of multidrug resistance–associated protein (MRP)messenger RNA in normal and malignant hematopoietic cell [J]. Cancer Res 1994,54:4676-4679
[28] Schneider E, Cowan KH, Bader H,etal .Increased expression of the multidrugresistance–associated protein gene in relapsed acute leukemia[J]. Blood 1995,85: 186-193
[29] Rappa G, Finch R A , Sartrelli A C , et al . New insights into the biolo- gy and pharmacology of the multidrug resistance protein (MRP) from gene knockout models. Biochem Pharmacol , 1999 ,58 (4) :557
[30] Benderra Z , Morjani H , Trussardi A , et al . Evidence for functionaldiscrimination between leukemic cells overexpressing multidrug resis-tance associated protein (MRP) and P2glycoprotein. Adv Exp Med Bi-ol , 1999 , 457 :151
[31] Izquiero MA, Scheffer GL, Flens MJ, etc. Broad distribution of the multidrug mresistance-related vault lung resistance protein in normal tissue and tumors[J]. Am J Pathol. 1996,148(3):877-87
[32] Broxtermans HJ, Schuurhuis GJ.Transport protein in drug resistance detection and prognostic significance in acute myeloid leukemia[J]. J Int Med 1997,740:S147-151
[33] KD Tew. Glutathione-associated enzymes in anticancer drug resistance[J]. Cancer Res, 1994, 54: 4313-4320
[34] Ban M, Takahashi Y, Takayama T, et al. Transfection of Glutathione Stransferase (GST)πantisense complementary DNA increases the sensitvity of a colon cancer cell line to adriamycin, cisplatin, melphalan, and etoposide[J]. Cancer Res, 1996, 56: 3577
[35] Pommier Y, Leteurte F, Fesen MR, et al. Cellular determinants of sensitivity and resistance to DNA topoisomerase inhibitors[J]. Cancer Invest, 1994, 12: 530–42
[36]陈中平,Areti MALAPETSA , Anne MONKS ,等.人肿瘤细胞核苷酸切除修复蛋白表达与抗癌药耐药的相关性.癌症,2002 ,21(3) :233
[37]杨晓葵,郑芳,陈建华,等.凋亡相关蛋白的表达及Caspase23活性改变与人卵巢癌细胞铂耐药的关系.癌症,2002 ,21 (12) : 1288
[38] Lebedeva I , Rando R , Ojwang J , et al . Bcl-xL in prostate cancer cells : effects of overexpression and down2regulation on chemotherapy. Caner Res , 2000 ,60 :6052
[39]王雨田,胡家潞,药立波,等. P38信号途径与胃癌细胞阿霉素耐药相关.解放军医学杂志,2001 ,26(1) :24
[40] Ohyashiki K, Ohyashiki JD, Nishimaki J, et al. Overexpression of P21/waf1 leads to increased inhibition of E2F1 phosphorylation and sensitivity to anticancer drugs in retinoblastoma negative human sarloma cells[J]. Cancer Res,1997,57: 2100
[41] Tetu B, Brisson J, Plante V, et al. P53and CerbB2 a 3 markers of resistance to adjuvant chemotherapy in breast cancer[J]. Mod Pathol, 1998, 11(9): 823
[42] Schneider HJ, Sampson SA, Cunningham D, et al. Bcl2 expression and response to chemotherapy in colorectal adenocarcinomas[J]. British J Cancer, 1997, 75: 427
[43] Kuhl FS, Krajwski S, Duran GE, et al. Spontaneous overexpression of the long form of the bclX protein in a highly resistant P338 leukaemia[J]. British JCancer, 1997, 75: 268
[44] Herr, I., Wilhelm,D., B?hler,T.,et al. JNK/SAPK activity is not sufficient for anticancer therapy-induced apoptosis involving CD95-L, TRAIL and TNF- . Int[J]. J. Cancer, 1999,80: 417-424
[45] Elliott T , Sethi T. Integrins and extracellular matrix : a novel mechanism of multidrug resistance. Expert Rev Anticancer Ther ,2002 , 2(4) :449
[46] Yang J M, Xu Z, Wu H , et al . Over expression of extracellular matrix metalloproteinase inducer in multidrug resistant cancer cells. Mol Cancer Res , 2003 , 1(6) :420
[47] Vadgama J V , Wu Y, Shen D , et al . Effect of selenium in combination with adriamycin or taxol on several different cancer cells. Anti-cancer Res , 2000 ,20 (3) :1391
[48] Epsztein S , Glickstein H , Picard V , et al . H2ferritin subunit overex pression in erythroid cells reduces the oxidative stress response and induces multidrug resistance properties. Blood ,1999 ,94 (10) :3593
[49] Robert J.Multidrug resistance in oncology :diagnostic and therapeutic approaches[J]. Eur J Clin Invest, 1999,29:536-545
[50] Naito M, Watanabe T, Tsuge H, et al. Potentiation of the reversal activity of SDZ-PSC833 on multi-drug resistance by an anti-poglycoprotein monoclonal antibody MRK-16 [J]. International J Cancer,1996,67:435-440
[51]李惠芳,孙桂香,卢微微.多药耐药基因反义寡核苷酸逆转肿瘤细胞耐药的初步研究[J].中华血液学杂志, 1997,18(2):76-79
[52]曹江,胡汛,潘锵荣,等.MDRl反义RNA表达质粒的构建及其在多药耐药细胞抗药机理研究中的应用[J].中华医学杂志,1995,75:557
[53]王宝成,郭军,顾广玉,等.切割MDR1 RNA的核酶(Ribozyme)肝癌多药耐药细胞株BEL-7402/DOX化疗耐药性的逆转作用[J].中国肿瘤生物治疗杂志,1997,4: 107
[54] Kikuchi A, Holan V,Minowada J.Effects of tumor necrosis factor alpha ,interferon alpha and interferon gamma on non lymphoid leukemia cell lines :growth inhibition ,differentiation induction and drug sensitivity modulation[J]. Cancer Immunol Immunother 1992,35:257-263
[55] BorsellinoN,CrescimannoM,FlandianC,etal.Combined activity of interleukin-1 alpha or TNF-alpha and doxorubicin on multidrug resistant cell lines evidence that TNF and DXR have synergistic antitumor and differntiation inducing effects[J]. Anticancer Res, 1994,14:2643-2648
[56] Kang Y, Perry RR.Effect of alpha interferon on Pgp expression and function and on verapmil modulation of doxorubicin resistance[J]. Cancer Res, 1994,54:2952-2958
[57] Scala S, Pacelli R, Iaffaioli RV, etal. Reversal of adriamycin resistance by recombinant alpha interferon in multidrug resistant human colon carcinoma LoVo doxorubicin cells [J]. Cancer Res, 1991,51:4898-4902
[58] Wlther W, Stein U. RNA analysis using miniprep RNA in RT-PCR[J].Bio Technique, 1994,17:674-675
[59]高贤钧.中草药钙通道阻滞剂的研究与展望[J].中西医结合杂志,1990,10(7):4721
[60]潘启超,田晖.多种中药单体逆转肿瘤多药耐药性[J].科学通报,1995,40(20): 190122
[61]李达,杨淑莲,梁冰.中医药抗白血病细胞耐药的临床研究探讨[J].中国中西医结合杂志,1995;15(10):63623
[62]陈泽涛,顾振东.中药对淋巴细胞白血病小鼠细胞膜流动的影响[J].中国中西医结合杂志,1991,11(1):39
[63]潘启超,田晖.多种中药单体逆转肿瘤多药耐药性[J].科学通报, 1995,40(2): 190122
[64]陈宝安,盛茗,程坚,等.汉防己甲素对HL-60/Adr细胞凋亡作用的实验研究[J].南京铁道医学院学报,1999,18(3):158-159
[65]梁蓉,杨平地,陈协群,等.川芎嗪(或)环孢素A对HL60/ HT细胞耐药的逆转[J ] .中华内科杂志,1999 ,38(4) :260– 261
[66]姜晓峰,甄永苏.大黄素逆转肿瘤细胞的多药耐药[J ] .国外医学·肿瘤学分册,1998 ,26(化疗分册) :42– 44
[67]王宝成,郭军,狄剑时,等.榄香稀乳剂于肿瘤多药耐药的基础研究[J ] .中国肿瘤临床,1996 ,23(2) :143– 146
[68]卢步峰,于丽敏,边春香,等.β2榄香烯吗素抗肿瘤作用的实验研究[J ] .中国组织化学与细胞化学杂志, 2000 ,19(1) :78– 81
[69]郭娟娟,潘祥林,冯长伟,等.冬凌草甲素诱导多药耐药细胞系K562/ A02凋亡?逆转耐药性的研究[J].安徽中医学院学报,2000 ,19 (3) :34– 36
[70]史曦凯,张翼军,赵春景.人参皂甙单体Rb1对多药耐药细胞系K562/ HHT的耐药逆转作用[J ] .第三军医大学学报,1999 ,21(11) :827– 826
[71]史噶凯,张冀军,赵春景.人参皂甙单体Rbl对多药耐药细胞系K562/ HHT的耐药逆转作用.第三军医大学学报, 1999 , 21 (11) :825
[72] Tian H, Pan Q C. Modulation of multidrug resistance by three bisben-zylisoquinolines in comparison with verapamil. Acta Phamacol Sin ,1997, 18(5):455
[73]李佩文,蒋礼年,陆杭双.金艾康合并化学药物治疗肿瘤临床疗效观察[J].中成药,1999 ,21(11) :575
[74]叶祖光,孙爱续,李兰芳,等.汉防己甲素对阿霉素或长春新碱耐药株人癌细胞的逆转抗药性作用[J].中国中药杂志, 1996 ,21(6) :369
[75]胡军,赵瑾瑶,杨佩满.β2榄香烯乳剂逆转多药耐药细胞株MCF27/ ADM对阿霉素耐药性研究[J].中国微生态学杂志,2002 ,14(4) :214
[76]胡凯文,郑洪霞,齐静,等.浙贝母碱逆转白血病细胞多药耐药的研究[J].中华血液学杂志,1999 ,20(12) :650
[77]李旭芬,张苏展,郑树.苦参碱对K562及其多药耐药细胞K562/VIN的细胞生物学影响[J].中国病理生理杂志, 2002 , 18(10) :1233
[78]刘叙仪,孟松浪,杨敬贤,等.中药R3(补骨脂抽提剂)对阿霉素人乳腺癌细胞MCF27adr多药耐药的逆转[J].中国肿瘤临床,1997 ,24 (5) :325
[79]杨国旺,石朝玉.中药联合化疗的抗肿瘤增效作用[J].中国实验方剂杂志, 2000,6(3) :59
[80]张慧珠,杨林,任雷鸣,等.中药活性成份逆转肿瘤细胞多药耐药作用的体外筛选[J].华北煤炭医学院学报2003;5(5):265
[81]冯正权,郭勇,朱宁希,等.复方三根制剂逆转多药耐药的实验研究[J].中国肿瘤2003;12(6):370
[82]王宝成,郭军,狄剑时,等.榄香烯乳剂与肿瘤多药耐药的基础研究[J].中国肿瘤临床1996;23(2):143
[83]胥彬,许建华.抗癌药物与肿瘤化学治疗进展.北京:科学出版社,2001,19-25
[84]梁蓉,杨平地,陈协群.川芎嗪对白血病HL260/ VCR细胞多药耐药的逆转及其机制研究[J].中华血液学杂志,1999 ,20(6) :323
[85]王金华,叶祖光,孙爱续,等.粉防己碱逆转人乳腺癌MCF27多药耐药细胞的抗凋亡作用[J].中国中药杂志,2002 ,27(1) :46
[86]孙华丽,余桂清.扶正增效方对恶性肿瘤放射增敏作用的临床和实验研究[J].中医杂志,1990 , (6) :2521
[87]李云凤,张永恒,于桂兰,等.十全大补冲剂对肿瘤化疗药物增效减毒作用的研究[J].肿瘤杂志,1996 ,1(16) :38– 39
[88]陈泽涛,顾振东.中药对淋巴细胞白血病小鼠细胞膜流动性的影响[J].中国中西医结合杂志,1991 ,11(1) :39
[89]张旋波,白绍怀,屈艺,等,中药制剂Fw132te41逆转裸鼠移植瘤多药耐药性的初步研究[J].华西医大学报,1999 ,30 (4) :360-362
[90]张代钊,于尔辛,余桂清,等.中医药对肿瘤放化疗的增敏减毒作用[J].中国中西医结合杂志,1992 ,3(2) ;135-137
[91]杨岚,杨平地,梁蓉,等.川芎嗪联合环胞霉素A逆转白血病多药耐药的研究[J].癌症,2000 ,19(4):304-306
[92]田韧,杨劲松,张保国,等.以榄香稀乳剂为调变剂联合化疗耐药胃癌临床观察[J].肿瘤防治研究,1999 ,26(3):215-216
[1]斯依提·穆哈穆德·候赛音,主编.麦合孜尼艾地维亚(草药宝库)(波斯文)[M].印度吉维力可西瓦出版社, 1988年(农历):251-292?
[2]伊沙克江·马合穆德,主编.中国医学百科全书维吾尔医学分册[M].第一册,乌鲁木齐:新疆人民卫生出版社, 1988,第一版.
[3]安尼瓦尔,阿不都热依木,哈木拉提,等.维吾尔医体液燃烧的本质[J].维吾尔医药杂志, 1998,(1):11-16.
[4]哈木拉提,安尼瓦尔,艾尼,等.异常黑胆质及其清除剂与自由基关系的研究[J].维吾尔医药杂志, 1996,(2):10-15.
[5]陈瑗,周玫主编.自由基医学[M].北京:人民军医出版社, 1991,42-53.
[6]哈木拉提,阿不都热依木,阿不都艾尼,热孜万古丽.维吾尔医成熟剂和清除剂抗活性氧的作用研究[J].中国民族医药杂志. 2000, 6 (3):31
[7]阿布力米提·玉素甫·阿吉主编.维吾尔医基础理论(维文).乌鲁木齐:新疆科技卫生出版社, 1988, 32-46.
[8]周志东,赵伟康.机体抗氧化系统研究进展[J].国外医学.老年医学分册, 1999, 20(4):172-1761
[9] Kankofer M. Antioxidative defence mechanisms against reactive oxygen species in bovine retained and not-retained placenta: activity of glutathione peroxidase, glutathione transferase, catalase and superoxide dismutase. Placenta, 2001,May, 22(5):466-4721
[10]潘华珍,冯立明,许彩民,等.丙二醛对红细胞的作用[J].生物化学与生物物理学进展, 1984,2:341
[11]Dizdaroglu M. Chemistry of free radical damage to DNA and nucleoproteins. DNA and Free Radical. London: Ellis Horwood, 1993:19~39
[12]Malins DC, Polissar NL, Gunselman SJ. Progressiol on human breast cancers to themeta staticstate is linked on OH·radical induced damage. Proc Natl Acad Sci USA, 1996, 93:2557~2563
[13]Patrizia M, Giorgio F, Stefania F, etal. Age dependent increase in Axidative damage to DNA, lipids and proteins in human skeletal muscle. Free Radic Biol Med, 1999, 26:303~317
[14]Wiseman H, Kaur H, Halliwell B. DNA damage and cancer : measurement and mechanism. Cancer Lett, 1995;93:113~120
[15]阿布都艾尼,阿不都热依木,哈木拉提.异常黑胆质成熟剂和清除剂对OH·引发的DNA损伤的保护作用[J].中药药理与临床. 2000;16(3)36
[16]阿不都热依木,哈木拉提异常黑胆质成熟剂和清除剂抗氧化作用的ESR研究中药新药与临床药理2001年第12卷第6期:422
[17]李林,姬艳丽,陈艳,武贵臻,哈木拉提·吾甫尔.异常黑胆质成熟剂与清除剂对H2O2诱导的淋巴细胞毒性的影响[J].新疆医科大学学报. 2005. , 28(4):292
[18]Barbouti A, Doulias PT, Zhu BZ, etal. Intracellulariron, but not copper, plays a critical role in hydrogen peroxide-induce DNA damage [J]. Free Radic Biol Med, 2001, 31(4):490-498.
[19]徐永俊. DNA氧化损伤生物标志物8-OH-dG的检测及其在医学上的应用[J].癌变·畸变·突变, 2002, 14(1):50253.
[20]Alicia J. Kowaltowski, Anibal E. Vercesi. Mitochondrial damage induced by conditions of oxidative stress[J]. Free Radic. Biol. Med. , 1999, (26):463-471.
[21]Turrens J. F. Superoxide production by the mitochondrial respitory chain [J]. Biosc. Rep. , 1997, (17):328.
[22]阿不都热依木,哈木拉提,斯拉甫,努尔买买提,肖开提.异常黑胆质清除剂对线粒体氧化损伤的保护作用[J].中国中医基础医学杂志. 2002, 8(7):40
[23]阿不都热依木·玉苏甫,哈木拉提·吾甫尔.异常黑胆质成熟剂水提物和醇提物对HepG2细胞m5dC及82OH2dG形成的影响[J].中国中医基础医学杂志2006, 12(10):730
[24]阿布都艾尼,阿不都热依木,哈木拉提.异常黑胆质成熟剂和清除剂对OH#引发的DNA损伤的保护作用[J].中药药理与临床, 2000, 16(3):34-36.
[25]阿不都热依木,哈木拉提,阿布都艾尼.维吾尔医成熟剂和清除剂抗活性氧的作用研究[J].中国民族医药杂志, 2000, 6(3):30-32.
[26]阿不都热依木,哈木拉提,阿布都艾尼.异常黑胆质成熟剂和清除剂抗氧化作用的ESR研究[J].中药新药与临床药理, 2001, 12(6):420-422.
[27]HalmuratU, AbdiryimY, AnwarU, MooreN. Uighur traditionalMedicine syndrome of Abnormal Savda in men is associated with Oxidative stress, which can be improved by Munziq and Mushil of Abnormal Savda [J]. Therapie, 2004, 59(4):483-484.
[28]姬艳丽,李林,武贵臻,陈艳,哈木拉提·吾甫尔.异常黑胆质成熟剂与清除剂对H2O2诱导的淋巴细胞凋亡的影响[J].新疆医科大学学报2005. , 28(4):294-298
[29]宝福凯.程序性细胞死亡的基因调控[J].生命科学, 1995, 7(5):15217.
[30]Clark AR, Purdie CA, etal. Thymocyte apoptosis induce by p53-dependent and indepandent pathway [J]. Nature, 1993, 362:849-852.
[31]Lowe SW, Schrmitt EM, Smith SW, etal. p53 is required for radiation-inducedapoptosis in mouse thymocytes [J]. Nature, 1993, 362:847-849.
[32]哈木拉提.吾甫尔,李林,陈艳,等.异常黑胆质成熟剂与清除剂对氧化损伤的淋巴细胞p53蛋白表达的影响[J].新疆医科大学学报, 2005,28(4):289
[33]Somasundaram K. Tumor suppression p53: regulation andf unction [J]. Frontiers Bioscience, 2000, 5:D424-437.
[34]Oren M. Regulation of the p53 tumer suppresspr protein [J]. Jbiol Chem, 1999, 274(51):36031-36034.
[35]Li Y, Chopp M, Zhang ZG, etal. P53–Immunore active Protein and P53 mRNA expression aftertr ansient middle cerebral artery occlusion in rats [J]. Stroke, 1994, 25(4):849-855.
[36]艾斯卡尔·依米提,哈木拉提·吾甫尔,布再娜甫·伊力哈木.维吾尔医成熟及清除剂诱导T淋巴瘤细胞凋亡的研究[J].中药药理与临床. 2000;16(2):34
[37]Perkins ND. The Rel/NF-kappaB family : friend and foe [J]. Trends Biochem Sci, 2000, 25(9):434-440.
[38]哈木拉提,阿不都热依木,阿不都艾尼.维吾尔医成熟剂和清除剂抗活性氧的作用研究[J].中国民族医药杂志, 2000, 6(3):30-32.
[39]阿不都热依木,阿不都艾尼,哈木拉提.五种维药的清除羟自由基及抗DNA损伤作用研究[J].中草药, 2001, 32(3):2362238.
[40]李林,哈木拉提,武贵臻,等.异常黑胆质成熟剂及清除剂对氧化诱导的淋巴细胞DNA损伤的保护作用[J].中华中西医杂志, 2004, 5(15):154021543.
[41]陈艳,李林,武贵臻,等.异常黑胆质成熟剂与清除剂对H2O2诱导的淋巴细胞NF2JB表达的影响.新疆医科大学学报[J]. 2005, 28(4):298
[42]Dumont A, Hehnet SP. Hofmann TG etal. Hydrogen peroxide induced apoptosis is CD95-independent, requires the release of mitochondria-derived reactive oxygen species and the activation of NF-kappaB [J]. Oncogene, 1999, 18(3):747-757.
[43]Brown JM, Wouters BG. Apoptosis, p53, and tumor cell sensitivity toAnticancer agents [J]. Cancer Res, 1999, 59(7):1391-13991
[44]Ma J, Reed KA, Gallo JM. Cells designed to deliver anticancer drugs by apoptosis [J]. Cancer Res, 2002, 62(5):1382-13871
[45]阿不都热依木·玉苏甫,哈木拉提·吾甫尔.异常黑胆质成熟剂乙酸乙酯萃取物对HepG2细胞生长和凋亡及相关基因调控的研究[J].中国药科大学学报2006, 37(2):161-164
[46]Gardner CR, Anticancer drug development based on modulation of the Bcl-a family apoptosis mechamism [J]Expert Rev anti-cancer ther, 2004, 4(6):1157-1177
[47]Brown JM, Kim BG, Apoptosis P53 and tumor cell sensitivity to anticancer agents[J]Cancer Res, 1999, 59(7):1391-1399
[48]阿不都热依木.玉苏甫1, 2,哈木拉提.吾甫尔2,吐尔洪.卡迪尔1, 3异常黑胆质成熟剂醇提物诱导HepG2细胞凋亡机制的研究中成药2006年第28卷第7期:1008
[49]Kwon KB, Kim EK, LimJG, etal. Molecular mechanisms of apoptosis induced by Scopio water extract in human hepatoma HePG2 cells[J]World J Gastroenterol, 2005, 11(7):943-947
[50]李莉. Caspase与细胞调亡[J].辽宁医学杂志, 2004, 18(3)151-153
[51]张莉,哈木拉提·吾甫尔,张仑.异常黑胆质成熟剂提取物对小鼠辐射的防护作用中南大学学报(医学版) 2007, 32(1):73
[52]哈木拉提·吾甫尔.异常黑胆质成熟剂和清除剂体内外抗氧化功能的研究[M]维吾尔医气质?体液论及其现代研究.乌鲁木齐:新疆科学技术出版社, 2003:100-115.
[53]阿依努尔·买提斯迪克,尼加提·热合曼,哈木拉提·吾甫尔等.异常黑胆质载体动物模型下丘脑-垂体-肾上腺轴形态学的观察[J].新疆医科大学学报, 2006, 28(10):907-909.
[54]阿依努尔·买提斯迪克,哈木拉提·吾甫尔.异常黑胆质载体动物模型饮食量和饮水量的观察[J].新疆中医药, 2006, 24(1):527.
[55]阿地力江·阿不力米提,胡汉华.异常黑胆质成熟剂对异常黑胆质载体动物模型下丘脑-垂体-肾上腺轴细胞超微结构的影响.国际病理科学与临床杂志[J]. 27(3):190
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |