核苷酸切除修复基因多态性与卵巢癌铂类药物耐药相关性研究
|
摘要
卵巢上皮癌是妇科恶性肿瘤中发病率占第三位,死亡率却居第一的恶性疾病。由于卵巢解剖上隐匿于盆腔深处,在发病早期缺乏特异性症状和体征,很难在早期发现和诊断,约60%-70%的卵巢癌患者确诊时已属于晚期。近30年来,虽然经过全世界妇科肿瘤专家的不懈努力,不断改进手术方式、现更新更好的化疗药物和增加新的化疗方案,但是5年生存率一直徘徊在20%-30%左右。
铂类药物是治疗卵巢癌、肺癌等实体瘤的常用药物,而DNA损伤修复能力增强是导致卵巢癌铂类耐药的主要原因之一, DNA修复途径中的核苷酸切除修复、错配修复、碱基切除修复等均与铂类药物耐药有关,而核苷酸切除修复(NER)通路被认为是机体内修复DNA损伤的最主要途径。NER通路主要基因有:①DNA损伤的识别:涉及XPA、XPC等基因;②损伤部位DNA链的打开:由TFIIH的亚基ERCC3/XPB和ERCC2/XPD解旋酶打开DNA双链;③寡核苷酸链的切断:XPG和XPF-ERCC1复合体分别在损伤部位的3’端和5’端切断DNA单链;④PCNA、RPA等基因完成缺损部位单链片段的再合成和修补缺口。其中,损伤的识别/切除是通路中的限速或调节环节。在通路中,各个基因发挥着相应的独特作用,并按照严格的顺序加入和置换出NER过程,其中任何一个基因的功能异常即可导致整个通路对损伤修复的效率。目前国内尚未见有关DNA修复基因ERCC1、XPA、XPC、XPD、XPG与卵巢癌铂类药物敏感性的关系的报道,为了了解ERCC1、XPA、XPC、XPD、XPG等基因与卵巢癌铂类药物化疗敏感性的关系,我们在本实验中应用PCR及测序方法筛查ERCC1、XPA、XPC、XPD、XPG外显子单核苷酸多态性在卵巢癌耐铂类药物的细胞株和敏感细胞株中的分布差异,探讨了XPGHis46His及XPGHis1104Asp的多态基因型102例卵巢癌患者化疗敏感性的关系,并通过构建人XPG基因的shRNA表达载体,转染卵巢癌SKOV3耐DDP细胞,检测其对XPG基因的干扰效率。继而筛选出稳定干扰的细胞株,进行一系列功能实验,以了解XPG在卵巢癌耐药细胞株中的作用。为提高卵巢癌铂类药物化疗敏感性提供一些的实验依据。
卵巢上皮癌铂类耐药与非耐药细胞间核苷酸切除修复酶类基因多态性的检测与比较
目的:肿瘤细胞对铂类药物的化疗敏感性与个体的DNA损伤修复能力关系密切, ERCC1、XPA、XPC、XPD、XPG基因是核苷酸切除修复系统( nucleotide excision repair,NER)中与铂类药物抵抗有关的关键因子,本实验拟筛查ERCC1、XPA、XPC、XPD、XPG遗传多态与卵巢癌耐铂类药物的细胞株的关系,为下一步实验打下基础。
方法:应用PCR及测序方法筛查ERCC1、XPA、XPC、XPD、XPG外显子单核苷酸多态性在卵巢癌耐铂类药物的细胞株和敏感细胞株中的分布差异,序列读解采用ChromaS软件,并结合NCBISNP数据库寻找和验证SNP位点,筛选出的SNP用于下一步实验。结果: DNA测序分析发现XPGHis46His及XPGHis1104Asp两个SNP位点在细胞株中存在分布差异。结论:核苷酸切除修复系统中XPGHis46His及XPG His1104Asp遗传多态可能与卵巢癌患者对铂类药物耐药性相关。
XPG遗传多态与卵巢癌患者铂类药物敏感性关系
目的:研究核苷酸切除修复基因XPG单核苷酸多态性与卵巢癌患者对铂类药物敏感性的关系。方法:对接受含铂类药物化疗的102例晚期卵巢癌患者进行临床疗效评价。以聚合酶链-限制性片段长度多态性( PCR- RFLP)的方法检测接受含铂类药物化疗的102例卵巢癌患者XPGHis46His及XPG His1104Asp的多态基因型,并比较不同基因型与化疗敏感性的关系。结果: His1104Asp多态在卵巢癌铂类药物化疗敏感组中分布与耐药组差异不显著。XPGHis46His在化疗敏感组T/T,T/C,C/C的基因型频率明显高于耐药组,二者差异有统计学意义(p=0.016),与携带XPG46T/T基因型比较,携带至少一个46C等位基因(即T/C和C/C基因型)的卵巢癌患者对铂类药物化疗敏感可能性增加3.096倍(95%CI:1.330-7.208)。XPG His46His及His1104Asp基因多态与临床病理特征之间的比较差异无显著意义(P>0.05)。T/T基因型组生存期短于T/C+C/C基因型组,差异有统计学意义(P<0.05);COX风险比例回归模型结果显示病理分级是卵巢癌患者的独立预后因素(P<0.05)。
结论:核苷酸切除修复系统中XPGHis46His遗传多态可能与卵巢癌患者对铂类药物敏感性相关。
RNAi阻断XPG基因表达对卵巢上皮性癌细胞顺铂耐药性影响的体外实验研究
目的:通过构建人XPG基因的shRNA表达载体,转染卵巢癌SKOV3耐DDP细胞,检测其对XPG基因的干扰效率。继而筛选出稳定干扰的细胞株,进行一系列功能实验,以了解XPG在卵巢癌耐药细胞株中的作用。方法:针对XPG mRNA的不同区域构建了不同的siRNA载体,应用脂质体法转染SKOV3耐DDP细胞,实时定量PCR检验干扰效率,选择抑制率最高的siRNA构建shRNA表达载体,转染SKOV3耐DDP细胞,G418筛选后经western-blot鉴定确认获得稳定转染的SKOV3耐DDP细胞株,然后进行细胞生长特性、细胞周期变化、细胞药敏试验及细胞内药物浓度的实验。结果:用荧光定量PCR对不同siRNA干扰载体的干扰效果进行检测,实验结果显示:在XPG-733组XPG的相对拷贝数为1.050±0.0230,与对照组相比有统计学意义,抑制率为52.05%。构建shRNA表达载体转染SKOV3耐DDP细胞,获得的该组稳定干扰表达株,western-blot检验其XPG蛋白表达明显减少。流式细胞仪对细胞检测结果显示实验组处于增殖状态(S+G2+M)的细胞为34%,G1期为66%,阴性对照组则相应为41.3%和58.7 %,其处于增殖周期的细胞有减少的趋势。实验组与阴性对照组的IC50差别有均统计学意义(P<0.05),经化疗药处理后,用高效液相色谱仪检测其细胞内药物浓度,实验组细胞内药物浓度低于对照组细胞(P<0.05)。结论:采用构建shRNA表达载体对XPG基因进行干扰,SKOV3耐DDP细胞的生长特性、细胞周期无明显变化。干扰后SKOV3耐DDP细胞对顺铂的化疗耐药性明显下降,我们推测这种改变可能与促进细胞对DNA-DDP加合物切除修复能力下降相关。
The morbility of epithelial ovarian cancer is the third in malignant gynecological tumors while the mortality is the first. Ovarian conceals cavum pelvis deeply. On the early pathogenetic stage, deficiency of characteristic symptom and physical symptom make the discovery and diagnosis difficult. About 60-70% of ovarian cancers are diagnosed at an advanced stage. Although in recent 30 years, chemotherapeutics modus were discovered, and modus operandi has been modified, the 5 years survival rate is still 20-30%.
Platinum drug is frequently used in the therapy of solid tumors, such as ovarian and lung cancers, and DNA damage repair capability is one of the cause of platinum drug resistance in ovarian cancer. DNA damage repair, such as nucleotide excision repair (NER)、mismatch repair、mismatch repair excision repair, is involved in platinum drug resistance. DNA lesions are preferentially repaired by the NER pathway. The mechanism of NER is quite complexity, involving in driving the process from damage recognition and removal to DNA resynthesis. Mutations in NER genes can result in many kinds of disorders. In the NER pathway, XPC, RPA and XPA are involved in the recognition step, two subunits of TFIIH, XPB and XPD, exhibit helicase activity and unwind the DNA around the lesion. After binding of XPF-ERCC1, dual incision occurs by XPG and XPF-ERCC1, which cut 3’and 5’to the damage, respectively.After that,the damage of DNA is repaired by PCNA、RPA,they completed the DNA synthesis and ligation.
The relationship between DNA damage repair genes ERCC1、XPA、XPC、XPD、XPG and platinum drug resistance in ovarian cancer has not been reported in domestically so far. To understand the roles of these genes in platinum drug therapy sensibility in ovarian, PCR and sequencing were performed to screen the single nucleotide Polymorphisms of exons of ERCC1、XPA、XPC、XPD、XPG in epithelial ovarian cancer cells which were resistant or sensitive to platinum-based treatment, and analysed the the relationship between polymorphisms of XPGHis46His、XPGHis1104Asp and clinical characteristics in 102 patients with ovarian cancer, and the expression vector of shRNA was constructed and transfected into ovarian cancer cell lines to establish gene knockdown cell lines, and then study on the effect of gene silencing in these cell lines. to provide insight into how to overcome Platinum drug resistance in overian cancer
Analysis of genetic polymorphisms in nucleotide excision repair system inplatinum drug resistant and non-resistant ovarian cancer cells
Objective: The tumor cell sensitivity to platinum-based chemotherapy was highly associated with DNA repair captability. ERCC1、XPA、XPC、XPD、XPG are crucial genes in nucleotide excision repair system to the sensitivity of platinum-based chemotherapy. This study was to examine the correlations of polymorphisms of ERCC1、XPA、XPC、XPD、XPG in nucleotide excision repair system and the sensitivity of platinum-based chemotherapy in epithelial ovarian cancer.
Method: PCR and sequencing were performed to screen the single nucleotide Polymorphisms of exons of ERCC1、XPA、XPC、XPD、XPG in epithelial ovarian cancer cells which were resistant or sensitive to platinum-based treatment. the results were analyzed by Chromas software and NCBI SNP data bank to search and authenticate the SNPs.At last, a few SNPs were chosen for further study.
Results: XPGHis46His and XPG His1104Asp had polymorphisms in cells .
Conclusion: The polymorphisms of XPGHis46His and XPG His1104Asp in nucleotide excision repair system may be associated with the resistance of epithelial ovarian cancer after platinum-based chemotherapy
The relation between XPG genetic polymorphism and the sensitivity toplatinum-based chemotherapy in patients with ovarian cancer
Objective:The goal of this study was to investigate the relation between nucleotide excision repair gene XPG mononucleotide polymorphism and the sensitivity to platinum-based chemotherapy in patients with ovarian cancer.
Methods: XPGHis46His and XPG His1104Asp were genotyped by polymerase chain reaction restrictive fragment length polymorphism ( PCR-RFLP) method in the 102 patients with advanced ovarian cancer with platinum-based chemotherapy, and the correlation of genetic polymorphisms and clinical response were analyzed .
Results: The polymorphism of His1104Asp was not significantly different between response group and un-response group. The frequency of T/T,T/C and C/C genotypes in drug sensitivity group was significantly increased as compared with that in the drug resistant group, and the differences had statistical significance(p=0.016). Individuals carrying at least one 46C variant allele (T/C and C/C genotypes) tended to have an increased sensitivity (3.096 times) to ovarian cancer patients with platinum-based chemotherapy as compared with those with the XPG46T/T genotype (95%CI:1.330-7.208). The polymorphism of XPG His46His and His1104Asp in various clinicopathologic characteristics of ovarian cancer was not significantly different (p>0.05).The survival time of T/T genotype group was shorter than T/C+C/C group(p<0.05); the COX risk risk regression model showed that the patho-grade was an independent factor for prognosis of ovarian cancer(P<0.05). Conclusion: Nucleotide excision repair gene XPGHis46His genetic polymorphism may be related to sensitivity to ovarian cancer patients platinum-based chemotherapy in ovarian cancer patients .
Effect of XPG silencing on platinum drug sensitivity in epithelial ovarian cancer in vitro
Objective: The expression vector of shRNA was constructed and transfected into ovarian cancer cell lines to establish gene knockdown cell lines, and then study on the effect of gene silencing in these cell lines.
Method: Several siRNA vectors were constructed and wrer transfected into SKOV3/DDP cell line with highly expression of XPG. Real-time PCR was used to test the efficacy of interfering RNA.Western-blot was also employed to confirm the silencing efficacy. Then growth of cells, cell cycle, cell susceptibility tests and measurement of intracellular drug concentration were tested. Results: Fluorescence quantitative PCR results show that, XPG copy number in XPG-733 group was 1.050±0.0230, significantly higher than in other three groups. Western-blot demonstraded that XPG protein expression was significant decreased in XPG shRNA vector transfected SKOV3/DDP cell line. Inhibition rate was 52.05% in XPG-733 group. FCM test showed that 34% and 66% of cells in pGPU6/GFP/Neo-XPG-733cell lines were in phase of cell proliferation (S + G2 + M) and G1, respectively while oly 41.3% and 58.7%, respectively, in control group. The growth curve in pGPU6/GFP/Neo-XPG-733 group was almost coincidence with that in control group. The difference of the IC50 to DDP level between the tow groups was significantly different (p<0.05). The intracellular drug levels in DDP inexperiment cells were significantly lower than that of the control cells measured by high performance liguid chromatograph(p<0.05).
Conclusion: There are no markedly changes of the growth characteristics and cell cycle in SKOV3/DDP cell line. However, knockdown of XPG increases the sensitivity to platinum drug in SKOV3/DDP cell line.We propose that this change may be relate to the degression of DNA-DDP- adducts excision repair capability.
铂类药物是治疗卵巢癌、肺癌等实体瘤的常用药物,而DNA损伤修复能力增强是导致卵巢癌铂类耐药的主要原因之一, DNA修复途径中的核苷酸切除修复、错配修复、碱基切除修复等均与铂类药物耐药有关,而核苷酸切除修复(NER)通路被认为是机体内修复DNA损伤的最主要途径。NER通路主要基因有:①DNA损伤的识别:涉及XPA、XPC等基因;②损伤部位DNA链的打开:由TFIIH的亚基ERCC3/XPB和ERCC2/XPD解旋酶打开DNA双链;③寡核苷酸链的切断:XPG和XPF-ERCC1复合体分别在损伤部位的3’端和5’端切断DNA单链;④PCNA、RPA等基因完成缺损部位单链片段的再合成和修补缺口。其中,损伤的识别/切除是通路中的限速或调节环节。在通路中,各个基因发挥着相应的独特作用,并按照严格的顺序加入和置换出NER过程,其中任何一个基因的功能异常即可导致整个通路对损伤修复的效率。目前国内尚未见有关DNA修复基因ERCC1、XPA、XPC、XPD、XPG与卵巢癌铂类药物敏感性的关系的报道,为了了解ERCC1、XPA、XPC、XPD、XPG等基因与卵巢癌铂类药物化疗敏感性的关系,我们在本实验中应用PCR及测序方法筛查ERCC1、XPA、XPC、XPD、XPG外显子单核苷酸多态性在卵巢癌耐铂类药物的细胞株和敏感细胞株中的分布差异,探讨了XPGHis46His及XPGHis1104Asp的多态基因型102例卵巢癌患者化疗敏感性的关系,并通过构建人XPG基因的shRNA表达载体,转染卵巢癌SKOV3耐DDP细胞,检测其对XPG基因的干扰效率。继而筛选出稳定干扰的细胞株,进行一系列功能实验,以了解XPG在卵巢癌耐药细胞株中的作用。为提高卵巢癌铂类药物化疗敏感性提供一些的实验依据。
卵巢上皮癌铂类耐药与非耐药细胞间核苷酸切除修复酶类基因多态性的检测与比较
目的:肿瘤细胞对铂类药物的化疗敏感性与个体的DNA损伤修复能力关系密切, ERCC1、XPA、XPC、XPD、XPG基因是核苷酸切除修复系统( nucleotide excision repair,NER)中与铂类药物抵抗有关的关键因子,本实验拟筛查ERCC1、XPA、XPC、XPD、XPG遗传多态与卵巢癌耐铂类药物的细胞株的关系,为下一步实验打下基础。
方法:应用PCR及测序方法筛查ERCC1、XPA、XPC、XPD、XPG外显子单核苷酸多态性在卵巢癌耐铂类药物的细胞株和敏感细胞株中的分布差异,序列读解采用ChromaS软件,并结合NCBISNP数据库寻找和验证SNP位点,筛选出的SNP用于下一步实验。结果: DNA测序分析发现XPGHis46His及XPGHis1104Asp两个SNP位点在细胞株中存在分布差异。结论:核苷酸切除修复系统中XPGHis46His及XPG His1104Asp遗传多态可能与卵巢癌患者对铂类药物耐药性相关。
XPG遗传多态与卵巢癌患者铂类药物敏感性关系
目的:研究核苷酸切除修复基因XPG单核苷酸多态性与卵巢癌患者对铂类药物敏感性的关系。方法:对接受含铂类药物化疗的102例晚期卵巢癌患者进行临床疗效评价。以聚合酶链-限制性片段长度多态性( PCR- RFLP)的方法检测接受含铂类药物化疗的102例卵巢癌患者XPGHis46His及XPG His1104Asp的多态基因型,并比较不同基因型与化疗敏感性的关系。结果: His1104Asp多态在卵巢癌铂类药物化疗敏感组中分布与耐药组差异不显著。XPGHis46His在化疗敏感组T/T,T/C,C/C的基因型频率明显高于耐药组,二者差异有统计学意义(p=0.016),与携带XPG46T/T基因型比较,携带至少一个46C等位基因(即T/C和C/C基因型)的卵巢癌患者对铂类药物化疗敏感可能性增加3.096倍(95%CI:1.330-7.208)。XPG His46His及His1104Asp基因多态与临床病理特征之间的比较差异无显著意义(P>0.05)。T/T基因型组生存期短于T/C+C/C基因型组,差异有统计学意义(P<0.05);COX风险比例回归模型结果显示病理分级是卵巢癌患者的独立预后因素(P<0.05)。
结论:核苷酸切除修复系统中XPGHis46His遗传多态可能与卵巢癌患者对铂类药物敏感性相关。
RNAi阻断XPG基因表达对卵巢上皮性癌细胞顺铂耐药性影响的体外实验研究
目的:通过构建人XPG基因的shRNA表达载体,转染卵巢癌SKOV3耐DDP细胞,检测其对XPG基因的干扰效率。继而筛选出稳定干扰的细胞株,进行一系列功能实验,以了解XPG在卵巢癌耐药细胞株中的作用。方法:针对XPG mRNA的不同区域构建了不同的siRNA载体,应用脂质体法转染SKOV3耐DDP细胞,实时定量PCR检验干扰效率,选择抑制率最高的siRNA构建shRNA表达载体,转染SKOV3耐DDP细胞,G418筛选后经western-blot鉴定确认获得稳定转染的SKOV3耐DDP细胞株,然后进行细胞生长特性、细胞周期变化、细胞药敏试验及细胞内药物浓度的实验。结果:用荧光定量PCR对不同siRNA干扰载体的干扰效果进行检测,实验结果显示:在XPG-733组XPG的相对拷贝数为1.050±0.0230,与对照组相比有统计学意义,抑制率为52.05%。构建shRNA表达载体转染SKOV3耐DDP细胞,获得的该组稳定干扰表达株,western-blot检验其XPG蛋白表达明显减少。流式细胞仪对细胞检测结果显示实验组处于增殖状态(S+G2+M)的细胞为34%,G1期为66%,阴性对照组则相应为41.3%和58.7 %,其处于增殖周期的细胞有减少的趋势。实验组与阴性对照组的IC50差别有均统计学意义(P<0.05),经化疗药处理后,用高效液相色谱仪检测其细胞内药物浓度,实验组细胞内药物浓度低于对照组细胞(P<0.05)。结论:采用构建shRNA表达载体对XPG基因进行干扰,SKOV3耐DDP细胞的生长特性、细胞周期无明显变化。干扰后SKOV3耐DDP细胞对顺铂的化疗耐药性明显下降,我们推测这种改变可能与促进细胞对DNA-DDP加合物切除修复能力下降相关。
The morbility of epithelial ovarian cancer is the third in malignant gynecological tumors while the mortality is the first. Ovarian conceals cavum pelvis deeply. On the early pathogenetic stage, deficiency of characteristic symptom and physical symptom make the discovery and diagnosis difficult. About 60-70% of ovarian cancers are diagnosed at an advanced stage. Although in recent 30 years, chemotherapeutics modus were discovered, and modus operandi has been modified, the 5 years survival rate is still 20-30%.
Platinum drug is frequently used in the therapy of solid tumors, such as ovarian and lung cancers, and DNA damage repair capability is one of the cause of platinum drug resistance in ovarian cancer. DNA damage repair, such as nucleotide excision repair (NER)、mismatch repair、mismatch repair excision repair, is involved in platinum drug resistance. DNA lesions are preferentially repaired by the NER pathway. The mechanism of NER is quite complexity, involving in driving the process from damage recognition and removal to DNA resynthesis. Mutations in NER genes can result in many kinds of disorders. In the NER pathway, XPC, RPA and XPA are involved in the recognition step, two subunits of TFIIH, XPB and XPD, exhibit helicase activity and unwind the DNA around the lesion. After binding of XPF-ERCC1, dual incision occurs by XPG and XPF-ERCC1, which cut 3’and 5’to the damage, respectively.After that,the damage of DNA is repaired by PCNA、RPA,they completed the DNA synthesis and ligation.
The relationship between DNA damage repair genes ERCC1、XPA、XPC、XPD、XPG and platinum drug resistance in ovarian cancer has not been reported in domestically so far. To understand the roles of these genes in platinum drug therapy sensibility in ovarian, PCR and sequencing were performed to screen the single nucleotide Polymorphisms of exons of ERCC1、XPA、XPC、XPD、XPG in epithelial ovarian cancer cells which were resistant or sensitive to platinum-based treatment, and analysed the the relationship between polymorphisms of XPGHis46His、XPGHis1104Asp and clinical characteristics in 102 patients with ovarian cancer, and the expression vector of shRNA was constructed and transfected into ovarian cancer cell lines to establish gene knockdown cell lines, and then study on the effect of gene silencing in these cell lines. to provide insight into how to overcome Platinum drug resistance in overian cancer
Analysis of genetic polymorphisms in nucleotide excision repair system inplatinum drug resistant and non-resistant ovarian cancer cells
Objective: The tumor cell sensitivity to platinum-based chemotherapy was highly associated with DNA repair captability. ERCC1、XPA、XPC、XPD、XPG are crucial genes in nucleotide excision repair system to the sensitivity of platinum-based chemotherapy. This study was to examine the correlations of polymorphisms of ERCC1、XPA、XPC、XPD、XPG in nucleotide excision repair system and the sensitivity of platinum-based chemotherapy in epithelial ovarian cancer.
Method: PCR and sequencing were performed to screen the single nucleotide Polymorphisms of exons of ERCC1、XPA、XPC、XPD、XPG in epithelial ovarian cancer cells which were resistant or sensitive to platinum-based treatment. the results were analyzed by Chromas software and NCBI SNP data bank to search and authenticate the SNPs.At last, a few SNPs were chosen for further study.
Results: XPGHis46His and XPG His1104Asp had polymorphisms in cells .
Conclusion: The polymorphisms of XPGHis46His and XPG His1104Asp in nucleotide excision repair system may be associated with the resistance of epithelial ovarian cancer after platinum-based chemotherapy
The relation between XPG genetic polymorphism and the sensitivity toplatinum-based chemotherapy in patients with ovarian cancer
Objective:The goal of this study was to investigate the relation between nucleotide excision repair gene XPG mononucleotide polymorphism and the sensitivity to platinum-based chemotherapy in patients with ovarian cancer.
Methods: XPGHis46His and XPG His1104Asp were genotyped by polymerase chain reaction restrictive fragment length polymorphism ( PCR-RFLP) method in the 102 patients with advanced ovarian cancer with platinum-based chemotherapy, and the correlation of genetic polymorphisms and clinical response were analyzed .
Results: The polymorphism of His1104Asp was not significantly different between response group and un-response group. The frequency of T/T,T/C and C/C genotypes in drug sensitivity group was significantly increased as compared with that in the drug resistant group, and the differences had statistical significance(p=0.016). Individuals carrying at least one 46C variant allele (T/C and C/C genotypes) tended to have an increased sensitivity (3.096 times) to ovarian cancer patients with platinum-based chemotherapy as compared with those with the XPG46T/T genotype (95%CI:1.330-7.208). The polymorphism of XPG His46His and His1104Asp in various clinicopathologic characteristics of ovarian cancer was not significantly different (p>0.05).The survival time of T/T genotype group was shorter than T/C+C/C group(p<0.05); the COX risk risk regression model showed that the patho-grade was an independent factor for prognosis of ovarian cancer(P<0.05). Conclusion: Nucleotide excision repair gene XPGHis46His genetic polymorphism may be related to sensitivity to ovarian cancer patients platinum-based chemotherapy in ovarian cancer patients .
Effect of XPG silencing on platinum drug sensitivity in epithelial ovarian cancer in vitro
Objective: The expression vector of shRNA was constructed and transfected into ovarian cancer cell lines to establish gene knockdown cell lines, and then study on the effect of gene silencing in these cell lines.
Method: Several siRNA vectors were constructed and wrer transfected into SKOV3/DDP cell line with highly expression of XPG. Real-time PCR was used to test the efficacy of interfering RNA.Western-blot was also employed to confirm the silencing efficacy. Then growth of cells, cell cycle, cell susceptibility tests and measurement of intracellular drug concentration were tested. Results: Fluorescence quantitative PCR results show that, XPG copy number in XPG-733 group was 1.050±0.0230, significantly higher than in other three groups. Western-blot demonstraded that XPG protein expression was significant decreased in XPG shRNA vector transfected SKOV3/DDP cell line. Inhibition rate was 52.05% in XPG-733 group. FCM test showed that 34% and 66% of cells in pGPU6/GFP/Neo-XPG-733cell lines were in phase of cell proliferation (S + G2 + M) and G1, respectively while oly 41.3% and 58.7%, respectively, in control group. The growth curve in pGPU6/GFP/Neo-XPG-733 group was almost coincidence with that in control group. The difference of the IC50 to DDP level between the tow groups was significantly different (p<0.05). The intracellular drug levels in DDP inexperiment cells were significantly lower than that of the control cells measured by high performance liguid chromatograph(p<0.05).
Conclusion: There are no markedly changes of the growth characteristics and cell cycle in SKOV3/DDP cell line. However, knockdown of XPG increases the sensitivity to platinum drug in SKOV3/DDP cell line.We propose that this change may be relate to the degression of DNA-DDP- adducts excision repair capability.
引文
[1] Parkin DM,Pisani P, Ferlay J.Global cancer statistics.CA Cancer J Clin 1999;49:33-46.
[2] McGuire v, Whittemore AS,NorrisR,et al.Survival in ePithelial ovarian cancer Patients with Prior breast cancor.Am J EPidemiol 2000;152(6):528-32.
[3] Cancer Facts and Figures一1996,Atlanta,American Cancer Society,1996.
[4]郑怀美主编.妇产科学(第三版),北京:人民卫生出版社1992:292-309.
[5 ] M cGuire W P,Ho sk ins WJ, B rady M F,et al .Cyclopho spham ide and cisp lat in compared w ith paclitaxel and cisp lat in in pat ients w ith stageⅢand stageⅣovarian cancer [J ] . N Engl J M ed,1996,334(1) :1- 6 .
[6 ] Bookman MA, Greer BE,O zo ls RF. Optimal therapy of advanced ovar ian cancer:carboplat in and paclitaxel vs cisplat in and paclitaxel (GO G 158) and an update on GO G0 1822ICON 5 [J ] . Int J Gyneco l Cancer,2003,13 (6) :735- 740 .
[7 ] Pf isterer J, W eber B,Reuss A, et al . Randomized phaseⅢtrial of topo tecan following carboplat in and paclitaxel in first line treatment of advanced ovariancancer:a gynecologic cancer intergroup trial of the AGO-OVAR and GI N ECO [J ] . J N at l Cancer Inst,2006,98 (15) :1036- 1045 .
[8]张覃沐,许长江,张予等.多药抗药性产生机制[M].中国药理学通报,1994,10(4): 246-249.
[9] Avendano C,Menendez JC.Inhibitors of multidrug resistance to antitumor agents (MDR).Curr Med Chem 2002;9(2):159-193
[10] Gottesman MM,Fojo T,Betas SE.Multidrug resistance in cancer:role of ATP- dependent transporters.Nat Rev Cancer 2002,2(1):48-58.
[11] Biedler JL.Genetic aspetcs of multidrug resistance.Cancer. 1992,70:1799.
[12] Kamazawa S,Kigawa J,Kanamori Y,etc. Multidrug resistance gene-1 is a useful predictor of Paclitaxel-based chemotherapy for patients with ovarian cancer. Gynecol Oncol. ,2002,86(2):171-176.
[13] Xing H,Wang S,Weng D,etc.Knock-down of P-glycoprotein reverses taxol resistance in ovarian cancer multicellar spheroids.Oncol Rep,2007,17(1): 117-122.
[14] Yang X,Zheng F,Xing H,etc.Resistance to chemotherapy-induced apotosis via decreased caspase-3 activity and overexpression of antiapoptotic protein in ovarian cancer.J Cancer Res Clin Oncol,2004,130(7):423-428.
[15] Yang HH,Ma MH,vescio RA,Berenson JR.Overcoming drugresistance in multiple myeloma:the emergence of therapeutic approaches to induce apoptosis.J Clin Oncol,2003,21(22):4239-4247.
[16] Shen F,Chu S,Bence AK,etc. Quantitation of doxorubicin uptake,efflux and modulation of multidrug resistance (MDR) in MDR human cancer cells. J Pharmacol Exp Ther.,2007,18(9):1523.
[17] Johnson DR, Finch RA,Lin ZP, et al . The pharmacological phenotype of combined multidrug resistance mdr1a/ 1b and mrp1 deficientmice[J ] . Cancer Res,2001,61 (4) :1469-1476.
[18] Larsen A K,Escargueil AE,Skladanowski A. Resistance mechanisms associated with altered intracellular distribution of anticancer agents[J] . Pharmacol Ther,2000,85 (3) :217-229.
[19] Jia P , Wu SB , Li F , et al . The mechanism of topotecan resistance in ovarian cancer cell line[J]. Zhonghua Zhong Liu Za Zhi , 2004 , 26(3) : 139-142.
[20]唐海桦,梁钢.肺耐药相关蛋白的研究进展[J]..2008,14(3)462-464.
[21] Ahmad H,Wilson DE,Fritz RR,etc.Primary and secondary structural analysesof glutathione Stransferase pifrom human placenta[J].Arch Biochem Biophys,1990,278(2):398-399.
[22] Goto S,Kamada K,Soh Y,etc.Significance of nuclear glutathione-S- transferase pi in resistance to anti-cancer drugs[J].Jpn J Cancer Res,2002,93(9):1047-1056.
[23] Nagle CM,Chenevix-Trench G,Spurdle AB,etc.The role of glutathione -S-transferase polymorphisms in ovarian cancer survival[J]. Eur J Cancer.,2007,43(2): 283-90.
[24]刘智鑫,刘国津.人非小细胞肺癌细胞药物敏感性检测及其与耐药因子p53抗体和GST2 -π表达的关系[J]..吉林大学学报(医学版) , 2005, 31 (5) : 795- 798.
[25]马荣,陈曦海,唐丽萍等.survivin反义核酸诱导卵巢癌细胞凋亡及逆转多西他赛耐药机制的实验研究[J] .第四军医大学学报,2006, 27(17):1616-1619.
[26] Ferry KV, Hamilton TC and Johnson SW. Increased nucleotide excision repair in cisplatin-resistan to varian cancer cells: role of ERCCI-XPF[J].. Biochem Pharmaco1, 2000, 60 (9):1305-131.
[27] Li Q,Y u J J, Mu C, et al. Association between the level of ERCC-1 expression and the repair of cisplatin-induced DNA damage in human ovarian cancer cells[J].. Anticancer Res, 2000,20(2A):645-52.
[28] Fine RL,Chambers TC,Sachs CW. P-glycoprotein,multidrug resistance and protein kinase C[J]. Stem Cells 1996;14,47-55.
[29] Gollapudi S,Soni V,Thadepalli H,et al . Gupta S. Role of protein kinase beta isozyme in multidrug resistance[J]. Journal of Chemotherapy,1995;7:157–159.
[30] Gupta KP,Ward NE, Gravitt KR,et al . Partial reversal of multidrug resistance in human breast cancer cells [J]. J Biol Chem,1996 ;271:2102-2111.
[31]金晶,吴绪峰,陈惠祯. P - g p、PKC -α和MRP在上皮性卵巢癌中的表达及其临床意义.现代肿瘤医学,2006,14(3)325-329.
[32] Trieb K,Kotz R. Proteins expressed in osteosarcoma and serum levels as prognostic factors[J].Int J Biochem Cell Biol,2001 ;33 :11-17.
[33] Bert ram J, Palfner K,Hiddemann W,er al.Increase of P-glycoprotein-mediated drug resistance byhsp90beta[J].Anticancer Drugs,1996;7:838-845.
[34] Vilaboa NE, Galan A, Troyano A,et al . Regulation of multidrug resistance 1 (MDR1)/P-glycoprotein gene expression and activity by heat-shock transcription factor 1 (HSF1) [J].J Biol Chem,2000;275:24970-24976.
[35] Kim SH,Yeo GS,Lim YS,et al . Suppression of multidrug resistance via inhibition of heat shock factor by quercetin in MDR cells[J].Exp Mol Med,1998 ;30(2):87-92.
[36] Schneider J , Miller GA , Wiemann MC , et al . Co2expression of theMDRI gene and hsp27 in human ovarian cancer[J]. Anticancer Res ,1998 , 18 (4c) :2967
[37] Chie L,Amar S,Kung HF,et al . Cancer Chemo Pharm,2000 ;45 :441-449
[38] Zilfou J T,et al . The molecular alterations of tumor suppressor genes p16INK4a and p15INK4b in human esophageal cancer[J]. Proc Am Assoc Cancer Res,1998;39.
[39] Serrone L,Horsey P. The chemoresistance of human malignant melanoma: an update[J].Melanoma Res,1999 ;9 :51-58.
[40] Tsuruo T,Nato M.Tomida A,etc.Molecular targeting t herapy of cancer:drug resistance,apoptosis and survival signa[J].Cancer Sci,2003,94(1):15-21.
[41] Fabbro D,Ruetz S,Bodis S,etc.PKC412 - a protein kinase in hibitorwith a broad therapeutic potential[J].Anti-cancerDrug Des,2000,15(1):17-28.
[42] Esteve MA, Carre M, Bourgarel-Rey V,etc. Bcl-2 down-regulation and tubulin subtype composition are involved in resistance of ovarian cancer cells to vinflunine. Mol Cancer Ther,2006,5(11):2824-33.
[43] Chekhun VE,Lukyanova NY,Urchenko OV,etc.Exp Oncol,2005,27(3):191-195.
[44] Witham J,Valenti MR,DeHavenBrandon AK,etc.The bcl-2/bcl-xl family inhibitor abt-737 sensitizes ovarian cancer cell to carboplatin.Clin Cancer Res,2007,13(23):7191-7198.
[45] Bharti AC,Aggarwal BB.Nuclear factor-kappa B and cancer:Its role in p revention and therapy[J].Biochem Pharmacol,2002,4 (526):83-88.
[46] Taylor DD,Metzinger DS,Gercel TC,Induction of p53 and drug resistancefollowing treatment with cisplatin or paclitaxel in ovarian cancer cell lines. Cancer Lett.2006,236 (2):302-308.
[47] Thigpen JT.The role of gemcitabine in first-line treatment of advanced ovarian malignant . Semin Oncol. 2006;33(2):S26-32.
[48] Goonewardene TI,Hall MR,Rustin GJ.Management of asymptomatic patients on follow-up for ovarian cancer with rising CA125 concentrations.Lancet Oncol. 2007,(9):813-821.
[49] Coleman RL,Gordon A,Barter J,etc. Early changes in CA125 after treatment with pegylated liposomal doxorubicin or topotecan do not always refletc best response in recurrent ovarian cancer patients. Oncologist.,2007,12(1):72-78.
[50] Gossner G,Coleman RL,Mutch DG,etc. CA125 response in patients with recurrent ovarian or primary peritoneal cancer treated with pegylated liposomal doxorubicin or topotecan.Gynecol Oncol..2006,103(1):212-218.
[51] Goonewardene TI,Hall MR,Rustin GJ.Management of asymptomatio patients on follow-up for ovarian cancer with rising CA125 concentrations.Lancet Oncol,2007,8(9):813-821
[52] Gadducci C.The concomitan detemination of different tumor marker on patients with epithelial ovarian cancer and benigh ovarian masses relevance for differential diagosis.Gynecol Oncol,1992,44(2):147.
[53] Yakirevich E,Sabo E,Naroditsky I,etc. Multidrug resistance- related phenotype and apoptosis-related protein expression in ovarian serous malignant s.Gynecol Oncol.,2006,100(1):152-159.
[54] Krasznai ZT , Friedlander E , Nagy A , etc.Quantitative and functional assay of MDR1/P170-mediated MDR in ascites cells of patients with ovarian cancer. Anticancer Res.,2005,25(2A):1187-1192.
[55] Rappa G,Finch RA,Sartrelli AC,etc.New insights into the biologyand pharmacology of the multidrug resistance protein (MRP) from geneknockout models.Biochem Pharmacol,1999,58(40):557-562.
[56] Nooter K,Mulder NH,Smith AJ,etc.Expression of mrp gene in human cancer.Clin CancerRes,1999,1:1301.
[57] Kolfschoten GM,Hulscher TM,Pinedo HM,etc.Drug resistancefeatures and S-phase fraction as possible determinants for drug responsein a panel of human ovarian cancer xenografts[J ] .Br J Cancer,2000,83(7):921-927.
[58] Qian XL,Peng ZL,Liu SL,etc.Expreeion of lung resistant-related protein in ovarian cancer and its clinical significance.Ai Zheng,2002,21(12):1332-1334.
[59]李文通,周庚寅,宋现让等.表达BCRP的卵巢癌耐药细胞系3AO/BCRP的建立及其生物学特征[J].基础医学与临床,2006,26(1):61-65.
[60] Beeghly A,Katsaros D,Chen H,etc.Glutathione S-transferase polymorphisms and ovarian cancer treatment and survival.Gynecol Oncol,2006,100(2):330-337.
[61]崔恒,钱和年.卵巢癌生物治疗的研究进展[J].中华妇产科杂志,2002,37 (4):193.
[62] Torre FJ,Garcia A,Gil-Moreno A,etc. Apoptosis in epithelial ovarian tumours Prognostic significance of clinical and histopathologic factors and its association with the immunohistochemical expression of apoptotic regulatory proteins (p53, bcl-2 and bax). Eur J Obstet Gynecol Reprod Biol,2007,130(1):121-128.
[63] WilliiamsJ,Lucas PC,Griffith KA,etc.Expression of BCL-XL in ovarian malignant is associated with chemoresistance and recurrent disease.Gynecol Oncol,2005,96(2):287- 295.
[64] Kim R,Emi M,Tanabe K,etc.Therapeutic potential of antisense Bcl-2 as a chemosensitizer for cancer therapy . Cancer,2004,101(11):2491-2502.
[65] Cloven NG,kyshtoobayeva A,Burger RA,etc.Invirto chemoresistance and biomarker profiles are unigue for histologic subtypes of epithelial ovarian cancer. Gynecol Oncol,2004,92(1):160-166.
[66] Lesperance S,Popa I,Bachvarova M,etc.Gene expression profiling of paried ovarian tumors obtained prior to and following adjuvant chemotherapy: molecular signatures of chemoresistant tumor.Int J Oncol,2006,29(1):5-24.
[67] Santin AD,Zhan F,BelloneS,etc.Discrimination between uterine serous papillary malignant s and ovarian serous papillary tumours by gene experessi- on profiling.Br J Cancer,2004,90(9):1814-1812.
[68] Sasaki N,Kudoh K,Kita T,etc.Effetc of HER-2/neu overexpreeion onchemoresistance and prognosis in ovarian malignant .J Obstet Gynaecol Res,2007,33(1):17-23.
[69] Scartozzi M,De Nictolis M,Galizia E,etc.Loss of Hmlhi expression corre- lates with improved survival in stage III-IV ovarian cancer patients Eur J Cancer,2003,39:1144-1149.
[70] Gifford G,Paul J,Vasey PA,etc. The acquisition of hMLH1 methylation in plasma DNA after chemotherapy predicts poor survival for ovarian cancer patients. , 2004,10(13):4420-4426.
[71] Helleman J,van Staveren IL,Dinjens WN,etc. Mismatch repair and treatment resistance in ovarian cancer. BMC Cancer,2006,31(6):201.
[72] Nakayama K,Kanzaki A,Ogawa K,etc.Copper-transporting P-type adenosine triphosphatase (ATP7B) as a cisplatin based chemoresistance marker in ovarian malignant : comparative analysis with expression of MDR1, MRP1, MRP2, LRP and BCRP. Int J Cancer.,2002,101(5):488-495.
[73] Raspollini MR,Amunni G,Villanucci A,etc. Analysis in ovarian malignant patients with low and high survival. Int J Gynecol Cance- r,2005,15(2):255-260.
[74] Ferrandia G,Ranelletti FO,Martinelli E,etc.Cyclo-oxygenase-2(Cox-2) expreeion and resistance to platinum versus platinum/paclitaxal containing chemotherapy in advanced ovarian cancer.BMC Cancer,2006,6:182.
[75] Obata H,Yahata T,Quan J,etc Association between single nucleotide polymorphisms of drug resistance-associated genes and response to chemotherapy in advanced ovarian cancer. Anticancer Res.,2006,26(3B): 2227-2232.
[76] Ikeda K,Sakai K,Yamamoto R,etc. Multivariate analysis for prognostic significance of histologic subtype, GST-pi, MDR-1, and p53 in stages II-IV ovarian cancer. Int J Gynecol Cancer, 2003,13(6):776-784.
[77] Naniwa J,Kigawa J,Kanamori Y,etc.Genetic diagnosis for chemosen- sitivity with drug-resistance genes in epithelial ovarian cancer. Int J Gynecol Cancer, 2007,17(1):76-82.
[78] Marsh S,Paul J,King CR.Pharmacogenetic assessment of toxicity and outcome after platinum plus taxane chemotherapy in ovarian cancer:the scottishrandomised trial in ovarian cancer.J Clin Oncol,2007,25(29):4513-4515.
[79]张覃沐,许长江,张予等.多药抗药性产生机制[M].中国药理学通报,1994,10(4): 246-249.
[80] Klopman G,Shi LM, Ramu A. Quantitative structure-activity relationship of multidrug resistance reversal agent s [ J] . Mol Pharmacol, 1997,52 (2) :323-334.
[81]马强,张振书.中药逆转肿瘤多药耐药研究进展[J] .湖南中医学院学报,2002, 22 (4) :70-72.
[82]靳英.周庚寅.张廷国.植物多酚类化合物逆转肿瘤多药耐药的筛选[J] .山东大学学报(医学版),2002, (6) :497-499.
[83] Fung-Kee-Fung M,Oliver T,Elit L,etc.Optional chemotherapy treatment for women with recurrent ovarian cancer.Curr Oncol.2007; 14(5):195-208.
[84] Forbes C,Shirran L,Bagnall AM,etc.A rapid and systematic review of the clinical effetciveness and cost-effetciveness of topotecan for ovarian cancer.Health Technology Assessment,2001,5(28):23785-23793.
[85] Thigpen JT,Aghajanian CA,Albert DS,etc.Role of pegylated liposomal doxorubicin in ovarian cancer.Gynecol Oncol,2005,96:10-18.
[86] Zalipsky S,Saad M,Kiwan R,etc.Antitumor activity of new liposomal prodrug of mitomycin C in multidrug resistant solid tumor:insights of the mechianism of action.J Drug Target.2007;15(7-8):518-530.
[87] Verborg WA,Campbell LR,Highley MS,etc.Weekly cisplatin with oral epoposide:a well-tolerated and highly effetcive regimen in relapsed ovarian cancer.Int J Gynecol Cancer,2007,May 19 [Epub ahead of print].
[89] Garcia AA,Oza AM,Hirte H,etc.Interim report ofa phaseⅡclinical trial of bevacizumab(Bev) and low dose metronomic oral cyclophosphamide(mCTX) in recurrent ovarian (OC) and primary peritoneal malignant :A California Cancer Consortium Trial.J Clin Oncol(Meeting Abstracts),2005,23: 50000.
[90] Aport GG,Fleming GF,Waggoner S,et al. Progenitor cell mobilization A phase II trial of docetaxel for peripheral blood stem cellmobilization for patients withbreast cancer and ovarian cancer [ J] .Bone MarrowTransplant,2001,27(7):677- 681.
[91] Viret F,Bertucci F,Genre D,et al. Intensive sequential dose dense chemotherapy with stem cell support as first - line treatment in advanced ovarian carcinoma:a phaseⅡstudy[ J] . Bone Marrow Transplant,2002,30(12):879- 884.
[92] Frickhofen N,Berdel WE,Opri F,et al. Ovarian cancer side population defines cells with stemcell- like characteristics and Mullerian Inhibiting Substance responsiveness[ J] . Proc Natl Acad Sci U S A,2006,103 (30):11154- 11159.
[93] Sehouli J,Stengel D,Oskay G,et al. A newtherapeutical approach:topotecan plus gemcitabine in the treatment of patients with relapsed ovarian cancer after failure of first- line chemotherapywith paclitaxel andplatinum[ J] . ObstetGynaecolRes, 2003,29(3) :123- 131.
[94] Miller DS,Blessing JA,Lentz SS,et al. PhaseⅡevaluation of three- day topotecan in recurrent platinum- sensitive ovarian carcinoma:a gynecologic oncology group study [ J] . Cancer,2003,98(8):1664- 1669.
[95] Rodriguez M,Rose G. Improved therapeutic index of lower dose topotecan chemotherapy in recurrent ovarian cancer [ J] . Gynecol Oncol,2001,83(2):257- 262.
[96] DenchlagD,Watermann D,H rigK,et al. Topotecan as a continuous infusion over 14 days in recurrent ovarian cancer patients [ J] .Anticancer Res,2004,24(2):1267- 1269.
[97] Tiersten A,Selleck M,Smith DH,et al. Phase I/II study of tandem cycles of high - dose chemotherapy followed by autologoushematopoietic stem cell support in women with advanced ovarian cancer[ J] . Int J Gynecol Cancer,2006,16(1):57- 64.
[98] Ferrandina G,Pierelli L,Perillo A,et al. Lymphocyte recovery in advanced ovarian cancer patients after high- dose chemotherapy and peripheral blood stemcell plus growth factor support:Clinical Impli-cations[ J] . Clin Cancer Res,2003,9(1):195- 200.
[99] DonatoML,Aleman A,Champlin RE,et al. Analysis of 96 patients with advanced ovarian carcinoma treated with high - dose chemo-therapy and autologous stemcell transplantation[ J] . Bone MarrowTransplant,2004,33(12):1219- 1224.
[100] Stiff PJ,Shpall EJ,Liu PY,et al. Randomized phase II trial of two high- dose chemotherapy regimens with stemcell transplantation for the treatment of advanced ovarian cancer in first remission or chemosensitive relapse:a Southwest Oncology Group study [ J] .Gynecol Oncol,2004,94(1):98- 106.
[101] Stiff PJ,Veum- Stone J,Lazarus HM,et al. High- dose chemotherapy and autologous stem- cell transplantation for ovarian cancer:an autologous blood and marrowtransplant registry report[ J] . Ann Intern Med,2000,133 (7):504- 515.
[102] Ward M, Richardson C, Pioli P, et al . Transfer and expression of t he human multiple drug resistance gene in human CD34 +cells[ J] . B lood, 1994,84 (5) :1408-1414.
[103] Hanania EG,Fu S, Zu Z, Chemot herapy resistance to taxol in clonogenic progenitor cells following t ransduction of CD34 selected marrow and peripheral blood cells wit h a ret rovirus t hat contains t he MDR21 chemot herapy resistance gene[ J] . Gene Ther, 1995,2 (4) :285-294.
[104]陈良安.多药耐药基因增强骨髓细胞对抗癌药物毒性的抵御能力[ J] .中华肿瘤杂志,2000,6 :389-392 .
[105] Motomura S, Motoji T, Takanashi M, et al . Inhibition of Pglycoprotein and recovery of drug sensitivity of human acuteleukemic blast cells by multidrug resistance gene (mdr1) antisense oligonucleotides[ J] . B lood, 1998,91 (9) :3163-3171.
[106] Li Y,Wang Y. Inhibition growt h of multidrug resistant KBV200 cells by MDR1 antisense RNA[ J] . B iochem B iophys Res Commun, 1997,239 (1) :345-348.
[107]高鹏,周庚寅,殷钢,等.负向调节多药耐药基因1转录逆转肿瘤细胞多药耐药[ J] .中华病理学杂志,2003, 32 ( 6) :563-566.
[108 ] Mat sumoto Y,Takano H, Nagao S, et al . Altered topoisomerase IIalpha and multidrug resistance2associated protein levels during drug selection :adaptations to increasing drug pressure[ J] . J pn J Cancer Res, 2001,92 (9) :968-974.
[109] Yang JM, Chin KV, Hait WN. Interaction of P2glycoprotein with protein kinase C in human multidrug resistant carcinoma cells[ J] . Cancer Res, 1996,56 (15) :3490-3494.
[110] Osada H, Tokunaga T, Abe Y,et al . Reversal of drug resistance mediated by hammerhead ribozyme against multidrug resistance associated protein 1 in a human glioma cell line[ J] . I nt J Oncol, 2003,22 (4) :823-827.
[111] Scanlon KJ, Ishida H, Kashani2Sabet M. Ribozyme mediatedreversal of the multidrug-resistant phenotype [J] . Proc N at lA cad Sci U S A, 1994,91 (23) :11123211127.
[112] Keit h FJ, Bradbury DA, Zhu YM, et al . Inhibition of bcl-2 with antisense oligonucleotides induces apoptosis and increases the sensitivity of AML blast s to Ara2C[ J] . L eukemia,1995,9(1) :131-138.
[113] Huang Y,Ibrado AM, Reed JC, et al . Co2expression of several molecular mechanisms of multidrug resistance and t heir significance for paclitaxel cytotoxicity in human AML HL260 cell s[ J] . L eukemia, 1997,11 (2) :253-257.
[114] Sumant ran VN, Lee DS, Woods Ignatoski KM, et al . A bcl2xS adenovirus selectively induces apoptosis in t ransformed cell scompared to normal mammary cells[ J] . Neoplasia, 2000,2(3) :251-260.
[115] Ikeda K,Sakai K,Yamamoto R, et al . Multivariate analysis for prognostic significance of histologic subtype, GST2pi, MDR21, and p53 in stages II2IV ovarian cancer[ J] . I nt J Gynecol Cancer, 2003,13 (6) :776-784.
[116] Stein U, Walt her W, Shoemaker RH. Modulation of mdr1 expression by cytokines in human colon carcinoma cells :an ap2proach for reversal ofmultidrug resistance [ J] . B r J Cancer,1996,74 (9) :1384-1391.
[117]郝权,田菁.卵巢癌靶向治疗研究进展[J].中国肿瘤临床,2005 ,32(22):1315-1318.
[118] Kramm CM,Niehues T,Rainow NG.Experinental stragies for combined suicide and immune cancer gene therapy.An overview.Methods Mol Biol,2003,215(6): 137-152.
[119] Segota E,Bukowshi RM.The promise of targeted therapy cancer drugs become more specific.Cleve Clin Jmed,2004,71(7):551-560.
[120]Mcquarrie SA,Mercer JR,Syeme A,etc.Prelininary results of nanophamaceuticals used in the radioimmunotherapy of ovarian cancer,Jpham Phamaceut Sci,2004,7(4):29-34.
[121] Menendez JA,Vellon L,Mehmi I,etc.Inhibition of fatty acid synthase (FAS) suppresses HER2/neu (erbB-2) oncogene overpression in cancer cell.PNAS,2004,101(29):10715 -10712.
[122] Disis ML,Schifman K,Guthrie K,etc.Effetc of dose on immune response in patients vaccinated with an her-2/neu intracellular domainprotein-based vaccine.J Clin Oncol,2004,22(10):1916-1925.
[123] Curiel TJ,Cheng P,Mottram P,etc.Dendritic cell subsets differentially regulate angiogenesis in human ovarian cancer. 2007;18(5): 511-517.
[124] Xie SZ,Wang J,Li DZ,etc.Medroxprogesterone acetate therapy against antiangiogenesis of translanted ovarian cancer in nude mice.Di Yi Jun Yi Da Xue Xue Bao,2004,24(7):821-823.
[125] Chen HH,Zhou HJ,Fang X.Inhibition of human cancer cell linee growth and human umbillical vein endothelial cell angiogenesis by artemisin inderivatives invitro.Phamacol Res,2003,48(3):231-236.
[126] Mahendra G,Kumar S,Isayeva T,etc.Antiangiogenic cancer gene therapy by adeno-associated virus 2-mediated stable expression of the soluble FMS-like tyrosine kinase-1 receptor.Cancer Gene Ther,2005,12(1):26-34.
[127] Markowska J,Azala S.Inhibitors of angiogenesis in therapy of ovarian cancer.Eur J Gynaecol Oncol,2004,25(5):562-567.
[128] Fehrmann RS,Li XY,Van der ZEE AG,etc.Profiling studies in ovarian cancer:a review.Oncologist,2007,12(8):190-196.
[129] Alberts DS.Treatment of refractory and recurrent ovarian cancer.Semin Oncol. 1999,26(4):8-14.
[130]连丽娟.林巧稚妇科肿瘤学.第4版.北京:人民教育出版社,2006,581.
[131] FungKeeFung M,Oliver T,Elit L.etc.Optimal chemotherapy treatment for women with recurrent ovarian cancer.Curr Oncol,2007,14(5):195-208.
[132] Pignata S,Scambia G,Savarese A,etc.Safety of a 3-weekly schedule of carboplatin plus peghylated liposomal doxorubicin as first line chemotherapy in patients with ovarian cancer:prelimiary results of the MITO-2 randomized trial.BMC Cancer,2006,6:202-210.
[133] Alberts DS,Liu PY,Wilczvnski SP,etc.Randomized trial of pegylated liposomal doxorubucin(PLD) plus carboplation versus carboplatin in platinum-sensitive(PS) patients with recurrent epithelial ovarian or peritoneal malignant after failure of initial platinum-based chemotherapy (Southwest Oncology Group Protocol S0200).Gynecol Oncol,2007,0ct 17[Epub ahead of print].
[134] Chasman D and Adams RM. Predicting the functional consequence of non- synonymous single nucleotide polymorphism: structure-based assessment of aminoacid variation . J Mol Biol, 2001,307(2):683-706.
[135] Bertin I, Zhu J H, Gale M D. SSCP-SNP in pearl millet—a new maker system for comparative genetics [J].Theoretical and Applied Genetics,2005,110:1467- 1472.
[136]张小燕,左明雪,张占军,等.用基因芯片检测单核苷酸多态性反应原理[J].中国生物工程杂志,2005,25(11):52-56.
[137]刘雅诚,郝金萍,严江伟,等.用dHPLC技术检测线粒体DNA编码区单核苷酸多态性[J].中国法医学杂志,2006,21(3):142-146.
[138]秦效英,李国选,江滨,等.应用变性高效液相色谱检测CD31563位点单核苷酸多态性[J].中华检验医学杂志,2006,29(7):627-630.
[139] Han W, Yip S P, Wang J, et al. Using denaturing HPLC for SNP discovery andestablishing the linkage disequilibrium pattern for the all-trans-retinol dehydrogenase (RDH8) gene [J].Journal of Human Genetics,2004,49:16-23.
[140] Karas M, Hillenkamp F. Laser desorption ionization of proteins with molecular masses exceeding 10000 daltons [J]. Analysis Chemistry, 1989,60:2299-2301.
[141] Sauer S. Gut I G.Genotyping single-nucleotide polymorphisms by ma-trix- assisted laser desorption/ionization time of flight mass spectrometry[J]. Journal of Chromatography B-Analtical Technologies in the Biomedical and Life Science,2002,782(1-2):73-87.
[142]刁现民,Damon L. Mutator转座子及MULE在植物基因与基因组进化中的作用[J].遗传学报,2006,33(6)477-487.
[143]卫波,景蕊莲,王成社,等.用等位基因特异PCR检测普通小麦( Triticum aestivum L.)的单核苷酸多态性[J].中国农业科学,2006,39(7): 1313-1320.
[144]单志新,谭虹虹,余细勇,等.基于荧光定量PCR扩增反应的SNP测定法[J].中国生物化学与分子生物学报,2005,21(6):827-830.
[145] Levy Lahad E, Lahad A, Eisenberg S, et al . A single nucleotide polymorphism in the RAD51 gene modifies cancer risk in BRCA2 but not BRCA1 carriers[J ] . Proc Natl Acad Sci USA,2001,98 (6) :3232-3236.
[146] Wang WW, Spurdle AB, Kolachana P, et al . A single nucleotide polymorphism in the 5′unt ranslated region of RAD51 and risk of cancer among BRCA1Π2 mutation carriers[J ] . Cancer Epidemiol Biomarkers Prev, 2001, 10 (9) :955-960.
[147] McCarron SL, Edwards S, Evans PR, et al . Influence of cytokine gene polymorphisms on the development of prostate cancer [ J ] .Cancer Res, 2002, 62 (12) :3369-3372.
[148] Quintela-Fandino M,Hitt R, Medina PP, et al. DNA-repair gene polymorphisms predict favorable clinical outcome among patients with advanced squamous cell carcinoma of the head and neck treated with cisplatin-based induction chemotherapy. J Clin Oncol. 2006,24(26):4333-9.
[149] Isla D, Sarries C, Rosell R, et al. Single nucleotide polymorphisms and outcomein docetaxel-cisplatin-treated advanced non-small-cell lung cancer. Ann Oncol, 2004, 15(8): 1194-203.
[150] Butkiewicz D, Rusin M, Enewold L, et al. Genetic polymorphisms in DNA repair genes and risk of lung cancer. Carcinogenesis, 2001,22(4):593-7.
[151] Liang G, Xing D, Miao X, et al. Sequence variations in the DNA repairs gene XPD and risk of lung cancer in a Chinese population. Int J Cancer, 2003, 105(5): 669-673.
[152] Blankenburg S, Konig IR,Moessner R,et al. Assessment of 3 xeroderma pigmentosum group C gene polymorphisms and risk of cutaneous melanoma: a case–control study. Carcinogenesis, 2005, 26(6): 1085-90.
[153] Moreno V, Gemignani F, Landi S, et al. Polymorphisms in genes of nucleotide and base excision repair: risk and prognosis of colorectal cancer. Clin Cancer Res, 2006,12(7 Pt 1):2101-8.
[154] Storgis FM, Zheng R, Castillo EJ, et al. XPD/ERCC2 pnlymorphisms and risk of head and neck cancer: a case-control analysis. Carcinogenesis, 2000, 21(12): 2219-23.
[155] Brinckerhoff CE, Rutter JL, Benbow U. Interstitial collagenases as markers of tumor progression[J ] . Clin Cancer Res,2000, 6 (12) :4823-4830.
[156] Wang WW, Spurdle AB, Kolachana P, et al . A single nucleotide polymorphism in the 5′unt ranslated region of RAD51 and risk of cancer among BRCA1Π2 mutation carriers[J ] . Cancer Epidemiol Biomarkers Prev, 2001, 10 (9) :955-960.
[157] Kannan K, Munirajan AK, Bhuvarahamurthy V, et al . FHIT gene mutations and single nucleotide polymorphism in Indian oral and cervical squamous cell carcinomas[J ] . Oral Oncol,2000,36 (2) :189-193.
[158] Feigelson HS, Coetzee GA, Kolonel LN, et al . A polymorphism in the CYP17 gene increases the risk of breast cancer [J ] . Cancer Res,1997,57 (6) :1063-1065.
[159] Kuligina ES, Togo AV, Suspitsin EN, et al . CYP17 polymorphism in the groups of distinct breast cancer susceptibility : comparison of patients with thebilateral disease vs. monolateral breast cancer patients vs. middle2aged female cont rols vs. elderly tumor free women[J] . Cancer Lett, 2000, 156 (1) :45-50.
[160]袁芃,缪小平,张雪梅,等. DNA损伤修复基因XRCC1和XPD遗传多态与晚期NSCLC对铂类药物的敏感性[ J ].中华肿瘤杂志, 2006, 28 (3) : 196-199.
[161]袁芃,缪小平,张雪梅,等.核苷酸修故系统基因遗传多态与晚期NSCLC患者铂类药物敏感性的关系[ J ].癌症, 2005, 24(12) : 1510-1513.
[162] Rosell R, Tar on M, Ariza A, et al . Molecular p redict ors of response t o chemotherapy in lung cancer[ J ]. Semin Oncol, 2004,31 (1 Supp l 1) : 20-27.
[163] ZhouW, Gurubhagavatula S, Liu G, et al . Excision repair cross-complementati on group 1 polymor phis m p redicts overall survivalin advanced non2small cell lung cancer patients treated with platinum based chemotherapy[ J ]. Clin Cancer Res, 2004, 10 ( 15) :4939-4943.
[164] Camps C, Alonso G, de las Penas R, et al. XPD polymorphism in second-line treatment with gemcitabine or irinotecan in advanced non-small cell lung cancer (NCSLC) patients. Lung Cancer, 2005, 49(Suppl2):S118.
[165] Sarries C, Alberola V, Mendez P, et al. Single nucleotide polmorphisms (SNPs) in DNA repair genes predict survival in gemcitabine(gem)/cisplatin(cis)- treated non-small-cell lung cancer (NSCLC) patients. Proc Am Soc Clin Oncol, 2003, 22(5): 859-64.
[166] Zhou W, Gurubhagavatula S, Liu G, et al. Excision repair cross-complement- ation group 1 polymorphism predicts overall survival in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy. Clin Cancer Res, 2004,10(15):4939-43.
[167] Isla D, Sarries C, Rosell R, et al. Single nucleotide polymorphisms and outcome in docetaxel-cisplatin-treated advanced non-small-cell lung cancer. Ann Oncol, 2004, 15(8):1194-203.
[168] Ryu JS, Hong YC, Han HS, et al. Association between polymorphisms of ERCC1 and XPD and survival in non-small cell lung cancer patients treated with cisplatin combination chemotherapy. LungCancer, 2004,44(3):311-4.
[169] Wang D and Lippard SJ. Cellular processing of platinum anticancer drugs. NatRev Drug Discov, 2005 ,4(4):307-20.
[170] Jordana P, Carmo-Fonsecab M .Molecular mechanisms involved in cisplatin cytotoxicity. Cell Mol Life Sci, 2000,57 (8-9):1229–35.
[171] Rosell R, Lord RV, Taron M, et al. DNA repair and cisplatin resistance in non-small-cell lung cancer. Lung Cancer, 2002,38(3):217-27.
[172] Wang D, Hara R, Singh G, et al.Nucleotide excision repair from site- specifically platinum modified nucleosomes. Biochemistry, 2003, 42(22): 6747– 53.
[173] Furuta T.et al. Transcription-coupled nucleotide excision repair as a determinant of cisplatin sensitivity of human cells.Cancer Res, 2002,62(17): 4899–902.
[174] Riedl T, Hanaoka F and Egly JM. The comings and goings of nucleotide excision repair factors on damaged DNA. EMBO, 2003, 22(19):5293-303.
[175] Reardon JT and Sancar A. Molecular anatomy of the human excision nuclease assembled at sites of DNA damage. Mol Cell Bio, 2002, 22(16):5938-45.
[176] Fleck O and Nielsen O.DNA repair. J Cell Sci , 2004,117(Pt4): 515-7.
[177] Hutsell SQ and Sancar A. Nucleotide excision repair, oxidative damage, DNA sequence polymorphisms, and cancer treatment. Clin Cancer Res, 2005,11(4): 1355-7.
[178] Rosell R, Taron M, Camp s C, et al. Influence of genetic markers onsurvival in non2small cell lung cancer [ J ]. D rug Today (B arc),2003, 39 (10) : 775-786.
[179] van DuinM, KokenMH, van den Tol J, et al. Genomic characteriza2tion of the human DNA excision repair gene ERCC1 [ J ]. N ucleicAcids Res, 1987, 15 (22) : 9195-9213.
[180] Pfeiffer P, Qvortrup C and Eriksen JG. Current role of antibody therapy in patients with metastatic colorectal cancer. Oncogene, 2007, 26(25):3661-78.
[181] Park YH, Lee JL, Ryoo BY,et al. Capecitabine in combination with Oxaliplatin (XELOX) as a first-line therapy for advanced gastric cancer. Cancer Chemother Pharmacol, 2007 May 24; [Epub ahead of print].
[182] Socinski MA. Cytotoxic chemotherapy in advanced non-small cell lung cancer: a review of standard treatment paradigms. Clin Cancer Res, 2004,10(12 Pt 2):4210s-14s.
[183] Gonzalez VM, Fuertes MA, Alonso C, et al. Is cisplatin-induced cell death always produced by apoptosis ? Mol Pharmacol, 2001,59(4):657-63.
[184] Ferry KV, Hamilton TC and Johnson SW. Increased nucleotide excision repair in cisplatin-resistan to varian cancer cells: role of ERCCI-XPF. Biochem Pharmaco1, 2000, 60 (9):1305-131.
[185] Li Q,Y u J J, Mu C, et al. Association between the level of ERCC-1 expression and the repair of cisplatin-induced DNA damage in human ovarian cancer cells. Anticancer Res, 2000,20(2A):645-52.
[186] Li Q,Yu JJ,Mu C, et al.Sssociation between the level of ERCC1 expression and the repair of cisplatin-induced DNA damage in human ovarian cancer cells. Anticancer Res,2000,20(2A):645-652.
[187] Ferry KV, Hamilton TC,Johnson SW.Increased nucleotide excision repair in cisplatin-resistant ovarian cancer cells: role of ERCC1-XPF.Biochem Pharmacol, 2000,60(9):1305-1313.
[188].Selvakumaran M,Pisarcik DA, Bao R.Enhanced cisplatin cytotoxicity by disturbing the nucleotide excission repair pathway in ovarian cancer cell lines.Cancer Res, 2003,63(6):1311-1316.
[189] Takebayashi Y,Nakayama K,Kanazaki A,et al.Loss of heterozygosity of nucleotide excission repair factors in sporadic ovarian,colon and lung carcinomas:implication for their rolesof carcinogenesis in human solid tumors.Cancer Lett, 2001,174(2):115-125.
[190] Yun JJ,Bicher A,Ma YK,et al.Absence of evidence for allelic loss or allelic gain for ERCC1or for XPD in human ovarian cancer cells and tissues. Cancer Lett,2000,152(2):127-132.
[191] Ryu JS, Hong YC, Han HS, et al. Association between polymorphisms of ERCC1 and XPD and survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy. Lung Cancer 2004;44(3):311-316.
[192] Rosell R, Taron M, Ariza A, et al. Molecular predictors of response to chemotherapy in lung cancer. Semin Oncol 2004;31(1):20-27.
[193] Park DJ, Stoehlmacher J, Zhang W, et al. A Xeroderma pigmentosum group D gene polymorphism predicts clinical outcome to platinum-based chemotherapy in patients with advanced colorectal cancer. Cancer Res 2001;61(24):8654-8658.
[194] Sarries C, Alberola V, Mendez V, et al. Single nucleotide polymorphisms (SNPs) in DNA repair genes predict survival in gemcitabine (gem)/cisplatin (cis)-treated non-small-cell lung cancer (NSCLC) patients (P). Proc Am Soc Clin Oncol 2003;22: 859, (abstr 3450).
[195] Gurubhagavatula S, Liu G, Park S, et al. XPD and XRCC1 genetic polymorphisms are prognostic factors in advanced non-small-cell lung cancer patients treated with platinum chemotherapy. J Clin Oncol 2004;22(13):2594-2601.
[196] Shirota Y, Stoehlmacher J, Brabender J, et al. ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil Chemotherapy. J Clin Oncol 2001;19: 4298-4304.
[197] Lord RVN, Brabender J, Gandara D, et al. Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small-cell lung cancer. Clin Cancer Res 2002;8:2286-2291.
[198] Ryu JS, Hong YC, Han HS, et al. Association between polymorphisms of ERCC1 and XPD and survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy. Lung Cancer 2004;44(3):311-316.
[199] Yu JJ, Lee KB, Mu C, et al. Comparison of two human ovarian carcinoma cell lines (A2780/CP70 and MCAS) that are equally resistant to platinum, but differ at codon 118 of the ERCC1 gene. Int J Oncol 2000 Mar;16(3):555-560.
[200] Rosell R, Lord RV, Taron M, et al. DNA repair and cisplatin resistance in non-small-cell lung cancer. Lung cancer 2002;38:217-227.
[201] Sarries C, Haura EB, Roig B, et al. Pharmacogenomics strategies for developing customized chemotherapy in non-small cell lung cancer. Pharmacogenomics 2002;3(6):763-780.
[202] Wu X, Zhao H, WeiQ, et al . XPA polymorphism ass ociated with reduced lung cancer risk and a modulating effect on nucleotide excision repair capacity[ J ]. Carcinogenesis, 2003, 24 (3) : 5052 509.
[203]李金恒,陈冰.基金芯片及其在突变检测中的应用[ J ].医学研究生学报, 2005, 18 (1) : 54-58.
[204] Butkiewicz D, Rusin M, Harris CC, et al . I dentification of foursingle nucleotide polymor phisms in DNA repair genes : XPA and XPB ( ERCC3 ) in Polish population [ J ]. Hum Mutat, 2000, 15(6) : 577- 578.
[205]Ulla V, Kim O, Hakan W, et al . Combinations of polymorphisms in XPD, XPC and XPA in relati on t o risk of lung cancer [ J ].Cancer Letters, 2005, 222 (1) : 672 74.
[206] Monz o M, Brunet S, Urbano2Is p izua A, et al . Genomic polymorphisms provide p r ognostic infor mati on in inter mediate risk acute myeloblastic leukemia[ J ]. Blood, 2006, 107 (12) : 4871- 4879.
[207]孙新臣,孙宁,成红艳,等. XPA单核苷酸多态与晚期非小细胞肺癌对铂类药物化疗敏感性的相关性研究[ J ].2007,20(12)1271-1273.
[208] de Boer J, Hoeijmakers JH. Nucleotide excision repair and human syndromes . Carcinogenesis, 2000, 21: 453- 460.
[209] Sugasawa K,Shimizu Y,Lwai S,et al.A molecular mechanism for DNAdamage recognition by thexeroderma pigmetosum group C protein complex [J].DNA Repair,2002,1(1):95-107.
[210] Qiao Y, Sp itzMR, Shen H, et al . Modulation of repair of ultraviolet damage in the host2 cell reactivati on assay by polymor phic XPC and XPD /ERCC2 genotypes . Carcinogenesis, 2002, 23: 295- 299.
[211] Khan SG, Metter EJ, Tarone RE, et al . A new xeroderma pigmentosum group C poly (AT) insertion/ deletion polymorphism. Carcinogenesis,2000, 21 : 1821-1825.
[212] Qiao Y, Spitz MR, Shen H, et al . Modulation of repair of ultraviolet damage in the host2cell reactivation assay by polymorphic XPC and XPD/ERCC2genotypes. Carcinogenesis, 2002, 23 : 295-299.
[213] Rosell R, Taron M, Ariza A, et al. Molecular predictors of response to chemotherapy in lung cancer. Semin Oncol 2004;31(1):20-27.
[214] Hemminki K, Xu G, Angelini S, et al. XPD exon 10 and 23 polymorphisms and DNA repair in human skin in situ. Carcinogenesis 2001;22:1185-1188.
[215] Spitz MR, Wu X, Wang Y, et al. Modulation of nucleotide excision capacity by XPD polymorphisms in lung cancer patients. Cancer Res 2001;61:1354-1357.
[216] Sturgis EM, Zheng R, Li L, et al. XPD/ERCC2 polymorphisms and risk of head and neck cancer: a case-control analysis: Carcinogenesis 2000;21:2219-2223.
[217] Tomescu D, Kavanagh G, Ha T, et al. Nucleotide excision repair gene XPD polymorphisms and genetic predisposition to melanoma. Carcinogenesis 2001;22: 403-408.
[218] Park DJ, Stoehlmacher J, Zhang W, et al. A Xeroderma pigmentosum group D gene polymorphism predicts clinical outcome to platinum-based chemotherapy in patients with advanced colorectal cancer. Cancer Res 2001;61(24):8654-8658
[219] Sarries C, Alberola V, Mendez V, et al. Single nucleotide polymorphisms (SNPs) in DNA repair genes predict survival in gemcitabine (gem)/cisplatin (cis)-treated non-small-cell lung cancer (NSCLC) patients (P). Proc Am Soc Clin Oncol 2003;22: 859, (abstr 3450)
[220] Rosell R, Taron M, Camps C, et al. Influence of genetic markers on survival in non-small cell lung cancer. Drugs Today (Barc) 2003;39(10):775-786.
[221] Stoehlmacher J, Park DJ, Zhang W, et al. A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU/oxaliplatin combination chemotherapy in refractory colorectal cancer. Br J Cancer 2004;91(2):344-354.
[222] Gurubhagavatula S, Liu G, Park S, et al. XPD and XRCC1 genetic polymorphisms are prognostic factors in advanced non-small-cell lung cancer patients treated with platinum chemotherapy. J Clin Oncol 2004;22(13):2594-2601.
[223] Jeon HS, Kim KM, Park SH, et al. Relationship between XPG codon 1104 polymorphism and risk of primary lung cancer. Carcinogenesis2003;24(10):1677-1681.
[224] Vila JM, Moreno I, Monzo M, et al. XPD, XPA, ERCC1 and XPG/ERCC5 single nucleotide polymorphisms (SNPs) in oxaliplatin-treated colorectal cancer (CRC). Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). 2004;22:3677
[225] Stoehlmacher J, Park DJ, Zhang W, et al. A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU/oxaliplatin combination chemotherapy in refractory colorectal cancer. Br J Cancer, 2004, 91(2): 344-354.
[226] Gurubhagavatula S, Liu G, Park S, et al. XPD and XRCC1 genetic poly- morphisms are prognostic factors in advanced non-small-cell lung cancer patients treated with platinum chemotherapy. J Clin Oncol, 2004, 22(13):2594- 601.
[227]袁芃,缪小平,张雪梅,等.核苷酸切除修复基因遗传多态性与晚期非小细胞肺癌患者铂类药物敏感性的关系.癌症, 2005,24(12):1510-1513.
[1] Kelland LR. Preclinical perspectives on platinum resistance [J]. Drugs, 2000, 59(S4) : 1- 8.
[2]栾英姿,李力,黎丹戎,等.五种卵巢癌耐药细胞系的建立及其部分耐药相关基因的表达[J].中华妇产科杂志,2004,39(6):403-407.
[3] Rosell R, Lord RV, Taron M, et al. DNA repair and cisplatin resistance in non-small-cell lung cancer[J]. Lung cancer 2002;38:217-227.
[4] Nagasubramanian R, Innocenti F, RatainMJ, et al . Pharmacogenetics in cancer treatment[J]. Annu RevMed, 2003,54: 437 .
[5] Reed E . Platinum2 DNA adduct, nucleotide excisi on repair and platinum based anti-cancer chemotherapy[J] . Cancer Treat Rev, 1998, 24: 331
[6]Rosell R,Lorsd RV, Tar onM, et al . DNA repair and cisplatin resistance in non-small-cell lung cancer[J] . Lung cancer, 2002, 38: 217 .
[7] Stoehlmacher J, Park DJ, Zhang W, et al. A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU/oxaliplatin combination chemotherapy in refractory colorectal cancer[J]. Br J Cancer, 2004, 91(2): 344-354.
[8] Ryu JS, Hong YC, Han HS, et al. Association between polymorphisms of ERCC1 and XPD and survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy[J]. Lung Cancer 2004;44(3):311-316.
[9] Rosell R, Taron M, Ariza A, et al. Molecular predictors of response to chemotherapy in lung cancer[J]. Semin Oncol 2004;31(1):20-27.
[10] Park DJ, Stoehlmacher J, Zhang W, et al. A Xeroderma pigmentosum group D gene polymorphism predicts clinical outcome to platinum-based chemotherapy in patients with advanced colorectal cancer[J]. Cancer Res 2001;61(24):8654-8658.
[11]Kumar R, Hoglund L, Zhao C, et al.Single nucleotide polymorphisms in the XPG gene: determination of role in DNA repair and breast cancer risk[J]. Int J Cancer, 2003,103(5):671-675.
[12]Jeon HS, Kim KM, Park SH, et al. Relationship between XPG codon 1104 polymorphism and risk of primary lung cancer[J]. Carcinogenesis,2003, 24(10): 1677-1681.
[13] Jeon HS, Kim KM, Park SH, et al. Relationship between XPG codon 1104 polymorphism and risk of primary lung cancer[J]. Carcinogenesis 2003;24(10):1677-1681.
[14] Vila JM, Moreno I, Monzo M, et al. XPD, XPA, ERCC1 and XPG/ERCC5 single nucleotide polymorphisms (SNPs) in oxaliplatin-treated colorectal cancer (CRC) [J]. Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). 2004;22(11):3677-3681
[1] Angela Reles, Wen H. Wen, Annette Schmider,Correlation of p53 Mutations with Resistance to Platinum-based Chemotherapy and Shortened Survival in Ovarian Cancer[J]. Clinical Cancer Research, 2001,10(7) 2984-2997.
[2] Vesell ES: Advances in Pharmacogenetics and Pharmacogenomies[J].J Clin Pharmacol.2000,40:930-938.
[3] Evans WE, MeLeod HL: Pharmacogenomies-Drug disposition drug targets,and site effects[J].N Engl J Med.2003,348:538-549.
[4] McLeod HL, Evans WE: Pharmacogenomies: Unlocking the human genome for better drug therapy[J].Annu Rev Pharmao Toxicol.2001,41:101-121.
[5] Crawford DC; Akey DT; Nickerson DA.The patterns of natural variation in human genes.Annu [J].Rev.Genomics Hum.Genet.2005,6,287-312.
[6] Crawford DC; Nickerson DA.Definition and clinical importance of haplotypes[J]. Annu.Rev.Med.2005,56,303-320.
[7] Weng,W.K.;Levy,R.Two immunoglobulin G fragment C receptor Polymorphisms independently predict response to rituximab in Patients with follicular lymphoma[J].Clin.Oncol.2003,21,3940-3947.
[8] Evans,W.E.Pharmacogenetics of thiopurine S-methyltransferase and thiopurine therapy[J].Ther.Drug Monit.2004,26,186-191.
[9] Mcleod,H.L;King,C.R;Marsh,S.Application of pharmacogenomics in the individualization of chemotherapy for gastrointestinal malignancies[J]. Clin.Colorectal.Cancer. 2004,4,S43-47.
[10] Nagasubramanian R, Innocenti F, RatainMJ, et al . Pharma-cogenetics in cancer treat ment[J]. Annu RevMed, 2003,54: 437 .
[11] Reed E . Platinum-DNA adduct, nucleotide excision repair and platinum based anti-cancer chemotherapy[J]. CancerTreat Rev, 1998, 24: 331 .
[12] Rosell R,Lorsd RV, Tar onM, et al . DNA repair and cisplatin resistance in non2small2 cell lung cancer[J]. Lung cancer, 2002, 38: 217 .
[13] O’Donovan A,Dvaies AA,MoggsJG,et al. XPG endonuelease makes the 3’Incision in human DNA nueleotide exeision repair[J].Nature1994;371:432-435.
[14] Elnrnert S,Sehneider TD,Khan SG,Kraemer KH.The human XPG gene:Gene architecture , alternative splieing and single nueleotide Polymoprhisms[J].Nueleie.Aeids.Res.2001;29:1443-1452.
[15] MaeInnes MK,Diekson JA,Hernandez RR,et al.Human XPG cDNA-Cosmid complementation for excision repair and bipartite amino acid domains conserved with RAD proteins of Saccharomyecs cerevisiae and Sehzosac-charomyces Pombe[J].Mol.Cell.Biol.1993:13:6393-6402.
[16] Vila JM, Moreno I, Monzo M, et al. XPD, XPA, ERCC1 and XPG/XPG single nucleotide polymorphisms (SNPs) in oxaliplatin-treated colorectal cancer (CRC). Journal of Clinical Oncology[J]. 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). 2004;22(11):3677-3681.
[17] Mariano Monzo, Isabel Moreno, Alfons Navarro,et al. Single Nucleotide Polymorphisms in Nucleotide Excision Repair Genes XPA, XPD, XPG and ERCC1 in Advanced Colorectal Cancer Patients Treated with First-Line Oxaliplatin/Fluoropyrimidine[J]. Oncology 2007;72:364-370
[18] ShenMR, Jones I M,Mohrenweiser H. Nonconservative amino acid substituti on variants exist at polymor phic frequency in DNA repair genes in healthy humans[J]. Cancer Res, 1998, 58 (4) : 604- 608.
[1] Bernstein C,Bernstein H,Payne CM,et al.DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways:fail-safe protection against carcinogenesis [J].Mutat Res,2002,511(2):145-178.
[2] Wang D and Lippard SJ. Cellular processing of platinum anticancer drugs [J]. Nat Rev Drug Discov, 2005 ,4(4):307-320.
[3] Jordana P, Carmo-Fonsecab M .Molecular mechanisms involved in cisplatin cytotoxicity [J]. Cell Mol Life Sci, 2000,57 (8-9):1229–1235.
[4] Rosell R, Lord RV, Taron M, et al. DNA repair and cisplatin resistance in non-small-cell lung cancer [J]. Lung Cancer, 2002,38(3):217-227.
[5] Yuan P, Miao XP, Zhang XM, et al. Correlation of genetic polymor phisms in nucleotide excision repair system to sensitivity of advanced non-small cell lung cancer patients to p latinum2based chemotherapy [J]. A i Zheng, 2005, 24 (12) : 1510-1513.
[6] Juhani A. Vilp O, Leena M. An XPG DNA Repair Defect Causing Mutagen Hypersensitivityin Mouse Leukemia L1210 Cells [J]. Molecular and cellular biology,1995,15(1)290-297.
[7] Inusha U. De Silva, Peter J. Defects in interstrand cross link uncoupling do not account for the extreme sensitivity of ERCC1 and XPF cells to cisp latin [J]. N ucleic Acids Res, 2002, 30 (17) : 3848-3856.
[8] Wu H , Hait WN , Yang JM et al1 Small Interfering RNA induced Suppression of MDR1 ( P-Glycoprotein) Restores Sensi tivity to Multidrug resistant Cancer Cells [J] . Cancer Res , 2003 , 63 (4) : 1515- 1519.
[9]彭智,肖志坚,王一,等.siRNA逆转K562/ A02细胞多药耐药的研究[J] .中华血液学杂志, 2004 , 25 (1) : 5-7.
[10] Peng Z , Xiao Z , Wang Y, et al1 Reversal of P-glycoprotein mediated multidrug resistance wit h small interference RNA( siRNA) in leukemia cells [J] . Cancer Gene Ther , 2004 , 11(11) : 707-712.
[11] Yague E , Higgins CF , Raguz S 1 Complete reversal of multidrug resistance bystable expression of small interfering RNAstargeting MDR1 [J] . Gene Therapy 2004 , 11 ( 14 ) :1170-1174.
[12]李劲涛,杨军,张秀丽等。RNAi最新研究概况。细胞与分子免疫学杂志[J].2007, 23 (11):1077-1079.
[13] Bustin SA. Absolute quantification of mRNA using realtime reverse transcription polymerase chain reaction assays [J] . Mol Endocrinol , 2000 , 25 : 169.
[14] Furuta T,Ueda T,Aune G,er al.Transcription-coupled nucleotide excision repair as a determinant of cisplatin sensitivity of human cell [J].Cancer Res,2002,62(17):4899-4902
[15] Dabholkar M,Vionnet J,Bostick-Bruton F ,et al.Messenger RNA levels of XPAC and ERCC1 in ovarian cancer tissue correlate with response to platinum-bases chemotherapy [J].J Clin Investig,1994,94(2):703-708.
[16] Metzger R,Leichman CG,Danenberg K,et al.ERCC1 mRNA levels complement thymidylate synthase Mrna levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluororacil chemotherapy [J].J Clin Oncol,1998,16(1):309-316.
[17] Yang LY,Li L,Jiang H, et al.Expression of ERCC1 antisense RNA abrogates gemcitabine-mediated cytotoxic synergism with cisplatin in human colon tumor cells defective in mismatch repair but proficient in nucleotide excision repair [J].Clin.cance Res.2000,6(3):773-781.
[18] Ryu JS, Hong YC, Han HS, et al . Association between polymorphis ms of ERCC1 and XPD and survival in non2small2 cell lung cancer patients treated with cis p latin combinati on chemotherapy [J]. Lung Cancer , 2004, 44 (3) : 3112 316.
[19] Sakamoto M, Kondo A, Kawasaki K, et al. Analysis of gene expression profiles associated with cisplatin resistance in human ovarian cancer cell lines and tissues using cDNA microarray [J]. Brain Res Mol Brain Res. 2003 Nov 26;119(2):170-183.
[20] Stevens EV, Nishizuka S, Antony S et al.Predicting cisplatin and trabectedin drug sensitivity in ovarian and colon cancers [J]. 2008 Jan;7(1):10-8. Epub 2008 Jan9.
[21] Ahmad H,Wilson DE,Fritz RR,etc.Primary and secondary structural analyses of glutathione Stransferase pifrom human placenta[J].Arch Biochem Biophys,1990,278(2):398-399.
[22] Christine S. Walsh, Seishi Ogawa, et al.XPG Is a Novel Biomarker of Ovarian Cancer Prognosis [J]. Journal of Clinical Oncology . 2008,26(18)2952-2958.
[2] McGuire v, Whittemore AS,NorrisR,et al.Survival in ePithelial ovarian cancer Patients with Prior breast cancor.Am J EPidemiol 2000;152(6):528-32.
[3] Cancer Facts and Figures一1996,Atlanta,American Cancer Society,1996.
[4]郑怀美主编.妇产科学(第三版),北京:人民卫生出版社1992:292-309.
[5 ] M cGuire W P,Ho sk ins WJ, B rady M F,et al .Cyclopho spham ide and cisp lat in compared w ith paclitaxel and cisp lat in in pat ients w ith stageⅢand stageⅣovarian cancer [J ] . N Engl J M ed,1996,334(1) :1- 6 .
[6 ] Bookman MA, Greer BE,O zo ls RF. Optimal therapy of advanced ovar ian cancer:carboplat in and paclitaxel vs cisplat in and paclitaxel (GO G 158) and an update on GO G0 1822ICON 5 [J ] . Int J Gyneco l Cancer,2003,13 (6) :735- 740 .
[7 ] Pf isterer J, W eber B,Reuss A, et al . Randomized phaseⅢtrial of topo tecan following carboplat in and paclitaxel in first line treatment of advanced ovariancancer:a gynecologic cancer intergroup trial of the AGO-OVAR and GI N ECO [J ] . J N at l Cancer Inst,2006,98 (15) :1036- 1045 .
[8]张覃沐,许长江,张予等.多药抗药性产生机制[M].中国药理学通报,1994,10(4): 246-249.
[9] Avendano C,Menendez JC.Inhibitors of multidrug resistance to antitumor agents (MDR).Curr Med Chem 2002;9(2):159-193
[10] Gottesman MM,Fojo T,Betas SE.Multidrug resistance in cancer:role of ATP- dependent transporters.Nat Rev Cancer 2002,2(1):48-58.
[11] Biedler JL.Genetic aspetcs of multidrug resistance.Cancer. 1992,70:1799.
[12] Kamazawa S,Kigawa J,Kanamori Y,etc. Multidrug resistance gene-1 is a useful predictor of Paclitaxel-based chemotherapy for patients with ovarian cancer. Gynecol Oncol. ,2002,86(2):171-176.
[13] Xing H,Wang S,Weng D,etc.Knock-down of P-glycoprotein reverses taxol resistance in ovarian cancer multicellar spheroids.Oncol Rep,2007,17(1): 117-122.
[14] Yang X,Zheng F,Xing H,etc.Resistance to chemotherapy-induced apotosis via decreased caspase-3 activity and overexpression of antiapoptotic protein in ovarian cancer.J Cancer Res Clin Oncol,2004,130(7):423-428.
[15] Yang HH,Ma MH,vescio RA,Berenson JR.Overcoming drugresistance in multiple myeloma:the emergence of therapeutic approaches to induce apoptosis.J Clin Oncol,2003,21(22):4239-4247.
[16] Shen F,Chu S,Bence AK,etc. Quantitation of doxorubicin uptake,efflux and modulation of multidrug resistance (MDR) in MDR human cancer cells. J Pharmacol Exp Ther.,2007,18(9):1523.
[17] Johnson DR, Finch RA,Lin ZP, et al . The pharmacological phenotype of combined multidrug resistance mdr1a/ 1b and mrp1 deficientmice[J ] . Cancer Res,2001,61 (4) :1469-1476.
[18] Larsen A K,Escargueil AE,Skladanowski A. Resistance mechanisms associated with altered intracellular distribution of anticancer agents[J] . Pharmacol Ther,2000,85 (3) :217-229.
[19] Jia P , Wu SB , Li F , et al . The mechanism of topotecan resistance in ovarian cancer cell line[J]. Zhonghua Zhong Liu Za Zhi , 2004 , 26(3) : 139-142.
[20]唐海桦,梁钢.肺耐药相关蛋白的研究进展[J]..2008,14(3)462-464.
[21] Ahmad H,Wilson DE,Fritz RR,etc.Primary and secondary structural analysesof glutathione Stransferase pifrom human placenta[J].Arch Biochem Biophys,1990,278(2):398-399.
[22] Goto S,Kamada K,Soh Y,etc.Significance of nuclear glutathione-S- transferase pi in resistance to anti-cancer drugs[J].Jpn J Cancer Res,2002,93(9):1047-1056.
[23] Nagle CM,Chenevix-Trench G,Spurdle AB,etc.The role of glutathione -S-transferase polymorphisms in ovarian cancer survival[J]. Eur J Cancer.,2007,43(2): 283-90.
[24]刘智鑫,刘国津.人非小细胞肺癌细胞药物敏感性检测及其与耐药因子p53抗体和GST2 -π表达的关系[J]..吉林大学学报(医学版) , 2005, 31 (5) : 795- 798.
[25]马荣,陈曦海,唐丽萍等.survivin反义核酸诱导卵巢癌细胞凋亡及逆转多西他赛耐药机制的实验研究[J] .第四军医大学学报,2006, 27(17):1616-1619.
[26] Ferry KV, Hamilton TC and Johnson SW. Increased nucleotide excision repair in cisplatin-resistan to varian cancer cells: role of ERCCI-XPF[J].. Biochem Pharmaco1, 2000, 60 (9):1305-131.
[27] Li Q,Y u J J, Mu C, et al. Association between the level of ERCC-1 expression and the repair of cisplatin-induced DNA damage in human ovarian cancer cells[J].. Anticancer Res, 2000,20(2A):645-52.
[28] Fine RL,Chambers TC,Sachs CW. P-glycoprotein,multidrug resistance and protein kinase C[J]. Stem Cells 1996;14,47-55.
[29] Gollapudi S,Soni V,Thadepalli H,et al . Gupta S. Role of protein kinase beta isozyme in multidrug resistance[J]. Journal of Chemotherapy,1995;7:157–159.
[30] Gupta KP,Ward NE, Gravitt KR,et al . Partial reversal of multidrug resistance in human breast cancer cells [J]. J Biol Chem,1996 ;271:2102-2111.
[31]金晶,吴绪峰,陈惠祯. P - g p、PKC -α和MRP在上皮性卵巢癌中的表达及其临床意义.现代肿瘤医学,2006,14(3)325-329.
[32] Trieb K,Kotz R. Proteins expressed in osteosarcoma and serum levels as prognostic factors[J].Int J Biochem Cell Biol,2001 ;33 :11-17.
[33] Bert ram J, Palfner K,Hiddemann W,er al.Increase of P-glycoprotein-mediated drug resistance byhsp90beta[J].Anticancer Drugs,1996;7:838-845.
[34] Vilaboa NE, Galan A, Troyano A,et al . Regulation of multidrug resistance 1 (MDR1)/P-glycoprotein gene expression and activity by heat-shock transcription factor 1 (HSF1) [J].J Biol Chem,2000;275:24970-24976.
[35] Kim SH,Yeo GS,Lim YS,et al . Suppression of multidrug resistance via inhibition of heat shock factor by quercetin in MDR cells[J].Exp Mol Med,1998 ;30(2):87-92.
[36] Schneider J , Miller GA , Wiemann MC , et al . Co2expression of theMDRI gene and hsp27 in human ovarian cancer[J]. Anticancer Res ,1998 , 18 (4c) :2967
[37] Chie L,Amar S,Kung HF,et al . Cancer Chemo Pharm,2000 ;45 :441-449
[38] Zilfou J T,et al . The molecular alterations of tumor suppressor genes p16INK4a and p15INK4b in human esophageal cancer[J]. Proc Am Assoc Cancer Res,1998;39.
[39] Serrone L,Horsey P. The chemoresistance of human malignant melanoma: an update[J].Melanoma Res,1999 ;9 :51-58.
[40] Tsuruo T,Nato M.Tomida A,etc.Molecular targeting t herapy of cancer:drug resistance,apoptosis and survival signa[J].Cancer Sci,2003,94(1):15-21.
[41] Fabbro D,Ruetz S,Bodis S,etc.PKC412 - a protein kinase in hibitorwith a broad therapeutic potential[J].Anti-cancerDrug Des,2000,15(1):17-28.
[42] Esteve MA, Carre M, Bourgarel-Rey V,etc. Bcl-2 down-regulation and tubulin subtype composition are involved in resistance of ovarian cancer cells to vinflunine. Mol Cancer Ther,2006,5(11):2824-33.
[43] Chekhun VE,Lukyanova NY,Urchenko OV,etc.Exp Oncol,2005,27(3):191-195.
[44] Witham J,Valenti MR,DeHavenBrandon AK,etc.The bcl-2/bcl-xl family inhibitor abt-737 sensitizes ovarian cancer cell to carboplatin.Clin Cancer Res,2007,13(23):7191-7198.
[45] Bharti AC,Aggarwal BB.Nuclear factor-kappa B and cancer:Its role in p revention and therapy[J].Biochem Pharmacol,2002,4 (526):83-88.
[46] Taylor DD,Metzinger DS,Gercel TC,Induction of p53 and drug resistancefollowing treatment with cisplatin or paclitaxel in ovarian cancer cell lines. Cancer Lett.2006,236 (2):302-308.
[47] Thigpen JT.The role of gemcitabine in first-line treatment of advanced ovarian malignant . Semin Oncol. 2006;33(2):S26-32.
[48] Goonewardene TI,Hall MR,Rustin GJ.Management of asymptomatic patients on follow-up for ovarian cancer with rising CA125 concentrations.Lancet Oncol. 2007,(9):813-821.
[49] Coleman RL,Gordon A,Barter J,etc. Early changes in CA125 after treatment with pegylated liposomal doxorubicin or topotecan do not always refletc best response in recurrent ovarian cancer patients. Oncologist.,2007,12(1):72-78.
[50] Gossner G,Coleman RL,Mutch DG,etc. CA125 response in patients with recurrent ovarian or primary peritoneal cancer treated with pegylated liposomal doxorubicin or topotecan.Gynecol Oncol..2006,103(1):212-218.
[51] Goonewardene TI,Hall MR,Rustin GJ.Management of asymptomatio patients on follow-up for ovarian cancer with rising CA125 concentrations.Lancet Oncol,2007,8(9):813-821
[52] Gadducci C.The concomitan detemination of different tumor marker on patients with epithelial ovarian cancer and benigh ovarian masses relevance for differential diagosis.Gynecol Oncol,1992,44(2):147.
[53] Yakirevich E,Sabo E,Naroditsky I,etc. Multidrug resistance- related phenotype and apoptosis-related protein expression in ovarian serous malignant s.Gynecol Oncol.,2006,100(1):152-159.
[54] Krasznai ZT , Friedlander E , Nagy A , etc.Quantitative and functional assay of MDR1/P170-mediated MDR in ascites cells of patients with ovarian cancer. Anticancer Res.,2005,25(2A):1187-1192.
[55] Rappa G,Finch RA,Sartrelli AC,etc.New insights into the biologyand pharmacology of the multidrug resistance protein (MRP) from geneknockout models.Biochem Pharmacol,1999,58(40):557-562.
[56] Nooter K,Mulder NH,Smith AJ,etc.Expression of mrp gene in human cancer.Clin CancerRes,1999,1:1301.
[57] Kolfschoten GM,Hulscher TM,Pinedo HM,etc.Drug resistancefeatures and S-phase fraction as possible determinants for drug responsein a panel of human ovarian cancer xenografts[J ] .Br J Cancer,2000,83(7):921-927.
[58] Qian XL,Peng ZL,Liu SL,etc.Expreeion of lung resistant-related protein in ovarian cancer and its clinical significance.Ai Zheng,2002,21(12):1332-1334.
[59]李文通,周庚寅,宋现让等.表达BCRP的卵巢癌耐药细胞系3AO/BCRP的建立及其生物学特征[J].基础医学与临床,2006,26(1):61-65.
[60] Beeghly A,Katsaros D,Chen H,etc.Glutathione S-transferase polymorphisms and ovarian cancer treatment and survival.Gynecol Oncol,2006,100(2):330-337.
[61]崔恒,钱和年.卵巢癌生物治疗的研究进展[J].中华妇产科杂志,2002,37 (4):193.
[62] Torre FJ,Garcia A,Gil-Moreno A,etc. Apoptosis in epithelial ovarian tumours Prognostic significance of clinical and histopathologic factors and its association with the immunohistochemical expression of apoptotic regulatory proteins (p53, bcl-2 and bax). Eur J Obstet Gynecol Reprod Biol,2007,130(1):121-128.
[63] WilliiamsJ,Lucas PC,Griffith KA,etc.Expression of BCL-XL in ovarian malignant is associated with chemoresistance and recurrent disease.Gynecol Oncol,2005,96(2):287- 295.
[64] Kim R,Emi M,Tanabe K,etc.Therapeutic potential of antisense Bcl-2 as a chemosensitizer for cancer therapy . Cancer,2004,101(11):2491-2502.
[65] Cloven NG,kyshtoobayeva A,Burger RA,etc.Invirto chemoresistance and biomarker profiles are unigue for histologic subtypes of epithelial ovarian cancer. Gynecol Oncol,2004,92(1):160-166.
[66] Lesperance S,Popa I,Bachvarova M,etc.Gene expression profiling of paried ovarian tumors obtained prior to and following adjuvant chemotherapy: molecular signatures of chemoresistant tumor.Int J Oncol,2006,29(1):5-24.
[67] Santin AD,Zhan F,BelloneS,etc.Discrimination between uterine serous papillary malignant s and ovarian serous papillary tumours by gene experessi- on profiling.Br J Cancer,2004,90(9):1814-1812.
[68] Sasaki N,Kudoh K,Kita T,etc.Effetc of HER-2/neu overexpreeion onchemoresistance and prognosis in ovarian malignant .J Obstet Gynaecol Res,2007,33(1):17-23.
[69] Scartozzi M,De Nictolis M,Galizia E,etc.Loss of Hmlhi expression corre- lates with improved survival in stage III-IV ovarian cancer patients Eur J Cancer,2003,39:1144-1149.
[70] Gifford G,Paul J,Vasey PA,etc. The acquisition of hMLH1 methylation in plasma DNA after chemotherapy predicts poor survival for ovarian cancer patients. , 2004,10(13):4420-4426.
[71] Helleman J,van Staveren IL,Dinjens WN,etc. Mismatch repair and treatment resistance in ovarian cancer. BMC Cancer,2006,31(6):201.
[72] Nakayama K,Kanzaki A,Ogawa K,etc.Copper-transporting P-type adenosine triphosphatase (ATP7B) as a cisplatin based chemoresistance marker in ovarian malignant : comparative analysis with expression of MDR1, MRP1, MRP2, LRP and BCRP. Int J Cancer.,2002,101(5):488-495.
[73] Raspollini MR,Amunni G,Villanucci A,etc. Analysis in ovarian malignant patients with low and high survival. Int J Gynecol Cance- r,2005,15(2):255-260.
[74] Ferrandia G,Ranelletti FO,Martinelli E,etc.Cyclo-oxygenase-2(Cox-2) expreeion and resistance to platinum versus platinum/paclitaxal containing chemotherapy in advanced ovarian cancer.BMC Cancer,2006,6:182.
[75] Obata H,Yahata T,Quan J,etc Association between single nucleotide polymorphisms of drug resistance-associated genes and response to chemotherapy in advanced ovarian cancer. Anticancer Res.,2006,26(3B): 2227-2232.
[76] Ikeda K,Sakai K,Yamamoto R,etc. Multivariate analysis for prognostic significance of histologic subtype, GST-pi, MDR-1, and p53 in stages II-IV ovarian cancer. Int J Gynecol Cancer, 2003,13(6):776-784.
[77] Naniwa J,Kigawa J,Kanamori Y,etc.Genetic diagnosis for chemosen- sitivity with drug-resistance genes in epithelial ovarian cancer. Int J Gynecol Cancer, 2007,17(1):76-82.
[78] Marsh S,Paul J,King CR.Pharmacogenetic assessment of toxicity and outcome after platinum plus taxane chemotherapy in ovarian cancer:the scottishrandomised trial in ovarian cancer.J Clin Oncol,2007,25(29):4513-4515.
[79]张覃沐,许长江,张予等.多药抗药性产生机制[M].中国药理学通报,1994,10(4): 246-249.
[80] Klopman G,Shi LM, Ramu A. Quantitative structure-activity relationship of multidrug resistance reversal agent s [ J] . Mol Pharmacol, 1997,52 (2) :323-334.
[81]马强,张振书.中药逆转肿瘤多药耐药研究进展[J] .湖南中医学院学报,2002, 22 (4) :70-72.
[82]靳英.周庚寅.张廷国.植物多酚类化合物逆转肿瘤多药耐药的筛选[J] .山东大学学报(医学版),2002, (6) :497-499.
[83] Fung-Kee-Fung M,Oliver T,Elit L,etc.Optional chemotherapy treatment for women with recurrent ovarian cancer.Curr Oncol.2007; 14(5):195-208.
[84] Forbes C,Shirran L,Bagnall AM,etc.A rapid and systematic review of the clinical effetciveness and cost-effetciveness of topotecan for ovarian cancer.Health Technology Assessment,2001,5(28):23785-23793.
[85] Thigpen JT,Aghajanian CA,Albert DS,etc.Role of pegylated liposomal doxorubicin in ovarian cancer.Gynecol Oncol,2005,96:10-18.
[86] Zalipsky S,Saad M,Kiwan R,etc.Antitumor activity of new liposomal prodrug of mitomycin C in multidrug resistant solid tumor:insights of the mechianism of action.J Drug Target.2007;15(7-8):518-530.
[87] Verborg WA,Campbell LR,Highley MS,etc.Weekly cisplatin with oral epoposide:a well-tolerated and highly effetcive regimen in relapsed ovarian cancer.Int J Gynecol Cancer,2007,May 19 [Epub ahead of print].
[89] Garcia AA,Oza AM,Hirte H,etc.Interim report ofa phaseⅡclinical trial of bevacizumab(Bev) and low dose metronomic oral cyclophosphamide(mCTX) in recurrent ovarian (OC) and primary peritoneal malignant :A California Cancer Consortium Trial.J Clin Oncol(Meeting Abstracts),2005,23: 50000.
[90] Aport GG,Fleming GF,Waggoner S,et al. Progenitor cell mobilization A phase II trial of docetaxel for peripheral blood stem cellmobilization for patients withbreast cancer and ovarian cancer [ J] .Bone MarrowTransplant,2001,27(7):677- 681.
[91] Viret F,Bertucci F,Genre D,et al. Intensive sequential dose dense chemotherapy with stem cell support as first - line treatment in advanced ovarian carcinoma:a phaseⅡstudy[ J] . Bone Marrow Transplant,2002,30(12):879- 884.
[92] Frickhofen N,Berdel WE,Opri F,et al. Ovarian cancer side population defines cells with stemcell- like characteristics and Mullerian Inhibiting Substance responsiveness[ J] . Proc Natl Acad Sci U S A,2006,103 (30):11154- 11159.
[93] Sehouli J,Stengel D,Oskay G,et al. A newtherapeutical approach:topotecan plus gemcitabine in the treatment of patients with relapsed ovarian cancer after failure of first- line chemotherapywith paclitaxel andplatinum[ J] . ObstetGynaecolRes, 2003,29(3) :123- 131.
[94] Miller DS,Blessing JA,Lentz SS,et al. PhaseⅡevaluation of three- day topotecan in recurrent platinum- sensitive ovarian carcinoma:a gynecologic oncology group study [ J] . Cancer,2003,98(8):1664- 1669.
[95] Rodriguez M,Rose G. Improved therapeutic index of lower dose topotecan chemotherapy in recurrent ovarian cancer [ J] . Gynecol Oncol,2001,83(2):257- 262.
[96] DenchlagD,Watermann D,H rigK,et al. Topotecan as a continuous infusion over 14 days in recurrent ovarian cancer patients [ J] .Anticancer Res,2004,24(2):1267- 1269.
[97] Tiersten A,Selleck M,Smith DH,et al. Phase I/II study of tandem cycles of high - dose chemotherapy followed by autologoushematopoietic stem cell support in women with advanced ovarian cancer[ J] . Int J Gynecol Cancer,2006,16(1):57- 64.
[98] Ferrandina G,Pierelli L,Perillo A,et al. Lymphocyte recovery in advanced ovarian cancer patients after high- dose chemotherapy and peripheral blood stemcell plus growth factor support:Clinical Impli-cations[ J] . Clin Cancer Res,2003,9(1):195- 200.
[99] DonatoML,Aleman A,Champlin RE,et al. Analysis of 96 patients with advanced ovarian carcinoma treated with high - dose chemo-therapy and autologous stemcell transplantation[ J] . Bone MarrowTransplant,2004,33(12):1219- 1224.
[100] Stiff PJ,Shpall EJ,Liu PY,et al. Randomized phase II trial of two high- dose chemotherapy regimens with stemcell transplantation for the treatment of advanced ovarian cancer in first remission or chemosensitive relapse:a Southwest Oncology Group study [ J] .Gynecol Oncol,2004,94(1):98- 106.
[101] Stiff PJ,Veum- Stone J,Lazarus HM,et al. High- dose chemotherapy and autologous stem- cell transplantation for ovarian cancer:an autologous blood and marrowtransplant registry report[ J] . Ann Intern Med,2000,133 (7):504- 515.
[102] Ward M, Richardson C, Pioli P, et al . Transfer and expression of t he human multiple drug resistance gene in human CD34 +cells[ J] . B lood, 1994,84 (5) :1408-1414.
[103] Hanania EG,Fu S, Zu Z, Chemot herapy resistance to taxol in clonogenic progenitor cells following t ransduction of CD34 selected marrow and peripheral blood cells wit h a ret rovirus t hat contains t he MDR21 chemot herapy resistance gene[ J] . Gene Ther, 1995,2 (4) :285-294.
[104]陈良安.多药耐药基因增强骨髓细胞对抗癌药物毒性的抵御能力[ J] .中华肿瘤杂志,2000,6 :389-392 .
[105] Motomura S, Motoji T, Takanashi M, et al . Inhibition of Pglycoprotein and recovery of drug sensitivity of human acuteleukemic blast cells by multidrug resistance gene (mdr1) antisense oligonucleotides[ J] . B lood, 1998,91 (9) :3163-3171.
[106] Li Y,Wang Y. Inhibition growt h of multidrug resistant KBV200 cells by MDR1 antisense RNA[ J] . B iochem B iophys Res Commun, 1997,239 (1) :345-348.
[107]高鹏,周庚寅,殷钢,等.负向调节多药耐药基因1转录逆转肿瘤细胞多药耐药[ J] .中华病理学杂志,2003, 32 ( 6) :563-566.
[108 ] Mat sumoto Y,Takano H, Nagao S, et al . Altered topoisomerase IIalpha and multidrug resistance2associated protein levels during drug selection :adaptations to increasing drug pressure[ J] . J pn J Cancer Res, 2001,92 (9) :968-974.
[109] Yang JM, Chin KV, Hait WN. Interaction of P2glycoprotein with protein kinase C in human multidrug resistant carcinoma cells[ J] . Cancer Res, 1996,56 (15) :3490-3494.
[110] Osada H, Tokunaga T, Abe Y,et al . Reversal of drug resistance mediated by hammerhead ribozyme against multidrug resistance associated protein 1 in a human glioma cell line[ J] . I nt J Oncol, 2003,22 (4) :823-827.
[111] Scanlon KJ, Ishida H, Kashani2Sabet M. Ribozyme mediatedreversal of the multidrug-resistant phenotype [J] . Proc N at lA cad Sci U S A, 1994,91 (23) :11123211127.
[112] Keit h FJ, Bradbury DA, Zhu YM, et al . Inhibition of bcl-2 with antisense oligonucleotides induces apoptosis and increases the sensitivity of AML blast s to Ara2C[ J] . L eukemia,1995,9(1) :131-138.
[113] Huang Y,Ibrado AM, Reed JC, et al . Co2expression of several molecular mechanisms of multidrug resistance and t heir significance for paclitaxel cytotoxicity in human AML HL260 cell s[ J] . L eukemia, 1997,11 (2) :253-257.
[114] Sumant ran VN, Lee DS, Woods Ignatoski KM, et al . A bcl2xS adenovirus selectively induces apoptosis in t ransformed cell scompared to normal mammary cells[ J] . Neoplasia, 2000,2(3) :251-260.
[115] Ikeda K,Sakai K,Yamamoto R, et al . Multivariate analysis for prognostic significance of histologic subtype, GST2pi, MDR21, and p53 in stages II2IV ovarian cancer[ J] . I nt J Gynecol Cancer, 2003,13 (6) :776-784.
[116] Stein U, Walt her W, Shoemaker RH. Modulation of mdr1 expression by cytokines in human colon carcinoma cells :an ap2proach for reversal ofmultidrug resistance [ J] . B r J Cancer,1996,74 (9) :1384-1391.
[117]郝权,田菁.卵巢癌靶向治疗研究进展[J].中国肿瘤临床,2005 ,32(22):1315-1318.
[118] Kramm CM,Niehues T,Rainow NG.Experinental stragies for combined suicide and immune cancer gene therapy.An overview.Methods Mol Biol,2003,215(6): 137-152.
[119] Segota E,Bukowshi RM.The promise of targeted therapy cancer drugs become more specific.Cleve Clin Jmed,2004,71(7):551-560.
[120]Mcquarrie SA,Mercer JR,Syeme A,etc.Prelininary results of nanophamaceuticals used in the radioimmunotherapy of ovarian cancer,Jpham Phamaceut Sci,2004,7(4):29-34.
[121] Menendez JA,Vellon L,Mehmi I,etc.Inhibition of fatty acid synthase (FAS) suppresses HER2/neu (erbB-2) oncogene overpression in cancer cell.PNAS,2004,101(29):10715 -10712.
[122] Disis ML,Schifman K,Guthrie K,etc.Effetc of dose on immune response in patients vaccinated with an her-2/neu intracellular domainprotein-based vaccine.J Clin Oncol,2004,22(10):1916-1925.
[123] Curiel TJ,Cheng P,Mottram P,etc.Dendritic cell subsets differentially regulate angiogenesis in human ovarian cancer. 2007;18(5): 511-517.
[124] Xie SZ,Wang J,Li DZ,etc.Medroxprogesterone acetate therapy against antiangiogenesis of translanted ovarian cancer in nude mice.Di Yi Jun Yi Da Xue Xue Bao,2004,24(7):821-823.
[125] Chen HH,Zhou HJ,Fang X.Inhibition of human cancer cell linee growth and human umbillical vein endothelial cell angiogenesis by artemisin inderivatives invitro.Phamacol Res,2003,48(3):231-236.
[126] Mahendra G,Kumar S,Isayeva T,etc.Antiangiogenic cancer gene therapy by adeno-associated virus 2-mediated stable expression of the soluble FMS-like tyrosine kinase-1 receptor.Cancer Gene Ther,2005,12(1):26-34.
[127] Markowska J,Azala S.Inhibitors of angiogenesis in therapy of ovarian cancer.Eur J Gynaecol Oncol,2004,25(5):562-567.
[128] Fehrmann RS,Li XY,Van der ZEE AG,etc.Profiling studies in ovarian cancer:a review.Oncologist,2007,12(8):190-196.
[129] Alberts DS.Treatment of refractory and recurrent ovarian cancer.Semin Oncol. 1999,26(4):8-14.
[130]连丽娟.林巧稚妇科肿瘤学.第4版.北京:人民教育出版社,2006,581.
[131] FungKeeFung M,Oliver T,Elit L.etc.Optimal chemotherapy treatment for women with recurrent ovarian cancer.Curr Oncol,2007,14(5):195-208.
[132] Pignata S,Scambia G,Savarese A,etc.Safety of a 3-weekly schedule of carboplatin plus peghylated liposomal doxorubicin as first line chemotherapy in patients with ovarian cancer:prelimiary results of the MITO-2 randomized trial.BMC Cancer,2006,6:202-210.
[133] Alberts DS,Liu PY,Wilczvnski SP,etc.Randomized trial of pegylated liposomal doxorubucin(PLD) plus carboplation versus carboplatin in platinum-sensitive(PS) patients with recurrent epithelial ovarian or peritoneal malignant after failure of initial platinum-based chemotherapy (Southwest Oncology Group Protocol S0200).Gynecol Oncol,2007,0ct 17[Epub ahead of print].
[134] Chasman D and Adams RM. Predicting the functional consequence of non- synonymous single nucleotide polymorphism: structure-based assessment of aminoacid variation . J Mol Biol, 2001,307(2):683-706.
[135] Bertin I, Zhu J H, Gale M D. SSCP-SNP in pearl millet—a new maker system for comparative genetics [J].Theoretical and Applied Genetics,2005,110:1467- 1472.
[136]张小燕,左明雪,张占军,等.用基因芯片检测单核苷酸多态性反应原理[J].中国生物工程杂志,2005,25(11):52-56.
[137]刘雅诚,郝金萍,严江伟,等.用dHPLC技术检测线粒体DNA编码区单核苷酸多态性[J].中国法医学杂志,2006,21(3):142-146.
[138]秦效英,李国选,江滨,等.应用变性高效液相色谱检测CD31563位点单核苷酸多态性[J].中华检验医学杂志,2006,29(7):627-630.
[139] Han W, Yip S P, Wang J, et al. Using denaturing HPLC for SNP discovery andestablishing the linkage disequilibrium pattern for the all-trans-retinol dehydrogenase (RDH8) gene [J].Journal of Human Genetics,2004,49:16-23.
[140] Karas M, Hillenkamp F. Laser desorption ionization of proteins with molecular masses exceeding 10000 daltons [J]. Analysis Chemistry, 1989,60:2299-2301.
[141] Sauer S. Gut I G.Genotyping single-nucleotide polymorphisms by ma-trix- assisted laser desorption/ionization time of flight mass spectrometry[J]. Journal of Chromatography B-Analtical Technologies in the Biomedical and Life Science,2002,782(1-2):73-87.
[142]刁现民,Damon L. Mutator转座子及MULE在植物基因与基因组进化中的作用[J].遗传学报,2006,33(6)477-487.
[143]卫波,景蕊莲,王成社,等.用等位基因特异PCR检测普通小麦( Triticum aestivum L.)的单核苷酸多态性[J].中国农业科学,2006,39(7): 1313-1320.
[144]单志新,谭虹虹,余细勇,等.基于荧光定量PCR扩增反应的SNP测定法[J].中国生物化学与分子生物学报,2005,21(6):827-830.
[145] Levy Lahad E, Lahad A, Eisenberg S, et al . A single nucleotide polymorphism in the RAD51 gene modifies cancer risk in BRCA2 but not BRCA1 carriers[J ] . Proc Natl Acad Sci USA,2001,98 (6) :3232-3236.
[146] Wang WW, Spurdle AB, Kolachana P, et al . A single nucleotide polymorphism in the 5′unt ranslated region of RAD51 and risk of cancer among BRCA1Π2 mutation carriers[J ] . Cancer Epidemiol Biomarkers Prev, 2001, 10 (9) :955-960.
[147] McCarron SL, Edwards S, Evans PR, et al . Influence of cytokine gene polymorphisms on the development of prostate cancer [ J ] .Cancer Res, 2002, 62 (12) :3369-3372.
[148] Quintela-Fandino M,Hitt R, Medina PP, et al. DNA-repair gene polymorphisms predict favorable clinical outcome among patients with advanced squamous cell carcinoma of the head and neck treated with cisplatin-based induction chemotherapy. J Clin Oncol. 2006,24(26):4333-9.
[149] Isla D, Sarries C, Rosell R, et al. Single nucleotide polymorphisms and outcomein docetaxel-cisplatin-treated advanced non-small-cell lung cancer. Ann Oncol, 2004, 15(8): 1194-203.
[150] Butkiewicz D, Rusin M, Enewold L, et al. Genetic polymorphisms in DNA repair genes and risk of lung cancer. Carcinogenesis, 2001,22(4):593-7.
[151] Liang G, Xing D, Miao X, et al. Sequence variations in the DNA repairs gene XPD and risk of lung cancer in a Chinese population. Int J Cancer, 2003, 105(5): 669-673.
[152] Blankenburg S, Konig IR,Moessner R,et al. Assessment of 3 xeroderma pigmentosum group C gene polymorphisms and risk of cutaneous melanoma: a case–control study. Carcinogenesis, 2005, 26(6): 1085-90.
[153] Moreno V, Gemignani F, Landi S, et al. Polymorphisms in genes of nucleotide and base excision repair: risk and prognosis of colorectal cancer. Clin Cancer Res, 2006,12(7 Pt 1):2101-8.
[154] Storgis FM, Zheng R, Castillo EJ, et al. XPD/ERCC2 pnlymorphisms and risk of head and neck cancer: a case-control analysis. Carcinogenesis, 2000, 21(12): 2219-23.
[155] Brinckerhoff CE, Rutter JL, Benbow U. Interstitial collagenases as markers of tumor progression[J ] . Clin Cancer Res,2000, 6 (12) :4823-4830.
[156] Wang WW, Spurdle AB, Kolachana P, et al . A single nucleotide polymorphism in the 5′unt ranslated region of RAD51 and risk of cancer among BRCA1Π2 mutation carriers[J ] . Cancer Epidemiol Biomarkers Prev, 2001, 10 (9) :955-960.
[157] Kannan K, Munirajan AK, Bhuvarahamurthy V, et al . FHIT gene mutations and single nucleotide polymorphism in Indian oral and cervical squamous cell carcinomas[J ] . Oral Oncol,2000,36 (2) :189-193.
[158] Feigelson HS, Coetzee GA, Kolonel LN, et al . A polymorphism in the CYP17 gene increases the risk of breast cancer [J ] . Cancer Res,1997,57 (6) :1063-1065.
[159] Kuligina ES, Togo AV, Suspitsin EN, et al . CYP17 polymorphism in the groups of distinct breast cancer susceptibility : comparison of patients with thebilateral disease vs. monolateral breast cancer patients vs. middle2aged female cont rols vs. elderly tumor free women[J] . Cancer Lett, 2000, 156 (1) :45-50.
[160]袁芃,缪小平,张雪梅,等. DNA损伤修复基因XRCC1和XPD遗传多态与晚期NSCLC对铂类药物的敏感性[ J ].中华肿瘤杂志, 2006, 28 (3) : 196-199.
[161]袁芃,缪小平,张雪梅,等.核苷酸修故系统基因遗传多态与晚期NSCLC患者铂类药物敏感性的关系[ J ].癌症, 2005, 24(12) : 1510-1513.
[162] Rosell R, Tar on M, Ariza A, et al . Molecular p redict ors of response t o chemotherapy in lung cancer[ J ]. Semin Oncol, 2004,31 (1 Supp l 1) : 20-27.
[163] ZhouW, Gurubhagavatula S, Liu G, et al . Excision repair cross-complementati on group 1 polymor phis m p redicts overall survivalin advanced non2small cell lung cancer patients treated with platinum based chemotherapy[ J ]. Clin Cancer Res, 2004, 10 ( 15) :4939-4943.
[164] Camps C, Alonso G, de las Penas R, et al. XPD polymorphism in second-line treatment with gemcitabine or irinotecan in advanced non-small cell lung cancer (NCSLC) patients. Lung Cancer, 2005, 49(Suppl2):S118.
[165] Sarries C, Alberola V, Mendez P, et al. Single nucleotide polmorphisms (SNPs) in DNA repair genes predict survival in gemcitabine(gem)/cisplatin(cis)- treated non-small-cell lung cancer (NSCLC) patients. Proc Am Soc Clin Oncol, 2003, 22(5): 859-64.
[166] Zhou W, Gurubhagavatula S, Liu G, et al. Excision repair cross-complement- ation group 1 polymorphism predicts overall survival in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy. Clin Cancer Res, 2004,10(15):4939-43.
[167] Isla D, Sarries C, Rosell R, et al. Single nucleotide polymorphisms and outcome in docetaxel-cisplatin-treated advanced non-small-cell lung cancer. Ann Oncol, 2004, 15(8):1194-203.
[168] Ryu JS, Hong YC, Han HS, et al. Association between polymorphisms of ERCC1 and XPD and survival in non-small cell lung cancer patients treated with cisplatin combination chemotherapy. LungCancer, 2004,44(3):311-4.
[169] Wang D and Lippard SJ. Cellular processing of platinum anticancer drugs. NatRev Drug Discov, 2005 ,4(4):307-20.
[170] Jordana P, Carmo-Fonsecab M .Molecular mechanisms involved in cisplatin cytotoxicity. Cell Mol Life Sci, 2000,57 (8-9):1229–35.
[171] Rosell R, Lord RV, Taron M, et al. DNA repair and cisplatin resistance in non-small-cell lung cancer. Lung Cancer, 2002,38(3):217-27.
[172] Wang D, Hara R, Singh G, et al.Nucleotide excision repair from site- specifically platinum modified nucleosomes. Biochemistry, 2003, 42(22): 6747– 53.
[173] Furuta T.et al. Transcription-coupled nucleotide excision repair as a determinant of cisplatin sensitivity of human cells.Cancer Res, 2002,62(17): 4899–902.
[174] Riedl T, Hanaoka F and Egly JM. The comings and goings of nucleotide excision repair factors on damaged DNA. EMBO, 2003, 22(19):5293-303.
[175] Reardon JT and Sancar A. Molecular anatomy of the human excision nuclease assembled at sites of DNA damage. Mol Cell Bio, 2002, 22(16):5938-45.
[176] Fleck O and Nielsen O.DNA repair. J Cell Sci , 2004,117(Pt4): 515-7.
[177] Hutsell SQ and Sancar A. Nucleotide excision repair, oxidative damage, DNA sequence polymorphisms, and cancer treatment. Clin Cancer Res, 2005,11(4): 1355-7.
[178] Rosell R, Taron M, Camp s C, et al. Influence of genetic markers onsurvival in non2small cell lung cancer [ J ]. D rug Today (B arc),2003, 39 (10) : 775-786.
[179] van DuinM, KokenMH, van den Tol J, et al. Genomic characteriza2tion of the human DNA excision repair gene ERCC1 [ J ]. N ucleicAcids Res, 1987, 15 (22) : 9195-9213.
[180] Pfeiffer P, Qvortrup C and Eriksen JG. Current role of antibody therapy in patients with metastatic colorectal cancer. Oncogene, 2007, 26(25):3661-78.
[181] Park YH, Lee JL, Ryoo BY,et al. Capecitabine in combination with Oxaliplatin (XELOX) as a first-line therapy for advanced gastric cancer. Cancer Chemother Pharmacol, 2007 May 24; [Epub ahead of print].
[182] Socinski MA. Cytotoxic chemotherapy in advanced non-small cell lung cancer: a review of standard treatment paradigms. Clin Cancer Res, 2004,10(12 Pt 2):4210s-14s.
[183] Gonzalez VM, Fuertes MA, Alonso C, et al. Is cisplatin-induced cell death always produced by apoptosis ? Mol Pharmacol, 2001,59(4):657-63.
[184] Ferry KV, Hamilton TC and Johnson SW. Increased nucleotide excision repair in cisplatin-resistan to varian cancer cells: role of ERCCI-XPF. Biochem Pharmaco1, 2000, 60 (9):1305-131.
[185] Li Q,Y u J J, Mu C, et al. Association between the level of ERCC-1 expression and the repair of cisplatin-induced DNA damage in human ovarian cancer cells. Anticancer Res, 2000,20(2A):645-52.
[186] Li Q,Yu JJ,Mu C, et al.Sssociation between the level of ERCC1 expression and the repair of cisplatin-induced DNA damage in human ovarian cancer cells. Anticancer Res,2000,20(2A):645-652.
[187] Ferry KV, Hamilton TC,Johnson SW.Increased nucleotide excision repair in cisplatin-resistant ovarian cancer cells: role of ERCC1-XPF.Biochem Pharmacol, 2000,60(9):1305-1313.
[188].Selvakumaran M,Pisarcik DA, Bao R.Enhanced cisplatin cytotoxicity by disturbing the nucleotide excission repair pathway in ovarian cancer cell lines.Cancer Res, 2003,63(6):1311-1316.
[189] Takebayashi Y,Nakayama K,Kanazaki A,et al.Loss of heterozygosity of nucleotide excission repair factors in sporadic ovarian,colon and lung carcinomas:implication for their rolesof carcinogenesis in human solid tumors.Cancer Lett, 2001,174(2):115-125.
[190] Yun JJ,Bicher A,Ma YK,et al.Absence of evidence for allelic loss or allelic gain for ERCC1or for XPD in human ovarian cancer cells and tissues. Cancer Lett,2000,152(2):127-132.
[191] Ryu JS, Hong YC, Han HS, et al. Association between polymorphisms of ERCC1 and XPD and survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy. Lung Cancer 2004;44(3):311-316.
[192] Rosell R, Taron M, Ariza A, et al. Molecular predictors of response to chemotherapy in lung cancer. Semin Oncol 2004;31(1):20-27.
[193] Park DJ, Stoehlmacher J, Zhang W, et al. A Xeroderma pigmentosum group D gene polymorphism predicts clinical outcome to platinum-based chemotherapy in patients with advanced colorectal cancer. Cancer Res 2001;61(24):8654-8658.
[194] Sarries C, Alberola V, Mendez V, et al. Single nucleotide polymorphisms (SNPs) in DNA repair genes predict survival in gemcitabine (gem)/cisplatin (cis)-treated non-small-cell lung cancer (NSCLC) patients (P). Proc Am Soc Clin Oncol 2003;22: 859, (abstr 3450).
[195] Gurubhagavatula S, Liu G, Park S, et al. XPD and XRCC1 genetic polymorphisms are prognostic factors in advanced non-small-cell lung cancer patients treated with platinum chemotherapy. J Clin Oncol 2004;22(13):2594-2601.
[196] Shirota Y, Stoehlmacher J, Brabender J, et al. ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil Chemotherapy. J Clin Oncol 2001;19: 4298-4304.
[197] Lord RVN, Brabender J, Gandara D, et al. Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small-cell lung cancer. Clin Cancer Res 2002;8:2286-2291.
[198] Ryu JS, Hong YC, Han HS, et al. Association between polymorphisms of ERCC1 and XPD and survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy. Lung Cancer 2004;44(3):311-316.
[199] Yu JJ, Lee KB, Mu C, et al. Comparison of two human ovarian carcinoma cell lines (A2780/CP70 and MCAS) that are equally resistant to platinum, but differ at codon 118 of the ERCC1 gene. Int J Oncol 2000 Mar;16(3):555-560.
[200] Rosell R, Lord RV, Taron M, et al. DNA repair and cisplatin resistance in non-small-cell lung cancer. Lung cancer 2002;38:217-227.
[201] Sarries C, Haura EB, Roig B, et al. Pharmacogenomics strategies for developing customized chemotherapy in non-small cell lung cancer. Pharmacogenomics 2002;3(6):763-780.
[202] Wu X, Zhao H, WeiQ, et al . XPA polymorphism ass ociated with reduced lung cancer risk and a modulating effect on nucleotide excision repair capacity[ J ]. Carcinogenesis, 2003, 24 (3) : 5052 509.
[203]李金恒,陈冰.基金芯片及其在突变检测中的应用[ J ].医学研究生学报, 2005, 18 (1) : 54-58.
[204] Butkiewicz D, Rusin M, Harris CC, et al . I dentification of foursingle nucleotide polymor phisms in DNA repair genes : XPA and XPB ( ERCC3 ) in Polish population [ J ]. Hum Mutat, 2000, 15(6) : 577- 578.
[205]Ulla V, Kim O, Hakan W, et al . Combinations of polymorphisms in XPD, XPC and XPA in relati on t o risk of lung cancer [ J ].Cancer Letters, 2005, 222 (1) : 672 74.
[206] Monz o M, Brunet S, Urbano2Is p izua A, et al . Genomic polymorphisms provide p r ognostic infor mati on in inter mediate risk acute myeloblastic leukemia[ J ]. Blood, 2006, 107 (12) : 4871- 4879.
[207]孙新臣,孙宁,成红艳,等. XPA单核苷酸多态与晚期非小细胞肺癌对铂类药物化疗敏感性的相关性研究[ J ].2007,20(12)1271-1273.
[208] de Boer J, Hoeijmakers JH. Nucleotide excision repair and human syndromes . Carcinogenesis, 2000, 21: 453- 460.
[209] Sugasawa K,Shimizu Y,Lwai S,et al.A molecular mechanism for DNAdamage recognition by thexeroderma pigmetosum group C protein complex [J].DNA Repair,2002,1(1):95-107.
[210] Qiao Y, Sp itzMR, Shen H, et al . Modulation of repair of ultraviolet damage in the host2 cell reactivati on assay by polymor phic XPC and XPD /ERCC2 genotypes . Carcinogenesis, 2002, 23: 295- 299.
[211] Khan SG, Metter EJ, Tarone RE, et al . A new xeroderma pigmentosum group C poly (AT) insertion/ deletion polymorphism. Carcinogenesis,2000, 21 : 1821-1825.
[212] Qiao Y, Spitz MR, Shen H, et al . Modulation of repair of ultraviolet damage in the host2cell reactivation assay by polymorphic XPC and XPD/ERCC2genotypes. Carcinogenesis, 2002, 23 : 295-299.
[213] Rosell R, Taron M, Ariza A, et al. Molecular predictors of response to chemotherapy in lung cancer. Semin Oncol 2004;31(1):20-27.
[214] Hemminki K, Xu G, Angelini S, et al. XPD exon 10 and 23 polymorphisms and DNA repair in human skin in situ. Carcinogenesis 2001;22:1185-1188.
[215] Spitz MR, Wu X, Wang Y, et al. Modulation of nucleotide excision capacity by XPD polymorphisms in lung cancer patients. Cancer Res 2001;61:1354-1357.
[216] Sturgis EM, Zheng R, Li L, et al. XPD/ERCC2 polymorphisms and risk of head and neck cancer: a case-control analysis: Carcinogenesis 2000;21:2219-2223.
[217] Tomescu D, Kavanagh G, Ha T, et al. Nucleotide excision repair gene XPD polymorphisms and genetic predisposition to melanoma. Carcinogenesis 2001;22: 403-408.
[218] Park DJ, Stoehlmacher J, Zhang W, et al. A Xeroderma pigmentosum group D gene polymorphism predicts clinical outcome to platinum-based chemotherapy in patients with advanced colorectal cancer. Cancer Res 2001;61(24):8654-8658
[219] Sarries C, Alberola V, Mendez V, et al. Single nucleotide polymorphisms (SNPs) in DNA repair genes predict survival in gemcitabine (gem)/cisplatin (cis)-treated non-small-cell lung cancer (NSCLC) patients (P). Proc Am Soc Clin Oncol 2003;22: 859, (abstr 3450)
[220] Rosell R, Taron M, Camps C, et al. Influence of genetic markers on survival in non-small cell lung cancer. Drugs Today (Barc) 2003;39(10):775-786.
[221] Stoehlmacher J, Park DJ, Zhang W, et al. A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU/oxaliplatin combination chemotherapy in refractory colorectal cancer. Br J Cancer 2004;91(2):344-354.
[222] Gurubhagavatula S, Liu G, Park S, et al. XPD and XRCC1 genetic polymorphisms are prognostic factors in advanced non-small-cell lung cancer patients treated with platinum chemotherapy. J Clin Oncol 2004;22(13):2594-2601.
[223] Jeon HS, Kim KM, Park SH, et al. Relationship between XPG codon 1104 polymorphism and risk of primary lung cancer. Carcinogenesis2003;24(10):1677-1681.
[224] Vila JM, Moreno I, Monzo M, et al. XPD, XPA, ERCC1 and XPG/ERCC5 single nucleotide polymorphisms (SNPs) in oxaliplatin-treated colorectal cancer (CRC). Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). 2004;22:3677
[225] Stoehlmacher J, Park DJ, Zhang W, et al. A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU/oxaliplatin combination chemotherapy in refractory colorectal cancer. Br J Cancer, 2004, 91(2): 344-354.
[226] Gurubhagavatula S, Liu G, Park S, et al. XPD and XRCC1 genetic poly- morphisms are prognostic factors in advanced non-small-cell lung cancer patients treated with platinum chemotherapy. J Clin Oncol, 2004, 22(13):2594- 601.
[227]袁芃,缪小平,张雪梅,等.核苷酸切除修复基因遗传多态性与晚期非小细胞肺癌患者铂类药物敏感性的关系.癌症, 2005,24(12):1510-1513.
[1] Kelland LR. Preclinical perspectives on platinum resistance [J]. Drugs, 2000, 59(S4) : 1- 8.
[2]栾英姿,李力,黎丹戎,等.五种卵巢癌耐药细胞系的建立及其部分耐药相关基因的表达[J].中华妇产科杂志,2004,39(6):403-407.
[3] Rosell R, Lord RV, Taron M, et al. DNA repair and cisplatin resistance in non-small-cell lung cancer[J]. Lung cancer 2002;38:217-227.
[4] Nagasubramanian R, Innocenti F, RatainMJ, et al . Pharmacogenetics in cancer treatment[J]. Annu RevMed, 2003,54: 437 .
[5] Reed E . Platinum2 DNA adduct, nucleotide excisi on repair and platinum based anti-cancer chemotherapy[J] . Cancer Treat Rev, 1998, 24: 331
[6]Rosell R,Lorsd RV, Tar onM, et al . DNA repair and cisplatin resistance in non-small-cell lung cancer[J] . Lung cancer, 2002, 38: 217 .
[7] Stoehlmacher J, Park DJ, Zhang W, et al. A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU/oxaliplatin combination chemotherapy in refractory colorectal cancer[J]. Br J Cancer, 2004, 91(2): 344-354.
[8] Ryu JS, Hong YC, Han HS, et al. Association between polymorphisms of ERCC1 and XPD and survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy[J]. Lung Cancer 2004;44(3):311-316.
[9] Rosell R, Taron M, Ariza A, et al. Molecular predictors of response to chemotherapy in lung cancer[J]. Semin Oncol 2004;31(1):20-27.
[10] Park DJ, Stoehlmacher J, Zhang W, et al. A Xeroderma pigmentosum group D gene polymorphism predicts clinical outcome to platinum-based chemotherapy in patients with advanced colorectal cancer[J]. Cancer Res 2001;61(24):8654-8658.
[11]Kumar R, Hoglund L, Zhao C, et al.Single nucleotide polymorphisms in the XPG gene: determination of role in DNA repair and breast cancer risk[J]. Int J Cancer, 2003,103(5):671-675.
[12]Jeon HS, Kim KM, Park SH, et al. Relationship between XPG codon 1104 polymorphism and risk of primary lung cancer[J]. Carcinogenesis,2003, 24(10): 1677-1681.
[13] Jeon HS, Kim KM, Park SH, et al. Relationship between XPG codon 1104 polymorphism and risk of primary lung cancer[J]. Carcinogenesis 2003;24(10):1677-1681.
[14] Vila JM, Moreno I, Monzo M, et al. XPD, XPA, ERCC1 and XPG/ERCC5 single nucleotide polymorphisms (SNPs) in oxaliplatin-treated colorectal cancer (CRC) [J]. Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). 2004;22(11):3677-3681
[1] Angela Reles, Wen H. Wen, Annette Schmider,Correlation of p53 Mutations with Resistance to Platinum-based Chemotherapy and Shortened Survival in Ovarian Cancer[J]. Clinical Cancer Research, 2001,10(7) 2984-2997.
[2] Vesell ES: Advances in Pharmacogenetics and Pharmacogenomies[J].J Clin Pharmacol.2000,40:930-938.
[3] Evans WE, MeLeod HL: Pharmacogenomies-Drug disposition drug targets,and site effects[J].N Engl J Med.2003,348:538-549.
[4] McLeod HL, Evans WE: Pharmacogenomies: Unlocking the human genome for better drug therapy[J].Annu Rev Pharmao Toxicol.2001,41:101-121.
[5] Crawford DC; Akey DT; Nickerson DA.The patterns of natural variation in human genes.Annu [J].Rev.Genomics Hum.Genet.2005,6,287-312.
[6] Crawford DC; Nickerson DA.Definition and clinical importance of haplotypes[J]. Annu.Rev.Med.2005,56,303-320.
[7] Weng,W.K.;Levy,R.Two immunoglobulin G fragment C receptor Polymorphisms independently predict response to rituximab in Patients with follicular lymphoma[J].Clin.Oncol.2003,21,3940-3947.
[8] Evans,W.E.Pharmacogenetics of thiopurine S-methyltransferase and thiopurine therapy[J].Ther.Drug Monit.2004,26,186-191.
[9] Mcleod,H.L;King,C.R;Marsh,S.Application of pharmacogenomics in the individualization of chemotherapy for gastrointestinal malignancies[J]. Clin.Colorectal.Cancer. 2004,4,S43-47.
[10] Nagasubramanian R, Innocenti F, RatainMJ, et al . Pharma-cogenetics in cancer treat ment[J]. Annu RevMed, 2003,54: 437 .
[11] Reed E . Platinum-DNA adduct, nucleotide excision repair and platinum based anti-cancer chemotherapy[J]. CancerTreat Rev, 1998, 24: 331 .
[12] Rosell R,Lorsd RV, Tar onM, et al . DNA repair and cisplatin resistance in non2small2 cell lung cancer[J]. Lung cancer, 2002, 38: 217 .
[13] O’Donovan A,Dvaies AA,MoggsJG,et al. XPG endonuelease makes the 3’Incision in human DNA nueleotide exeision repair[J].Nature1994;371:432-435.
[14] Elnrnert S,Sehneider TD,Khan SG,Kraemer KH.The human XPG gene:Gene architecture , alternative splieing and single nueleotide Polymoprhisms[J].Nueleie.Aeids.Res.2001;29:1443-1452.
[15] MaeInnes MK,Diekson JA,Hernandez RR,et al.Human XPG cDNA-Cosmid complementation for excision repair and bipartite amino acid domains conserved with RAD proteins of Saccharomyecs cerevisiae and Sehzosac-charomyces Pombe[J].Mol.Cell.Biol.1993:13:6393-6402.
[16] Vila JM, Moreno I, Monzo M, et al. XPD, XPA, ERCC1 and XPG/XPG single nucleotide polymorphisms (SNPs) in oxaliplatin-treated colorectal cancer (CRC). Journal of Clinical Oncology[J]. 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). 2004;22(11):3677-3681.
[17] Mariano Monzo, Isabel Moreno, Alfons Navarro,et al. Single Nucleotide Polymorphisms in Nucleotide Excision Repair Genes XPA, XPD, XPG and ERCC1 in Advanced Colorectal Cancer Patients Treated with First-Line Oxaliplatin/Fluoropyrimidine[J]. Oncology 2007;72:364-370
[18] ShenMR, Jones I M,Mohrenweiser H. Nonconservative amino acid substituti on variants exist at polymor phic frequency in DNA repair genes in healthy humans[J]. Cancer Res, 1998, 58 (4) : 604- 608.
[1] Bernstein C,Bernstein H,Payne CM,et al.DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways:fail-safe protection against carcinogenesis [J].Mutat Res,2002,511(2):145-178.
[2] Wang D and Lippard SJ. Cellular processing of platinum anticancer drugs [J]. Nat Rev Drug Discov, 2005 ,4(4):307-320.
[3] Jordana P, Carmo-Fonsecab M .Molecular mechanisms involved in cisplatin cytotoxicity [J]. Cell Mol Life Sci, 2000,57 (8-9):1229–1235.
[4] Rosell R, Lord RV, Taron M, et al. DNA repair and cisplatin resistance in non-small-cell lung cancer [J]. Lung Cancer, 2002,38(3):217-227.
[5] Yuan P, Miao XP, Zhang XM, et al. Correlation of genetic polymor phisms in nucleotide excision repair system to sensitivity of advanced non-small cell lung cancer patients to p latinum2based chemotherapy [J]. A i Zheng, 2005, 24 (12) : 1510-1513.
[6] Juhani A. Vilp O, Leena M. An XPG DNA Repair Defect Causing Mutagen Hypersensitivityin Mouse Leukemia L1210 Cells [J]. Molecular and cellular biology,1995,15(1)290-297.
[7] Inusha U. De Silva, Peter J. Defects in interstrand cross link uncoupling do not account for the extreme sensitivity of ERCC1 and XPF cells to cisp latin [J]. N ucleic Acids Res, 2002, 30 (17) : 3848-3856.
[8] Wu H , Hait WN , Yang JM et al1 Small Interfering RNA induced Suppression of MDR1 ( P-Glycoprotein) Restores Sensi tivity to Multidrug resistant Cancer Cells [J] . Cancer Res , 2003 , 63 (4) : 1515- 1519.
[9]彭智,肖志坚,王一,等.siRNA逆转K562/ A02细胞多药耐药的研究[J] .中华血液学杂志, 2004 , 25 (1) : 5-7.
[10] Peng Z , Xiao Z , Wang Y, et al1 Reversal of P-glycoprotein mediated multidrug resistance wit h small interference RNA( siRNA) in leukemia cells [J] . Cancer Gene Ther , 2004 , 11(11) : 707-712.
[11] Yague E , Higgins CF , Raguz S 1 Complete reversal of multidrug resistance bystable expression of small interfering RNAstargeting MDR1 [J] . Gene Therapy 2004 , 11 ( 14 ) :1170-1174.
[12]李劲涛,杨军,张秀丽等。RNAi最新研究概况。细胞与分子免疫学杂志[J].2007, 23 (11):1077-1079.
[13] Bustin SA. Absolute quantification of mRNA using realtime reverse transcription polymerase chain reaction assays [J] . Mol Endocrinol , 2000 , 25 : 169.
[14] Furuta T,Ueda T,Aune G,er al.Transcription-coupled nucleotide excision repair as a determinant of cisplatin sensitivity of human cell [J].Cancer Res,2002,62(17):4899-4902
[15] Dabholkar M,Vionnet J,Bostick-Bruton F ,et al.Messenger RNA levels of XPAC and ERCC1 in ovarian cancer tissue correlate with response to platinum-bases chemotherapy [J].J Clin Investig,1994,94(2):703-708.
[16] Metzger R,Leichman CG,Danenberg K,et al.ERCC1 mRNA levels complement thymidylate synthase Mrna levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluororacil chemotherapy [J].J Clin Oncol,1998,16(1):309-316.
[17] Yang LY,Li L,Jiang H, et al.Expression of ERCC1 antisense RNA abrogates gemcitabine-mediated cytotoxic synergism with cisplatin in human colon tumor cells defective in mismatch repair but proficient in nucleotide excision repair [J].Clin.cance Res.2000,6(3):773-781.
[18] Ryu JS, Hong YC, Han HS, et al . Association between polymorphis ms of ERCC1 and XPD and survival in non2small2 cell lung cancer patients treated with cis p latin combinati on chemotherapy [J]. Lung Cancer , 2004, 44 (3) : 3112 316.
[19] Sakamoto M, Kondo A, Kawasaki K, et al. Analysis of gene expression profiles associated with cisplatin resistance in human ovarian cancer cell lines and tissues using cDNA microarray [J]. Brain Res Mol Brain Res. 2003 Nov 26;119(2):170-183.
[20] Stevens EV, Nishizuka S, Antony S et al.Predicting cisplatin and trabectedin drug sensitivity in ovarian and colon cancers [J]. 2008 Jan;7(1):10-8. Epub 2008 Jan9.
[21] Ahmad H,Wilson DE,Fritz RR,etc.Primary and secondary structural analyses of glutathione Stransferase pifrom human placenta[J].Arch Biochem Biophys,1990,278(2):398-399.
[22] Christine S. Walsh, Seishi Ogawa, et al.XPG Is a Novel Biomarker of Ovarian Cancer Prognosis [J]. Journal of Clinical Oncology . 2008,26(18)2952-2958.
© 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 |