三维培养药敏实验测定的胃癌药物敏感性与多药耐药基因蛋白表达的关系

背景与目的：目前胃癌化疗疗效尚不理想,通过预测个体肿瘤对药物的敏感性来指导临床治疗,以提高疗效,早已成为化疗界瞩目的问题。本研究通过三维培养药敏实验测定胃癌的药物敏感性,并通过测定多药耐药基因表达产物水平,分析两者之间的关系。方法：应用三维培养体外药敏实验技术,测定表阿霉素、顺铂、草酸铂、5-FU、泰素帝、伊立替康6种单药和5-FU＋表阿霉素＋顺铂、5-FU＋伊立替康、5-FU＋草酸铂、5-FU＋泰素帝＋顺铂4组联合用药对22例胃癌组织的抑制率,并计算敏感率;应用逆转录聚合酶链反应（RT—PCR）和免疫组化法检测胃癌组织中MDR1、MRP1、ABCG2基因蛋白的表达。结果：单药组中5-FU对胃癌组织的抑制率和敏感率最高,分别为29．8％和50．0％：联合用药组抑制率最高为5-FU＋泰素帝＋顺铂（59．8％）,敏感率最高为5-FU＋表阿霉素＋顺铂（77．3％）;联合用药组抑制率和敏感率均高于单药组（P〈0．05）。胃癌组织中MDR1、MRP1、ABCG2 mRNA的阳性率分别为90．9％、54．5％、77．3％,MDR1、MRP1、ABCG2蛋白的阳性率分别为36．4％、54．5％、36．4％;多药耐药蛋白高表达与胃癌对表阿霉素的耐药有相关性（P〈0．05）。结论：胃癌组织中多药耐药基因MDR1、MRP1、ABCG2蛋白高表达与胃癌组织对表阿霉素的耐药有关。提示这三种耐药基因可能参与介导表阿霉素的耐药。     

草酸铂的神经毒性及其预防和治疗

草酸铂是第3代铂类抗癌药物，与顺铂或卡铂不同之处在于它包含1个环状大基团（1，2-二氨基环己烷），草酸铂-DNA复合物一旦形成，对DNA修复有更大的抵抗力，能更有效的抑制DNA复制。在临床前和临床研究中，草酸铂对许多不同类型的肿瘤都显示出抗瘤活性，尤其对顺铂和卡铂耐药的结直肠癌瘤株有抗瘤活性，因此被用于许多肿瘤的治疗，在结直肠癌中的作用更重要，以草酸铂为基础的化疗方案，尤其是草酸铂联合5-FU／CF已经成为晚期结直肠癌的一线或二线治疗和术后辅助化疗的标准方案。     

非小细胞肺癌多药耐药性病理学检测的临床意义

 目的 检测113例非小细胞肺癌（NSCLC）中谷胱甘肽巯基转移酶π（GST-π）、肺耐药相关蛋白（LRP）、DNA拓扑异构酶Ⅱa（TopoⅡa）、多药耐药相关蛋白（MRP）和多药耐药基因（MDRt）的表达，观察上述指标与肿瘤I临床病理因素的关系及各指标表达之间的相关性。方法 采用免疫组化SP法检测GST-π、LRP、TopoⅡa蛋白的表达；应用原位杂交技术检测MRP和MDR1 mRNA表达。结果 （1）GST-π、LRP、TopoⅡa蛋白及MRP、MDR1 mRNA在113例NSCLC中的阳性表达率分别为75.2％、80．5％、60．2％、79．6％、51．3％。其中LRP表达最高，MDR1表达最低。（2）LRP、TopoⅡa和MRP的表达分别与肿瘤组织学类型有关。（3）GST-π与MRP（P〈0．05）、LRP与MRP（P〈0．01）、MDR，与MRP（P〈0．01）的表达间具有相关性。结论 （1）多种耐药相关基因的过度表达及其相互作用可能是NSCLC产生原发MDR的重要原因。（2）LRP和MRP过度表达，TopoⅡa高表达和MRP低表达可能分别与肺腺癌、鳞癌的化疗敏感性有关。     

耐药相关基因MDR1、MRP、LRP及其表达产物P-gp、MRP、LRP在非小细胞肺癌组织中的表达及意义

目的：研究探讨非小细胞肺癌（NSCLC）组织和癌旁组织中多药耐药基因1（muhidrug resistance genel，MDR1）、多药耐药相关蛋白（multidrug resistance-related proteins，MRP）、肺耐药蛋白（lung resistance protein，LRP）mRNA及其相应蛋白P—gP、MRP、LRP的表达情况及临床意义。方法：运用聚合酶链反应（RT-PCR）、免疫组织化学法（IHC）检测43例NSCLC组织及癌旁组织标本中耐药基因MDR1、MRP、LRPmRNA及其蛋白P-gP、MRP、LRP的表达水平。结果：MDR1、MRP和LRP mRNA3种基因在43例肿瘤组织中的表达率分别为79．06％（34／43）、65．17％（28／43）和86．05％（37／43），癌旁组织中的表达率分别为20．00％（3／15）、13．33％（2／15）和13．33％（2／15）；P—gP、MRP和LRP3种耐药蛋白在肺癌组织中的表达率分别为74．42％（32／43）、67．44％（29／43）和88．37％（38／43），癌旁组织中的表达率分别为13．33％（2／15）、20．00％（3／15）和6．67％（1／15），上述3种基因及其蛋白在肺癌组织与癌旁组织的表达差异有显著性（P〈0．05）。肺癌组织中既存在耐药基因MDR1、MRP和LRP的共表达，也存在耐药蛋白P-gP、MRP和LRP的共表达，3种基因与其相应蛋白表达密切相关。肺腺癌组织中MDR1及其蛋白P-gP、LRP mRNA表达率较高，与其它病理类型相比差异有显著性（P〈0．05），MRP mRNA及其蛋白MRP表达与肺癌病理类型、临床分期和组织学分级无关（P〉0．05）。结论：NSCLC存在着广泛的原发性多药耐药现象，耐药基因MDR1、MRP和LRPmRNA及其相应蛋白参与了肺癌多药耐药的形成，检测多药耐药基因可为指导临床用药提供一定的理论依据及策略。     

氟尿嘧啶和奥沙利铂在胃癌中的体外化疗敏感性检测

目的：探讨氟尿嘧啶（5-FU）和奥沙利铂（OX）在胃癌中的体外化疗敏感性。方法：纳入病理确诊并自愿接受检测的胃癌患者,采用ATP肿瘤化疗敏感性检测法（ ATP-TCA）检测新鲜手术标本对5-FU和OX的体外化疗敏感性。结果：纳入27例,男性21例、女性6例,中位年龄60．0岁,远侧部胃癌14例（51．9%）,低分化及印戒细胞癌共20例（74．1%）,TNM Ⅲ＋Ⅳ期21例（77．8%）。 ATP-TCA检测显示5-FU＋OX在各药物浓度的肿瘤生长抑制率均显著高于5-FU或OX（P〈0．05）,5-FU＋OX的抑制曲线下面积显著高于5-FU或OX（P〈0．05）;而其化疗敏感指数、IC90和IC50显著低于5-FU或OX （ P〈0．05）。5-FU、OX和5-FU＋OX的体外化疗敏感性依次为18．5%、14．8%和55．6%,5-FU＋OX的敏感性显著高于5-FU或OX（5-FU＋OX vs．5-FU：P=0．001和5-FU＋OX vs． OX：P=0．003）。 Logistic回归分析显示5-FU的敏感性与临床病理特征无显著相关性,而OX和5-FU＋OX的敏感性分别与Borrmann分型（OR=7．570,P=0．025）和肿瘤位置（OR=3．427,P=0．019）有显著相关性。结论：5-FU＋OX在胃癌中显示出较高的体外化疗敏感性,但其与体内疗效的相关性有待进一步临床观察。     

卵巢恶性肿瘤体外药物敏感试验及其临床意义

目的：探讨卵巢恶性肿瘤体外药物敏感试验的临床意义。方法：采用四氮唑蓝显色反应药敏分析法（ＭＴＴ）检测６０例卵巢恶性肿瘤组织（Ⅰ期８例、Ⅱ期２例、Ⅲ期２２例、Ⅳ期１例、复发２７例）对化疗药物的敏感性。结果：体外试验单药对肿瘤的中位抑制率为：泰素６１．５％、表阿霉素５２．４％、卡铂４２．１％、平阳霉素３３．５％、长春新碱１０．７％。联合用药的中位抑制率为：ＶＢＰ（长春新碱＋平阳霉素＋卡铂）７９．９％、ＶＡＰ（长春新碱＋表阿霉素＋卡铂）７５．３％。ＶＢＰ、ＶＡＰ方案对上皮必卵巢产中位抑制率分别为７７．３％和７１．０％。初治术后残留灶≤２ｃｍ者中２６例可评价,体外试验与临床疗效的符合率为８４．６％。复发术后残留灶≤２ｃｍ者中１５例可评价,１０例使用体外敏感药物进行化疗,术后１年生存率８０．０％,５例患者体外试验不敏感     

卵巢上皮癌淋巴结转移化疗的临床疗效分析

背景与目的：卵巢上皮癌属化疗中度敏感肿瘤,随着肿瘤细胞减灭术及铂类联合化疗的应用,其疗效有明显改善,但其淋巴结转移病灶对化疗的敏感性尚存异议。本研究通过回顾性分析临床资料,以评价卵巢上皮癌患者淋巴结转移对化疗的敏感性及其预后,方法：对1986年6月－2001年2月收治的50例卵巢上皮癌淋巴结转移患者进行回顾性分析,其中Ⅲ-Ⅳ期32例,治疗后复发18例,50例均有可评价疗交的淋巴结转移灶,其中38例有可评价的盆腔,腹腔肿瘤。46例接受术前化疗1－3疗程,肿瘤细胞减灭术、术后化疗。化疗疗效评价按实体瘤疗效评价标准。化疗包括术前、术后或复发患者的化疗,其中45例接受含铂类联合化疗,包括CP（环磷酰胺＋顺铂）,CAP（环磷酰胺＋顺铂＋阿霉素或表阿霉素）,TC（紫杉醇＋卡铂）,TP（紫杉醇＋顺铂）,吉西他滨＋卡铂及IEP（顺铂＋异环磷酰胺＋足叶乙甙）方案,1例用美法仑,1例用CF（环磷酰胺和5－氟尿嘧啶）方案,3例用IFO＋VP－16（异环磷酰胺＋足叶乙甙）,结果：全组淋巴结转移灶和肿瘤的有效率分别为68．0％、71．1％,Ⅲ-Ⅳ期初治患者淋巴结转移和盆腹腔肿瘤有效率分别为78．1％,76．6％,而复发组两者有效率均为50．0％,结论：卵巢上皮癌的淋巴结转移,无论Ⅲ-Ⅳ期还是复发患者,其对化疗敏感性与盆腹腔肿瘤相近,Ⅲ-Ⅳ期患者预后与减瘤术是否彻底,以及化疗的疗程数多少有明显的相关性。     

MDR1和GST-π在骨软组织肉瘤中的表达及其与化疗耐药的关系

目的 探讨多药耐药基因1（MDR1）和谷胱苷肽-S-转移酶-π（GST-π）在骨软组织肉瘤组织中的表达及其与化疗耐药的关系。方法应用荧光定量PCR（FQ-PCR）和流式细胞术（FCM）,分别在mRNA水平和蛋白水平检测MDR1和GST-π的表达;以四甲基偶氮唑盐法（MTT）法检测瘤组织对阿霉素（ADM）、顺铂（DDP）、5-氟脲嘧啶（5-Fu）、丝裂霉素C（MMC）、氮烯咪胺（DTIC）、长春新碱（VCR）和氨甲喋呤（MTX）的敏感性。结果 患者瘤组织对ADM、DDP、5-Fu、MMC、lyric、VCR和MTX的不敏感率分别为41．18％、17．65％、47．06％、50．00％、76．47％、61．76％和52．94％。瘤组织中P-gp和GST-π相对荧光强度的表达分别为1．54和为2．58。X^2分析显示,P-gp的表达与ADM耐药、GST-π的表达与ADM、DDP、MMC耐药均呈正相关（P〈0．05）。MDR1和GST-π的表达与患者年龄、性别、病理类型、肿瘤大小均无关（P〉0．05）。GST-π在术前化疗患者的瘤组织中表达升高,且术前表达升高者,术后复发率高于术前GST-π表达水平较低者（P〈0．05）。结论 骨软组织肉瘤患者的MDR1、GST-π表达及化疗敏感性存在个体差异;化疗引起GST-π表达上调;原发GST-π高表达是骨软组织肉瘤耐药的主要机制,并与患者预后不良有关。     

X线照射对人鼻咽癌细胞株耐药基因及其蛋白表达的影响

[目的]检测X射线照射前后鼻咽癌CNE-1细胞多药耐药基因(MDR1)及其编码产物P糖蛋白(P-gp)、多药耐药相关蛋白基因(MRP基因)及其编码产物多药耐药相关蛋白(MRP)的表达随时间变化的情况。[方法]对CNE-1细胞进行X射线照射,总剂量10Gy/(5d·5f)。利用RT-PCR检测照射前、照射开始后第7、14、21、28和35d细胞的MDR1、MRP基因的表达;Westernblotting检测照射前后P-gp、MRP的表达;MTT法检测照射前后顺铂(DDP)对细胞的半数抑制率(IC50)。[结果]CNE-1细胞X射线照射前MDR1、MRP基因、P-gp和MRP呈弱表达;照射后35d内耐药基因及蛋白表达均显著增高(P<0.05)。[结论]CNE-1细胞X射线照射后耐药基因(MDR1、MRP)及其蛋白(P-gp、MRP)表达显著增强,同时CNE-1细胞对顺铂产生抵抗。     

多药耐药相关蛋白反义RNA对耐阿霉素人小细胞肺癌细胞株GLC4/ADR耐药性的调节

目的 构建表达多药耐药相关蛋白（MRP）反义RNA的真核表达载体,转染耐药细胞株,初步探讨其影响多药耐药（MDR）的作用机理。方法 以MRPcDNA为模板,应用PCR扩增MRPmRNA5′端（含起始子密码）及MRP mNRA3′端（含终止子密码）片段,通过定向克隆方法,构建表达MRP反义RNA的两个重组载体。通过Lipofectamine将其导入小细胞肺癌（SCLC）耐阿霉素（ADR）的细胞株GLC4／ADR中,经G418筛选,得到分别含pcDNA3空载（MO）、MRP mRNA5′端为靶区的反义RNA（Ma),MRPmRNA3′端为靶区的反义RNA（Mb)的3个细胞克隆。检测细胞内ADR的蓄积改变以及荷瘤裸鼠对ADR的敏感性。结果 经RT－PCR检测,外源片段可获稳定表达。Ma细胞及Mb细胞中,MRP表达分别抑制约14．0％和83．0％,且胞内ADR蓄积量均有一定程度的增加;对ADR的耐药倍数与对照细胞MO相比,分别下降9．5％和28．4％。虽然,MRP反义RNA对细胞的生长、细胞周期及ADR诱导的早期凋亡均无明显影响,但可提高荷瘤裸鼠对ADR的敏感性。结论 MRP反义RNA能抑制MRP蛋白的表达,并使转染细胞内ADR浓度增加,从而逆转MRP介导的MDR。对于配合化疗,提高MRP高表达患者的疗效,具有潜在的应用意义。     

In vitro evaluation of anticancer drugs in relation to development of drug resistance in the human tumor clonogenic assay

Summary The efficacy of anticancer drugs against ovarian cancer, breast cancer, and colorectal cancer has been evaluated in vitro by the human tumor clonogenic assay developed by Hamburger and Salmon. The in vitro colony assay method used in this study is a minor modification of their method and was used in 83 patients with ovarian cancer, 47 patients with breast cancer, and 13 patients with colorectal cancer. The total numbers of assays performed in vitro were 258 for ovarian cancer, 87 for breast cancer, and 38 for colorectal cancer. The average chemosensitivity rates to single agents tested were 35% and 32% in the untreated patients with ovarian and breast cancer, respectivety. In contrast to this result, the chemosensitivity rate of the untreated patients with colorectal cancer was only 16%. Consisting the clinical efficacy of anticancer drugs against these tumors, these results suggest that there is a correlation between chemosensitivity in the human tumor clonogenic assay and clinical responsiveness. In this assay the chemosensitivity in specimens from ovarian cancer patients who had had prior chemotherapy was significantly lower than in those from nonpretreated patients (P0.05). This seems to indicate the development of drug resistance after treatment with anticancer drugs. These results suggest that the human tumor clonogenic assay is a useful tool for the evaluation of antitumor effects of drugs in vitro.     

ＡＴＰ生物荧光体外药敏检测在中晚期结直肠癌化疗药物筛选中的应用

目的　探讨ＡＴＰ生物荧光体外药敏检测法（ＡＴＰ-ＴＣＡ）的特点及其在中晚期结直肠癌患者化疗方案中的指导价值。方法　应用ＡＴＰ-ＴＣＡ体外检测５９例结直肠癌细胞对常用抗癌药物的敏感性。结果　ＡＴＰ-ＴＣＡ法对结直肠癌标本的可评估率为９６.６１％。５７例结直肠癌细胞对４组联合化疗药物氟尿嘧啶＋丝裂霉素、氟尿嘧啶＋奥沙利铂、氟尿嘧啶＋伊立替康、氟尿嘧啶＋奥沙利铂＋伊立替康相比氟尿嘧啶、丝裂霉素、伊立替康、奥沙利铂４种单药的敏感度有高度显著性差异（Ｐ＝０.０００６）。应用ＡＴＰ-ＴＣＡ检测结果指导中晚期结直肠癌患者化疗,临床近期有效率为５９.６５％（３４／５７）,总预测准确率为６３.１６％（３６／５７）,阳性符合率为６１.８２％（３４／５５）,阴性符合率为１００％（２／２）。结论　ＡＴＰ-ＴＣＡ能有效检测化疗药物的敏感性,对指导中晚期结直肠癌患者化疗有重要的临床意义。     

Relationship of P-glycoprotein and p53 protein to chemosensitivity in colorectal cancer

Background Resistance of tumors to chemotherapeutic agents is a major problem in cancer treatment. Recent advances in molecular biology have shown a role for oncogenes in this resistance. Methods We determined the positive or negative expression of P-glycoprotein and mutant p53 protein by immunohistochemistry on 101 human colorectal cancer and correlated the expression of these proteins with the chemosensitivity of the tumors to various anticancer agents using the succinate dehydrogenase inhibition (SDI) test. Results Fifty-five (54.5%) of 101 tumors expressed P-glycoprotein and 53 (52.5%) expressed a mutant p53 protein. Thirty-seven of 55 tumors positive for P-glycoprotein also expressed a mutant p53 protein. The association between the coexpression of P-glycoprotein and p53 protein was statistically significant (P=0.001). Neither the expression of P-glycoprotein nor p53 protein affected the chemosensitivity of the tumor to doxorubicin hydrochloride, aclarubicin hydrochloride, pirarubicin, epirubicin hydrochloride, mitomycin C, 5-fluorouracil, cisplatin, carboplatin, or etoposide. However, a positive correlation was found between the control optical density and chemosensitivity in the P-glycoprotein or mutant p53 protein negative tumors. Oppositely, some P-glycoprotein or mutant p53 protein positive tumors showed low chemosensitivity in spite of their high control optical density. Conclusions A highly statistically significant coexpression of P-glycoprotein and mutant p53 protein was found in colorectal cancer. Furthermore, differences in cell growth between the tumor samples indicate the possibility that the expression of P-glycoprotein and mutant p53 protein in colorectal cancer tumors could be associated with chemoresistance.     

83例结直肠癌体外药物敏感性及临床病理参数相关性

目的：通过结直肠癌体外药物敏感性实验，分析临床病理因素与7种化疗药物体外药敏结果相关性，从而为临床选择化疗药物提供理论依据。方法：收集100例新鲜人结直肠癌标本，均经病理证实为癌。采用三维微组织块培养法（ HDRA）比较7种化疗药物的体外敏感性。成功完成83例，同时评价体外药敏结果与临床病理参数之间的相关性。结果：7种化疗药物的体外敏感性结果依次为：5-FU 43.93%、奥沙利铂52.00%、伊立替康25.39%、培美曲塞33.13%、雷替曲塞32.01%、多西紫杉醇16.73%、吉西他滨23.14%。体外药敏结果与患者年龄、性别、部位、淋巴结转移、分期没有明显相关性，而与分化程度呈负相关。结论：体外药敏实验对临床用药具有一定指导意义，结直肠癌分化水平与化疗药物体外药敏结果具有一定相关性。     

Microvascular architecture of human gastrointestinal and breast cancer xenografts in nude mice, and its relation to chemosensitivity

As a tumor factor possibly responsible for chemosensitivity of human cancer xenografts in nude mice, the vascular architecture of tumors growing in mice was investigated in 15 kinds of cancer lines. These consisted of 7 gastric, 3 colorectal, 3 breast and 2 pancreatic cancers. Whole body angiograms of tumor-bearing mice were obtained by perfusing a radiopaque silicone rubber compound (Microfil) through the left ventricle of each mouse. Each cancer retained a characteristic vascular architecture comparable to its histopathological finding. According to the vascularity of the viable part of the tumor, the 15 lines of cancer were classified into 5 groups. Compared with colorectal cancers, stomach cancers had a tendency to decline to a more hypervascular group. There was no apparent relation between vascularity and growth rate, or histological differentiation of the tumors. Among 14 anticancer agents studied, statistically significant correlation between chemosensitivity and vascularity of the 15 cancer lines was observed in 2 drugs, 5'-DFUR and adriamycin. The vascular architecture of the tumors would have some influence in their chemosensitivity through drug accessibility to cancer cells.     

Putative chemosensitivity predictive genes in colorectal cancer cell lines for anticancer agents

In order to identify genes which could predict chemosensitivity in colorectal cancer, gene expression and chemosensitivity were examined in colorectal cancer cell lines. Gene expression profiling of 5 colorectal cancer and 3 normal cell lines was performed using a 22K spotted oligonucleotide microarray. The IC50s of 17 anticancer drugs were determined using the MTT assay for chemosensitivity. The SOURCE database, KEGG Pathway database, and Molecular Diagnosis Score (MDS) were used for data analysis. Two representative colorectal cancer cell lines were identified which were resistant or sensitive to drugs commonly used for colon cancer treatment (5-FU, irinotecan and topotecan). Six hundred and eighty-three genes that were up- or down-regulated by >4-fold between the two cell lines were selected. Pathway analysis was performed with 147 of the 683 genes using the KEGG Pathway database. This analysis revealed 27 genes in the apoptosis, MAPK signaling, and focal adhesion pathways, which could explain the mechanism of chemosensitivity in colorectal cancer cell lines. In addition, the chemosensitivity of other colorectal cancer and normal cell lines was predictable with the selected 27 genes. These genes may act as putative predictive markers for chemosensitivity in chemo-naive colorectal cancer patients following functional analysis and clinical validation.     

Clinical significance of serum p53 antibody detection on chemosensitivity assay in human colorectal cancer.

BACKGROUND AND OBJECTIVES: Alteration of the p53 gene product occurs frequently during progression of colorectal cancer. Recently, mutated p53 protein was found to induce the production of anti-p53 antibodies in the serum of patients. The purpose of this study was to evaluate the relationship between p53 status in serum and chemosensitivity in resectable colorectal cancer patients. METHODS: A total of 22 patients with primary colorectal cancer who underwent surgical treatment were examined for chemosensitivity with iable tumor samples using the Histoculture Drug Response Assay (HDRA). Serum samples of these patients for p53 antibodies were obtained before tumor resection and assayed in duplicate using an enzyme-linked immunosorbent assay kit. RESULTS: The inhibition index of 5-fluorouracil and cis-diamminedichloroplatinum (CDDP), determined by the HDRA method, in the seropositive group was significantly lower than that in the seronegative group (P < 0.01). Furthermore, significant statistical differences in chemosensitivity to 5-fluorouracil and CDDP were revealed depending on the presence of serum p53 antibodies. CONCLUSIONS: Detection of serum p53 antibodies, which reflects p53 mutations in tumor tissue, is a simpler method which correlates with chemosensitivity and may contribute to the selection of favorable chemotherapeutic strategies for colorectal cancer.     

Clinical significance of serum p53 antibody detection in a chemosensitivity assay in cases of human colorectal cancer

Alteration of the p53 gene product occurs frequently during the progression of colorectal cancer. Recently, mutated p53 protein was found to induce the production of anti-p53 antibodies in the serum of patients. The purpose of this study was to evaluate the relationship between p53 status in serum and chemosensitivity in resectable colorectal cancer patients. A total of 35 patients with primary colorectal cancer who underwent surgical treatment were examined by chemosensitivity test with the viable tumor samples using Histoculture Drug Response Assay (HDRA). Serum samples of these patients to test for p53 antibodies were obtained before tumor resection, and assayed in duplicate by using an enzyme-linked immunosorbent assay (ELISA) kit. The inhibition index of 5-FU and CDDP, determined by the HDRA method, in the sero-positive group was significantly lower than that of the sero-negative group (p < 0.01). Furthermore, significant statistical differences in chemosensitivity to 5-FU and CDDP were revealed depending on the presence of serum p53 antibodies. There was no relationship between chemosensitivity assay and tumor marker positivity or clinicopathological features in these patients. Detection of serum p53 antibodies, which reflects p53 mutations in tumor tissue, is a simple method which correlates with chemosensitivity, and may contribute to the selection of favorable chemotherapeutic strategies of colorectal cancer.