MicroRNA-21调控乳腺癌对吉西他滨耐药的机制

背景与目的：以吉西他滨为基础的联合用药在转移性乳腺癌中展示出很好的临床疗效和安全性,但耐药的出现导致治疗失败。MicroRNA是一类非编码小分子RNA,起到类似癌基因或抑癌基因的作用。虽然肿瘤中关于化疗药物耐药的机制报道很多,但microRNA异常表达与耐药之间的关系及机制还不十分清楚。本研究旨在探讨microRNA-21在乳腺癌吉西他滨耐药中的作用及其可能机制。方法：采用低浓度持续诱导MDA-MB-231细胞的方式构建人乳腺癌耐吉西他滨细胞株,药物敏感性差异达10倍以上,继而通过实时荧光定量PCR(real-time PCR,RT-PCR)、CCK-8、蛋白［质］印迹法(Western blot)、转染、划痕和Transwell等实验分别检测microRNA-21对药物的敏感性及上皮-间充质转化(epithelial-mesenchymal transition,EMT)标志物的影响。结果：在乳腺癌吉西他滨耐药细胞株中存在EMT现象,相比亲代细胞,microRNA-21呈高表达,并与吉西他滨敏感性呈负相关。转染microRNA-21的抑制剂和mimic可以分别下调和上调microRNA-21表达,同时EMT现象和药物敏感性也发生了相应的变化。结论：MicroRNA-21可能通过诱导肿瘤细胞的EMT发生而介导乳腺癌对吉西他滨的耐药。     

吉西他滨治疗转移性三阴性乳腺癌的疗效和进展

三阴性乳腺癌(triple negative breast cancer,TNBC)作为乳腺癌的一种特殊亚型,特指雌激素受体(estrogen receptor,ER)、孕激素受体(progestin receptor,PR)及人类表皮生长因子2(humanepidermal growth factor receptor-2,HER-2)均为阴性的乳腺癌。目前全球每年约有100多万人被诊断出乳腺癌,TNBC约占乳腺癌的12%～17%。吉西他滨作为一种抗代谢类肿瘤药物,以其特有的作用机制,与其它多种抗肿瘤药物联合用于治疗晚期TNBC。本文总结了国内外相关临床研究,完整地对含吉西他滨的联合治疗在转移性TNBC中的疗效和进展作一综述。     

卡培他滨联合吉西他滨二线治疗晚期乳腺癌的临床观察

目的:观察卡培他滨联合吉西他滨二线治疗蒽环类或紫杉类耐药的晚期乳腺癌疗效与毒副反应。方法:蒽环类或紫杉类药物耐药的晚期乳腺癌患者30例,应用卡培他滨联合吉西他滨方案化疗:卡培他滨2 000 mg/(m2.d),d1～d14;吉西他滨1 000 mg/m2,d1、d8。21 d为1个周期,至少化疗2个周期。结果:30例患者中,CR 3例,PR 13例,SD 9例,PD 5例,有效率(ORR)53.3%,中位生存期(MST)14个月,1年生存率(OS)为56.7%;主要毒副反应为白细胞和血小板减少、胃肠道反应和手足综合征,均在可耐受范围内。结论:卡培他滨联合吉西他滨二线治疗蒽环类或紫杉类耐药的晚期乳腺癌有较好疗效,且毒副反应可以耐受。     

吉西他滨联合顺铂治疗耐药转移性乳腺癌的临床观察

观察吉西他滨联合顺铂(DDP)方案治疗蒽环类和(或)紫杉类耐药转移性乳腺癌的疗效和不良反应.采用吉西他滨联合DDP方案治疗蒽环类和(或)紫杉类均耐药转移性乳腺癌患者52例.吉西他滨1 000 mg/m2,静脉滴入,d1,d8;DDP 25 mg/m2,静脉滴入,d1～d3.21 d为1个周期,至少用2个周期.本组患者治疗有效率为44.2%(23/52),中位生存时间11.0个月,中位疾病进展时间为5.3个月,1年生存率为42.3%.主要不良反应为胃肠道反应和骨髓抑制.Ⅲ～Ⅳ度呕吐发生率为28.9%(15/52).Ⅲ～Ⅳ度中性粒细胞减少发生率为15.4%(8/52),Ⅲ～Ⅳ度血小板减少发生率为17.3%(9/52).初步研究结果显示,吉西他滨联合DDP方案治疗蒽环类和(或)紫杉类均耐药的转移性乳腺癌疗效较好,毒副反应可耐受,是蒽环类及紫杉类耐药的转移性乳腺癌的有效选择.     

吉西他滨联合卡培他滨治疗蒽环类与紫杉类耐药转移性乳腺癌的临床观察

为了探讨吉西他滨联合卡培他滨方案治疗蒽环类与紫杉类药物耐药的晚期转移性乳腺癌的近期疗效及不良反应,选取37例耐药的晚期乳腺癌患者,接受吉西他滨1 000 mg/m2,静脉滴入,d1、d8;卡培他滨950 mg/m2,2次/d,口服,d1～d14.每3周重复.2个周期化疗后,总有效率(CR+PR)为29.7%(11/37),疾病控制率(CR+PR+SD)为70.3%(26/37).中位进展时间为6.9个月,中位生存时间为15.5个月.最常见的毒性为骨髓抑制、手足综合征及胃肠道反应.初步研究结果提示,吉西他滨联合卡培他滨是治疗蒽环类和紫杉类耐药的晚期乳腺癌的有效方法,不良反应可以耐受.     

CEA、CA125、CA15-3在吉西他滨治疗乳腺癌化疗前后的表达及意义

目的 探讨血清肿瘤标志物癌胚抗原(CEA)、糖类抗原125(CA125)和糖类抗原15-3(CA15-3)在吉西他滨治疗乳腺癌化疗前后的表达及意义.方法 选取接受吉西他滨药物化疗的70例女性原发性乳腺癌患者,治疗21 d后评价疗效,并用电化学发光免疫分析技术检测患者化疗前后血清中CEA、CA125、CA15-3的浓度并进行比较.结果 患者血清CEA、CA125和CA15-3浓度在吉西他滨化疗后明显降低,差异均有统计学意义(P﹤0.01).且患者血清CEA、CA125和CA15-3浓度与吉西他滨的疗效呈正相关(rs﹥0,P﹤0.05).结论 CEA、CA125、CA15-3对临床诊断乳腺癌的发生发展过程具有重要作用.乳腺癌患者应用吉西他滨化疗可明显降低血清CEA、CA125、CA15-3水平,且3种肿瘤标志物与吉西他滨的化疗疗效具有相关性.     

吉西他滨联合希罗达方案治疗乳腺癌术后复发转移化疗失败患者的应用效果

目的探讨吉西他滨联合希罗达方案在乳腺癌术后复发转移化疗失败者中的应用效果。方法 2009年3月至2012年3月间收治的60例乳腺癌术后复发转移化疗失败患者,随机分为两组,分别给予吉西他滨治疗(对照组)和吉西他滨+希罗达治疗(观察组)。观察记录两组的治疗效果,并进行比较。结果观察组的患者满意度和治疗总缓解率以及1年生存率均显著高于对照组,两组的不良反应情况比较,差异无统计学意义(P>0.05)。观察组患者生活质量改善情况显著优于对照组,差异均有统计学意义(均P<0.05)。两组的中位生存期比较,差异无统计学意义(P>0.05)。结论吉西他滨联合希罗达方案治疗乳腺癌术后复发转移化疗失败患者,可以获得较好的临床疗效,且不良反应较轻,应用效果较好,值得推广。     

新辅助化疗治疗三阴性乳腺癌的疗效及预后对比分析

目的:通过新辅助化疗提高三阴性乳腺癌(TNBC)手术切除的近期和远期疗效并比较两种不同方案新辅助化疗的治疗效果.方法:128例局部晚期TNBC患者分为两组,A组采取ET(吡柔比星联合多西他赛)方案.B组采取GP(顺铂联合吉西他滨)方案进行新辅助化疗,观察化疗后病理反应及其与远期生存的关系.结果:ET组有效率为88.7%,GP组为82.0%.两组5年总生存率和5年无病生存率(DFS)分别为75.4%、71.4%和85.3%、58.9%.结论:TNBC对紫杉联合蒽环类(ET组)较顺铂联合吉西他滨的(GP组)新辅助化疗更敏感,更易获cCR、pCR.     

吉西他滨联合顺铂或卡培他滨治疗晚期乳腺癌的疗效比较

乳腺癌的辅助治疗已很规范,但晚期乳腺癌的治疗仍是临床十分棘手的问题.近年来的研究表明,吉西他滨联合顺铂(GP)或吉西他滨联合卡培他滨(GX)治疗进展期乳腺癌疗效确切,并在乳腺癌的治疗中显示出了低毒、有效的优势[1].但目前尚没有直接比较两个化疔方案的临床试验.我院从2006年1月至2008年12月,应用吉西他滨联合顺铂或卡培他滨方案,治疗晚期乳腺癌患者72例,疗效满意,总结报告如下.     

吉西他滨联合顺铂治疗三阴性和非三阴性乳腺癌的临床疗效及安全性分析

目的 探讨晚期三阴性乳腺癌(TNBC)和非三阴性乳腺癌(non-TNBC)使用吉西他滨联合顺铂治疗的临床疗效及临床安全性.方法 选择晚期乳腺癌患者120例,按照免疫组化表达分为TNBC组(52例)和non-TNBC组(68例).化疗方案为:第1、8天给予静脉滴注吉西他滨1000 mg/m2.顺铂一般80～100 mg/m2,每3周1次;或20 mg/m2,连用5天,每3～4周重复1次.分析2组患者临床病理特征、近期疗效及不良反应.结果 TNBC组有效率为38.5％(20/52),控制率为75.0％ (39/52);non-TNBC组有效率为22.1％ (15/68),控制率为57.4％ (39/68).2组患者有效率和控制率的组间比较均存在统计学差异(P＜0.05);患者无进展生存期的组间比较也存在统计学差异(P＜0.05).吉西他滨联合顺铂化疗方案的不良反应主要为胃肠道反应和血液学毒性,2组患者的不良反应的组间比较无统计学差异(P＞0.05).结论 吉西他滨联合顺铂化疗对TNBC和non-TNBC患者均有效,而TNBC患者的近期疗效优于non-TNBC患者;在不良反应方面TNBC和non-TNBC患者则没有明显差别,2组患者均能对化疗药的毒副作用耐受,其安全性较好.     

Induction of apoptosis and tumor regression by vesicular stomatitis virus in the presence of gemcitabine in lung cancer

Vesicular stomatitis virus (VSV) has been shown to replicate rapidly in vitro and kill selectively a variety of tumor cell lines. The present study was designed to determine whether gemcitabine potentiates the antitumor activity of VSV in vitro and in vivo. A549 human lung adenocarcinoma cells and LLC Lewis lung carcinoma cells were treated with VSV (0.1-10 plaque-forming units per cell) plus gemcitabine (20 nM to 20 microM). Mice bearing A549 or LLC were treated with VSV (5 x 10(4) to 1 x 10(8) plaque-forming units) daily for 5 days plus gemcitabine (5-125 mg/kg/day) once every 3 days for 4 times. Induction of apoptosis and effects on growth inhibition were assessed. The lung cancer cells treated with VSV plus gemcitabine displayed the apparently increased apoptotic cells compared with treatment with VSV or gemcitabine alone. The combined treatment with VSV plus gemcitabine induced the apparent antitumor activity with complete regression of the established lung cancer in both A549 and LLC lung cancer models and augmented the induction of apoptosis in lung cancer cells in vivo as well. This study suggests that the combined treatment with VSV plus gemcitabine may augment the induction of apoptosis in lung cancer cells in vitro and in vivo, and that the augmented antitumor activity in vivo may result from the increased induction of apoptosis in lung cancer cells. The present findings may be of importance to the further exploration of the potential application of this combined approach in the treatment of lung cancer.     

Enhanced antitumor efficacy by the combination of emodin and gemcitabine against human pancreatic cancer cells via downregulation of the expression of XIAP in vitro and in vivo

XIAP and NF-κB play an important role in chemotherapy resistance in pancreatic cancer. The purpose of this study was to explore the role of XIAP and NF-κB in potentiating the antitumor effect of gemcitabine by emodin in pancreatic cancer. SW1990 cells were treated by sodium chloride, gemcitabine, emodin or their combination (gemcitabine plus emodin). Cellular proliferation and apoptosis were detected by Cell Counting kit-8 (CCK-8) assay and flow cytometry in?vitro. The combination therapy more significantly inhibited SW1990 cell growth and induced a higher percentage of apoptosis than monotherapy. Gemcitabine upregulated the expression of XIAP and NF-κB, while emodin or emodin plus gemcitabine downregulated them compared to the control group in?vitro. SW1990 cells were used to establish orthotopic pancreatic tumor models in nude mice. Tumor-bearing mice were treated with sodium chloride, emodin, gemcitabine or their combination. After being treated for 4 weeks, the nude mice were imaged with high-resolution positron emission tomography (microPET) and fluorine-18-labeled fluorodeoxyglucose (18F-FDG) to detect the tumor/non-tumor ratio (T/NT ratio) and standard uptake value (SUV). The mice were sacrificed to determine tumor weight. The combination of emodin and gemcitabine showed more significant reduction in the T/NT ratio, SUV and tumor weight compared to monotherapy. The mRNA levels and the protein expression of XIAP and NF-κB were upregulated in the gemcitabine group, while they were downregulated in the emodin group and the combination group in?vivo. Ki-67 prolif-eration index and TUNEL assay results also showed that emodin enhanced tumor apoptosis induced by gemcitabine in?vivo. This study suggests that emodin enhances the antitumor effect of gemcitabine in SW1990 pancreatic cancer in?vitro and in?vivo, which may be via the downregulation of NF-κB expression, thus inhibiting the expression of XIAP.     

Cisplatin and TRAIL enhance breast cancer stem cell death

Triple negative breast cancer (TNBC) has increased recurrence and poor survival, despite a high response rate to neoadjuvant chemotherapy. The aim of this study was to determine whether current drug treatment(s) eliminates bulk of tumor cells, but it has a minimal effect on cancer stem cells (CSCs) leading to tumor recurrence. We studied the effects of PARP inhibitors (AZD2281 and BSI-201), paclitaxel, docetaxel, cisplatin and cisplatin plus TRAIL on CSCs derived from CRL-2335 and MDA-MB-468 TNBC cells in?vitro. The in?vitro data indicate that cisplatin plus TRIAL treatment was most effective in eliminating CSCs compared to PARP inhibitors, cisplatin, paclitaxel and docetaxel. Treatment with cisplatin plus TRAIL also inhibits Wnt-1 signaling and its downstream target, β-catenin, phospho β-catenin, cyclin D1, increased apoptosis, reduced proliferation and mammosphere formation. Inhibition of Wnt-1 by siRNA significantly reduced the ability of CSCs to form mammospheres compared to control. However, maximum effect was seen in cisplatin plus TRAIL-treated cells. Taken together the data suggest that cisplatin plus TRAIL treatment has the potential of providing a new strategy for improving the therapeutic outcome in TNBC patients.     

BRD4通过SHH信号通路诱导甲状腺癌细胞增殖、侵袭与迁移

背景与目的：甲状腺癌是目前发病率最高的内分泌系统恶性肿瘤之一,目前的综合治疗手段虽然效果较好,但是部分患者在随后的治疗中会出现继发性摄碘率下降,¹³¹I治疗效果差,从而导致复发及远处转移。近年来的研究发现,溴样结构域蛋白4(double bromodomain-containing protein 4,BRD4)可促进多种恶性肿瘤的进展,因此本研究旨在探究BRD4在甲状腺乳头状癌(papillary thyroid cancer,PTC)细胞中的作用,寻找治疗甲状腺癌的特异性靶点。方法：应用实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction,RTFQ-PCR)检测PTC组织和癌周组织中BRD4的表达差异,应用siBRD4干扰基因转染PTC细胞株TPC-1,应用蛋白［质］印迹法(Western blot)检验沉默效果,通过MTT实验、平板克隆实验、Transwell小室侵袭与迁移实验检验沉默BRD4前后PTC细胞株TPC-1活力、增殖、迁移及侵袭等生物学行为的变化。进一步应用Western blot及RTFQ-PCR检测钠碘转运体(sodium iodide symporter,NIS)基因及蛋白的表达变化,以及SHH信号通路下游基因SHH、GLI1表达变化情况。结果：BRD4在PTC组织中表达明显增高(P＜0.05);在体外实验中BRD4沉默后PTC细胞株TPC-1的细胞活力、增殖、迁移与侵袭能力下降。此外,BRD4沉默后NIS基因及蛋白表达增高,SHH信号通路下游基因SHH、GLI1表达降低(P＜0.05)。结论：BRD4通过上调SHH信号通路相关基因促进PTC细胞的侵袭与迁移,沉默BRD4可以促进NIS的表达,BRD4有望成为治疗甲状腺癌的新靶点。     

K-ras oncogene silencing strategy reduces tumor growth and enhances gemcitabine chemotherapy efficacy for pancreatic cancer treatment

Pancreatic adenocarcinoma remains a fatal disease characterized by rapid tumor progression, high metastatic potential and profound chemoresistance. Gemcitabine is the current standard chemotherapy for advanced pancreatic cancer, but it is still far from optimal and novel therapeutic strategies are needed urgently. Mutations in the k-ras gene have been found in more than 90% of pancreatic cancers and are believed to play a key role in this malignancy. Thus, the goal of this study was to investigate the impact of k-ras oncogene silencing on pancreatic tumor growth. Additionally, we examined whether combining k-ras small interfering RNA (siRNA) with gemcitabine has therapeutic potential for pancreatic cancer. The treatment of tumor cell cultures with the corresponding k-ras siRNA resulted in a significant inhibition of k-ras endogenous expression and cell proliferation. In vivo, tumor xenografts were significantly reduced with k-ras siRNA(GAT) delivered by electroporation. Moreover, combined treatment with pSsik-ras(GAT) plus gemcitabine resulted in strong growth inhibition of orthotopic pancreatic tumors. Survival rate was significantly prolonged and the mean tumor volume was dramatically reduced in mice receiving the combined treatment compared with single agents. Collectively, these findings show that targeting mutant k-ras through specific siRNA might be effective for k-ras oncogene silencing and tumor growth inhibition. The improvement of gemcitabine-based chemotherapy suggests that this strategy might be used therapeutically against human pancreatic cancer to potentiate the effects of conventional therapy.     

Cross-species genomic and functional analyses identify a combination therapy using a CHK1 inhibitor and a ribonucleotide reductase inhibitor to treat triple-negative breast cancer

ABSTRACT: INTRODUCTION: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is diagnosed in approximately 15% of all human breast cancer (BrCa) patients. Currently, no targeted therapies exist for this subtype of BrCa and prognosis remains poor. Our laboratory has previously identified a proliferation/DNA repair/cell cycle gene signature (Tag signature) that is characteristic of human TNBC. We hypothesize that targeting the dysregulated biological networks in the Tag gene signature will lead to the identification of improved combination therapies for TNBC. METHODS: Cross-species genomic analysis was used to identify human breast cancer cell lines that express the Tag signature. Knock-down of the up-regulated genes in the Tag signature by siRNA identified several genes that are critical for TNBC cell growth. Small molecule inhibitors to two of these genes were analyzed, alone and in combination, for their effects on cell proliferation, cell cycle, and apoptosis in vitro and tumor growth in vivo. Synergy between the two drugs was analyzed by the Chou-Talalay method. RESULTS: A custom siRNA screen was used to identify targets within the Tag signature that are critical for growth of TNBC cells. Ribonucleotide reductase 1 and 2 (RRM1 and 2) and checkpoint kinase 1 (CHK1) were found to be critical targets for TNBC cell survival. Combination therapy, to simultaneously attenuate cell cycle checkpoint control through inhibition of CHK1 while inducing DNA damage with gemcitabine, improved therapeutic efficacy in vitro and in xenograft models of TNBC. CONCLUSIONS: This combination therapy may have translational value for patients with TNBC and improve therapeutic response for this aggressive form of breast cancer.     

BET proteins regulate homologous recombination-mediated DNA repair: BRCAness and implications for cancer therapy

Bromodomain and Extra-Terminal (BET) proteins are historically involved in regulating gene expression and BRD4 was recently found to be involved in DNA damage regulation. Aims of our study were to assess BRD4 regulation in homologous recombination-mediated DNA repair and to explore novel clinical strategies through the combinations of the pharmacological induction of epigenetic BRCAness in BRCA1 wild-type triple negative breast cancer (TNBC) cells by means of BET inhibitors and compounds already available in clinic. Performing a dual approach (chromatin immunoprecipitation and RNA interference), the direct relationship between BRD4 and BRCA1/RAD51 expression was confirmed in TNBC cells. Moreover, BRD4 pharmacological inhibition using two BET inhibitors (JQ1 and GSK525762A) induced a dose-dependent reduction in BRCA1 and RAD51 levels and is able to hinder homologous recombination-mediated DNA damage repair, generating a BRCAness phenotype in TNBC cells. Furthermore, BET inhibition impaired the ability of TNBC cells to overcome the increase in DNA damage after platinum salts (i.e., CDDP) exposure, leading to massive cell death, and triggered synthetic lethality when combined with PARP inhibitors (i.e., AZD2281). Altogether, the present study confirms that BET proteins directly regulate the homologous recombination pathway and their inhibition induced a BRCAness phenotype in BRCA1 wild-type TNBC cells. Noteworthy, being this strategy based on drugs already available for human use, it is rapidly transferable and could potentially enable clinicians to exploit platinum salts and PARP inhibitors-based treatments in a wider population of TNBC patients and not just in a specific subgroup, after validating clinical trials.     

TIPIN depletion leads to apoptosis in breast cancer cells

Triple‐negative breast cancer (TNBC) is the breast cancer subgroup with the most aggressive clinical behavior. Alternatives to conventional chemotherapy are required to improve the survival of TNBC patients. Gene‐expression analyses for different breast cancer subtypes revealed significant overexpression of the Timeless‐interacting protein (TIPIN), which is involved in the stability of DNA replication forks, in the highly proliferative associated TNBC samples. Immunohistochemistry analysis showed higher expression of TIPIN in the most proliferative and aggressive breast cancer subtypes including TNBC, and no TIPIN expression in healthy breast tissues. The depletion of TIPIN by RNA interference impairs the proliferation of both human breast cancer and non‐tumorigenic cell lines. However, this effect may be specifically associated with apoptosis in breast cancer cells. TIPIN silencing results in higher levels of single‐stranded DNA (ssDNA), indicative of replicative stress (RS), in TNBC compared to non‐tumorigenic cells. Upon TIPIN depletion, the speed of DNA replication fork was significantly decreased in all BC cells. However, TIPIN‐depleted TNBC cells are unable to fire additional replication origins in response to RS and therefore undergo apoptosis. TIPIN knockdown in TNBC cells decreases tumorigenicity in vitro and delays tumor growth in vivo. Our findings suggest that TIPIN is important for the maintenance of DNA replication and represents a potential treatment target for the worst prognosis associated breast cancers, such as TNBC.     

吉西他滨和顺铂联合用药治疗晚期胰腺癌患者利弊的Meta分析

目的:通过Meta分析，探讨吉西他滨和顺铂联合与吉西他滨单药治疗晚期胰腺癌的优缺点。方法:计算机检索中国知网、维普、万方数据库及中国生物医学数据库、PubMed、Sciencedirect、Embase、Cochrane Database、OVID Medline、Springer Link、EBSCO数据库，筛选观察组为吉西他滨与顺铂联合用药，对照组为吉西他滨单药治疗晚期胰腺癌的试验。检索期限为建库至2018年3月31日，同时手工查阅检索相似文献及参考文献。以上资料均由两位研究者独立进行文献筛选和资料提取，采用Review Manager 5.3软件进行Meta分析，计算结果以HR或OR值及95%置信区间（95%CI）表示。结果:共纳入文献12篇，包括观察组850例和对照组753例。Meta分析结果显示:疗效方面，总生存期、1年生存率及半年生存率方面吉西他滨和顺铂联合用药与吉西他滨单独用药无明显区别［HR总生存期=0.97，95%CI为（0.83，1.12）,P=0.65＞0.05；OR1年生存率=1.02，95%CI为（0.76，1.38），P=0.89＞0.05；OR半年生存率=1.12，95%CI为（0.77，1.64），P=0.56＞0.05］；而客观缓解率（ORR）则具有边缘性统计意义［OR客观缓解率=1.54，95%CI为（1.00，2.37），P=0.05］；毒副反应方面，吉西他滨和顺铂联合用药的毒副作用明显高于吉西他滨单独用药［OR3/4度中性粒细胞减少=1.70，95%CI为（1.27，2.27），P=0.000 4＜0.05；OR3/4度血小板减少=1.96，95%CI为（1.55，2.49），P＜0.000 01；OR胃肠道毒副作用=2.98，95%CI为（1.95，4.55），P＜0.000 01］。结论:吉西他滨联合顺铂治疗晚期胰腺癌虽然在ORR中能使患者受益，但不能使患者获得比单用吉西他滨更好的临床疗效及远期预后，反而使中性粒细胞减少、血小板减少及胃肠道反应等毒副反应加剧。因此，临床上不应提倡吉西他滨联合顺铂用药作为一线临床用药，应选用更加合理有效的化疗用药方案。