Experimental study on effect of recombinant human growth hormone combined with chemotherapy on stomach neoplasms implanted in nude mice

Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stom- ach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5- FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index (PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.

Postoperative chemoradiotherapy with capecitabine and oxaliplatin vs.capecitabine for pathological stage N2 rectal cancer

Objective:Several studies have been conducted on the effects and toxicity of adding oxaliplatin to fluorouracilbased or capecitabine-based chemoradiotherapy(CRT)regimens as significantly increasing the toxic response without benefit to survival.In this study,we further explored the role of these two postoperative CRT regimens in patients with pathological stage N2 rectal cancer.Methods:This study was a subgroup analysis of a randomized clinical trial.A total of 180 patients with pathological stage N2 rectal cancer were eligible,85 received capecitabine with radiotherapy(RT),and 95 received capecitabine and oxaliplatin with RT.Patients in both groups received adjuvant chemotherapy[capecitabine and oxaliplatin(XELOX);or fluorouracil,leucovorin,and oxaliplatin(FOLFOX)]after CRT.Results:At a median follow-up of 59.2[interquartile range(IQR),34.0−96.8]months,the three-year diseasefree survival(DFS)was 53.3%and 64.9%in the control group and the experimental group,respectively[hazard ratio(HR),0.63;95%confidence interval(95%CI),0.41−0.98;P=0.04].There was no significant difference between the groups in overall survival(OS)(HR,0.62;95%CI,0.37−1.05;P=0.07),the incidence of locoregional recurrence(HR,0.62;95%CI,0.24−1.64;P=0.33),the incidence of distant metastasis(HR,0.67;95%CI,0.42−1.06;P=0.09)and grade 3−4 acute toxicities(P=0.78).For patients with survival longer than 3 years,the conditional overall survival(COS)was significantly better in the experimental group(HR,0.39;95%CI,0.16−0.96;P=0.03).Conclusions:Our results indicated that adding oxaliplatin to capecitabine-based postoperative CRT is safe and effective in patients with pathological stage N2 rectal cancer.

Immunotherapy for recurrent hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is presented frequently in late stages that are not amenable for curative treatment.Even for patients who can undergo resection for curative treatment of HCC,up to 50%recur.For patients who were not exposed to systemic therapy prior to recurrence,recurrence frequently cannot be subjected to curative therapy or local treatments.Such patients have several options of immunotherapy(IO).This includes programmed cell death protein 1(PD-1)and cytotoxic T-lymphocyte associated protein 4 treatment,combination of PD-1 and vascular endothelial growth factor inhibitor or single agent PD-1 therapy when all other options are deemed inappropriate.There are also investigational therapies in this area that explore either PD-1 and tyrosine kinase inhibitors or a novel agent in addition to PD-1 with vascular endothelial growth factor inhibitors.This minireview explored IO options for patients with recurrent HCC who were not exposed to systemic therapy at the initial diagnosis.We also discussed potential IO options for patients with recurrent HCC who were exposed to first-line therapy with curative intent at diagnosis.

Prevention of metastasis to liver by using 5-FU intraperitoneal chemotherapy in nude mice inoculated with human colonic cancer cells

AIMS Using a new approach of regional adjuvant chemotherapy to prevent cancer cells hepatic metasta- sis after radical surgery of large bowel cancer. METHODS A model of liver with metastasis of hu- man colonic cancer (HCC) cells in nude mice was used to observe the effect in prevention of metastasis of HCC cells inoculated via spleen applied with early postoper- ative intraperitoneal (IP) chemotherapy using large dose of 5-FU. RESULTS The incidence of metastasis to liver was decreased by 40%,the mean number of metastatic liv- er nodules in each animal was reduced by 50.89% and the mean survival times of each animal was prolonged by 48.21% by using 5-FU 40 mg/NS 40 ml/kg IP for two consecutive days as compared with the controls. CONCLUSIONS IP is a new and more effective re- gional adjuvant chemotheraputic approach in the pre- vention of liver metastasis HCC cells after radical surgery of large bowel cancer.

肝癌靶向联合免疫治疗耐药后的二线治疗方案研究进展

近年来,靶向和免疫单药及联合治疗晚期肝癌的临床研究为一线用药方案选择提供了丰富的疗效与安全性证据。然而,对于肝癌二线治疗方案的选择,目前各项临床指南尚无统一意见,原因在于现有循证医学证据局限于索拉非尼失败后的选择,而对于新的一线方案,如靶向免疫联合治疗肝癌耐药后的二线治疗方案,依然缺乏高证据等级的临床试验结论。本文回顾了目前临床试验研究结果,根据药物作用的不同机制,对靶向免疫一线治疗耐药后肝癌二线治疗方案的研究进行了归纳,并系统总结近年研究进展。对于一线靶免联合治疗耐药的肝癌患者,靶向联合治疗、免疫双抗治疗均有望提高疗效、改善生存,未来还需更多前瞻性临床研究数据,为靶免联合治疗耐药的肝癌患者提供有效、安全的治疗方案。

垂体催乳素瘤的临床特点及诊治要点更新--基于《2022版ICCE/AME垂体催乳素瘤临床实践共识》解读

垂体催乳素瘤是一种由垂体催乳素细胞瘤过量合成和分泌催乳素引起的神经内分泌疾病,垂体催乳素瘤的规范化诊疗对于恢复并维持患者的正常垂体功能并提高其生活质量具有重要意义。2022年1月,《欧洲内分泌杂志》发布了国际临床内分泌学分会(ICCE)与意大利临床内分泌学家协会(AME)关于垂体催乳素瘤的临床实践最新共识申明——《2022版ICCE/AME垂体催乳素瘤临床实践共识》(简称2022版ICCE/AME新共识)。2022版ICCE/AME新共识立足最新循证医学证据,对于垂体催乳素瘤的临床诊治问题进行系统性阐述、分析和建议。本文围绕2022版ICCE/AME新共识关于垂体催乳素瘤的诊断、治疗、特殊人群、多巴胺激动剂抵抗及侵袭性疾病等诊治要点更新进行解读,希望有助于全科医生及内分泌专科医生对于垂体催乳素瘤的认识,为其临床实践的规范化诊疗提供参考。

A clinical and long-term follow-up study of perioperative sequential triple therapy for gastric cancer

INTRODUCTIONAlthough the long-term postoperative survival rateof gastric cancer(GC) patients has been improvedsignificantly since the local dissection of lymph nodewas widely used in China,yet the low curativeresection rate and the high recurrence rate fromperitoneal and hepatic metastases hinder it fromfurther improvement.To alter the currentunsatisfactory status of GC treatment,a

免疫细胞及炎症因子对晚期肺癌一线化疗效果的预测价值

【目的】探讨T淋巴细胞亚群、肿瘤浸润T淋巴细胞(Tils)及炎症因子对晚期肺癌一线化疗效果的预测价值。【方法】检测98例首诊TNM分期为Ⅲ/Ⅳ期的非小细胞肺腺癌患者的血清白细胞介素1α(IL-1α)、IL-6、IL-17、γ-干扰素(INF-γ)水平及T淋巴细胞亚群CD4^(+)T、CD8^(+)T、调节性T细胞、CD57^(+)细胞、Granzyme B^(+)细胞、CD45RO^(+)细胞比例;所有患者均接受紫杉醇注射液+顺铂化疗,治疗4个周期后评定疗效,并据此分为有效组和无效组,分析化疗无效的影响因素及预测疗效的有效标志物。【结果】化疗后,98例患者中69例化疗有效,29例无效。无效组患者淋巴结转移占比及调节性T细胞、IL-1α表达水平均高于有效组(P<0.05),CD57^(+)细胞、CD45RO^(+)细胞比例均低于有效组(P<0.05)。多因素逐步Logistic回归分析结果显示,调节性T细胞、IL-1α水平高是肺癌患者化疗无效的危险因素(P<0.05),CD57^(+)细胞、CD45RO^(+)细胞比例高是保护因素(P<0.05)。受试者工作特征(ROC)曲线分析显示,调节性T细胞、CD57^(+)细胞、CD45RO^(+)细胞、IL-1α水平预测化疗效果的灵敏度分别为82.76%、86.21%、89.66%、93.10%,四者联合的灵敏度、特异度和曲线下面积(AUC)分别为82.76%、97.10%、0.957。【结论】T淋巴细胞亚群、Tils及炎症因子水平与晚期肺癌治疗效果密切相关,其可作为预测疗效的敏感指标。

揿针联合穴位贴敷治疗对胃肠道肿瘤化疗患者胃肠道反应及睡眠质量的影响

目的 探讨胃肠道肿瘤化疗患者应用揿针联合穴位贴敷治疗对胃肠道反应及睡眠质量的影响效果。方法 选择河南省肿瘤医院中西结合科住院的胃肠道肿瘤化疗患者96例(2021年10月至2023年6月入组)患者研究,参照计算机数字表法分为2组,每组48例,包括对照组(穴位贴敷治疗)与试验组(揿针联合穴位贴敷治疗)。比较干预前后2组患者胃肠道反应及睡眠质量的变化。结果 治疗前,2组恶心程度评分、呕吐程度评分、食欲情况评分差异无统计学意义(P>0.05),治疗5 d、治疗7 d 2组均有改善,且试验组恶心程度评分、呕吐程度评分、食欲情况评分更低,差异有统计学意义(P<0.05);治疗7 d,试验组恶心频率与呕吐频率均低于对照组(P<0.05);治疗前,2组睡眠质量差异无统计学意义(P>0.05),治疗7 d试验组睡眠质量PSQI评分低于对照组(P<0.05);试验组总并发症发生率比对照组低(P<0.05)。结论 胃肠道肿瘤化疗患者应用揿针联合穴位贴敷治疗可以更好地减轻化疗所致的胃肠道反应,改善食欲及睡眠质量,值得应用。

The value of postoperative hepatic regional chemotherapy in prevention of recurrence after radical resection of primary liver cancer

INTRODUCTIONIn China,primary liver cancer (PLC) ranks secondin cancer mortality since the 1990s.In the field ofPLC treatment,surgical resection remains the best,which includes large PLC resection,small PLCresection,re-resection of subclinical recurrence,aswell as cytoreduction and sequential resection forunresectable PLC.However,recurrence

A study of preoperative methionine-depleting parenteral nutrition plus chemotherapy in gastric cancer patients

AIM To investigate the interference ofmethionine.free parenteral nutrition plus 5-Fu（-MetTPN+5-Fu）in gastric cancer cell kineticsand the side effects of the regimen.METHODS Fifteen patients with advancedgastric cancer were randomly divided into twogroups,7 patients were given preoperatively aseven-day course of standard parenteralnutrition in combination with a five-day courseof chemotherapy（sTPN+5-Fu）,while the other8 patients were given methionine-deprivedparenteral nutrition and 5-Fu（-MetTPN+5-Fu）.Cell cycles of gastric cancer and normal mucosawere studied by flow cytometry（FCM）.Bloodsamples were taken to measure the serumprotein,methionine（Met）and cysteine（Cys）levels,and liver and kidney functions.RESULTS As compared with the resultsobtained before the treatment,the percentage ofG0/G1 tumor cells increased and that of S phasedecreased in the-MetTPN+5-Fu group,while thecontrary was observed in the sTPN+5-Fu group.Except that the ALT,AST and AKP levels wereslightly increased in a few cases receiving-MetTPN+5-Fu,all the other biochemicalparameters were within normal limits.Serum Cys level decreased slightly after the treatmentin both groups.Serum Met level of patientsreceiving sTPN+5-Fu was somewhat higher aftertreatment than that before treatment;however,no significant change occurred in the -MetTPN+5-Fu group,nor operative complications in bothgroups.CONCLUSION -MetTPN+5-Fu exerted asuppressive effect on cancer cell proliferation,probably through a double mechanism ofcreating a state of'Met starvation'adverse tothe tumor cell cycle,and by allowing 5-Fu to killspecifically cells in S phase.Preoperative short-term administration of -MetTPN+5-Fu had littleundesirable effect on host metabolism.

Early prediction of pathological outcomes to neoadjuvant chemotherapy in breast cancer patients using automated breast ultrasound

Objective： Early assessment of response to neoadjuvant chemotherapy （NAC） for breast cancer allows therapy to be individualized. The optimal assessment method has not been established. We investigated the accuracy of automated breast ultrasound （ABUS） to predict pathological outcomes after NAC. Methods： A total of 290 breast cancer patients were eligible for this study. Tumor response after 2 cycles of chemotherapy was assessed using the product change of two largest perpendicular diameters （PC） or the longest diameter change （LDC）. PC and LDC were analyzed on the axial and the coronal planes respectively. Receiver operating characteristic （ROC） curves were used to evaluate overall performance of the prediction methods. Youden＇s indexes were calculated to select the optimal cut-off value for each method. Sensitivity, specificity, positive and negative predictive values （PPV and NPV） and the area under the ROC curve （AUC） were calculated accordingly.Results： ypT0/is was achieved in 42 patients （14.5%） while ypT0 was achieved in 30 patients （10.3%） after NAC. All four prediction methods （PC on axial planes, LDC on axial planes, PC on coronal planes and LDC on coronal planes） displayed high AUCs （all〉0.82）, with the highest of 0.89 [95% confidence interval （95% CI）, 0.83-0.95] when mid-treatment ＆BUS was used to predict final pathological complete remission （pCR）. High sensitivities （85.7%-88.1%） were observed across all four prediction methods while high specificities （81.5%-85.1%） were observed in two methods used PC. The optimal cut-off values defined by our data replicate the WHO and the RECIST criteria. Lower AUCs were observed when mid-treatment ABUS was used to predict poor pathological outcomes. Conclusions：ABUS is a useful tool in early evaluation of pCR after NAC while less reliable when predicting poor pathological outcomes.

胰腺癌类器官模型的构建及其对化疗药物的敏感性试验

目的建立及鉴定患者来源的类器官模型,并利用该模型进行化疗药物敏感性检测。方法利用已确诊胰腺癌的2例女性患者的手术标本获取肿瘤组织消化后获取胰腺癌细胞,利用基质胶接种于培养皿中进行三维培养;制备石蜡切片并进行苏木精-伊红(HE)染色和免疫组化染色,通过与亲本肿瘤组织对比,检测其能否保留体内肿瘤的组织病理学特征;利用不同浓度的7种化疗药物处理胰腺癌类器官,使用Cell Titer-Glo®3D试剂测定细胞活力,分析药敏结果。结果成功建立了2例患者来源的胰腺癌类器官,HE染色和免疫组化染色结果显示胰腺癌类器官与其来源的患者肿瘤在组织病理学特征上一致;2例胰腺癌类器官均对吉西他滨单药、奥沙利铂与SN38+氟尿嘧啶联用更为敏感,患者1较患者2敏感性更高,来自不同患者的类器官对药物反应存在个体差异。结论本研究成功构建的胰腺癌类器官模型能够反映亲本胰腺肿瘤的组织学分型,并能够进行体外化疗药物敏感性试验,有望为患者临床用药提供参考。

心血管磁共振成像评估肿瘤治疗相关心血管损伤的应用进展

随着肿瘤治疗技术的发展,肿瘤患者的生存率得到大幅改善。但肿瘤治疗可能伴有潜在的心血管毒性作用,导致心血管疾病的发病率和死亡率增加,最终肿瘤患者可能并非死于肿瘤,而死于肿瘤治疗,早期识别心血管损伤并制订相关策略改善这种副作用至关重要。心血管磁共振成像可实现对心脏结构、心脏功能、心肌组织特征及心脏大血管血流动力学的“一站式”评价,在评价心血管损伤,尤其是早期损伤方面具有重要作用。本综述回顾各种心血管磁共振成像方法在评估肿瘤治疗相关心血管损伤中的应用和进展。

Evaluation of menopausal status among breast cancer patients with chemotherapy-induced amenorrhea

Objective： In patients with chemotherapy-induced amenorrhea （CIA）, the menopausal status is ambiguous anddifficult to evaluate. This study aimed to establish a discriminative model to predict and classify the menopausalstatus of breast cancer patients with CIA.Methods： This is a single center hospital-based study from 2013 to 2016. The menopausal age distribution andaccumulated incidence rate of CIA are described. Multivariate models were adjusted for established and potentialconfounding factors including age, serum concentration of estradiol （E2） and follicle-stimulating hormone （FSH）,feeding, pregnancy, parity, abortions, and body mass index （BMI）. The odds ratio （OR） and 95% confidenceinterval （95% CI） of different risk factors were estimated.Results： A total of 1,796 breast cancer patients were included in this study, among whom, 1,175 （65.42%） werepremenopausal patients and 621 （34.58%） were post-menopause patients. Five hundred and fifty patients wereincluded in CIA analysis, and a cumulative CIA rate of 81.64% was found in them. Age （OR： 1.856, 95% CI：1.732-1.990）, serum concentration of E2 （OR： 0.976, 95% CI： 0.972-0.980） and FSH （OR： 1.060, 95% CI：1.053-i.066）, and menarche age （OR： 1.074, 95% CI： 1.009-1.144） were found to be associated with the patients＇menopausal status. According to multivariate analysis, the discriminative model to predict the menopausal status isLogit （P）=-28.396＋0.536Age-0.014E2＋0.031FSH. The sensitivities for this model were higher than 85%, and itsspecificities were higher than 89%.Conclusions： The discriminative model obtained from this study for predicting menstrual state is important forpremenopausal patients with CIA. This model has high specificity and sensitivity and should be prudently used.

滋肾润肺方辅助化疗治疗中晚期肺癌气阴两虚证患者的临床疗效

【目的】探讨滋肾润肺方联合化疗治疗中晚期肺癌气阴两虚证患者的疗效。【方法】两院收治的80例中晚期肺癌气阴两虚证患者,随机分为化疗组与联合组,每组40例。化疗组采用常规肺癌化疗方案,联合组在此基础上同时给予滋肾润肺方口服。比较两组患者的疗效、疾病进展时间(TTP)、1年存活率、1年无进展生存(PFS)率,治疗前后中医症状积分、卡氏评分(KPS)改善情况,骨髓抑制发生情况。【结果】联合组治疗总有效率(RR)为37.5%(15/40)、疾病控制率(DCR)为82.5%(33/40),化疗组RR为27.5%(11/40)、DCR为70.0%(28/40),两组比较差异均无统计学意义(P>0.05)。化疗组TTP为6.5(4.2~8.4)个月,1年存活率为30.0%(12/40),1年PFS率为85.0%(34/40);联合组TTP为7.2(5.5~9.3)个月,1年存活率35.0%(14/40),1年PFS率为87.5%(35/40),两组比较差异均无统计学意义(P>0.05)。与治疗前比较,两组治疗后中医症状积分均明显降低,且观察组各项指标下降更显著(P<0.05)。治疗后,联合组KPS评分稳定率为90.00%(36/40),明显高于化疗组的70.00%(28/40)(P<0.05)。联合组骨髓抑制的总发生率为17.5%(7/40),低于化疗组的42.5%(17/40)(P<0.05)。【结论】滋肾润肺方联合化疗可有效改善患者的生活质量,且能降低骨髓抑制的发生率。

基于妇科肿瘤耐药治疗中工程化外泌体的应用研究进展

妇科恶性肿瘤严重威胁着女性健康,在女性各类疾病中其发病率和死亡率均位居前列,关键原因在于传统化疗对复发、耐药患者的疗效欠佳。近年来,探讨肿瘤细胞化疗的耐药机制,开发新型药物逆转耐药已成为妇科肿瘤研究者关注的热点。外泌体(exosome)是一种来源于细胞内溶酶体微粒内陷的多囊泡体,具有低免疫原性、先天靶向性及获得靶向性和高传递效率等生物学特性。因此,外泌体可作为一种理想的、天然的纳米递送药物载体,不仅可以降低肿瘤细胞对化疗药物的耐药性,提高药物治疗效果,还可以减少化疗药物对全身的毒副反应。本文就外泌体作为妇科肿瘤耐药治疗中药物载体的研究进展进行综述,以期对妇科肿瘤的临床治疗提供帮助。

Effects of Taxotere on invasive potential and multidrug resistance phenotype in pancreatic carcinoma cell line SUIT-2

INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relationship between expression of multidrugresistance (MDR) phenotype P-glycoprotein (P-gp)and the malignant properties of tumors, but theresults are often conflicting[1-8]. The difference intumor types or MDR phenotype induced by specificagents might account for this discrepancy. Taxotere(TXT), a member of the family of taxanes, hasantitumor activity through its effect of promotingthe polymerization of tubulin[9,10].

血流向量成像技术评估卵巢癌术后化疗后左心室舒张功能

目的观察血流向量成像(VFM)技术评估卵巢癌(OC)术后化学治疗(简称化疗)后左心室舒张功能改变的价值。方法前瞻性以37例OC术后接受化疗患者为化疗组,以同期40名健康成人为对照组。对化疗组分别于化疗前、化疗3及6个周期后,对照组于入组时行常规超声心动图及VFM检查,比较化疗前组间及化疗组内不同时间点资料,分析化疗组VFM与血红蛋白及常规超声心动图结果的相关性。结果化疗组年龄、体质量、体表面积(BSA),化疗前血红蛋白水平、常规超声心动图及VFM结果与对照组差异均无统计学意义(P均>0.05)。化疗组内,随化疗周期增加,血红蛋白水平渐次降低、等容舒张期(IR)及心房收缩期(AS)左心室内压力差(IVPD)及压力差梯度(IVPG)逐渐增大(校正P均<0.05);而常规超声心动图仅化疗6个周期后左心房容积指数(LAVI)及二尖瓣舒张早期血流峰值速度/二尖瓣环舒张早期平均运动峰值速度(E/e’)较化疗前升高(校正P均<0.05)。化疗组舒张期各时相VFM结果均与血红蛋白水平呈强相关(|r|=0.718~0.836,P均<0.05),与LAVI呈弱至中度相关(|r|=0.375~0.525,P均<0.05),与E/e’呈中度相关(|r|=0.424~0.537,P均<0.05)。结论OC术后化疗早期即可出现左心室舒张功能受损。VFM可较常规超声心动图更敏感地检出左心室舒张早期功能轻微改变。

Adeno-associated virus mediated endostatin gene therapy in combination with topoisomerase inhibitor effectively controls liver tumor in mouse model

AIM:rAAV mediated endostatin gene therapy has been examined as a new method for treating cancer.However, a sustained and high protein delivery is required to achieve the desired therapeutic effects.We evaluated the impact of topoisomerase inhibitors in rAAV delivered endostatin gene therapy in a liver tumor model. METHODS:rAAV containing endostatin expression cassettes were transduced into hepatoma cell lines.To test whether the topoisomerase inhibitor pretreatment increased the expression of endostatin,Western blotting and ELISA were performed.The biologic activity of endostatin was confirmed by endothelial cell proliferation and tube formation assays. The anti-tumor effects of the rAAV-endostatin vector combined with a topoisomerase inhibitor,etoposide,were evaluated in a mouse liver tumor model. RESULTS:Topoisomerase inhibitors,including camptothecin and etoposide,were found to increase the endostatin exPression level in vitro.The over-expressed endostatin, as a result of pretreatment with a topoisomerase inhibitor, was also biologically active.In animal experiments,the combined therapy of topoisomerase inhibitor,etoposide with the rAAV-endostatin vector had the best tumor- suppressive effect and tumor foci were barely observed in livers of the treated mice.Pretreatment with an etoposide increased the level of endostatin in the liver and serum of rAAV-endostatin treated mice.Finally,the mice treated With rAAV-endostatin in combination with etoposide showed the longest survival among the experimental models. CONCLUSION:rAAV delivered endostatin gene therapy in combination with a topoisomerase inhibitor pretreatment is an effective modality for anticancer gene therapy.