Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription

BACKGROUND Colorectal cancer(CRC)is the third most common cancer and a significant cause of cancer-related mortality globally.Resistance to chemotherapy,especially during CRC treatment,leads to reduced effectiveness of drugs and poor patient outcomes.Long noncoding RNAs(lncRNAs)have been implicated in various pathophysiological processes of tumor cells,including chemotherapy resistance,yet the roles of many lncRNAs in CRC remain unclear.AIM To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance.METHODS Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance.Various bioinformatics tools were employed to elucidate molecular mechanisms.The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction.Functional assays,including MTT,wound healing,and Transwell,were conducted to investigate the functional implications of lncRNA alterations.Interactions between lncRNAs and trans-cription factors were examined using RIP and luciferase reporter assays,while Western blotting was used to confirm downstream pathways.Additionally,a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance.RESULTS LncRNA prion protein testis specific(PRNT)was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2(HIPK2)expression.PRNT was demonstrated to sponge transcription factor zinc finger protein 184(ZNF184),which in turn could regulate HIPK2 expression.Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin,with overexpression leading to decreased sensitivity and decreased expression reducing resistance.Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT.The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC progression and oxaliplatin resistance both in vitro and in vivo.CONCLUSION The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184.This regulatory mechanism enhances CRC progression and resistance to oxaliplatin,positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.

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.

Impact of oxaliplatin and trastuzumab combination therapy on tumor markers and T lymphocyte subsets for advanced gastric cancer

BACKGROUND Advanced gastric cancer(AGC)remains a challenging malignancy with poor prognosis.The combination of oxaliplatin and trastuzumab has shown promising results in AGC treatment.This study aimed to investigate the effects of oxaliplatin and trastuzumab combination therapy on serum tumor markers and T lymphocyte subsets in patients with AGC and to explore their potential as predictive biomarkers for treatment response.AIM To investigate the impact of oxaliplatin and trastuzumab combination therapy on serum markers and T cell subsets in patients with AGC.METHODS This prospective study enrolled 60 patients with AGC.All patients received oxaliplatin(130 mg/m^(2),every 3 weeks)and trastuzumab(8 mg/kg loading dose,followed by 6 mg/kg every 3 weeks)for six cycles.Serum carcinoembryonic antigen(CEA),cancer antigen 19-9(CA19-9),and cancer antigen 72-4(CA72-4)were measured before and after treatment.T-lymphocyte subsets,including CD3+,CD4+,CD8+,and CD4+/CD8+ratios,were also evaluated.The clinical response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1.RESULTS After six cycles of treatment,the CEA,CA19-9,and CA72-4 serum levels significantly decreased compared to baseline levels(P<0.001).The percentages of CD3+and CD4+T lymphocytes increased significantly(P<0.05),whereas the percentage of CD8+T lymphocytes decreased(P<0.05).The CD4+/CD8+ratio also significantly increased after treatment(P<0.05).Patients with a higher decrease in serum tumor markers(≥50%reduction)and a higher increase in CD4+/CD8+ratio(≥1.5-fold)showed better clinical response rates(P<0.05).CONCLUSION Oxaliplatin and trastuzumab combination therapy effectively reduced serum tumor marker levels and modulated T lymphocyte subsets in patients with AGC.Combination therapy not only has a direct antitumor effect,but also enhances the immune response in patients with AGC.Serum tumor markers and T lymphocyte subsets may serve as potential predictive biomarkers for treatment response in patients with AGC receiving combination therapy.

Evaluation of oxaliplatin and tigio combination therapy in locally advanced gastric cancer

BACKGROUND Locally advanced gastric cancer(LAGC)is a common malignant tumor.In recent years,neoadjuvant chemotherapy has gradually become popular for the treatment of LAGC.AIM To investigate the efficacy of oxaliplatin combined with a tigio neoadjuvant chemotherapy regimen vs a conventional chemotherapy regimen for LAGC.METHODS Ninety patients with LAGC were selected and randomly divided into control and study groups with 45 patients in each group,according to the numerical table method.The control group was treated with conventional chemotherapy,and the study group was treated with oxaliplatin combined with tigio-neoadjuvant che-motherapy.The primary outcome measures were the clinical objective response rate(ORR)and surgical resection rate(SRR),whereas the secondary outcome measures were safety and Karnofsky Performance Status score.RESULTS The ORR in the study group was 80.00%,which was significantly higher than that of the control group(57.78%).In the study group,SRR was 75.56%,which was significantly higher than that of the control group(57.78%).There were 15.56%adverse reactions in the study group and 35.56%in the control group.These differences were statistically significant between the two groups.CONCLUSION The combination of oxaliplatin and tigio before surgery as neoadjuvant chemotherapy for patients with LAGC can effectively improve the ORR and SRR and is safe.

L-OHP联合HCPT治疗难治性晚期大肠癌临床观察

目的 :观察草酸铂 (L OHP)联合羟基喜树碱 (HCPT)治疗晚期大肠癌的近期疗效及毒性反应。方法 :采用L OHP 130mg/m2 ,静滴 2小时 ,d1 ;HCPT 10mg/d ,静滴 3小时 ,d1～ 5,联合治疗Dukes D期大肠癌患者 36例 ,2 8天为一周期 ,连用 3个周期。结果 :全组中CR 2例 ,PR 12例 ,有效率为 38 9% (14 / 36 )。主要毒性反应为轻、中度的消化道反应 ,脱发 ,骨髓抑制和外周感觉神经异常 ,均为可逆性的 ,可以耐受。结论 :L OHP +HCPT方案治疗晚期大肠癌具有较好的疗效 ,毒性反应可以耐受 ,作为治疗晚期大肠癌的二线方案 。

L-OHP联合5-FU/LV二线治疗晚期大肠癌2周方案与3周方案的临床比较

目的：比较奥沙利铂（L-OHP）联合氟尿嘧啶/亚叶酸钙（5-FU/LV）的2周方案与3周方案二线治疗晚期结直肠癌的临床疗效及不良反应.方法：晚期复治的结直肠癌病例,A组22例,予L-OHP 85mg/m^2,d1,静脉滴注3小时,同时或之后予CF 200mg/m^2,静脉滴注2小时,续5-FU 400mg/m^2,静脉推注,600mg/m^2持续静脉滴注22小时,次日重复CF与5-FU.每2周重复1次,每2次计为1周期.B组24例,予L-OHP 130mg/m^2,d1,静脉滴注3小时,CF 200mg/m^2,静脉滴注2小时,续5-FU 375～425mg/m^2静脉滴注4～6小时,连用5天.每3周重复1次,每次计为1周期.结果：A、B两组分别有21例和23例可评价,RR分别为19.05%和8.70%,中位TTP分别为4.0和3.0月,两组病例不良反应发生率相似,主要表现为消化道反应、神经系统毒性和脱发.结论：L-OHP联合5-FU/LV的2周方案在临床疗效方面优于3周方案.

RNA干扰联合阻断MMS2和REV3基因表达减轻结肠癌细胞系THC8307/L-OHP对奥沙利铂的耐药性

目的探讨沉默REV3和MMS2逆转结肠癌耐药细胞系THC8307/L-OHP细胞对奥沙利铂(L-OHP)的耐药性。方法 THC8307/L-OHP细胞转染含microRNA片段重组质粒后,用实时荧光定量PCR法(qRT-PCR)和免疫荧光法检测目的基因表达,选择低表达效率具有统计学意义的细胞作为实验组细胞。分别应用MTT法、罗丹明123实验、流式细胞术检测细胞对L-OHP药物敏感度和细胞凋亡。结果与对照组相比,L-OHP对实验组细胞的半数抑制浓度(IC50)及耐药指数(RI)减低(P<0.05),实验组细胞经L-OHP处理后凋亡率显著增高(P<0.05),实验组细胞MMS2和REV3蛋白表达水平降低(P<0.05)。结论下调REV3和MMS2在逆转人结肠癌细胞对L-OHP的耐药性和促进肿瘤细胞的凋亡上有一定作用。

肠胃清方对人结肠癌HCT116/L-OHP裸鼠皮下移植瘤miR-30a/Beclin1通路的影响

目的本课题旨在分子生物学技术和中医基础理论指导下,从miRNAs与自噬相关联的角度,讨论miR-30a与自噬基因Beclin1在结肠癌化疗耐药中的相关性,并探讨肠胃清对miR-30a介导自噬的调控作用及逆转结肠癌耐药的分子机制.方法建立人结肠癌耐奥沙利铂(L-OHP)细胞株HCT116/L-OHP裸鼠皮下移植瘤模型,随机分为空白组、L-OHP组、肠胃清方组、肠胃清方低剂量+L-OHP组、肠胃清方高剂量+L-OHP组.治疗结束后采用RT-PCR、免疫组织化学、Tunnel等研究肠胃清对瘤体组织中miR-30a、Beclin1、LC3的表达及细胞凋亡的影响.结果奥沙利铂组可见Beclin1、LC3的上调,miR-30a的下调,细胞凋亡的减少.而肠胃清联用奥沙利铂组可见Beclin1、LC3的下调,miR-30a的上调,细胞凋亡的增加(P<0.05或P<0.01).结论奥沙利铂诱导保护性自噬导致细胞凋亡减少可能是其耐药的机制.肠胃清可通过调控miR-30a/Beclin1通路而抑制自噬逆转结肠癌耐药.

卡培他滨联合多西紫杉醇与L-OHP+5-FU+LV方案治疗晚期胃癌近期疗效对比研究

目的:观察卡培他滨联合多西紫杉醇与L-OHP+5-FU+LV方案治疗晚期和复发胃癌的临床疗效及毒副反应。方法:治疗组23例采用卡培他滨2500mg/(m2·d),分早晚两次口服,第1～14天;多西紫杉醇75mg/m2,静滴,第1天和第8天。每21d为1个周期,共2～4周期,对照组23例采用L-OHP+5-FU+LV方案:L-OHP130mg/m2静滴,第1天,亚叶酸钙(LV)200mg/m2,静脉推注,第1～5天;氟尿嘧啶(5-FU)500mg/m2,静滴6h,第1～5天。结果:治疗组23例总有效率为63.2%(12/19)。12例初治病例有效率为66.7%(8/12),其中CR2例;7例复治病例有效率为57.1%(4/7),其中CR1例。初治和复治病例的中位缓解期分别为7个月和5.3个月。对照组23例总有效率(CR+PR)为52.9%(9/17),CR1例(5.8%),PR8例(47%),中位缓解期为5.2个月。治疗组血液毒性主要表现为白细胞减少,发生率为68.4%,其中Ⅲ～Ⅳ度白细胞减少26.3%。手足综合征发生率为42.1%;对照组血液毒性轻微,末梢神经炎发生率52.9%。结论:卡培他滨联合多西紫杉醇治疗晚期和复发胃癌有较好的疗效,不良反应较少,是治疗晚期和复发胃癌的有效方案。

HCPT联合L-OHP方案治疗复发转移结直肠癌的近期临床疗效

背景与目的:虽然含氟尿嘧啶(5-fluarouracil,5-FU)联合方案是目前治疗结直肠癌的标准方案,但是作为二线治疗的疗效不高,探索新的替代方案显得十分必要。本研究拟应用羟基喜树碱(hydroxycampothecin,HCPT)联合草酸铂(oxaliplatin,L-OHP)方案治疗复发转移结直肠癌,并观察其近期疗效、不良反应及1年生存率。方法:47例经病理学检查证实的复发转移结直肠癌,采用HCPT+L-OHP方案治疗86个周期,HCPT6mg/m2+NS500ml,静脉滴注d1～4;L-OHP130mg/m2+5%GS500ml,静脉滴注d1。每例治疗2个周期后进行近期临床疗效和不良反应评定,两次化疗间隔为3周。结果:38例可进行疗效评价,总有效率(CR+PR)为36.8%(14/38)。化疗后KPS改善和显著改善者20例,占52.6%。白细胞下降59周期,占68.6%,其中Ⅲ～Ⅳ度白细胞下降18周期,占30.5%;腹泻48周期,占55.8%,其中Ⅲ～Ⅳ度腹泻18周期,占37.5%。1年生存率为40.0%,中位总生存期(medianoverallsurvival,mOS)和中位无进展生存期(medianprogressionfreesurvival,mPFS)分别为11.7和7.8个月。结论:HCPT+L-OHP方案治疗一线化疗后复发的结直肠癌病例有较好的近期临床疗效,主要不良反应是白细胞下降和腹泻。

人结肠癌耐药细胞系HT29／L-OHP的建立及其生物学特性

目的建立人结肠癌奥沙利铂耐药细胞系HT29/L-OHP,探讨结肠癌对奥沙利铂(Oxaliplatin,L-OHP)产生耐药的特征规律和耐药的机制。方法采用逐步递增L-OHP浓度,间歇作用体外诱导法培养建立了人结肠癌L-OHP耐药细胞模型HT29/L-OHP。MTT法测定生长曲线、交叉耐药性和耐药指数;并用光镜、电镜、流式细胞仪(FCM)等方法观察其一般生物学特性的改变。结果历时3个月建成了L-OHP耐药细胞模型HT29/L-OHP,其耐药性能稳定,耐药指数为10.64;并且与5-氟尿嘧啶、长春新碱、阿霉素等多种抗癌药有不同程度的交叉耐药性。HT29/L-OHP的细胞形态及染色体数目发生了改变;体外细胞群体倍增时间较亲代细胞延长29.71h;细胞周期分析结果显示其S期与G0/G1期细胞减少、G2/M期细胞增多。结论HT29/L-OHP细胞是模拟临床用药特点建立的耐药性较稳定的多药耐药细胞,具有耐药细胞的基本生物学特性,是研究L-OHP耐药机制及筛选逆转剂的理想细胞模型。

肠胃清逆转结肠癌HCT116/L-OHP细胞草酸铂耐药作用及对Pt-DNA加合物的影响

目的探讨中药复方肠胃清(黄芪、白术、党参、猪苓、薏苡仁、八月札、野葡萄藤、红藤等)对结肠癌HCT116/L-OHP细胞草酸铂耐药的逆转作用及对Pt-DNA加合物的影响。方法将HCT116/L-OHP细胞种植于裸小鼠皮下,建立肿瘤耐药模型,随机分为5组,A组为对照组,B组为草酸铂组,C组为肠胃清组,D组为草酸铂+肠胃清低剂量组,E组为草酸铂+肠胃清高剂量组,治疗前后测量移植瘤体积及荷瘤鼠体质量;采用细胞增殖抑制实验MTT法观察肠胃清药物血清对HCT116/L-OHP细胞株耐药性的逆转作用,并采用原子吸收分光光度法检测细胞内铂(Platinum,Pt)药物及核内Pt-DNA水平。结果肠胃清联合草酸铂组与肠胃清或草酸铂单独用药组相比,有更高的肿瘤抑制率(P<0.01),其中肠胃清高剂量联合草酸铂组抑瘤率最高;与对照组相比,含肠胃清组荷瘤鼠体质量减轻好于单用草酸铂;MTT结果显示7.5%肠胃清药物血清能够增加耐药细胞株HCT116/L-OHP对草酸铂敏感性,逆转指数为2.74;肠胃清药物血清可以增加HCT116/L-OHP细胞内草酸铂水平,并能使细胞核内Pt-DNA加合物水平增加15.74%。结论肠胃清能够逆转HCT116/L-OHP细胞对草酸铂的耐药性,其机制与肠胃清增加细胞内Pt-DNA加合物水平有关。

肠胃清含药血清对人结肠癌HCT116/L-OHP耐药细胞凋亡作用的影响

目的探讨中药复方肠胃清(CWQ)逆转人结肠癌HCT116/L-OHP细胞耐药的分子机制。方法提取肠胃清含药血清,设置不同浓度,采用MTT法确定肠胃清的最大无毒剂量和逆转指数(RI);采用彗星实验法检测肠胃清联合奥沙利铂(L-OHP)对耐药细胞DNA损伤的影响,流式细胞术观察肠胃清联合奥沙利铂(L-OHP)对耐药细胞凋亡的影响。结果肠胃清含药血清可以逆转人结肠癌HCT116/L-OHP耐药细胞对L-OHP的耐药性,逆转指数(RI)为2.63倍。肠胃清联合L-OHP能促进耐药细胞发生DNA损伤(P<0.001)及凋亡(P<0.01)。结论肠胃清能够逆转人结肠癌铂类化疗耐药,其机制与促进肿瘤细胞DNA损伤、诱导凋亡有关。

5-Fu/LV+L-OHP方案静脉及腹腔热灌注化疗对T_4期结直肠癌的疗效对比观察

目的观察比较草酸铂腹腔热灌注与单纯静脉化疗治疗T4期结直肠癌的疗效和毒副作用。方法将病理检查确诊的60例T4期结直肠癌患者随机分成2个组,2组均先给予亚叶酸钙和氟脲嘧啶静脉输注。比较草酸铂腹腔热灌注化疗配合局部射频透热治疗和单纯静脉输注的疗效。结果静脉化疗+腹腔热灌注组有效率为59.3%,中位生存期11.0个月,中位无进展生存期9.2个月。单纯静脉化疗组有效率为35.7%,中位生存期9.7个月,中位无进展生存期7.0个月。静脉化疗+腹腔热灌注组中位生存期(11.0个月)长于单纯静脉化疗组(9.7个月),有统计学差异(P<0.05)。静脉化疗+腹腔热灌注组腹水治疗有效率86.7%,单纯静脉化疗组有效率50.0%,2个组有显著差异(P<0.05)。静脉化疗+腹腔热灌注组毒副反应主要为腹部不适。结论草酸铂腹腔热灌注化疗疗效有所提高,毒性尚可耐受,值得进一步研究。

L-OHP联合不同使用方法5-FU/FA方案治疗晚期结直肠癌的疗效比较

目的比较L-OHP(奥沙利铂)联合不同使用方法5-FUFA(氟尿嘧啶亚叶酸钙)方案治疗晚期结直肠癌的疗效及不良反应。方法62例患者均可参加疗效评价。ArmA方案(32例):L-OHP130mgm2静滴d1;FA200mg(m2·d),5-FU425mg(m2·d)分别静滴,均d1～5,每3周重复,3周为1周期。ArmB方案(30例):L-OHP85mgm2静滴d1;FA200mg(m2·d)静滴后,5-FU400mg(m2·d)静推,然后5-FU600mg(m2·d)持续微量泵注射22小时,d1～2,每2周重复,4周为1周期。结果ArmA方案CR1例,PR14例,总有效率46.9%。ArmB方案CR1例,PR11例,总有效率40%。严重不良反应较少。结论L-OHP联合不同使用方法5-FUFA方案治疗晚期结直肠癌均有较高疗效,毒副作用相近。

L-OHP和HCPT分别联合5-Fu/CF治疗晚期大肠癌对照研究

目的对照研究奥沙利铂(L-OHP)和羟基喜树碱(HCPT)分别联合5-Fu/CF治疗晚期大肠癌的临床效果。方法将符合入选条件的79例晚期大肠癌患者,随机分为观察组40例(含L-OHP方案)及对照组39例(含HCPT方案),2组均完成3个疗程化疗,每3周重复。对照观察2组的近期疗效及毒副反应。结果观察组CR 1例,PR 18例,总有效率(CR+PR)为47.5%;对照组CR 0例,PR 10例,总有效率(CR+PR)为25.6%,P<0.05。观察组神经毒性及腹泻发生率较高(45%及35%),对照组粒细胞减少发生率较高(61.5%),P<0.05,但2组恶心呕吐、脱发等毒性反应无明显差异。结论奥沙利铂联合5-Fu/CF是治疗大肠癌的有效化疗方案,特别适宜晚期大肠癌以及对5-Fu耐药的病例。

L-OHP、DOC和HCPT联合5-Fu序贯化疗治疗晚期胃癌的临床研究

目的探讨奥沙利铂(oxaliplatin,L-OHP)、多西紫杉醇(docetaxel,DOC)和羟基喜树碱(hydroxycamptothecine,HCPT)联合5-氟尿嘧啶(5-Fluorouracil,5-Fu)/亚叶酸钙(calcium folinate,CF)组成的序贯化疗方案治疗晚期胃癌(advanced gastric cancer,AGC)的疗效和不良反应。方法入组35例AGC患者,以序贯方式依次接受L-OHP+5-Fu/CF、DOC+5-Fu/CF和HCPT+5-Fu/CF方案化疗,每个方案连用2周期,均每3周重复,共6周期化疗;观察疗效和不良反应,并随访疾病进展情况。结果35例均能评价疗效,总缓解率(RR)为60%(21/35),中位肿瘤进展时间(TTP)为7.6月,95%置信区间(CI)(7.0～8.2),中位生存期(OS)15.1月,95%CI(14.2～16.0);不良反应程度较轻,主要为骨髓抑制、胃肠道反应、脱发及过敏反应,但均可逆,未出现因化疗毒性而死亡病例。结论 L-OHP、DOC和HCPT联合5-Fu/CF的序贯化疗是AGC有效治疗方案,化疗耐受性好,新颖的序贯化疗模式在AGC中应用值得进一步研究。

结肠癌耐药细胞株LoVo/L-OHP的建立及其耐药机制

目的:建立获得性奥沙利铂(L-OHP)耐药的结肠癌细胞模型LoVo/L-OHP,并初步研究其耐药机制。方法:采用L-OHP浓度递增法建立人结肠癌细胞耐药模型LoVo/L-OHP,观察其生长规律并绘制细胞生长曲线;用MTT法鉴定耐药细胞株耐药性并计算耐药指数(RI);用半定量RT-PCR方法对部分耐药相关基因在耐药细胞及其亲本细胞中的表达情况进行分析。结果:成功建立了耐药的结肠癌细胞模型LoVo/L-OHP,LoVo/L-OHP细胞与LoVo细胞相比,生长缓慢,触角增多。通过RT-PCR半定量分析,P-gp、bcl-2、ERCC-1在LoVo/L-OHP中的表达上调,而p53基因表达下调。结论:LoVo/L-OHP细胞株耐药性稳定,耐药机制可能与P-gp、bcl-2、ERCC-1基因上调、p53基因下调多因素有关。

L-OHP联合5-FU/CF方案不同给药方法治疗晚期大肠癌的疗效观察

目的比较奥沙利铂（L-OHP）联合氟尿嘧啶（5-Fu）／甲酰四氢叶酸（CF）方案的不同给药方法治疗晚期大肠癌的疗效和不良反应。方法32例晚期大肠癌患者均可参加疗效评价，A组（15例）：L-OHP 130mg／m^2、静滴、第1d，CF 200mg／m^2、静滴2h、第1-5d，5-FU 375-400mg／m^2、静滴、第1-5d、4-6h，每3周重复，3周为1个周期。B组（17例）：L-OHP 85mg／m^2、静滴、第1d，CF 200mg／m^2、静滴2h、第1-2d，5-FU 500mg／m^2、静推，再以600mg／m^2持续泵入22h、第1-2d，每2周重复，4周为1个周期。结果A组CR1例，PR6例，总有效率为46.6％。B组CR 1例，PR7例，总有效率41.1％。结论L-OHP联合5-FU／CF不同的给药方法治疗晚期大肠癌疗效相近，毒副作用少。

LF+DDP和LF+L-OHP方案在晚期胃腺癌化疗中的对照观察

目的 在晚期胃腺癌化疗中 ,对LF +DDP和LF +L OHP两方案进行评价。方法 6 0例晚期胃癌病人被随机分成甲、乙两组。甲组 30例给予LF +DDP方案两周期 ,乙组 30例给予LF LOHP方案两周期。结果 LF +DDP方案中肌酐升高发生率和呕吐发生率高于LF +L OHP方案 ,差异有意义 (P <0 .0 5 ) ,神经系统毒性发生率低于LF +L OHP方案 ,差异有意义 (P <0 .0 5 ) ,两方案有效率无差异 (P >0 .0 5 ) ,但LF +DDP方案在化疗费用上只占LF +L OHP方案的 4 3.5 %。结论 LF +DDP是治疗晚期胃腺癌有效且低费用方案。