局部进展期直肠癌新辅助治疗研究进展

<正>迄今为止,完全手术切除肿瘤病灶仍是结直肠癌的唯一根治性治疗手段,也是决定患者预后的最重要因素。由于直肠解剖结构、瘤灶侵袭或转移等特点,手术治疗对微小病灶难以彻底切除,术后仍有较高的远处转移和局部复发。进展期结直肠癌术后5年生存率徘徊在50%左右~([1])。如何提升进展期直肠癌的治疗效果,增加生存率一直都是需要克服的难点。新辅助治疗近些年来开始在消化道进展期恶性肿瘤治疗过程中越来越多的应用。本文拟就直肠癌新辅助治疗研究进展作一综述。1新辅助治疗方式1.1新辅助放疗新辅助放疗主要方式有两种,一种为短程快速大分割放疗,多     

结直肠癌组织TP、DPD不同表达水平与XELOX化疗效果的关系及意义?

【目的】探讨胸腺嘧啶磷酸化酶(TP)、二氢吡啶脱氢酶(DPD)在结直肠癌组织中的表达情况及其与 XELOX化疗效果的相关性。【方法】用 ELISA 双抗体夹心法检测58例结直肠癌患者癌组织中 TP 和DPD的表达量,以 TP 和 DPD的中位数为分界,将患者分为高表达组和低表达组,患者术后均接受 XELOX方案进行化疗,4个疗程后,比较不同TP和DPD的表达水平患者的早期疗效。对所有患者进行随访12~36个月,行Kaplan-Meier生存分析,比较比较不同TP和DPD的表达水平患者的预后生存情况。【结果】TP 高表达组和低表达组行 XELOX化疗方案的短期临床疗效相比差异无显著性(P >0.05);TP 高表达组中位生存时间显著高于低表达组(P <0.05)。DPD高表达组 XELOX化疗方案早期有效率及中位生存时间均低于于低表达组,差异具有统计学意义(P <0.05)。各组患者的并发症发生情况无显著性差异(P >0.05)。【结论】结直肠癌组织TP、DPD表达水平对XELOX化疗方案的临床疗效有关,可以作为预测XELOX化疗方案疗效的重要指标之一。     

9-硝基喜树碱及其脂质体对HepG2、L02细胞周期和凋亡作用的研究

目的 研究9-硝基喜树碱及其脂质体对人肝癌细胞株HepG2和人正常肝细胞L02细胞周期、凋亡的影响及其可能的作用机制.方法 HepG2、L02细胞用含不同浓度9-硝基喜树碱及其脂质体的培养液孵育后,利用MTT法测定细胞活性,流式细胞术检测细胞周期及细胞凋亡,WesternBlot验证周期相关蛋白和凋亡相关蛋白的表达变化.结果 9-硝基喜树碱及其脂质体对两种细胞生长呈时间和剂量依赖性抑制.药物处理后S期和G2/M期细胞明显增多,浓度大于0.1 μmol/L时24 h后HepG2细胞完全阻滞于S期;0.1 μmol/L孵育72 h后,超过95%HepG2细胞阻滞于G2/M期.药物对细胞凋亡的诱导作用也呈明显的剂量和时间依赖关系.Western Blot显示:Bax、Caspase3表达增高,Cyclin A、Cdk2、Cyclin E、Bcl-2表达减低.与L02相比,HepG2细胞对药物更加敏感.结论 9-硝基喜树碱及其脂质体可以通过调控细胞周期和诱导凋亡有效抑制细胞生长,其对肿瘤细胞的抑制作用强于正常肝细胞.9-硝基喜树碱脂质体体外抗肿瘤效果略强于9-硝基喜树碱单体.

Abstract：

Objective To investigate the modulating effects and explore their mechanism of 9-nitrocamptothecin and its liposomes to induce apoptosis and inhibit cell cycle in HepG2 and L02 cell lines. Methods Cells were incubated with 9-nitrocamptothecin(9NC) or with 9-nitrocamptothecin liposomes for 24 h, 48 h and 72 h, then, the cell viability was measured via MTT assay; cell cycle and apoptosis was evaluated by flow cytometry after stained by PI and Annexin V-PE/7AAD. Additional, Western Blot was used to evaluate the expression of cell cycle and apoptosis related protein. Results Both cells viability were apparently inhibited by the 9-nitrocamptothecin and 9-nitrocamptothecin liposomes, the inhibitory effect showed a time-dependent and dose-dependent manner. Both S and G2/M phases arrest were observed after incubated with drugs. HepG2 cell was completely arrested in S phase when 9NC concentration over than 0. 1 μmol/L after incubation for 24 h, while more than 95% cells arrested in G2/M phase when 9NC concentration is 0. 1 μmol/L after incubation for 72 h. Apoptosis induction effect also showed a time-dependent and dose-dependent manner. Western Blot results showed the expression of Bax and Caspase-3 were upregulated while Cyclin A, Cdk2, Cyclin E and Bcl-2 were downregulated. More importantly, the compounds were more cytotoxic to the cancer cell lines than to the normal liver cell. Conclusions 9-nitrocamptothecin and 9-nitrocamptothecin liposomes can potently inhibit cell growth via regulation of cell cycle and induction of apoptosis, and this effect was preferentially in cancer cell. Inhibitory of 9-nitrocamptothecin liposomes was slightly better than the 9-nitrocamptothecin.     

新辅助放化疗对直肠癌治疗效果的影响

目的分析新辅助放化疗对直肠癌治疗效果的影响。方法该研究选取2008年7月-2010年6月120例直肠癌患者为对象,回顾性分析其临床资料,根据其放化疗时间分组。术后放化疗患者56例纳入对照组,术前新辅助放化疗患者64例纳入试验组。术后随访5年,对比分析两组患者术后并发症发生率,术后1、3、5年局部复发率,远处转移率,死亡率的差异。结果对照组和试验组患者术后并发症发生率无显著的统计学差异(P0.05)。两组术后1年局部复发率、远处转移率、死亡率差异无显著统计学意义(P0.05)。试验组患者术后3、5年局部复发率、远处转移率、死亡率均明显低于对照组,差异有统计学意义(P0.05)。结论直肠癌患者术前进行放化疗有助于保证手术效果,降低局部复发率、远处转移、死亡等不良后果的发生风险,具有更好的远期疗效。     

雷公藤内酯醇及雷公藤内酯醇聚合物胶束对HT29细胞增殖及凋亡的影响

目的研究雷公藤内酯醇(Triptolide TP)和雷公藤内酯醇聚合物胶束(Triptolide loaded poly-meric micelles,TP-PM)对人结肠癌HT29细胞增殖及凋亡的作用及机制,评价聚合物胶束作为雷公藤内酯醇纳米载体的可行性。方法用含不同浓度的TP和TP-PM(1-100ng/mL)培养液孵育HT29细胞24h、48h和72h后,利用WST-1、BrdU试剂盒测定细胞的存活率、增殖率;通过测定LDH活性判断细胞膜完整性;利用流式细胞仪测定细胞死亡、存活和凋亡率;并通过Caspase-Glo3/7定量试剂盒测定细胞caspase3/7的表达情况。结果 TP和TP-PM对HT29细胞活性和细胞增殖的抑制作用显著,呈明显的剂量、时间依赖性,TP-PM对HT29的抑制作用优于TP(P0.05)。TP和TP-PM对HT29细胞膜的破坏轻微。FDA-PI双染结果显示,两组中FDA阳性细胞均呈现时间、剂量依赖性的下降(P0.01);PI阳性细胞率呈现时间、剂量依赖性的上升(P0.01);FDA、PI双阴性细胞也明显上升,但不呈时间、剂量依赖关系。Caspase测定结果显示TP和TP-PM均可引起Caspase3/7活性增高,TP-PM组引起的凋亡作用强于TP组(P0.05)。结论 TP和TP-PM可以通过诱导凋亡的方式抑制肿瘤细胞生长和增殖,且TP-PM的作用强于TP,聚合物胶束是一种极具前景的载药体系。     

超声引导下经皮穿刺置管引流在重症急性胰腺炎治疗价值的探讨:附57例报告

目的:探讨超声引导下经皮穿刺置管引流(PCD)在治疗重症急性胰腺炎急性液体积聚的应用价值。方法:回顾性分析1998年1月—2008年12月57例重症急性胰腺炎患者的临床资料进行回顾性分析,57例患者均有急性液体积聚,28例行超声引导下经皮穿刺置管引流治疗(引流治疗组),29例未穿刺引流行保守治疗(保守治疗组);两组患者在年龄,性别,CT严重指数(CTSI),APACHEⅡ评分等方面无统计学差异,具可比性。结果:引流治疗组与保守治疗组病死率比较,差异无统计学意义(P=1.000);引流治疗组与保守治疗组比较,胰腺假性囊肿的发生率低(P=0.033),住院时间短(P=0.002),中转手术率低(P=0.043)。结论:超声引导下经皮穿刺置管引流治疗重症急性胰腺炎可降低并发症,在治疗重症急性胰腺炎急性液体积聚有一定的治疗价值。     

血塞通对腹腔镜胆囊切除术后患者凝血功能的影响

目的探讨腹腔镜胆囊切除术（LC）对患者凝血功能的影响及血塞通的应用。方法将参与研究的54例患者分为观察组与治疗组,观察组30例术后不给予血塞通治疗,治疗组给予血塞通治疗。观察腹腔镜胆囊切除术前后患者活化部分凝血活酶时间（APTT）、纤维蛋白原（FIB）、凝血酶原时间（PT）以及凝血酶原国际标准化值（INR）和D-二聚体（DD）等血浆凝血指标,以及血塞通对术后凝血状态的影响。结果腹腔镜胆囊切除术后,患者PT显著缩短,FIB及DD水平显著升高,且差异具有统计学意义（P〈0.05）;术后应用血塞通治疗可使PT、FIB及DD水平基本恢复正常,且差异具有统计学意义（P〈0.05）。结论腹腔镜胆囊切除术可能导致患者术后出现血液高凝状态,术后应用血塞通可取得较好的疗效。     

9-硝基喜树碱脂质体对肝癌细胞株HepG2的抑制作用及机制

目的 观察9-硝基喜树碱脂质体对HepG2肝癌细胞的抑制作用及其机制.方法 9-硝基喜树碱(9NC)及其脂质体(9NC-LP)处理HepG2细胞后,MTT法测定细胞活性,流式细胞术检测细胞周期及凋亡相关蛋白表达.建立HepG2细胞裸鼠皮下移植瘤模型,随机分为空白对照组,空白脂质体组,DMSO组,9NC低、高剂量组,9NC-LP低、高剂量组,每组10只.尾静脉给药后持续监测各组裸鼠肿瘤体积、体重变化.给药后28 d处死裸鼠,切取肿瘤提取总蛋白后Western Blot检测蛋白表达变化.结果 在体外实验,9NC-LP对肿瘤细胞生长呈时间和剂量依赖性抑制.药物处理后S期和G2/M期细胞明显增多,浓度大于0.1 btmol/L时24 h后细胞完全阻滞于S期;0.1μmol/L 孵育72 h后,超过95%HepG2细胞阻滞于G2/M期.在体内实验,与空白对照组比较,各剂量的9NC及9NC-LP均引起肿瘤体积下降(P<0.05)和裸鼠体重减轻(P<0.05).空白脂质体组与空白对照组、DMSO组比较差异无显著性(P>0.05).肿瘤生长最高抑制率9NC-LP(2.5 mg/kg)组、9NC-LP(1.5 mg/kg)组、9NC(1.5 mg/kg)组,分别为87.02%、51.57%和35.47%.9NC (2.5 mg/kg)组用药14 d过半动物死亡.结论 9NC及9NC-LP可以通过调控细胞周期和诱导凋亡有效抑制肝癌细胞生长.与原料药相比9-硝基喜树碱脂质体在体内对肝癌细胞的抑制增强,副作用减弱.9-硝基喜树碱脂质体是一种极具前景的纳米靶向药物.

Abstract：

Objective To observe the inhibitory effect and mechanism of 9-nitrocamptothecin liposomes on HepG2 liver carcinoma cells. Methods HepG2 cells were incubated with 9-nitrocampto-thecin(9NC) or with 9-nitrocamptothecin liposomes(9NC-LP) for 24 h, 48 h and 72 h. Cell viability was then measured by the MTT assay. Cell cycle and apoptosis were evaluated by flow cytometry.Western Blot was used to determine the expression of cell cycle and apoptosis related proteins. HepG2tumor-bearing mouse models were then established. The HepG2 tumor-bearing mice were randomly divided into control group, free liposomes group, DMSO group, 9NC low dose group, 9NC high dose group, 9NC-LP low dose group and 9NC-LP high dose group. There were 10 mice in each group.Drugs were administered by tail vein and tumor volume and body weight were observed 28 days after administration. Then animals were sacrificed and the expression of proteins from tumor homogenates was analyzed by Western blotting. Results In vitro, HepG2 cell viability was apparently inhibited by 9NC and 9NC-LP, and the inhibitory effect increased in a time-dependent and dose-dependent manner.Both S and G2/M phase arrests were observed after incubation with drugs. HepG2 cells were completely arrested in S phase with 9NC concentration over than 0.1 μmol/L after incubation for 24 h,while more than 95% of cells arrested in G2/M phase when 9NC concentration was 0.1 μmol/L after incubation for 72 h. In vivo, compared with the control group, the average tumor volume was reduced in both the 9NC and 9NC-LP group (P<0.05) , and the average animal body weight also decreased in both the 9NC and 9NC-LP group (P<0.05). There was no significant difference among the control group, free liposomes group, and DMSO group. The lights inhibition rates of tumor growth in the 9NC-LP(2.5 mg/kg),9NC-LP(1.5 mg/kg),and 9NC(1.5 mg/kg)groups were 87.02%, 51.57%and 35.47%, respectively. In the 9NC-LP(2.5 mg/kg)group, >50% of animals died 14 days after drug administration. Conclusion 9NC and 9NC-LP can inhibit HepG2 cell growth via cell cycle arrest and apoptosis induction. 9NC-LP has a more potent anti-tumor effect and fewer side effects in vivo,which means 9NC-LP is a promising compound for cancer therapy via intravenous administration.