ATP结合盒转运载体超家族与胰腺癌耐药

虽然吉西他滨(Gemcitabine)是治疗胰腺癌的一线化疗药物,较其他传统的化疗药物有较好的疗效,但胰腺癌化疗的总体效果仍然不理想~([1]).其主要原因是胰腺癌对多种化疗药物耐药~([2]),而耐药与ATP结合盒(ATP-binding cassette,ABC)转运载体超家族有关~([2]).

过表达Plk-1对gemcitabine诱导的胰腺癌细胞化疗敏感性的影响

目的 观察Plk-1基因过表达对gemcitabine诱导胰腺癌细胞AsPC-1化疗敏感性的影响.方法 ①将携带有人外源性Plk-1基因的真核表达质粒转染AsPC-1细胞系设为处理组,转染空载体设为对照组,无处理组设为空白组,转染24h后,提取细胞总RNA和总蛋白,利用RT-PCR法及Western blot鉴定AsPC-1细胞内Plk-1基因和蛋白表达水平.②采用流式细胞术检测转染组细胞凋亡的改变.③不同浓度gemcitabine作用于转染细胞,MTT法测定转染48 h后细胞增殖能力.结果 ①测序结果表明成功的从AsPC-1细胞总RNA中扩增Plk-1基因.RT-PCR结果表明:未转染组AsPC-1细胞组、转染空载体pcDNA3.1组及pcDNA3.1/Plk-1组24 h各组细胞内Plk-1 mRNA相对量分别为(2.14±0.16)、(2.18±0.15)、(2.58±0.18),转染pcDNA3.1/Plk-1组与其他各组相比,差异有高度统计学意义(P＜0.01).Westernblot结果显示:未转染组AsPC-1细胞组、转染空载体pcDNA3.1及pcDNA3.1/Plk-1组24 h各组细胞内Plk-1基因的蛋白表达水平为(0.989±0.018)、(1.022±0.021)、(1.243±0.143),转染pcDNA3.1/Plk-1组与其他各组相比,差异有高度统计学意义(P＜0.01).②在gemcitabine作用下,pcDNA3.1/Plk-1转染组细胞凋亡率明显低于未转染组及空载体转染组,差异有高度统计学意义(P＜0.01).③AsPC-1/Plk-1转染组细胞的生长抑制率亦明显高于未转染组及空载体转染组,差异有高度统计学意义(P＜0.01).结论 胞浆过表达Plk-1活性分子可明显降低gemcitabine诱导的AsPC-1细胞凋亡,增强其对化疗药物的耐受性.

吉西他滨纳米载药囊泡控释行为的研究

目的 制备吉西他滨(Gemcitabine)纳米载药囊泡,对其表面形态、粒径分布、微粒结构、体外释放等性能进行评估.方法 以两亲性共聚物聚乙二醇-聚乳酸(PEG-PDLLA)为原料,采用双乳化法制备载药囊泡,Gemcitabine为模型药物.通过电子显微镜观察纳米载药囊泡的形态和结构,用紫外可见分光光度计测定囊泡的载药量、包封率和体外释放量.结果 纳米载药囊泡呈球形或近似球形,具有明显的空心结构,平均粒径为200.6 nm,载药量和包封率分别为4.14%和20.54%,体外释放实验表明该囊泡具有良好的控释特性.结论 以PEG-PDLLA为原料制备的Gemcitabine纳米载药囊泡具有良好的控释性能,为胰腺癌动物体内实验研究提供了可靠的依据.

Effect of Endostar Combined with Gemcitabine on the Mouse Model of Human Pancreatic Cancer

Objective To investigate the effects of recombinant human endostatin,that is,endostar combined with gemcitabine on the mouse model of human pancreatic cancer.Methods We use the cell line PANC-1 and the severe combined immune deficient mice to set up the mouse model of human pancreatic cancer,then devide them into three groups,treat them with gemcitabine,gemcitabine combined with endostar,and 0.9% saline water respectively.We observe the change of the tumor volumn,use ELISA method to detect the serum VEGF level,stain the micro vessel in the tumor tissue with immunohistochemistry method,and compare the data among the different groups respectively.Results On the twenty-eighth day,the tumor volume of the control group,the monotherapy group and the combination group,averaged 1 700 mm3,19.2 mm3,10.4 mm3,serum VEGF level 88.6 L,35.5,26.3 pg/mL and MVD 43.9,30.3,19.2 respectively,which had significant difference.Conclusion Endostar can strengthen the lethal effect of gemcitabine on the mouse model of human pancreatic cancer.

Objective:The aim of this study was to investigate the ef ect of toremifene on A549 human lung adenocarci-noma cells, and its sensibilization with gemcitabine, so that to provide a new clinical approach for non-smal-celllung cancer (NSCLC). Methods:A549 cells were seeded into 96-wel plates and exposed to dif erent agents (gemcitabine or gemcitabine with toremifene). The cytotoxicity of each agent was evaluated by MTT, cellcycle and apoptotic rate were detected by flow cytometry (FCM). Results:1. By using FCM, we found A549 cells in S and G2/M phases with toremifene decreased but increased in G0/G1 phase. The higher concentration of toremifene, the more decreased was when compared with the control group. 2. FCM showed toremifene’s apoptosis ef ect on A549 cells increased with its increasing dose. 3. By MTT, toremifene had no cytotoxic ef ect on A549 cells at the concentration of 5 or 2.5 μmol/L. The IC50 of gemcitabine to A549 was 34.51 μmol/L, and the combined group was 13.59 μmol/L. Conclusion:Toremifene could inhibit the growth of A549 human lung adenocarcinoma cells. Toremifene combined with gemcitabine showed significantly remarkable chemotherapy sensibilization on A549 human lung adenocarcinoma cells.

The prognosis of locally advanced or recurrent squamous cell carcinoma (SCC) of the penis after conventional treatment is dismal. This study aimed to evaluate the therapeutic effects of intraarterial chemotherapy with gemcitabine and cisplatin on local y advanced or recurrent SCC of the penis. Between April 1999 and May 2011, we treated 5 patients with locally advanced penile SCC and 7 patients with recurrent disease with intraarterial chemotherapy. The response rate and toxicity data were analyzed, and survival rates were calculated. After 2 to 6 cycles of intraarterial chemotherapy with gemcitabine and cisplatin, 1 patients with locoregional y advanced disease achieved a complete response, and 4 achieved partial response. Of the 7 patients with recurrent disease, 2 achieved complete response, 3 achieved partial response, 3 had stable disease, and 1 developed progressive disease. An objective tumor response was therefore achieved in 10 of the 12 patients. The median overal survival for the patients was 24 months (range, 10-50 months). Three out of 10 patients who responded were long-term survivors after intraarterial chemotherapy. Intraarterial chemotherapy with gemcitabine and cisplatin may be effective and potential y curative in locoregional y advanced or recurrent penile SCC. The contribution of this therapy in the primary management of advanced or recurrent penile SCC should be prospectively investigated.

Despite recent improvements to current therapies and the emergence of novel agents to manage advanced non-smal celllung cancer (NSCLC), the patients′overal survival remains poor. Re-chal enging with first-line chemotherapy upon relapse is common in the management of smal celllung cancer but is not wel reported for advanced NSCLC. NSCLC relapse has been attributed to acquired drug resistance, but the repopulation of sensitive clones may also play a role, in which case re-chal enge may be appropriate. Here, we report the results of re-chal enge with gemcitabine plus carboplatin in 22 patients from a single institution who had previously received gemcitabine plus platinum in the first-line setting and had either partial response or a progression-free interval of longer than 6 months. In this retrospective study, the charts of patients who underwent second-line chemotherapy for NSCLC in our cancer center between January 2005 and April 2010 were reviewed. Al the patients who received a combination of gemcitabine and carboplatin for re-challenge were included in the study. These patients were offered second-line treatment on confirmation of clear radiological disease progression. The overall response rate was 15%and disease control rate was 75%. The median survival time was 10.4 months, with 46%of patients alive at 1 year. These results suggest that re-chal enge chemotherapy should be considered in selected patients with radiological partial response or a progression-free survival of longer than 6 months to the initial therapy.

细胞膜核苷载体表达与肿瘤化疗关系的研究进展

5-氟尿嘧啶(5-fluorouracil,5-FU)、吉西他滨(gemcitabine)及阿糖胞苷(cytarabine)等核苷类药物是很多抗肿瘤化疗方案的基础用药,临床应用广泛.细胞膜核苷载体对核苷类化疗药物的细胞内外转运起着决定性作用,细胞膜核苷载体的表达水平,直接决定了细胞内核苷类药物的浓度,从而决定了肿瘤的化疗效果.

Background and objective Recent studies have showed that combination of chemotherapy and radiotherapy might result in better outcome for locally advanced non-small cell lung cancer (NSCLC). The aim of this study is to determine the maximal tolerance dose (MTD) and efficacy of full-dose gemcitabine and oxaliplatin when given concurrently with 3-dimentional radiation therapy (3D-RT) for locally advanced NSCLC. Methods Oxaliplatin was administered at a fixed dose of 130 mg/m2, and gemcitabine was administered at a starting dose of 800 mg/m2 with an incremental dose gradient of 200 mg/m2 for 3 dose levels. MTD was defined as the immediate dose level lower than the dose at which dose-limiting toxicity (DLT) occurred in more than one-third of the patients. The chemotherapy was administered at 3-week cycle. The RT was given as 3-D conformal manner at a single daily dose of 2 Gy for 5 days per week. Results Twenty-two patients were evaluable and distributed to three different dose levels: 6 at level 1, 8 at level 2 and 8 at level 3. Pulmonary toxicity, esophageal and hematologic toxicity were the main DLT. Grade Ⅲ acute pulmonary toxicity occurred in one patient each at level 2 and level 3, both with V20＞20%, and grade Ⅲ esophagitis in two patients at level 3. The MTD of gemcitabine in this study was 1000 mg/m2. The overall response rate was 75.0% (9/12). The 1- and 2-year survival rate was 70.0% and 30.5% respectively. The median time to progression was 8.7 months (range 5--11.8 months). Conclusion With reduced radiation volume, gemcitabine of 1000 mg/m2 in combination with oxaliplatin of 130 mg/m2 was effective and could be safely administered for NSCLC.

吉西他滨治疗RRM1阴性晚期难治非小细胞肺癌患者1例

目前吉西他滨/铂类方案是晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的标准治疗方法之一.Anderson等[1]报告吉西他滨单药治疗NSCLC客观缓解率(objective response rate,ORR)为20%;国内管忠震等[2]报道吉西他滨联合顺铂方案的疾病控制率为56.1%,部分缓解率为43.9%,中位缓解时间(174±18.5)天.

肺癌GP方案化疗后急性心梗死亡1例报告

1 临床资料患者,女,48岁,因咳嗽、咳痰半月入院.入院查体:神志清,浅表淋巴结未触及肿大,双肺呼吸动度均等,叩诊两侧清音,双肺呼吸音粗,可闻及少量干湿啰音,未闻及胸膜摩擦音.CT检查示:右肺门增大并软组织密度影,纵隔内多发淋巴结肿大.