卡培他滨联合奥沙利铂治疗晚期胃癌30例分析

目的:观察卡培他滨联合奥沙利铂治疗晚期胃癌的疗效及毒副反应.方法:30例晚期胃癌患者采用奥沙利铂130mg/m2+5/%葡萄糖500ml稀释,静注第1天,卡培他滨1000mg/m2,日二次口服,第1-14天,21天为1周期,一般为2周期后评价疗效.按WHO标准评估疗效和副作用.结果:CR1例、PR15例、SD8例、PD6例.总有效率53.3%,疾病控制率80%.中位生存期8.5个月.生活质量提高,KPS评分平均提高12分.结论:卡培他滨联合奥沙利铂治疗晚期胃癌患者中,毒副反应较轻,临床应用安全、方便,可作为晚期胃癌的治疗方案选择之一.     

吉西他滨联合顺铂治疗局部晚期非小细胞肺癌疗效观察

目的:探讨吉西他滨联合顺铂治疗局部晚期非小细胞肺癌(NSCLC)的方法和临床疗效.方法:将2006年6月至2010年6月我院收治的60例NSCLC的患者随机分为观察组40例和对照组20例,观察组采用吉西他滨联合顺铂治疗,对照组采用长春地辛、异环磷酰胺、顺铂方案化疗,比较两组患者的临床疗效及不良反应.结果:观察组的近期总有效率为82.5%(33/40)显著高于对照组的近期总有效率45.0%(9/20),P<0.05.观察组与对照组的不良反应物显著性差异,P>0.05.结论:吉西他滨联合顺铂治疗NSCLC有较好的近期疗效,不良反应可耐受,有利于改善患者的生存质量.     

GDP方案节拍化疗治疗复发难治性非霍奇金淋巴瘤28例

目的 观察吉西他滨联合顺铂及地塞米松(GDP方案)节拍化疗治疗复发难治性非霍奇金淋巴瘤(NHL)的疗效和不良反应.方法 对28例复发或难治性NHL给予吉西他滨联合顺铂及地塞米松方案化疗:吉西他滨200 mg,静脉滴注,隔天1次×14 d;顺铂10 mg,静脉滴注,隔天1次×14 d;地塞米松2.5 mg,静脉注射,2次/d×14d,每21 d为1个周期,治疗2个周期后进行疗效评价.结果 28例患者中完全缓解3例,部分缓解12例,有效率53.6%.疾病进展时间 4.6个月,1年生存率39.3%.不良反应主要为中度骨髓抑制及轻度消化道反应.结论 GDP方案节拍化疗治疗复发或难治性NHL有效率高,不良反应轻.     

DCF方案治疗局部晚期胃癌疗效观察

目的:探讨多西他赛、顺铂和氟尿嘧啶(DCF)方案对局部晚期胃癌疗效.方法:采用DCF方案治疗50例局部晚期胃癌患者:多西他赛75mg/m2,溶于生理盐水静脉滴注,d1;顺铂20mg/m2,溶于生理盐水静脉滴注,d1-3;氟尿嘧啶500mg/m2,d1-5,每21d为1个周期.结果:50例局部晚期胃癌患者化疗后疗效评价,CR4例(8.0%),PR8例 (16.0%),SD9例(18.0%),PD29例(58.0%),疾病控制率为42.0%;生存期3～25个月,中位生存期10.6个月.化疗治疗中未发生死亡,主要化疗不良反应为白细胞下降(58.0%)、血红蛋白下降(42.0%)、血小板下降(34.0%)、肝功能损害(28.0%)、肾功能损害(22.0%)、黏膜炎(10.0%)和恶心呕吐(8.0%).结论:DCF方案治疗局部晚期胃癌疗效较好,不良反应较少.     

地西他滨联合三氧化二砷对NB4细胞凋亡作用的研究

目的 研究去甲基化制剂地西他滨(DAC)单用或联合三氧化二砷(As2O3)对NB4细胞凋亡的作用机制.方法 将不同浓度的DAC、As2O3以及两药联合作用于NB4细胞,不加药为对照组,采用四甲基偶氮唑蓝(MTT)法检测细胞增殖抑制作用,流式细胞术检测细胞凋亡.结果 DAC与As2O3单药对NB4细胞的抑制作用呈浓度时间依赖性(DAC 1 μmol/L作用24、48、72 h的抑制率分别为12.18%、22.72%、35.54%;DAC 2 μmol/L作用24、48、72 h的抑制率分别增高为22.14%、31.18%、45.21%;As2O3 0.5 μmol/L作用24、48、72 h的抑制率分别21.09%、32.43%、44.93%;As2O3 1.0 μmol/L作用24、48、72 h的抑制率分别增高为31.69%、41.12%及54.27%),两药联合抑制作用较单药明显(DAC 1 μmol/L+As2O3 0.5 μmol/L作用24、48、72 h抑制率分别为42.10%、48.75%、60.78%)(P<0.05),各浓度组与对照组比较差异均有统计学意义(P值均<0.05);As2O3 1 μmol/L作用于NB4细胞株48 h可见5.8%的细胞凋亡,联合组增高为17.3%.结论 DAC能显著抑制NB4细胞的增殖并诱导其凋亡,DAC联合As2O3对NB4细胞增殖抑制及诱导凋亡有协同作用.     

低剂量地西他滨联合伊马替尼对K562细胞的增殖抑制作用

目的 研究低剂量地西他滨(DAC)联合伊马替尼(IM)对K562细胞株的增殖抑制作用及对bcr-abl表达的影响.方法 单药及两药联合后,通过四甲基偶氮唑蓝(MTT)法观察药物对K562细胞株的增殖抑制作用,流式细胞术检测药物对K562细胞株早期凋亡率及细胞周期,巢式反转录-聚合酶链反应(RT-PCR)半定量检测药物对K562细胞株bcr-abl mRNA表达.结果 DAC与IM单药对K562细胞的抑制作用呈浓度时间依赖性.两药联合用药抑制作用较单药组明显(F=43.947、165.580、321.193、296.101,均P<0.05),24、48、72 h各浓度组与对照组比较差异均有统计学意义(F=202.759、168.457、417.538,均P<0.05).DAC及IM单药作用药物对K562细胞株均使G,期细胞明显增多,IM0.2μmol/L作用于K562细胞株48 h可见6.7%早期凋亡细胞,IM 0.2 μmol/L联合DAC 4μmol/L早期凋亡细胞增加至8.4%.bcr-abl mRNA表达水平降低,DAC 4 μmol/L作用48 h后可降低K562细胞中bcr-abl mRNA表达(约14%),IM 0.2 μmol/L降低约40%,联合用药表达量明显降低(约60%).联合用药组与单药组比较差异有统计学意义(F=71.981,P<0.05).结论 DAC对K562细胞的增殖抑制作用与细胞周期阻滞、诱导凋亡及降低bcr-abl mRNA表达有关,两药联合可显著抑制K562细胞增殖.     

调强放疗结合腔内放疗同步化疗治疗中晚期宫颈癌的临床观察

目的 研究调强放疗、腔内治疗并同步化疗治疗中晚期(IIB-ⅢB)宫颈癌的疗效及毒副反应.方法 选择宫颈癌患者60例,随机分为调强组(调强放疗,腔内放疗结合同步化疗,30例),常规组(常规四野箱式外照射,腔内放疗结合同步化疗,30例).治疗方法:调强组给予56～60 Gy剂量,常规组予50～54 Gy盆腔照射.腔内放疗:A点给予5 Gy/次,2次/周,共6～8次.所有病人接受多西他赛和顺铂同步化疗,每3周一次,共3个疗程.比较临床疗效和急性、晚期毒副反应.结果 两组病人资料类似.中位随访时间是47个月.调强组与常规组的1,2,3年生存率分别为90.0%,86.7%,80.0%以及86.7%,70.0%,60.0%;两组比较差异没有显著性(P>0.05).调强组中有7例(23.33%)患者复发,常规组有17例(56.67%)复发,两组比较差异有统计学意义(P＜0.05).常规组中3,4级急性和晚期消化道反应和泌尿道反应的发生率比调强组高,差异有统计学意义(P＜0.05).血液骨髓毒副反应的比较,两组结果相似.结论 调强放疗结合腔内放疗并同步多西他赛、顺铂化疗,是治疗局部晚期宫颈癌有效的方法.     

吉西他滨联合树突状细胞对HepG2细胞增殖的抑制作用

目的:观察肿瘤细胞裂解物致敏的树突状细胞(DC)联合吉西他滨(GEM)体外抑制肝癌HepG2 细胞系增殖的作用,为临床探索有效的肝癌综合治疗方案提供实验依据.方法:采用反复冻融法裂解HepG2 细胞,提取肿瘤细胞抗原后致敏DC,并以DC刺激自身T 细胞的增殖和活化.按不同处理因素分组:①空白对照组,只含空白培养液;②阴性对照组,只含HepG2 细胞;③单纯T 细胞组,将未经致敏DC 刺激的T细胞与靶细胞按20∶1 的比例接种;④单纯活化T 细胞组,将经致敏DC 刺激后的活化T 细胞与靶细胞按20∶1 的比例接种;⑤单纯GEM 处理组,靶细胞接种后在培养基中分别添加终浓度为50、100、150、200 μg·L-1 的GEM;⑥T细胞+GEM 处理组,在单纯T 细胞组的培养基中分别添加上述4个浓度梯度的GEM;⑦活化T 细胞+GEM 处理组,在活化T 细胞组的培养基中分别添加上述4个浓度梯度的GEM.MTT 法检测细胞杀伤率,流式细胞仪检测细胞凋亡率,观察应用T 细胞、不同浓度的GEM 以及两者联合应用对HepG2 细胞的体外杀伤效应.结果:空白对照组刺激指数(SI)为1.34,阴性对照组SI 为3.48,两者比较差异有统计学意义(P<0.01).与单纯T细胞组[(4.81±2.54)%]比较,单纯活化T 细胞组细胞杀伤率[(21.68±4.39)%]明显升高(P<0.01);与活化T细胞+50、100 和150 μg·L-1 GEM组比较,活化T细胞+200 μg·L-1 GEM组细胞杀伤率明显升高(P<0.05).单纯T 细胞组细胞凋亡率为(5.45±0.94)%,与阴性对照组 [(4.47±1.98)%]比较差异无统计学意义(P>0.05);活化T 细胞组细胞凋亡率为(14.32±1.16)%,与前两组比较差异有统计学意义(P<0.01).活化T细胞+100 μg·L-1 GEM组细胞凋亡率为(24.52±0.85)%,与其他各组比较差异均有统计学意义(P<0.05).结论:负载肿瘤细胞抗原的DC 可诱导出抗肿瘤的细胞毒性T细胞,活化的T细胞联合GEM 能显著提高其杀伤肿瘤细胞的作用.     

FOLFOX6序贯周剂量多西紫杉醇及顺铂方案一线治疗老年晚期胃癌临床观察

目的:观察FOLFOX6序贯周剂量多西紫杉醇及顺铂方案一线治疗老年晚期胃癌的疗效和安全性.方法:32例晚期胃癌患者先采用FOLFOX6方案化疗.14天为1个周期.FOLFOX6方案化疗3个周期结束后第14天开始给予多西紫杉醇+顺铂方案化疗,每周给药一次,每4周为1 周期,治疗2周期.结果:全组32例均可评价疗效,完全缓解 0例(0%),部分缓解 14例(43.8%),稳定13例(40.6%),进展5例(15.6%),总有效率为43.8% (14/32),临床获益率84.0%(27/32).中位疾病进展时间为7.6个月(95%可信区间,3.6～12.12个月),中位生存期为10.9个月(95%可信区间,5.4～15.5个月),1年生存率为40.6% (13/32).主要毒性反应为骨髓抑制、消化道反应和脱发,多数为1～2度.结论:FOLFOX6序贯周剂量多西紫杉醇及顺铂方案一线治疗老年晚期胃癌疗效较好,毒性反应较轻,耐受性好.     

MT方案治疗急性单核细胞白血病的疗效及其与染色体核型的关系

目的 研究米托蒽醌联合替尼泊苷(MT)方案在急性单核细胞白血病(M5)诱导缓解中的疗效及患者不良反应,并观察疗效与白血病染色体核型的关系.方法 将33例M5患者按治疗史分两组:初治组23例(A组)、DA(柔红霉素联合阿糖胞苷)或HDA(三尖杉酯碱、柔红霉素和阿糖胞苷)1个疗程无效组10例(B组).按核型预后分两组:预后中等组29例(C组),预后不良组4例(D组),均采用MT方案2个疗程诱导缓解,分别统计4组的临床疗效及患者不良反应.结果 MT方案对A、B组的M5诱导完全缓解(CR)率分别为83%(19/23)及60%(6/10),有效率达91%(21/23)及70%(7/10).C、D组CR率分别为83%(24/29)及25%(1/4),有效率为88%(26/29)及50%(2/4),其中复杂核型CR率为0(0/3),非复杂核型的11q23染色体异常患者一次化疗达CR率100%(4/4).MT方案对M5化疗后白细胞最低点在第(7±3)天出现,为(0.4±0.2)×109/L,白细胞<1×109/L时间达(8±5)d,未见化疗相关死亡病例.结论 MT方案简单有效、较安全,是治疗M5的较佳化疗方案,对1个疗程DA、HDA方案无效者亦可试用.MT方案化疗疗效与核型预后分组有关,对11q23染色体异常的M5患者疗效较好,对复杂核型患者疗效欠佳.     

多西他赛与吉西他滨分别顺泊治疗晚期非小细胞肺癌的临床研究

Objective: The aim of this study was to evaluate the clinical efficacy and side effects of docetaxel/cisplatin regiment and gemcitabine/cisplatin regiment in the patients with advanced non-small-cell lung cancer (NSCLC). Methods: Seventy six patients with advanced NSCLC who were chemotherapy-naive were enrolled in two groups. In docetaxel group (DP group) the patients received docetaxel 75 mg/m2 and cisplatin 60 mg/m2 on day 1. In gemcitabine group (GP group) the patients received gemcitabine 1000 mg/m2 on day 1 and day 8. The dosage of cisplatin was the same as DP group. The two regiments were administrated intravenously every 21 days as a cycle, each patient received 2-4 cycles. All patients were followed up until disease progressed or patients died. Results: The overall response rates were 43.5% in DP group and 45.9% in GP group. The response rate was significantly different between the initial treated group and retreated group in both two groups (53.8% vs 23.0% in DP group and 56% vs 25% in GP group, P < 0.05, respectively). The main side effects were bone marrow suppression and thrombocytopenia. Conclusion: Docetaxel/cisplatin regiment and gemcitabine/cisplatin regiment for the patients with advanced NSCLC were efficient and well-tolerated chemotherapeutic approachs with low toxicity levels. The efficacy and major toxicity in two groups were similar.     

The effect of docetaxel on malignant tumors

In recent years numerous molecular biological discoveries enlightened the various steps of the neoplastic transformation. Based on new targets, this development made it possible to synthetize new tumour inhibitory substances. Among them taxanes capable to block depolymerization of tubulin--which is an essential molecule in cell division--play an important role. Docetaxel (Taxotere) belongs to this group and is an active drug in the treatment of breast cancer. Moreover, platinum-resistant tumours may also respond to the therapy. It is important to note that even visceral (hepatic) metastases may express chemosensitivity. Results of combination chemotherapy seem to be also promising. The antitumour effect of Taxotere in NSCLC and other malignant neoplasms in under investigation. The toxicity of Taxotere may be successfully reduced by premedication of steroids. The necessary protective measures render the Taxotere therapy safe and of being perspectivistic.     

Cryopreservation of equine embryos with glycerol plus sucrose and glycerol plus 1,2-propanediol

Six or 7-day-old equine embryos were divided into 4 groups; Group 1, n = 15, Day 7 embryos destined for immediate transfer; Group 2, n = 15, Day 6 embryos destined for deep-freezing with glycerol plus sucrose as cryoprotectant; Group 3, n = 10, Day 6 embryos destined for deep-freezing with glycerol plus 1,2-propanediol as cryoprotectant and Group 4, n = 3, fresh embryos destined for ultrastructural analysis. All the frozen/thawed embryos were transferred to recipient mares, except 3 embryos in Group 3 that were subjected to ultrastructural analysis. After thawing the cryoprotectants were removed by successive dilutions in PBS + 15% v:v fetal calf serum (FCS) containing decreasing concentrations of the cryoprotectants. Pregnancy was diagnosed ultrasonographically in 53.3%, 13.3% and 0% of the mares in Groups 1, 2 and 3 respectively. Ultrastructural analysis showed differences between frozen/thawed and fresh embryos. In the former, embryonic cells were deformed and showed dilation of the intercellular and perivitelline spaces, a decrease of desmosome number in the junctional complexes, few microvilli on the apical surface of the trophectoderm and an almost total absence of pinocytotic vesicles. Most of the mitochondria showed regions containing dilation and irregularities on the cristae, which appeared electron-dense. The results obtained with Groups 2 and 3 embryos showed that the cryoprotectants employed were not effective in protecting the embryos against damage during freezing and thawing. Indeed, the ultrastructural changes observed in the Group 3 embryos explained the absence of any established pregnancies in this group of mares.     

Cost-utility model comparing docetaxel and paclitaxel in advanced breast cancer patients

Relevant data from direct comparisons in clinical trials are not available for economic evaluations of docetaxel and paclitaxel in the management of metastatic breast cancer. A modified Markov model is used to estimate the incremental cost in US$ per quality-adjusted life-year (QALY) for docetaxel versus paclitaxel in managing metastatic breast cancer patients in the US. The model incorporates the latest available clinical trial data (response rates of 47.8% for docetaxel and 25% for paclitaxel, chemotherapy-specific toxicities, time to progression, and 1-year survival) from studies against other comparators. Medical care resources were estimated by US oncologists and costed using US data sources. Utility scores were obtained from 29 US oncology nurses. The base case and subsequent sensitivity analyses show that docetaxel management of advanced breast cancer is more costly per patient but yields higher health benefits than paclitaxel therapy. The cost per QALY gained by docetaxel is $8615, and ranges between $3943 and $9416 in sensitivity analyses. These results confirm those of an earlier model using preliminary data and compare favorably with other cost-utility results in this patient group.     

Comparison of the pharmacodynamic activity of cefotaxime plus metronidazole with cefoxitin and ampicillin plus sulbactam

STUDY OBJECTIVE: To compare the pharmacokinetic and pharmacodynamic activity of three drug regimens: cefotaxime plus metronidazole, cefoxitin, and ampicillin-sulbactam against two organisms frequently isolated in intraabdominal infection, Escherichia coli and Bacteroides fragilis. DESIGN: Open-label, three-way crossover study. SETTING: Hartford Hospital Clinical Research Center. PARTICIPANTS: Nine healthy volunteers. INTERVENTIONS: Subjects received the following regimens: (1) a single 1-g intravenous dose of cefotaxime plus a single 500-mg oral dose of metronidazole; (2) two intravenous doses of cefoxitin, 2 g each dose given every 6 hours; and (3) two intravenous doses of ampicillin-sulbactam, 3 g each dose given every 6 hours. MEASUREMENTS AND MAIN RESULTS: Serum bactericidal titers and drug concentrations were measured over a 12-hour period. The cefotaxime-metronidazole regimen showed superior activity against E. coli compared with ampicillin-sulbactam and cefoxitin. The mean areas under the bactericidal activity curve (AUBC) for the three regimens were 550.2, 68.7, and 48.9, respectively (p = 0.0001). There was no significant difference in AUBC among the three regimens for B. fragilis. Serum concentrations of cefotaxime remained above the minimum inhibitory concentration (MIC) for E. coli significantly longer than did concentrations of ampicillin-sulbactam and cefoxitin (p = 0.0002 and p = 0.0023, respectively). Serum concentrations of metronidazole were still at 9 times the MIC for B. fragilis at the end of the 12-hour dosing interval; for ampicillin-sulbactam and cefoxitin concentrations remained above the MIC for one-half and less than one-fourth, respectively, of the dosing interval (p < 0.0001). The ratio of AUC:MIC was also favorable for metronidazole (212.2) compared with 63.4 for ampicillin-sulbactam and 9.2 for cefoxitin. CONCLUSIONS: The combination of cefotaxime-metronidazole, even at the relatively low doses used in this study, provides coverage against gram-negative and anaerobic pathogens that is at least as effective as that of cefoxitin and ampicillin-sulbactam. In addition, its cost is considerably less expensive than that of the other regimens.     

A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy

Recent research on development of the implantable artificial pancreas for treatment of diabetes is reviewed, based on a Medline literature search that focused on glucose sensors, insulin pumps, and pump control systems. To achieve a closed feedback loop, a clinically applicable implantable artificial pancreas requires miniaturization and coordination of three components: an insulin pump, a blood glucose monitor, and a control system. Recent clinical studies have demonstrated that implantable insulin pumps are feasible for satisfactory control of diabetes for over a year, with the major complication being obstruction of the infusion catheter. Research on continuous glucose sensors has predominantly used the glucose-oxidase reaction or near-infrared light spectroscopy. Implantable glucose oxidase sensors have been limited by local factors causing unstable signal output, whereas optical sensors must overcome interference by substances with absorption spectra similar to glucose. Investigators have developed control algorithms in an effort to stabilize operation of the integrated artificial pancreas in the face of variations in sensor output and pump function. The ultimate goals of fully automatic glucose control by an artificial pancreas include prevention or delay of chronic complications of diabetes, lowered risk of hypoglycemia, and less patient inconvenience and discomfort than with multiple daily glucose self-tests and insulin injection. The recent developments of optical glucose sensing, radiotelemetry systems to link pump and sensor, and miniaturization and refinement of insulin pumps are significant steps toward a clinically applicable artificial pancreas.