胃癌单克隆抗体-柔红霉素结合物的制备及其细胞毒作用

柔红霉素(Daunomycin,DNR)是一广谱抗癌药物,由于其对心肌、骨髓等正常组织有毒性作用而常常发生严重的毒副反应,致使临床应用受到很大的限制。本文用葡聚糖作为中间载体,将DNR和胃癌单克隆抗体MG_7联接制备成一种免疫抗癌药,发现其中的单抗MG_7对胃癌细胞具有选择性作用,结合物中的DNR也具有抗肿瘤效应。 一、单克隆抗体的纯化 将含有抗胃癌单克隆抗体MG_7的BALB/c小鼠腹水用50％硫酸铵沉淀、再经DEAE-52离子交换层析、提取物在SDS-PAGE上显示单带,免疫组化证实其     

超声评价维生素C静脉输注对原发性高血压病患者肱动脉内皮功能的影响

目的应用高分辨力超声测量反应性充血前后肱动脉内径的百分变化率,评价维生素C静脉输注对原发性高血压病患者肱动脉内皮功能的影响。方法分别于维生素C静脉输注前后,应用高分辨力超声测量50例原发性高血压病患者静息状态下、反应性充血后、舌下含服硝酸甘油后的肱动脉内径,并计算反应性充血和硝酸甘油诱发的内径百分变化率。结果维生素C静脉输注后,原发性高血压病患者反应性充血前后肱动脉内径百分变化率(16.8%±2.9%)明显高于静脉输注前(5.8%±2.7%,P<0.001),硝酸甘油诱发的肱动脉内径百分变化率(23.1%±4.6%)与静脉输注前(22.3%±4.2%,P=0.29)差别无统计学意义。结论维生素C静脉输注可以恢复原发性高血压病患者肱动脉内皮功能。     

进展期胃癌围手术期腹腔热灌注化疗的临床观察

目的 探讨围手术期腹腔热灌注化疗(IPHPC)对进展期胃癌术后的疗效及并发症.方法 将67例接受根治性胃切除手术的进展期胃癌患者随机分成治疗组和对照组,两组均给予静脉化疗.治疗组35例术中和术后早期采用IPHPC联合静脉化疗;对照组32例只进行静脉化疗.比较两组术后并发症、不良反应、局部复发率、远处转移率及1～3年生存率.结果 治疗组出现腹胀的副作用明显高于对照组(P<0.05),但经对症处理后,腹胀病例均在1～3d内自行缓解,两组均未出现严重毒副反应.治疗组复发率及远处转移率明显低于对照组,2年和3年的生存率高于对照组(P<0.05).结论 胃癌围手术期IPHPC能显著降低局部复发率和远处转移率,可提高生存率,毒副作用小.     

多西紫杉醇联合卡培他滨与FOLFOX4方案治疗晚期胃癌疗效对比

目的比较多西紫杉醇联合卡培他滨或FOLFOX4方案治疗晚期胃癌的近期疗效及毒副反应。方法52例晚期胃癌的患者随机分为2组,实验组即多西紫杉醇联合卡培他滨治疗组,多西紫杉醇40mg／（m^2,w）d1．d8静脉输注,卡培他滨片每日口服2000mg／m^2每日二次d1—14,21d为1周期：对照组即FOLFOX4方案组,奥沙利铂85mg／m2dl静脉输注,亚叶酸钙200mg／m^2d1-2静脉输注2h,5-Fu400mg／m^2 d1-2快速静点。5-Fu600mg／m2d1-2持续静脉泵入22h,每14d重复,28d为1周期。均化疗2个周期以上,观察2纽药物的近期疗效及毒副反应。结果实验组CR2例．PR12例,有效率53．8％;对照组CR1例,PR12例,有效率50％,两组疗效无显著性差异。实验组与对照组的骨髓抑制及胃肠道反应发生率均较为常见．两组之间发生率无统计学差异。手足综合征发生率实验组明显高于对照组,但其多为Ⅰ-Ⅱ度,患者多能耐受,对生活质量影响轻微。对照组的毒副反应主要是外周神经毒性及腹泻,发生率显著高于实验组,两组数据比较在统计学上有显著性差异。结论多西紫杉醇联合卡培他滨治疗晚期胃癌的疗效确切,毒性反应发生程度轻,对晚期胃癌治疗有着积极的意义。     

肝动脉灌注~(131)I-抗人肝癌单克隆抗体治疗不能切除的肝癌

32例经剖腹探查证实不能手术切除、病理诊断为肝细胞肝癌(HCC,下称肝癌)的患者行肝动脉结扎加插管,经导管灌注~(131)I标记的抗人肝癌单克隆抗体Hepama-1(~(131)I-Hepama-1).放射免疫显像显示,标记抗体浓聚瘤内,第5天平面扫描显像,瘤/肝比值中位数为1.7(0.8～3.8),并随时间延长而增高。治疗后,甲胎蛋白(AFP)下降占55％(11/20),71.9％(23/32)病人肿瘤有不同程度缩小,17例     

全胸腔镜心脏手术体外循环插管的选择

目的总结电视胸腔镜心脏手术体外循环动静脉插管的选择方法及对体外循环灌注过程的影响。方法 205例心脏病手术患者,其中男性87例,女性118例;年龄3～46岁,平均年龄16.2岁;体质量13～84kg,平均体质量38.2kg。对其采用胸腔镜建立体外循环,分析股动脉、股静脉及上腔静脉插管型号与患者体质量关系及插管型号对体外循环灌注过程中灌注流量及动脉灌注管阻力的影响。结果 114患者例采用股动脉、股静脉插管,91例采用股动脉、股静脉/腔静脉插管建立体外循环。205例患者中有15例在高于2.2L/min流量灌注过程中动脉灌注管阻力高于40kPa（300mmHg）,其他患者灌注流量与动脉灌注管阻力均能达到临床要求。结论全胸腔镜体外循环下实施心脏手术选择合适的股动静脉插管可以保证体外循环灌注的有效性与安全性。     

PD-1单克隆抗体瘤内用药对小鼠肺癌疗效的影响

目的探索PD-1单克隆抗体瘤内用药对小鼠肺癌的治疗作用,旨在寻找更安全、有效的免疫治疗方案。方法将皮下荷瘤成功的C57BL/6J肺癌小鼠随机分为5组:尾静脉注射生理盐水组(intravenous injection,IV)、瘤内注射生理盐水组(intratumoral injection,IT)、尾静脉注射PD-1单抗组(IV 10 mg/kg)、瘤内注射PD-1单抗组(IT 10 mg/kg)、瘤内注射PD-1单抗剂量减半组(IT 5 mg/kg),分析各组小鼠的生存率和小鼠荷瘤生长情况;运用流式细胞术分析CD8⁺T细胞/CD4⁺T细胞比例,使用免疫组织化学分析各组小鼠荷瘤组织CD45、Ki67的表达,并对上述数据进行统计学分析。结果瘤内注射PD-1单抗可显著抑制小鼠肺癌组织的生长、延长小鼠生存时间,且瘤内组织Ki67表达下调,CD45表达、CD8⁺T细胞/CD4⁺T细胞免疫细胞比例增加。结论瘤内注射组小鼠荷瘤组织生长速度明显受抑、肿瘤细胞增殖指数和生存时间显著降低,提示瘤内注射PD-1单抗对小鼠肺癌的发展进程具有抑制作用,此创新式的治疗方法将为临床治疗肿瘤提供新的思路和策略。     

贝伐珠单抗联合化学药物治疗晚期胃癌的疗效观察

目的:贝伐珠单抗是血管内皮生长因子的重组人源化单克隆IgGI抗体,通过抑制肿瘤血管生成而发挥抗肿瘤作用.本研究旨在观察贝伐珠单抗联合化学药物治疗晚期胃癌的疗效与安全性.方法:12例晚期胃癌患者均经病理组织学确诊后接受贝伐珠单抗联合化学药物治疗.贝伐珠单抗的剂量为7.5 mg/kg,第1天给药,21d1个周期,每2个周期评价疗效.结果:12例患者均可评价疗效和毒副反应,一线治疗5例,二线治疗7例,根据实体瘤的疗效(response evaluation criteria in solid tumors,RECIST)评定标准,无完全缓解患者,部分缓解8例(66.7％),病情稳定3例(25.0％),病情进展1例(8.3％),客观有效率67％,疾病控制率91％.中位无进展生存时间5.5个月,中位总生存期7.0个月.骨髓抑制6例,肝损害3例,胃肠道反应2例,高血压1例,均为Ⅰ～Ⅱ度,经对症治疗后好转,无严重不良事件.结论:贝伐珠单抗联合化学药物治疗晚期胃癌临床疗效较好,用药期间不良反应可耐受.     

卡介苗素膀胱灌注预防膀胱癌术后复发的临床研究

目的探讨卡介苗素膀胱内灌注预防膀胱癌术后复发的疗效、安全性.方法 47例膀胱癌术后患者分2组,分别应用卡介苗素和卡介苗定期行膀胱内灌注,随访10～32个月,了解灌注后肿瘤复发情况及并发症,并于灌注前、后检测2组尿液中IL-2、IL-6、IL-8的变化情况.结果卡介苗膀胱灌注组肿瘤复发4例(17.4%),副反应发生18例(78.3%),卡介苗素膀胱灌注组肿瘤复发5例(20.8%),副反应发生率11例(45.8%),2组尿液中IL-2、IL-6、IL-8值灌注后高于灌注前(p<0.05).两组肿瘤复发率、IL-2、IL-6、IL-8值灌注前后比较无显著差异,副反应卡介苗组明显高于卡介苗素组(p<0.05).结论卡介苗素膀胱灌注预防膀胱癌术后复发的有效率与卡介苗相同,但不良反应明显减少,患者耐受性好,因此卡介苗素可成为膀胱浅表移行上皮细胞癌临床治疗和预防复发的一种有效药物.     

直肠上动脉插管注射美蓝染色在直肠癌根治术中的应用

目的探讨直肠上动脉插管注射美蓝对直肠癌根治术中全直肠系膜切除(TME)的指示作用及染色后清除淋巴结数量的变化。方法将我科2002年1月至2003年12月行直肠癌手术的病人58例随机分为两组,其中经直肠上动脉插管注射美蓝组28例,普通根治组30例,观察两组淋巴结清除情况。结果注射美蓝组患者直肠系膜染色良好,骶前间隙界限清楚,无输尿管损伤及骶前静脉丛损伤,淋巴结检出数明显高于对照组。结论直肠癌术中经直肠上动脉插管注射美蓝能清楚显示直肠系膜,避免输尿管和骶前静脉丛的损伤,同时能提高系膜淋巴结检出数,便于病理分期。     

恶性肿瘤的90Y-玻璃微球瘤内注射治疗及其临床效果观察

目的 探讨90Y-玻璃微球介入治疗晚期恶性肿瘤的疗效.方法 共18例恶性肿瘤病人,其中肝癌6例,肺癌5例,颈部淋巴结转移癌5例,上颌窦癌1例,肺癌胸壁转移1例,均经病理诊断证实.采取直接注入或者利用B超和CT引导下将90Y-玻璃微球引入肿瘤组织.结果 18例肿瘤中,完全消失（CR）为2例,部分缩小（PR）为9例,肿瘤稳定（SD）为6例,肿瘤进展（PD）为1例.14例病人可见疼痛减轻,4例疼痛未见明显缓解.结论 本方法可在晚期恶性肿瘤治疗上发挥重要作用,有较大临床应用前景.     

Intensive short-term chemotherapy in patients with advanced breast cancer

Summary Aiming at a high complete remission rate with an intensive induction regimen, 27 patients with advanced breast cancer were given three cycles of VAC chemotherapy consisting of vinde-sine 3 mg/m² i.v. on days 1 and 12, adriamycin 40 mg/m² i.v. on days 1 and 12, and cyclophosphamide 200 mg/m² p.o. on days 3–6 and 14–17 together with medroxyprogesterone acetate (MPA) 1,500 mg p.o. daily during the induction phase and 1,000 mg p.o. thereafter until relapse. These VAC double cycles were repeated twice with 3-weekly intervals for a total induction period of 15 weeks. In responders, including no change, the chemotherapy was discontinued thereafter, and the patients were observed until relapse with a maintenance therapy of MPA 1,000 mg p.o. daily.A complete remission (CR) was achieved in 8 (29.6%) and a partial remission (PR) in 13 (48.2%) of the 27 patients (CR + PR 77.8%). A no change (NC) status was found in 6 patients (22.2%). There were no nonresponders. The median duration of the CR was 20 (5–42) months with two patients still in CR at 33 and 36 months, of the PR 8.3 (4–13.5) months, and of the NC 6.7 (2–13) months. The treatment was tolerated without life-threatening toxicity or interval prolongation by all patients. No dose-limiting cardiac toxicity was observed in these patients regularly controlled by left ventricular ejection fraction (LVEF). The high response rate of this intensive induction regimen warrants further investigation. Complete remission was achieved only in patients without previous chemotherapy, with marked tumor regression after the first chemotherapy cycle and when there was no extensive bone involvement.Abbreviations ADR Adriamycin - CK Creatinine kinase - CK-MB Cardiac muscle specific isoenzymes - CMF Cyclophosphamide, methotrexate, 5-FU - CNS Central nervous system - CR Complete remission - CYC Cyclophosphamide - DFI Disease-free interval - ECG Electrocardiogram - LMF Chlorambucil, methotrexate, 5-FU - LVEF Left ventricular ejection fraction - MPA Medroxyprogesterone acetate - NC No change - PD Progressive disease - PR Partial remission - VAC Vincristine, adriamycin, cyclophosphamide - VEC Vincristine, epirubicin, cyclophosphamide - VDS Vindesine - WBC White blood cell count     

单药替吉奥胶囊治疗老年晚期胃癌的临床观察

目的：观察单药替吉奥胶囊治疗晚期胃癌的临床疗效及毒副反应。方法：选择50例经病理证实的老年晚期胃癌患者,随机分为治疗组32例及对照组18例。治疗组根据体表面积给予替吉奥胶囊治疗,对照组给予营养等最佳支持治疗。每2周期后行影像学检查评价疗效、记录不良反应及随访情况。结果：治疗组32例患者CR(完全缓解)0例,PR(部分缓解)10例,SD(病情稳定)12例,PD(病情进展)10例,临床总缓解率31.3%,临床获益率68.8%。治疗组中位无疾病进展时间及中位生存期分别为5.7及11.5个月,对照组分别为3.1及7.6个月。毒副反应主要为I-III度骨髓抑制、消化道反应、肝功能损伤及手足综合症。结论：单药替吉奥胶囊治疗老年晚期胃癌效果肯定,生活质量高、毒副作用小。     

经CDFI引导125I粒子植入治疗转移性浅表肿瘤疗效观察

目的探讨彩色多普勒超声（CDFI）引导下125I粒子组织间植入治疗转移性浅表肿瘤的疗效。方法回顾性分析156例确诊为恶性转移性浅表肿瘤患者进行125I粒子治疗结果,利用薄层CT扫描图像进行计算机三维治疗计划系统（TPS）术前计划、术中调整、术后验证粒子分布及数量。局部浸润麻醉后,CDFI引导下植入125I粒子。结果术后3个月,16.7%（26/156）患者肿瘤完全缓解,51.3%（80/156）患者肿瘤部分缓解,21.1%（33/156）肿瘤稳定,10.9%（17/156）肿瘤进展,总有效率（CR＋PR）为68%。术后6个月,18.6%（29/156）患者肿瘤完全缓解,53.2%（83/156）患者肿瘤部分缓解,22.4%（35/156）肿瘤稳定,5.8%（9/156）肿瘤进展,总有效率（CR＋PR）为71.8%。无严重皮肤反应、骨髓抑制及其它并发症发生。结论 CDFI引导下125I粒子植入治疗转移性浅表肿瘤具有方法简单、定位准确、疗效确切、无严重并发症等优点,是一种安全的微创治疗手段。     

Temozolomide chemotherapy in patients with recurrent malignant gliomas

Numerous studies have demonstrated the clinical activity of temozolomide, a second-generation alkylating agent, against malignant brain tumors, however, its activity has not been reported in an Asian population. This study analyzed the efficacy and toxicity of temozolomide in 25 adult patients with recurrent or progressive malignant gliomas after surgery and standard radiation therapy with or without chemotherapy, enrolled in our institution since July 2000. Sixteen patients had glioblastoma multiforme (GBM), six with anaplastic astrocytoma, and three with anaplastic oligodendroglioma. Of the 25 patients, 3 (12%) achieved a complete response (CR), 8 (32%) achieved a partial response (PR), 6 (24%) had stable disease (SD), and 8 (32%) had progressive disease (PD). Two patients achieved a CR, 4 patients achieved a PR, 3 patients had SD and 7 patients had PD in GBM, and 1 patient achieved a CR, 4 patients achieved a PR, 3 patients had SD, 1 patient had PD in the non-GBM patients. Median progression free survival was 8 weeks in GBM and 22 weeks in the non-GBM patients. The median overall survival of each group was 17 weeks and 28 weeks. Temozolomide demonstrated moderate activity in recurrent and progressive malignant gliomas without serious toxicity.     

CT导向下^125I粒子植入治疗肺转移癌15例疗效观察

目的观察CT导向下125I粒子植入治疗肺转移癌的临床疗效。方法15例肺转移癌患者,男8例,女7例,15例病灶数为58个,平均每人3.9个病灶,病灶平均直径为2.5cm。在CT导向下将125I粒子植入肺转移瘤灶内,采用治疗计划系统计算布源;对残留厚度≤1.0cm的肿瘤选择平面植入方法,采用18.5~29.6MBq活度的125I粒子相隔1.0~1.5cm平面播植。结果15例58个病灶,完全缓解31个;部分缓解14个;无变化8个;进展5个。总有效率77.6%。结论放射性粒子植入治疗肺部转移癌临床疗效好,创伤小,并发症发生率低。     

Sequentielle Induktionschemotherapie und Strahlenbehandlung inoperabler kleinzelliger Bronchialkarzinome

Summary To study the potential benefit of sequential chemotherapy in inoperable small cell lung cancer (SCLC), from 1982 to 1986 ninety-one patients with histologically proven and previously untreated SCLC (median age: 53 years; median Karnofsky status: 80%) were randomly assigned to an initial therapy with adriamycin (since 1984 epirubicin), cyclophosphamide, vincristine (ACO resp. EPICO) or etoposide/cisplatin (VP16/DDP). Treatment courses were repeated every 3 weeks for a total of 6 courses with a crossover after a maximum of 3 cycles of either regimen. Limited disease (LD) patients with bronchoscopical, computertomographical and (re-) mediastinoscopical complete remission (CR) randomly received either a thoracic irradiation with 40 Gy or observation only. Overall, 60 out of 85 evaluable patients achieved an objective remission. A CR was observed in 24/51 patients (47%) with limited disease, and in 8/34 patients (24%) with extensive disease. Both, ACO (EPICO) and VP16/DDP were equally effective as initial and second-line therapy. Moreover, after failure to the initial therapy an objective remission could be achieved in 13% of the patients following the alternative second line combination. In 28% of LD patients with an otherwise complete remission residual tumor was detected by (re-) mediastinoscopy. Median survival times were 14 (CR: 16) months in LD patients and 10 (CR: 15) months in ED patients. At present, median survival is significantly improved in irradiated versus non-irradiated LD patients (25 vs. 13 months, p<0.04). The remission rates and median survival times observed in this study are comparable to those of a historical control group treated with ACO plus radiotherapy alone.

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Abkürzungsverzeichnis LD limited disease - ED extensive disease - ACO Adriamycin, Cyclophosphamid, Vincristin - EPICO Epirubicin, Cyclophosphamid, Vincristin - VP/DDP etoposide, cisplatin - CR complete remission - PR partial remission - NC no change - PD progressive disease Die vorliegende Arbeit enthält wesentliche Teile der Dissertation von Herrn W. Eberhardt.Die Untersuchungen wurden mit Mitteln des Bundesministers für Forschung und Technologie gefördert (038457).     

Chemo-immunotherapy in patients with metastatic melanoma using sequential treatment with dacarbazine and recombinant human interleukin-2: evaluation of hematologic and immunologic parameters and correlation with clinical response.

We have treated 18 patients with metastatic malignant melanoma (MM) with high-dose IL-2 administered by continuous iv infusion in combination with dacarbazine (DTIC), and correlated the clinical response with various hematologic and immunologic parameters. Two regimens differing in the sequence of treatment were employed, and 1-6 treatment cycles were given, depending on patient response. Two patients had a complete response (CR, 46+m, 14m), two patients a partial response (PR, 16m,6m), one a minimal response and four had a stable disease lasting 2-7 months, thus the response rate (CR+PR) was 22%. None of the following parameters, tested prior to initiation of the therapy and 1-2 days after termination of each course of IL-2, correlated with the clinical response: WBC counts (total and differential), levels of blood CD4 and CD8 T cells, NK cells, monocytes and B cells, production of IL-1 and IL-1 inhibitor by monocytes, responsiveness to 3 mitogens, NK/LAK cell activity, and serum levels of IL-1 alpha, IL-2, soluble IL-2 receptor, and TNF alpha. The only prognostic parameter was the greater increase in the level of IL-2 receptor (Tac)-bearing lymphocytes in the responding patients after 1-3 cycles of IL-2. The data suggests that non-specific immune parameters have no prognostic value for patients undergoing IL-2-based immunotherapy.     

肿瘤标志物CEA、CA15-3和CA125在乳腺癌化疗疗效评估中的价值

目的：探讨CEA、CA15-3以及CA125在监测乳腺癌化疗疗效评估中的价值。方法：选择2005年6月～2008年1月在我科行化疗的晚期乳腺癌患者共45例，采用化学发光法测定血清CEA、CA15-3和CA125水平。化疗方案采用标准FAC、AC-D、DA、XD、GC等方案。化疗临床疗效评价采用WHO标准，肿瘤标志物疗效评价标准参考Bac[1]等的方法。结果：治疗后CEA、CA15-3在完全缓解组（CR）和部分缓解组（PR）组出现明显减低、进展组（PD）组明显升高（P〈0.05），而在稳定组（SD）组则无显著变化（P〉0.05）；CA125在CR和PR组出现显著降低（P〈0.05），在SD、PD组治疗前后无显著变化（P〉0.05）。CEA、CA15-3、CA125以及三者联合进行的肿瘤标志物评价与临床疗效评价的总符合率分别为60.0%（27/45）、55.6%（25/45）、31.1%（14/45）和73%（33/45）。结论：CEA、CA15-3和CA125可较好地监测乳腺癌化疗疗效，三者联检将提高监测效果。     

Chemotherapie mit Cisplatin-Bleomycin und nachfolgende Strahlentherapie bei fortgeschrittenen Kopf-Hals-Tumoren

Summary 42 patients with advanced stage III and IV squamous cell carcinoma of the head and neck were treated with initial cisplatin and bleomycin chemotherapy and subsequent radiotherapy. 39 were evaluable for results, and 3 for toxicity only. 8 patients suffered from stage III and 31 from stage IV tumors, of these 10 with distant metastases. 5 patients underwent later a rescue operation. 27 were previously untreated (= group A) including 2 cases with localized relapses beyond the margins of surgical and/or radiotherapeutic treatment fields. 12 patients had a recurrence within pretreated areas (= group B). The induction chemotherapy alone showed the following results: In group A 4 (15%) CR, 10 (37%) PR, 7 (26%) MR; in group B 3 (25%) PR, 2 (17%) MR. The subsequent radiotherapy mostly consisted of a 65 Gy tumor dose given in 61/2 weeks. The results after completion of the combined modality therapy were: In group A 44% CR, 28% PR; in group B 10% CR and 30% PR. No patient resistant to the initial chemotherapy responded to the radiotherapy. The median survival time of stage III patients was 20 months but only 7 months in stage IV patients. 4 of all live with NED now between 30+ and 41+ months; 1 patient is alive with relapse. All the others are dead after a survival time of max. 32 months, included the 5 with rescue operation. In general, hematologic and renal toxicities were not severe, but nausea and vomiting were the worst tolerated side effects. 1 patient died from septic myocarditis having a WBC nadir of 2000/µl, probably due to additional immunologic deficiency because of inactive liver cirrhosis. The poor results concerning NED survival are discussed. We conclude, that an initial chemotherapy with CDDP and BLM gives good remission effects but its combination with radiotherapy at present fails to produce a NED survival benefit. Further efforts are necessary to improve the CR and the long time survivor rates.

Die Autoren danken folgenden Kollegen für ihre Mitarbeit: Drs. Garbea (HNO), B. Bienko, M. Danker, N. Birke, M. Klessing, K. Lottner, W. Palm