DDC提高纳米级阿霉素磺油乳剂抗肿瘤作用的实验研究

目的：探讨二乙基二硫代氨基甲酸酯（DDC）对提高纳米级阿霉素碘油乳剂在体内外的抗肿瘤作用。方法：用MTT试验评价纳米级阿霉素碘油乳剂对耐药细胞及肿瘤细胞的杀灭作用，用SD大鼠建立Walk-256肝癌模型，通过肝动脉分别注入生理盐水、阿霉素、纳米级阿霉素碘油乳剂，DDC加纳米级阿霉素碘油乳剂以及DDC加阿霉素脂质体碘油乳剂，分别测定各组的肿瘤生长率和小鼠生命延长率。结果：经过DDC预处理后，阿霉素对阿霉素耐药肿瘤细胞SGC7901／CVR和SGC790／WT的IC50（μg/ml）分别从原来的18．40降至0．74和4．00降至0．32。未经DDC处理过的各组平均肿瘤生长率远高于预先用DDC处理过的各组（P＜0．01）。而小鼠生命延长率则明显低于预先用DDC处理过的各组（P＜0．05）。结论：用DDC预先处理抑制肿瘤细胞中的超氧化物歧化酶（SOD）可提高阿霉素的抗肿瘤作用。     

药物碘油乳剂介入治疗肝血管瘤的疗效观察

目的：观察药物碘油乳剂肝动脉介入栓塞治疗肝血管瘤的疗效。方法：经彩超及CT证实的患者38例，其中随机选取15例进行单纯碘油栓塞(对照组)，23例用药物碘油乳剂栓塞(治疗组)。结果：6个月后行CT复查，药物碘油乳剂组病灶明显缩小，有效率为95．65％，单纯碘油组肿瘤变化不明显，有效率为33．33％。结论：药物碘油乳剂在介入治疗肝血管瘤中起着明显的治疗作用。     

肝细胞癌碘油-阿霉素乳剂动脉注射疗法

为了寻求治疗肝细胞癌的局灶性长效化疗药物。作者对9例肝细胞癌病人以碘油-阿霉素(LPD/ADM)乳剂行肝动脉注射的效果进行了观察。9例经LPD/ADM动脉注射的肝细胞癌病例中,计注射后肝切除4例、切除后复发2例、非切除3例。在3例AFP高值的病例中,切除后复发1例、未切除2例。经血管造影后,用制备的LPD/ADM乳剂,由肝固有动脉或肝总动脉注入,分别于5、15、30分钟后由末梢静脉抽血,用高压液相色谱仪测定血清ADM浓度,并定时进行AFP测定和CT扫描。结果     

DDC提高纳米级阿霉素碘油乳剂抗肿瘤作用的实验研究

目的　探讨二乙基二硫代氨基甲酸酯 (DDC )对提高纳米级阿霉素碘油乳剂在体内外的抗肿瘤作用。方法　用MTT试验评价纳米级阿霉素碘油乳剂对耐药细胞及肿瘤细胞的杀灭作用 ,用SD大鼠建立Walk -2 5 6肝癌模型 ,通过肝动脉分别注入生理盐水、阿霉素、纳米级阿霉素碘油乳剂 ,DDC加纳米级阿霉素碘油乳剂以及DDC加阿霉素脂质体碘油乳剂 ,分别测定各组的肿瘤生长率和小鼠生命延长率。结果　经过DDC预处理后 ,阿霉素对阿霉素耐药肿瘤细胞SGC 790 1/CVR和SGC 790 /WT的IC5 0 (μg/ml)分别从原来的 18.40降至 0 .74和 4.0 0降至 0 .3 2。未经DDC处理过的各组平均肿瘤生长率远高于预先用DDC处理过的各组 (P <0 .0 1)。而小鼠生命延长率则明显低于预先用DDC处理过的各组 (P <0 .0 5 )。结论　用DDC预先处理抑制肿瘤细胞中的超氧化物歧化酶 (SOD)可提高阿霉素的抗肿瘤作用。     

丝裂霉素纳米微粒-碘油乳剂经动脉给药对兔肝肿瘤的疗效观察

目的观察丝裂霉素纳米微粒-碘油乳剂经动脉给药对兔肝肿瘤的疗效.方法将丝裂霉素纳米微粒与碘油制成乳剂,建立兔肝VX-2移植癌改良模型并随机分为六组,经肝动脉分别注入生理盐水(NS)、碘油(Lipi)、游离丝裂霉素(MMC,0.4 mg/kg)、游离丝裂霉素加空白纳米微粒(MMC+NP,0.4mg/kg)、丝裂霉素纳米微粒组(NMMC,0.4 mg/kg)与丝裂霉素纳米微粒-碘油乳剂(Lip-NMMC,0.4 mg/kg).结果经Lip-NMMC治疗的兔生存期显著延长,P<0.01;与其他各组相比对肿瘤生长的抑制更为明显,P<0.01;肿瘤坏死更广泛,更彻底.结论与其他各组相比,Lip-NMMC经动脉给药具有更好的疗效.     

药物碘油乳剂介入治疗肝血管瘤的疗效观察

目的:观察药物碘油乳剂肝动脉介入栓塞治疗肝血管瘤的疗效.方法:经彩超及CT证实的患者38例,其中随机选取15例进行单纯碘油栓塞(对照组),23例用药物碘油乳剂栓塞(治疗组).结果:6个月后行CT复查,药物碘油乳剂组病灶明显缩小,有效率为95.65%,单纯碘油组肿瘤变化不明显,有效率为33.33%.结论:药物碘油乳剂在介入治疗肝血管瘤中起着明显的治疗作用.     

肝细胞癌的栓塞化疗

作者前瞻性研究了经肝动脉注射碘油阿霉素乳化剂,或加用明胶海绵栓塞对阿霉素的药物动力学和生物分布的影响.不能手术治疗经组织学证实的肝硬化性肝细胞癌(HCC)18例,年龄25～76岁.肝功能Child A级或B级,CT半定量测定,肿瘤大小相当于肝脏容积的25%～50%,无门静脉栓塞.随机分为3组,经肝动脉给药.1组4例接受50mg阿霉素;2组7例接受50mg阿霉素与10ml碘油所配制的乳化剂;3组7例接受药物同2组,继用明胶海绵颗粒栓塞.给药治疗前,先经肝固有动脉注入     

碘油乳剂经动脉栓塞治疗16例肝海绵状血管瘤

目的：探讨碘油乳剂经动脉内栓塞治疗肝海绵状血管瘤的临床应用。方法：16例肝海绵状血管瘤患者用动脉栓塞治疗。结果：所有病例均栓塞成功，14例患者栓塞后碘油沉积良好。治疗后14例取得最佳疗效。全部病例临床症状消失，瘤体平均缩小50％，且未见胆囊坏死等并发症。结论：磺油乳剂动脉栓塞治疗肝海绵状血管瘤是安全、简便、并发症少且十分有效的治疗方法。     

抗癌药复合性粗颗粒乳剂的制备,实验研究及临床应用

碘油抗癌药乳剂行肝动脉内化疗栓塞治疗肝癌已广泛应用于临床，且取得了较明显效果，但大多数采用的是碘油与抗癌药直接混合制成的极不稳定的乳剂，对剂型考虑得较少。我们对碘油与抗癌药配制成的稳定型复合性乳剂进行了动物实验研究及初步临床应用，取得了较满意的效果，现报告如下。一、材料和方法（一）抗癌药复合性乳剂的制备及物理性质测定40％碘油10ml、注射用水15ml、顺铂60mg、多种表面活性剂及其他物质适量混合后，用乳均机乳化成40％的乳剂，并将乳剂的颗粒控制在一定范围。乳剂呈乳白色，光镜下观察并测定颗粒大小。100℃30分钟…     

碘油阿霉素混合乳剂栓塞治疗肝癌114例报告

对不能手术的中晚期肝癌患者,目前多采用碘油阿霉素乳剂经肝动脉栓塞治疗。我院于1988年至1990年12月收治中晚期肝癌114例,均采取碘油阿霉素肝动脉栓塞治疗,取得较好的疗效,现报告如下。临床资料一、一般情况本组114例,男性105例,女性9例,平均年龄42.6岁,30岁～60岁患者占85.9％(98例)。发病三个月内就医者为81.5％,部分患者延误数个月,甚至一年以上才确诊。二、症状和体征     

Transarterial chemoembolization (TAE) with degradable starch microspheres (DSM) in advanced hepatocellular carcinoma]

This study was undertaken to evaluate the clinical utility of chemoembolization using degradable starch microspheres (DSM), which resolve in a short period in patients with advanced hepatocellular carcinoma (HCC). Twenty-one patients underwent DSM chemoembolization 24 times. After a mixture of iodized oil and epirubicin was injected into the hepatic arteries, the patients were embolized with DSM alone 16 times. In the other 8 times, embolization was done in one hepatic lobe with DSM and in the other hepatic lobe with gelatin sponge (GS). There was no major complication related to chemoembolization. Tumor response (complete, partial, and minor responses) was found in 46% of patients after TAE. Tumor recurrence was found in 64% of responders after a mean period of 2.0 months. The response rate was significantly higher when chemoembolization was performed using both DSM and GS than when it was done with DSM alone (63% vs 37%, p < 0.04). Although the response rate after DSM-TAE is low, its anticancer effect is reinforced when used as an adjuvant therapy of GS-TAE.     

经药盒导管系统化疗栓塞治疗肝癌及相关药物监测

目的探讨经药盒导管系统(PCS)化疗栓塞治疗肝癌的临床价值。方法100例患者分成两组,PCS组(56例)经药盒导管系统灌注抗癌药与碘油混合成的乳剂,TACE组(44例)按常规方法栓塞治疗,对每组患者的疗效及药物代谢特征分别进行观察。结果PCS组患者肿瘤内的阿霉素可维持相当持久的较高浓度,7周后平均值7.9ug/克并取得较好治疗效果,其1、3年生存率分别为36/56(64%)及13/56(23%)。TACE组结果则较差,其阿霉素值为4.4ug/克,1、3年生存率分别为19/44(43%)及5/44(11%)。结论经PCS给药方法简便,疗效确切,经药物监测符合药代动力学规律,是治疗肝癌的较好方法。     

Pharmacokinetic study of adriamycin in the emulsion mixed with lipiodol-difference resulting from composition and methods of preparation, and behavior after mesenteric arterial injection in rat]

We experimentally investigated the pharmacokinetics of adriamycin (ADM) in a similar of transcatheter arterial chemoembolization therapy (TAE) of hepatocellular carcinoma using emulsion of lipiodol (Lp) mixed with ADM followed by gelatin sponge, and the difference resulting from composition and method of preparation of the emulsion as well as behavior after mesenteric arterial injection in rat. In in vitro study, the emulsion with iopamidol (iopamiron 300 : IP) was more stable than with amidotrizoic acid (60% Urografin : UG). The highest stability was found in the mixing ratio of Lp. IP and distilled water at 1 : 0.42 : 0.08. Frequent pumping also made the emulsion more stable. But in optimally composed emulsion, pumping 20 or 50 times made no difference in the stability during 30 min. which may be longer than the time from preparation to injection time of the emulsion in clinical application. After injection of the emulsion into the mesenteric artery which may simulate injection into the hepatic artery in hepatocellular carcinoma, the arterial blood flow was suspended. In the peripheral arteries the emulsion separated into two phases of Lp and ADM solution, forming striped pattern, and Lp embolization of the peripheral artery persisted for over 45 min. while ADM extravasated. These findings suggest that after Lp-TAE, Lp maintains an embolizing effect while ADM penetrates into the surrounding tumor tissue, and that this is an underlying mechanism for the anti-cancer effect of Lp-TAE.     

Chemoembolization of hepatocellular carcinomas. A study of the biodistribution and pharmacokinetics of doxorubicin.

BACKGROUND. This study evaluated the effects of an association of ethiodized oil (Lipiodol Ultra Fluide, Laboratoires Guerbet, Aulnay-sous-Bois, France), with or without gelatin sponge, with doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH) on the biodistribution and kinetics of doxorubicin during intraarterial injection. METHODS. Eighteen patients with hepatocellular carcinoma on cirrhotic liver received a therapeutic injection into the hepatic artery of 50 mg of doxorubicin alone (Group 1; n = 4), or emulsified in 10 ml of ethiodized oil and 2.5 ml of ioxaglate (Hexabrix, Laboratoires Guerbet) with (Group 2; n = 7) or without (Group 3; n = 7) gelatin sponge embolization. Before treatment, the absence of intrahepatic shunts was verified by an injection of technetium-labeled albumin macroaggregates. The biodistribution of doxorubicin was studied on two fronts: (1) pharmacokinetic--by measurement of the doxorubicin blood level during the 48 hours after injection; and (2) scintigraphic (2 mg of doxorubicin were labeled with 2 mCi of iodine 131)--by examination of the scintigrams and calculation of the following parameters: tumours liver/nontumorous liver binding ratio (T/NT ratio), liver/liver+lungs+abdomen binding ratio, and doxorubicin half-life in tumorous tissue. RESULTS. Pharmacokinetics results showed the following: the peak plasma concentration was significantly higher in Group 1 as compared with Groups 2 or 3 (Group 1: 2.1 +/- 0.9 mg/ml; Group 2: 0.9 +/- 0.3 mg/ml; Group 3: 0.5 +/- 0.2 mg/ml); the area under curve calculated from time zero to 1 hour was lower in Groups 2 and 3 compared with Group 1. Examination of the scintigrams showed the following: diffuse activity throughout the organism (Group 1), diffuse activity with strong hepatic and tumorous binding (Group 2), and mostly hepatic and tumoral binding (Group 3). The liver/liver+lungs+abdomen binding ratio was 28% +/- 1% in Group 1, 36% +/- 5% in Group 2, and 63% +/- 7% in Group 3. The T/NT ratios were 1.0 +/- 0 (Group 1), 1.5 +/- 0.1 (Group 2), and 4.7 +/- 0.5 (Group 3). The doxorubicin half-lives in tumourous tissue were 0.7 +/- 0.1 days (Group 1), 1.8 +/- 0.2 days (Group 2), and 2.6 days (n = 1; Group 3). CONCLUSIONS. This study shows (1) that the association of ethiodized oil with doxorubicin lowers the peak concentration of doxorubicin and increases the intratumoral concentration and half-life of doxorubicin, and (2) that these kinetic ameliorations are even more pronounced after embolization. Therefore, from a kinetic standpoint, the doxorubicin-ethiodized oil-gelatin sponge association is the best.     

A Correlative Study of CT, MR and Pathology in Rabbit Liver after Embolization by a China-Formulated Lipiodol Emulsion

OBJECTIVE To explore the MR characteristics following lipiodol retention in rabbit liver and to evaluate the sensitivity of CT (CT value ＞400 HU) and MR in displaying the hepatic degeneration and necrosis following embolization.METHODS Thirty-two rabbits were randomly divided into 3 groups. In the control group (n=8), 2 ml of normal saline was injected into the right branch of the portal vein. In the first experimental group(n=12), 4 ml of lipiodol emulsion was injected into the main portal vein. In the second experimental group (n= 12), 2 ml of lipiodol emulsion was injected into the right branch of the portal vein. CT and MR images were obtained before and after surgery in each group. The histopathologic condition was determined for all liver tissue specimens.RESULTS In the control group, CT and MR did not show any significant changes in the livers after surgery. After the operations in the experimental groups, the regional CT attenuation was 601 ±101 HU in the largest slice,which had no abnormal signals on T1WI and T2WI. In the first group, histologic examinations showed there were concentrated lipiodol droplets around the portal areas. In the second group, serious degeneration and necrosis in the right hepatic lobe occurred in 9 rabbits. T1Wl displayed homogenous or non-homogenous low signals and T2Wl mainly displayed a high signal.However, these pathologic changes did not appear on CT scanning due to high attenuation of the lipiodol.CONCLUSION There were no remarkable hepatic changes on MR in rabbits following good retention of the formulated lipiodol emulsion mixture of lipiodol and urografin(CT value ＞ 400 HU). MR displayed serious degeneration and necrosis of the liver following embolization.     

Outcome of localized hepatocellular carcinoma treated with segmental arterioportal chemoembolization

When lipiodol is injected into the hepatic artery at a dose exceeding a certain level, it flows into the portal vein. On the basis of this feature, an emulsion of Adriamycin with lipiodol was injected into a segmental or subsegmental artery such that it was delivered to the portal vein of the same segment, and the artery was then embolized with Gelfoam. This segmental arterioportal chemoembolization (cement therapy) was performed in 50 patients with localized hepatocellular carcinoma. A posttreatment CT scan showed that almost 100% of the lesions were occupied by lipiodol. The cumulative survival values determined for the 50 patients were very high: 83.4% after 1 year and 62.7% after 2 years.Presented at the Second International Symposium on Treatment of Liver Cancer, Taipei, 3–4 February 1991     

A pre-operative chemoembolization therapy using lipiodol, cisplatin and gelatin sponge for hepatocellular carcinoma

The significance of pre-operative transcatheter arterial chemoembolization therapy using lipiodol, cisplatin and gelatin sponge (Gelfoam) for the prevention of the recurrence of hepatocellular carcinoma (HCC) was evaluated. On the 103 patients who underwent radical operations for HCC with a tumor size less than 10 cm, 52 patients received no pre-operative therapy (group C), and 51 patients received pre-operative chemoembolization using lipiodol, a chemotherapeutic agent and Gelfoam. Of these 51 patients, 37 patients received a combination of lipiodol, cisplatin and Gelfoam (group A), while the remaining 14 patients received lipiodol, adriamycin and Gelfoam (group B). The disease-free survival rates after surgery were compared between group A, group B and group C. The 2-year disease-free survival rates in group A, group B and group C were 72%, 46% and 54%, respectively. These rates therefore suggest that pre-operative chemoembolization using lipiodol, cisplatin and Gelfoam is a useful method to prevent the recurrence of HCC after surgery.     

肝巨大海绵状血管瘤的介入栓塞治疗

 目的　探讨肝脏巨大海绵状血管瘤 (HHCH)的介入治疗与疗效。方法　经导管注入超液化碘油和平阳霉素 (PYM )混合乳剂 ,再用明胶海绵颗粒适量栓塞肿瘤周围小血管治疗肝巨大海绵状血管瘤 12例。结果　所有病例术前肝动脉造影显示“枝上挂果、早出晚归”的异常血管湖样改变 ;术后肿瘤均有缩小 ,其中 10例明显缩小 ,异常血管湖消失。结论　采用超液化碘油和PYM混合剂加适量明胶海绵颗粒联合栓塞是治疗肝巨大海绵状血管瘤较为理想的方法     

A correlative study of CT, MR and pathology in rabbit liver after embolization by a China - Formulated lipiodol emulsion

Objective

To explore the MR characteristics following lipiodol retention in rabbit liver and to evaluate the sensitivity of CT (CT value >400 HU) and MR in displaying the hepatic degeneration and necrosis following embolization.

Methods

Thirty-two rabbits were randomly divided into 3 groups. In the control group (n=8), 2 ml of normal saline was injected into the right branch of the portal vein. In the first experimental group(n=12), 4 ml of lipiodol emulsion was injected into the main portal vein. In the second experimental group (n=12), 2 ml of lipiodol emulsion was injected into the right branch of the portal vein. CT and MR images were obtained before and after surgery in each group. The histopathologic condition was determined for all liver tissue specimens.

Results

In the control group, CT and MR did not show any significant changes in the livers after surgery. After the operations in the experimental groups, the regional CT attenuation was 601 ±101 HU in the largest slice, which had no abnormal signals on T₁WI and T₂WI. In the first group, histologic examinations showed there were concentrated lipiodol droplets around the portal areas. In the second group, serious degeneration and necrosis in the right hepatic lobe occurred in 9 rabbits. T₁WI displayed homogenous or non-homogenous low signals and T₂WI mainly displayed a high signal. However, these pathologic changes did not appear on CT scanning due to high attenuation of the lipiodol.

Conclusion

There were no remarkable hepatic changes on MR in rabbits following good retention of the formulated lipiodol emulsion mixture of lipiodol and urografin(CT value > 400 HU). MR displayed serious degeneration and necrosis of the liver following embolization.     

聚乙烯醇栓塞微球可载药微球介入治疗中晚期肝癌的临床疗效及安全性观察

目的 探究聚乙烯醇可载药栓塞微球介入治疗中晚期肝癌的临床疗效及安全性.方法 将60例中晚期肝细胞癌患者,根据患者的疾病实际情况和患者的意愿结合,随机分为对照组,治疗组和实验组,每组20例.对照组采用传统的单纯碘化油乳剂栓塞TACE术,治疗组采用碘化油乳剂+明胶海绵栓塞TACE术,实验组采用碘化油乳剂+Callispheres可载药微球栓塞TACE术,对比3组患者TACE术后的不良反应、1个月后的肿瘤坏死率和术前、术后AFP变化.结果 实验组和对照组术后不良反应较少,均少于治疗组;实验组和治疗组术后1月肿瘤坏死率明显高于对照组,实验组与治疗组术后1月肿瘤坏死率相当;3组患者的术后AFP水平均明显低于术前.结论 应用聚乙烯醇可载药栓塞微球+碘油对中晚期肝癌患者行TACE术,比传统的应用碘化油的TACE术,手术效果好;比明胶海绵+碘化油的TA-CE术,手术效果相当,但是其导致的并发症较少,更利于患者术后恢复.