Multiorgan dysfunction syndrome due to high-dose cantharidin poisoning:A case report

BACKGROUND This report delves into the diagnostic and therapeutic journey undertaken by a patient with high-dose cantharidin poisoning and multiorgan dysfunction syndrome(MODS).Particular emphasis is placed on the comprehensive elucidation of the clinical manifestations of high-dose cantharidin poisoning,the intricate path to diagnosis,and the exploration of potential underlying mechanisms.CASE SUMMARY A patient taking 10 g of cantharidin powder orally subsequently developed MODS.The patient was treated with supportive care,fluid hydration and antibiotics,and hemoperfusion and hemofiltration therapy for 24 h and successfully recovered 8 d after hospital admission.Cantharidin poisoning can cause lifethreatening MODS and is rare clinically.This case underscores the challenge in diagnosis and highlights the need for early clinical differentiation to facilitate accurate assessment and prompt intervention.CONCLUSION This article has reported and analyzed the clinical data,diagnosis,treatment,and prognosis of a case of high-dose cantharidin poisoning resulting in MODS and reviewed the relevant literature to improve the clinical understanding of this rare condition.

Protective effect of glycyrrhetinic acid against cantharidin-induced hepatotoxicity through reducing oxidative stress in mice

Background:Cantharidin(CTD)is a commonly used natural product with anticancer properties;however,it has significant adverse effects,particularly hepatotoxicity.Glycyrrhetinic acid(GA),the active component of licorice,shows potential hepatoprotective effects.The protective effects and mechanism of GA against CTD-induced hepatotoxicity are still unclear.Objective:This study aims to elucidate the effect and mechanism of GA on CTD-induced hepatotoxicity in mice experiments.Methods:Construction of CTD-induced hepatotoxicity models and oral gavage GA intervention for 14 d.The liver index,ALT,AST and LDH levels in the serum of the mice were examined;HE staining was performed to observe pathological changes in the liver.The MDA level and SOD activities in liver tissue were tested.Western blot was conducted to determine Keap1/Nrf2 signaling pathway-related protein expression.Results:The results showed that GA significantly reduced the levels of ALT,AST,and LDH in the serum,which were increased by CTD.Additionally,it also exerted a substantial inhibitory effect on the reduction of SOD activity and the elevation of malondialdehyde content in liver tissue.Notably,the phenomena of nuclear swelling,necrosis,and inflammatory infiltration of liver tissue were significantly attenuated following oral administration of GA in mice.Subsequent research has demonstrated that GA effectively suppressed the CTD-triggered upregulation of Keap1 while increasing the CTD-induced downregulation of Nrf2,HO-1,and NQO1.Conclusion:These findings suggested that GA may protect against CTD-induced hepatotoxicity in mice by exerting antioxidative stress through the Keap1/Nrf2 signaling pathway.

Cantharidin and Its Analogues:Anticancer and Ser/Thr Protein Phosphatase Inhibitory Activities

This paper mainly describes the anticancer activities and Ser/Thr protein phosphatase inhibitory activities of cantharidin and its analogues.

1,2-Cyclic Monoacyl-rac-Glycerothio-phosphates of Cantharidin Analogues

A series of 1,2-cyclic monoacyl-rac-glycerothiophosphates of cantharidin and its analogues were synthesized in a one-pot procedure in overall yields of 44 similar to 55.5% by means of hexaethylphosphorus triamide as phosphorylating reagent.

Inhibitory Effect of Cantharidin on Proliferation of A549 Cells

Objective： To study the inhibition of Cantharidin against the proliferation of human lung cancer A549 cells and its mechanism. Methods： MTT assay was employed to determine the inhibition of Cantharidin against proliferation of A549 cells and flow Cytometry was applied to analyze A549 cell cycle and the effect of Cantharidin on cell cycle. Results： Cantharidin showed inhibition against the proliferation of A549 cells, and the inhibition was mediated by blocking A549 cell cycle at G2/M phase significantly. Conclusion： Cantharidin exhibits inhibition against the proliferation of human lung cancer A549 cells.

Cantharidin suppresses HCT116 colorectal carcinoma cell proliferation and migration by changing the cytoskeleton structure

Background:Cantharidin (CTD),a natural toxin produced from Chinese blister beetles,has extensive anti-tumor activity.The present study investigated the effect of CTD on a human colon cancer cell line to elucidate potential new insights regarding the mechanism(s) through which CTD exerts its anti-tumor effects.Materials and methods:The inhibitory effect of CTD on human colon cancer HCT116 cells was evaluated using the IncuCyte ZOOMTM analyzer.Apoptotic cells were detected by Annexin V-FITC/PI assay and cell cycle was evaluated with flow cytometry following propidium iodide staining.Alterations in F-actin microfilaments were analyzed by FITC-phalloidin staining and morphological changes were evaluated with a laser scanning confocal microscope.Cell migration assay was carried out to investigate the effects of CTD on migration of HCT116 cells in vitro.Results:CTD exhibited a significant growth inhibitory effect on HCT116 cells accompanied by an increase in G2/M phase cells,without a significant effect on apoptosis.CTD-treated cells also exhibited a dramatic collapse in their microfilament network and a significant reduction in cell adhesion.Conclusion:CTD inhibits growth by increasing G2/M phase cells and decreasing S phase cells,revealing that CTD exerts a significant growth inhibitory effect primarily through an inhibition of cell cycle progression (a cytostatic effect).Moreover,a negative effect on cell migration may also constitute a contributing factor to its anti-tumor potential.These findings suggest the potential use for developing CTD as a novel anti-cancer therapy that targets metastasis Giving full play to CTD may inhibit tumor transfer.

Analysis of the metabolic mechanism in Cantharidin-induced hepatotoxicity in LO2 cells using lipidomics analysis

Background:Cantharidin is a major active compound from Banmao(Mylabris).Cantharidin has obvious anticancer activity.However,its clinical application is limited due to serious hepatotoxicity.Methods:To evaluate the toxicity of human liver LO2 cells exposed to cantharidin by lipidomics.After exposing LO2 cells to different doses of cantharidin,the metabolites in LO2 cells were analyzed by nontargeted lipidomics based on liquid chromatography-mass spectrometry.Partial least-squares discriminant analysis and orthogonal partial least-squares discriminant analysis were used to screen differentially expressed metabolites,and then the main metabolic pathways were analyzed.Results:Pattern recognition analysis showed that the lipid metabolite profiles were changed significantly after cantharidin treatment,and 39 differential lipid metabolites were found.Additional analysis showed that these metabolites could mainly involve the metabolic pathways of triglyceride and acylcarnitine for cantharidin toxicity to LO2 cells.Conclusion:Cantharidin has obvious toxic effects on LO2 cells from the perspective of lipid metabolism.Moreover,the LO2 cytotoxicity induced by cantharidin is mainly related to the disorder of triglyceride and acylcarnitine metabolism.It can provide a scientific basis for cantharidin-induced hepatotoxicity.

斑蝥酸钠维生素B_(6)联合化疗药物胸腔内热灌注治疗肺癌合并恶性胸腔积液的疗效和安全性

目的观察斑蝥酸钠维生素B_(6)联合化疗药物胸腔内热灌注治疗肺癌合并恶性胸腔积液的疗效和安全性。方法选取2018—2022年扬中市人民医院收治的肺癌合并恶性胸腔积液患者130例,按照随机抽签法分为A组与B组,各65例。所有患者将胸腔积液完全排出后,A组经导管注入注射用顺铂、地塞米松磷酸钠注射液、注射用人白介素-2胸腔内热灌注,B组在A组基础上加用斑蝥酸钠维生素B_(6)注射液胸腔内热灌注。比较2组临床疗效,KPS评分改善分级,治疗前后肿瘤标志物[癌胚抗原(CEA)、细胞角蛋白19片段抗原21-1(CYFRA21-1)和神经元特异性烯醇化酶(NSE)],不良反应。结果B组客观缓解率高于A组(82.67%vs.50.67%,χ^(2)=17.280,P<0.001)。B组KPS评分改善分级优于A组(u=2.053,P=0.040)。治疗后,2组血清CEA、CYFRA21-1、NSE水平低于治疗前,且B组低于A组(P<0.01)。B组与A组不良反应总发生率比较,差异无统计学意义(34.67%vs.29.33%,χ^(2)=0.490,P=0.484)。结论斑蝥酸钠维生素B_(6)联合化疗药物胸腔内热灌注治疗肺癌合并恶性胸腔积液可提高疗效、改善患者功能状态,抑制肿瘤标志物表达,延缓病情进展,且未提高不良反应发生率。

复方斑蝥胶囊联合旋转容积调强技术对头颈部放疗生存期及血清XRCC1、XRCC3mRNA水平的影响

目的探究复方斑蝥胶囊联合旋转容积调强技术对头颈部放疗患者生存期及血清X线修复交错互补基因1(X-ray Repair Cross Complementing 1,XRCC1)、X线修复交错互补基因3(X-ray Repair Cross Complementing 3,XRCC3)信使核糖核酸(Messenger RNA,mRNA)水平的影响。方法选取2019年6月—2021年7月医院收治的头颈部肿瘤患者97例作为研究对象,根据治疗方法不同进行分组,对照组(48例)采用旋转容积调强技术结合放疗治疗,联合组(49例)在对照组基础上加用复方斑蝥胶囊治疗。观察比较临床疗效、中医证候积分、血清XRCC1及XRCC3mRNA水平、生存期、不良反应。结果联合组客观缓解率高于对照组(P<0.05),但疾病控制率与对照组比较差异无统计学意义(P>0.05)。联合组自汗、恶心呕吐、神疲乏力、食欲差、失眠、头晕眼花等得分低于对照组(P<0.05)。联合组血清XRCC1、XRCC3水平及外周血XRCC1、XRCC3 mRNA表达均低于对照组(P<0.05)。联合组无进展生存期和总生存期均高于对照组(P<0.05)。联合组不良反应发生率(34.69%,17/49)低于对照组不良反应发生率(72.92%,35/48)(P<0.05)。结论复方斑蝥胶囊联合旋转容积调强技术能改善头颈部放疗患者肿瘤客观缓解率,缓解临床症状,降低血清XRCC1、XRCC3mRNA水平,减少不良反应。

斑蝥素及其衍生物抗癌作用机制的研究进展

斑蝥素(cantharidin)是斑蝥(Mylabrisphalerata Pallas)分泌的一种萜类化合物,在多种癌症中都有明显的抑制癌细胞生长、增殖和迁移的作用。斑蝥素抗癌的作用机制涉及诱导细胞周期停滞和调亡、抑制自噬、增强DNA损伤、抑制DNA修复、调控多种细胞信号通路等方面。本文针对斑蝥素及其衍生物在多种常见癌症中的作用机制和研究进展进行综述,以期寻找斑蝥素在癌症治疗中的新靶点,为抗癌领域的临床研究提供新的方向。

斑蝥酸钠维生素B_(6)注射液联合顺铂治疗恶性胸腔积液的效果观察

目的:观察斑蝥酸钠维生素B_(6)注射液联合顺铂治疗恶性胸腔积液的效果。方法:选取2022年1月—2023年4月江西省胸科医院收治的60例恶性胸腔积液患者,用随机数字表法分为对照组和治疗组,各30例。对照组采用单纯顺铂胸腔灌注,治疗组采用顺铂联合斑蝥酸钠维生素B_(6)注射液胸腔灌注。比较两组近期疗效、不良反应、肿瘤标志物及血清T细胞亚群。结果:治疗组完全缓解率和总有效率均高于对照组,差异均有统计学意义(P<0.05)。治疗组不良反应总发生率低于对照组,差异有统计学意义(P<0.05)。治疗后1个月,治疗组CEA、CA125及CA199均低于对照组,差异均有统计学意义(P<0.05)。治疗后1个月,治疗组CD4^(+)T细胞、CD8^(+)T细胞及CD4^(+)/CD8^(+)均高于对照组,差异均有统计学意义(P<0.05)。结论:对恶性胸腔积液患者,斑蝥酸钠维生素B_(6)与顺铂联合胸腔灌注,近期疗效较佳,加强抗癌抑癌效应,能有效减少不良反应,机体免疫力可受到保护并有一定程度的提升。

斑蝥酸钠注射液中蛋白质的含量测定

目的:建立2,2′-联喹啉-4,4′-二羧酸(BCA)测定斑蝥酸钠注射液中残留蛋白质含量的方法。方法:依据蛋白质分子在碱性溶液中将Cu^(2+)还原为Cu^(+),2,2′-联喹啉-4,4′-二羧酸(BCA)与Cu^(+)结合形成紫色复合物,在一定范围内其颜色深浅与蛋白质浓度呈正比,以蛋白质对照品溶液作标准曲线,采用紫外-分光光度法测定供试品中蛋白质含量。结果:蛋白质在20~100μg范围内,线性关系良好(R=0.9979),精密度RSD为1.6%,稳定性RSD为3.2%,重现性RSD为3.2%,平均回收率为93%,RSD为1.3%(n=9)。结论:此方法专属性强、精密度稳定性良好、准确度较高,可用作斑蝥酸钠中蛋白质的含量测定方法,确保用药安全及关注厂家的工艺是否合理并建立斑蝥酸钠中蛋白质残留的检测标准,以便更科学地进行斑蝥酸钠的质量控制。

斑蝥酸钠在诱导人宫颈癌Hela细胞凋亡相关基因表达中的作用机制研究

目的:探讨斑蝥酸钠在诱导人宫颈癌Hela细胞凋亡相关基因表达中的作用机制。方法:2023年1月—2023年12月购买1株人宫颈癌Hela细胞,培养至对数生长期后开始实验,将其分为4组,分别加斑蝥酸钠0μmol/L(空白对照组)、4μmol/L(4μmol/L组)、8μmol/L(8μmol/L组)和16μmol/L(16μmol/L组),每个浓度分别设置5个复孔(每组样本量为5),以细胞活力试验(CCK-8)检测细胞增殖情况,以流式细胞仪检测细胞凋亡情况,以实时荧光定量多聚核苷酸链式反应(Real-time PCR)检测B淋巴细胞瘤2(BCL-2)、人细胞凋亡调节因子(Bax)、人半胱氨酸蛋白酶3(Caspase-3)的表达情况。结果:4μmol/L组、8μmol/L组和16μmol/L组的细胞增殖抑制率、凋亡率和Caspase-3相对表达量水平均高于空白对照组,BCL-2/Bax相对表达量水平低于空白对照组,差异均有统计学意义(P<0.05)。随着斑蝥酸钠浓度的升高,人宫颈癌Hela细胞增殖抑制率、凋亡率和Caspase-3随之也升高,BCL-2/Bax相对表达量逐渐下降,差异均有统计学意义(P<0.05)。经斑蝥酸钠处理后可见细胞皱缩、变圆,细胞边缘出芽形成多花环结构的凋亡小体。结论:斑蝥酸钠具有抑制人宫颈癌Hela细胞增殖、促进其凋亡的作用,具有剂量依赖性,其对细胞凋亡的调控作用可能与调控BCL-2,Bax和Caspase-3表达有关。

Physicochemical Properties and Gastric Mucosa Irritation of Cantharidin-hydroxypropyl-β-cyclodextrin Inclusion Complex

Objective To increase the solubility and relieve the mucous irritation of cantharidin (CA) by preparing cantharidin-hydroxypropyl-β-cyclodextrin (CA/HP-β-CD) inclusion complex. Methods The inclusion complex was prepared by co-evaporation method and characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and nuclear magnetic resonance (NMR). Results The disappearance of CA as well as the shift of exothermic peaks shown in DSC results indicated the complexation phenomenon. XRD results showed that the crystalline CA pattern had disappeared, and in NMR results, H-5 shifted from δ 3.731 to 3.695 after complexation and H-2 shifted from δ 3.626 to 3.598, which suggested that part of the drug had entered the HP-β-CD cavity to form an inclusion complex. The solubility increased 10.3 times after complexation and the mucous irritation of CA was relieved remarkably. Conclusion Through complexation with HP-β-CD, the solubility and dissolution rate of CA are improved significantly, and the irritation of musous is relieved.

斑蝥酸钠联合常规化疗治疗非小细胞肺癌的临床疗效和安全性Meta分析

目的:探讨斑蝥酸钠联合常规化疗治疗非小细胞肺癌(NSCLC)的临床疗效和安全性,为临床用药提供循证参考。方法:计算机检索中国知网(CNKI)、万方数据库、维普中文科技期刊数据库(VIP)、中国生物医学文献数据库(CBM)、PubMed、Embase、Web of Science、Cochrane Library,并补充检索临床试验注册库National Library of Medicine、中国临床试验注册中心,检索时间均为建库至2023年6月,收集斑蝥酸钠联合常规化疗治疗NSCLC患者的随机对照试验文献。通过Cochrane系统评价手册5.1.0版进行文献质量评价,并采用RevMan 5.3软件进行Meta分析。结果:本研究共检索出251篇文献,最终纳入28篇文献,共计2167例患者,其中对照组(常规化疗)1077例,联合组(斑蝥酸钠联合常规化疗)1090例。Meta分析结果显示,联合组患者ORR[RR=1.47,95%CI(1.31,1.64),P<0.00001]和DCR[RR=1.14,95%CI(1.09,1.20),P<0.00001]均高于对照组。联合组患者生活质量的改善效果优于对照组[RR=1.76,95%CI(1.51,2.04),P<0.00001]。联合组患者白细胞减少[OR=0.32,95%CI(0.25,0.41),P<0.00001]、胃肠道反应[OR=0.39,95%CI(0.30,0.52),P<0.00001]、血小板减少[OR=0.48,95%CI(0.25,0.94),P=0.03]的发生率均低于对照组。结论:斑蝥酸钠联合常规化疗可显著提高NSCLC患者的治疗有效率,改善患者生活质量,且能降低血液毒性、胃肠道反应的发生风险。

高载药量斑蝥素聚合物胶束递送系统制备及其抗乳腺癌研究

为制备高载药量的斑蝥素聚合物胶束给药系统(CTD@Sol),并初步探讨该给药系统抗乳腺癌的可行性。首先,以聚乙烯己内酰胺-聚乙酸乙烯酯-聚乙二醇接枝共聚物(Sol)为载体材料,以斑蝥素(CTD)为模型药物,采用溶剂注入法制备得到CTD@Sol,并对其外观形貌、粒径、电位、体外释放度等药剂学属性进行评价。通过MTT法、Annexin V-FITC/PI双染法考察了CTD@Sol对乳腺癌(4T1)细胞的生长抑制及凋亡情况;利用流式细胞术研究了4T1对该给药系统的摄取效率;通过小动物活体成像考察了给药系统在体内的组织分布及对肿瘤组织的靶向性。结果表明,CTD@Sol外观呈微弱淡蓝色乳光,平均粒径为(159.73±1.96)nm、PDI为0.198±0.006、Zeta电位为-(47.60±1.77)mV、包封率为(90.29±1.69)%、载药量为(45.00±0.84)%;体外释放及溶血实验表明,相较于中性环境(pH 7.4)下,CTD@Sol在酸性环境(pH 5.5)下药物明显加速释放,提示该体系具有细胞内吞体pH条件下的酸敏感性和良好的生物安全性。细胞摄取、细胞毒、凋亡实验表明,CTD@Sol对4T1细胞更具有杀伤力,且Sol聚合物胶束作为药物递送载体能显著增强细胞对药物的摄取效率;体内实验表明该递送系统对肿瘤组织具有显著的靶向性。综上,本研究成功制备了高载药量(>45%)CTD@Sol给药系统,该系统药剂学性能良好,靶向性强,生物安全性良好,具有应用于乳腺癌治疗的潜力。

复方斑蝥胶囊联合放疗治疗前列腺癌骨转移患者的疗效

目的观察复方斑蝥胶囊联合放疗治疗前列腺癌(PCa)骨转移(BM)患者的疗效。方法选取2022年1月至2023年3月宝鸡高新医院肿瘤诊疗中心收治的92例PCa BM患者作为研究对象。采用随机数字表法分为对照组和研究组,每组46例。对照组进行放疗,研究组在对照组基础上联合复方斑蝥胶囊治疗。比较两组疗效、视觉模拟评分法(VAS)评分、免疫指标、不良骨事件发生情况,比较两组血清碱性磷酸酶(ALP)、前列腺特异性抗原(PSA)、血管内皮生长因子(VEGF)、前梯度蛋白2(AGR2)水平。结果研究组总有效率高于对照组(P<0.05)。治疗后,两组的血清PSA、VEGF、AGR2水平及VAS评分均小于治疗前,且研究组小于对照组,差异具有统计学意义(P<0.05)。治疗后,两组的血清ALP水平均大于治疗前,且研究组小于对照组,差异具有统计学意义(P<0.05)。治疗后,两组的CD4^(+)/CD8^(+)、CD4^(+)、CD3^(+)、IgA、IgM均小于治疗前,且研究组大于对照组,差异具有统计学意义(P<0.05)。研究组不良骨事件总发生率低于对照组(P<0.05)。结论复方斑蝥胶囊联合放疗治疗PCa BM患者的疗效较好,能缓解疼痛,改善骨代谢和免疫能力,安全性较好。

秸秆木醋液的制备及其斑蝥复合剂抗菌活性

分别以玉米和芝麻秸秆为原料,采用低温分段热解技术制备了不同热解温度下的秸秆木醋液(SWV),测定了秸秆木醋液的基本性质,将秸秆木醋液与斑蝥原液复配制备了木醋液-斑蝥原液复合剂,并分别进行了抗菌活性试验。结果表明,在设定的热解温度范围内,玉米秸秆和芝麻秸秆木醋液总收率分别为20.92%和18.75%,最佳热解温度分别为180℃和220℃。抗菌活性试验表明,2种秸秆木醋液-斑蝥原液复合剂具有较好的广谱抗菌活性。就大肠杆菌而言,玉米秸秆木醋液-斑蝥原液复合剂、芝麻秸秆木醋液-斑蝥原液复合剂体积比均为1∶2(220℃木醋液)的抗菌活性最佳;就金黄色葡萄球菌而言,玉米秸秆木醋液-斑蝥原液复合剂体积比为1∶8(180℃木醋液),芝麻秸秆木醋液-斑蝥原液复合剂体积比为1∶4(240℃木醋液)的抗菌活性最佳。复合剂对金黄色葡萄球菌的抗菌活性明显优于大肠杆菌,秸秆木醋液对斑蝥原液的抗菌活性有明显的增强作用。

枯草杆菌二联活菌颗粒联合斑蝥酸钠维生素B_(6)辅助治疗在慢性阻塞性肺疾病合并非小细胞肺癌中的效果研究

目的探讨枯草杆菌二联活菌颗粒联合斑蝥酸钠维生素B_(6)辅助治疗在慢性阻塞性肺疾病(COPD)合并非小细胞肺癌(NSCLC)中的效果。方法选取2020年1月—2022年10月收治的COPD合并NSCLC 60例,采用随机数字表法分为观察组和对照组各30例。2组均给予化疗联合免疫治疗,在此基础上对照组给予斑蝥酸钠维生素B_(6)治疗,观察组给予枯草杆菌二联活菌颗粒联合斑蝥酸钠维生素B_(6)治疗,2组均持续治疗4个周期。统计2组治疗4个周期后总缓解率及治疗前、治疗2个周期、治疗4个周期肿瘤因子[癌胚抗原(CEA)、癌抗原125(CA125)、血管内皮生长因子(VEGF)、缺氧诱导因子(HIF-1α)]、免疫功能指标(CD3+、CD4+、CD4+/CD8+)、肠道微生态指标(肠道菌群丰富度、多样性指数)、治疗期间毒副反应、治疗后1年生存率。结果2组总缓解率比较差异无统计学意义(P>0.05)。治疗后2组CEA、CA125、VEGF、HIF-1α呈下降趋势,CD3+、CD4+、CD4+/CD8+呈升高趋势,差异有统计学意义(P<0.05)。治疗后2组肠道菌群丰富度、多样性指数呈升高趋势,且观察组高于对照组(P<0.05)。观察组胃肠道反应发生率为16.67%(5/30)低于对照组的46.67%(14/30)(P<0.05)。2组治疗后1年生存率比较差异无统计学意义(P>0.05)。结论枯草杆菌二联活菌颗粒联合斑蝥酸钠维生素B_(6)辅助治疗能有效纠正COPD合并NSCLC患者化疗及免疫治疗后肠道菌群紊乱,改善机体免疫应答,抑制肿瘤因子表达,减少毒副反应的发生。

Hydroxycamptothecine and Cantharidin Combined with Cisplatinand Lipiodol Through Transcatheter Arterial Embolizalionin Hepatocellular Carcinoma

Transcatheter arterial embolization with hydroxycamptothecine, cantharidin and cisplatin,thoroughly mixed with large doses of interferon and interleukin-2, was performed in 48 cases with unre-sectable intermediate or advanced hepatocellular carcinoma. The results demonstrate a partial remissionrate of 54. 2%, significantly higher than that in embolization with chemotherapeutic agents alone (cis-platin, adriamycin and mitomycin, 32. 1%, P<O. 01) . Morever, the adverse reactions of hydroxycamp-tothecine and cantharidin, when applied systemically, including hematuria or urodynia were successfullyeliminated.