Miriplatin,a cisplatin derivative with a high affinity for iodized oil,is a novel chemotherapeutic agent designed for use in the transarterial treatment of hepatocellular carcinoma.This case report describes our exper...Miriplatin,a cisplatin derivative with a high affinity for iodized oil,is a novel chemotherapeutic agent designed for use in the transarterial treatment of hepatocellular carcinoma.This case report describes our experience with transarterial chemoembolization(TACE) using miriplatin in 2 patients with neuroendocrine liver metastases.A 38-year-old man with multiple neuroendocrine liver metastases was treated by whole liver chemoembolization,and a 35-year-old woman with a single hepatic lesion was treated by superselective chemoembolization.No serious adverse events were noted during the interventional procedures,or during the observation period of 3 mo in either patient.Sufficient iodized oil uptake was observed in the hypervascular lesions on the unenhanced computed tomography(CT) at 7 d after the procedure.Contrast-enhanced CT obtained at 3 mo after chemoembolization revealed that all hepatic lesions were substantially reduced in size irrespective of tumor vascularity or degree of cystic degeneration,although iodized oil accumulation was only marginal for lesions with cystic degeneration.Thus,TACE with miriplatin can be a safe and effective therapeutic option for the treatment of neuroendocrine metastases of the liver.展开更多
Background: Miriplatin is a slow-release, lipophilic platinum complex, developed to produce a superior antitumor effect for hepatocellular carcinoma (HCC). However, the miriplatin suspension is highly viscous and can ...Background: Miriplatin is a slow-release, lipophilic platinum complex, developed to produce a superior antitumor effect for hepatocellular carcinoma (HCC). However, the miriplatin suspension is highly viscous and can form an embolism in the hepatic artery, which can result in insufficient antitumor effect. Thus, reducing the viscosity of the suspension compound by combining it with the less-viscous cisplatin suspension might reduce or even prevent vessel embolism, while providing the quick-release effects of cisplatin. Purpose: To compare the outcomes of therapy using miriplatin plus cisplatin and cisplatin monotherapy in transcatheter arterial chemoembolization (TACE) for HCC. Methods: We retrospectively evaluated a total of 87 patients with Barcelona Clinic Liver Cancer (BCLC) stage A or B HCC who received conventional TACE using a combination of platinum agents (cisplatin and miriplatin) (n = 50) or cisplatin alone (n = 37) for the first time from September 2006 to December 2012. Short term therapeutic effect was measured by dynamic computed tomography 1 - 3 months after TACE, in reference to the modified Response Evaluation Criteria in Solid Tumors. Treatment-related adverse effects were graded by the National Cancer Institute Common Terminology Criteria (ver. 4.0). 1-, 3-, and 5-year survival rates were calculated. Subgroup analyses were performed by Child-Pugh classification and BCLC criteria. Results: Median duration of follow-up was 35 months (range 7 - 90). Median overall survival was 38 months. Patients who had combination therapy had better 1-, 3-, and 5-year survival rates: 100%, 56.7%, and 26.2%, respectively, compared to monotherapy: 100%, 42.1%, and 9.0%, respectively (p = 0.034). No serious complication or treatment-related mortality was observed in both groups. Conclusion: TACE using miriplatin plus cisplatin was related to a prolonged survival, with comparable adverse effects of TACE using cisplatin alone.展开更多
Miriplatin, a novel lipophilic platinum complex has been developed to treat hepatocellular carcinoma. An improvd synthetic route was designed and used to prepare the target compound. The intermediate Pt(C6H14N2)(I) 2 ...Miriplatin, a novel lipophilic platinum complex has been developed to treat hepatocellular carcinoma. An improvd synthetic route was designed and used to prepare the target compound. The intermediate Pt(C6H14N2)(I) 2 was synthesized from K 2 PtCl 4 , KI and (1R,2R)-1,2-cyclohexanediamine, Pt(C 6 H 14 N 2 )(I) 2 was reacted with AgNO 3 to prepare Pt(C 6 H 14 N 2 )(H 2 O) 2 (NO 3 ) 2 solution then was subsequently reacted with CH 3 (CH 2 ) 12 COONa in n-butanol to give target compound with satisfied yield 81%(based on Pt(C 6 H 14 N 2 )I 2 ). The structure of the target compound was identified by elemental analysis, ESI-MS, FT-IR, 1H-NMR, thermal analysis, the structure was consistent with the target compound.展开更多
Immunosuppressive microenvironments present critical problems in clinical chemotherapy.To regulate the tumor immune microenvironment for enhancing antitumor effect,a combination of immune checkpoint inhibitors(ICIs)wi...Immunosuppressive microenvironments present critical problems in clinical chemotherapy.To regulate the tumor immune microenvironment for enhancing antitumor effect,a combination of immune checkpoint inhibitors(ICIs)with chemotherapeutics has been applied clinically.In this study,miriplatin(MiPt),the lipidic derivative of 5-fluorouracil(Fu-OA),as well as the programmed death ligand 1(PD-L1)target si RNA(siPD-L1)were integrated into Lip-Pt/Fu@siPD-L1 nanoparticles(NPs)for chemo-immunotherapy.In vitro results showed that Lip-Pt/Fu@siPD-L1 NPs could exhibit effective siRNA gene silencing and promote the phagocytosis of tumor cells by macrophages.Furthermore,in vivo results revealed that LipPt/Fu@siPD-L1 NPs showed significantly higher anti-tumor efficiency than that of the physical mixing of Mi Pt,5-fluorouracil,and Lip@siPD-L1 NPs(delivery of siPD-L1 by liposomes).The best anti-tumor efficiency of Lip-Pt/Fu@siPD-L1 NPs resulted from the synergistic immunotherapeutic effects of Mi Pt and siPD-L1 based on the inhibition of CD47 expression and the downregulation of PD-L1 in tumor cells,which elicited a robust anti-tumor immune response through the activation of macrophage phagocytosis and immune checkpoint inhibition.The Lip-Pt/Fu@siPD-L1 NPs provide a potential strategy for tumor chemo-immunotherapy.展开更多
对铂类抗肿瘤药物米铂的热稳定性和晶型进行了分析与研究.通过热分析(DSC-TG)法测定药物的熔点及结晶水的含量,并结合X射线粉末衍射仪(XPRD)及其原位高温(in-situ high temperature)附件测定了样品米铂的晶型结构及在加热过程中的晶型...对铂类抗肿瘤药物米铂的热稳定性和晶型进行了分析与研究.通过热分析(DSC-TG)法测定药物的熔点及结晶水的含量,并结合X射线粉末衍射仪(XPRD)及其原位高温(in-situ high temperature)附件测定了样品米铂的晶型结构及在加热过程中的晶型热稳定性.结果表明,试样米铂含有一个结晶水,加热到51.64℃时开始失去结晶水,在74.18℃发生微小的晶相转变,从亚稳态晶型转变为稳态晶型,210℃时转变为非晶态,221.81℃发生熔融变化,开始分解.展开更多
文摘Miriplatin,a cisplatin derivative with a high affinity for iodized oil,is a novel chemotherapeutic agent designed for use in the transarterial treatment of hepatocellular carcinoma.This case report describes our experience with transarterial chemoembolization(TACE) using miriplatin in 2 patients with neuroendocrine liver metastases.A 38-year-old man with multiple neuroendocrine liver metastases was treated by whole liver chemoembolization,and a 35-year-old woman with a single hepatic lesion was treated by superselective chemoembolization.No serious adverse events were noted during the interventional procedures,or during the observation period of 3 mo in either patient.Sufficient iodized oil uptake was observed in the hypervascular lesions on the unenhanced computed tomography(CT) at 7 d after the procedure.Contrast-enhanced CT obtained at 3 mo after chemoembolization revealed that all hepatic lesions were substantially reduced in size irrespective of tumor vascularity or degree of cystic degeneration,although iodized oil accumulation was only marginal for lesions with cystic degeneration.Thus,TACE with miriplatin can be a safe and effective therapeutic option for the treatment of neuroendocrine metastases of the liver.
文摘Background: Miriplatin is a slow-release, lipophilic platinum complex, developed to produce a superior antitumor effect for hepatocellular carcinoma (HCC). However, the miriplatin suspension is highly viscous and can form an embolism in the hepatic artery, which can result in insufficient antitumor effect. Thus, reducing the viscosity of the suspension compound by combining it with the less-viscous cisplatin suspension might reduce or even prevent vessel embolism, while providing the quick-release effects of cisplatin. Purpose: To compare the outcomes of therapy using miriplatin plus cisplatin and cisplatin monotherapy in transcatheter arterial chemoembolization (TACE) for HCC. Methods: We retrospectively evaluated a total of 87 patients with Barcelona Clinic Liver Cancer (BCLC) stage A or B HCC who received conventional TACE using a combination of platinum agents (cisplatin and miriplatin) (n = 50) or cisplatin alone (n = 37) for the first time from September 2006 to December 2012. Short term therapeutic effect was measured by dynamic computed tomography 1 - 3 months after TACE, in reference to the modified Response Evaluation Criteria in Solid Tumors. Treatment-related adverse effects were graded by the National Cancer Institute Common Terminology Criteria (ver. 4.0). 1-, 3-, and 5-year survival rates were calculated. Subgroup analyses were performed by Child-Pugh classification and BCLC criteria. Results: Median duration of follow-up was 35 months (range 7 - 90). Median overall survival was 38 months. Patients who had combination therapy had better 1-, 3-, and 5-year survival rates: 100%, 56.7%, and 26.2%, respectively, compared to monotherapy: 100%, 42.1%, and 9.0%, respectively (p = 0.034). No serious complication or treatment-related mortality was observed in both groups. Conclusion: TACE using miriplatin plus cisplatin was related to a prolonged survival, with comparable adverse effects of TACE using cisplatin alone.
基金The Yunnan science and technology project(2010DH021)Kunming Wuhua Zoon science and technology project(201037)
文摘Miriplatin, a novel lipophilic platinum complex has been developed to treat hepatocellular carcinoma. An improvd synthetic route was designed and used to prepare the target compound. The intermediate Pt(C6H14N2)(I) 2 was synthesized from K 2 PtCl 4 , KI and (1R,2R)-1,2-cyclohexanediamine, Pt(C 6 H 14 N 2 )(I) 2 was reacted with AgNO 3 to prepare Pt(C 6 H 14 N 2 )(H 2 O) 2 (NO 3 ) 2 solution then was subsequently reacted with CH 3 (CH 2 ) 12 COONa in n-butanol to give target compound with satisfied yield 81%(based on Pt(C 6 H 14 N 2 )I 2 ). The structure of the target compound was identified by elemental analysis, ESI-MS, FT-IR, 1H-NMR, thermal analysis, the structure was consistent with the target compound.
基金financial support from the Basic Research Cooperation Project of Beijing,Tianjin,Hebei from the Natural Science Foundation of Beijing(No.J200018),Tianjin(No.20JCZXJC00070),and Hebei(No.H2020206649)Beijing Natural Science Foundation(No.7214281)the projects of National Natural Science Foundation of China(No.81973259)。
文摘Immunosuppressive microenvironments present critical problems in clinical chemotherapy.To regulate the tumor immune microenvironment for enhancing antitumor effect,a combination of immune checkpoint inhibitors(ICIs)with chemotherapeutics has been applied clinically.In this study,miriplatin(MiPt),the lipidic derivative of 5-fluorouracil(Fu-OA),as well as the programmed death ligand 1(PD-L1)target si RNA(siPD-L1)were integrated into Lip-Pt/Fu@siPD-L1 nanoparticles(NPs)for chemo-immunotherapy.In vitro results showed that Lip-Pt/Fu@siPD-L1 NPs could exhibit effective siRNA gene silencing and promote the phagocytosis of tumor cells by macrophages.Furthermore,in vivo results revealed that LipPt/Fu@siPD-L1 NPs showed significantly higher anti-tumor efficiency than that of the physical mixing of Mi Pt,5-fluorouracil,and Lip@siPD-L1 NPs(delivery of siPD-L1 by liposomes).The best anti-tumor efficiency of Lip-Pt/Fu@siPD-L1 NPs resulted from the synergistic immunotherapeutic effects of Mi Pt and siPD-L1 based on the inhibition of CD47 expression and the downregulation of PD-L1 in tumor cells,which elicited a robust anti-tumor immune response through the activation of macrophage phagocytosis and immune checkpoint inhibition.The Lip-Pt/Fu@siPD-L1 NPs provide a potential strategy for tumor chemo-immunotherapy.
文摘对铂类抗肿瘤药物米铂的热稳定性和晶型进行了分析与研究.通过热分析(DSC-TG)法测定药物的熔点及结晶水的含量,并结合X射线粉末衍射仪(XPRD)及其原位高温(in-situ high temperature)附件测定了样品米铂的晶型结构及在加热过程中的晶型热稳定性.结果表明,试样米铂含有一个结晶水,加热到51.64℃时开始失去结晶水,在74.18℃发生微小的晶相转变,从亚稳态晶型转变为稳态晶型,210℃时转变为非晶态,221.81℃发生熔融变化,开始分解.