The incidence and mortality of hepatocellular carcinoma have continued to increase over the last few years,and the medicine-based outlook of patients is poor.Given great ideas from the development of nanotechnology in...The incidence and mortality of hepatocellular carcinoma have continued to increase over the last few years,and the medicine-based outlook of patients is poor.Given great ideas from the development of nanotechnology in medicine,especially the advantages in the treatments of liver cancer.Some engineering nanoparticles with active targeting,ligand modification,and passive targeting capacity achieve efficient drug delivery to tumor cells.In addition,the behavior of drug release is also applied to the drug loading nanosystem based on the tumor microenvironment.Considering clinical use of local treatment of liver cancer,in situ drug delivery of nanogels is also fully studied in orthotopic chemotherapy,radiotherapy,and ablation therapy.Furthermore,novel therapies including gene therapy,phototherapy,and immunotherapy are also applied as combined therapy for liver cancer.Engineering nonviral polymers to function as gene delivery vectors with increased efficiency and specificity,and strategies of co-delivery of therapeutic genes and drugs show great therapeutic effect against liver tumors,including drug-resistant tumors.Phototherapy is also applied in surgical procedures,chemotherapy,and immunotherapy.Combination strategies significantly enhance therapeutic effects and decrease side effects.Overall,the application of nanotechnology could bring a revolutionary change to the current treatment of liver cancer.展开更多
Intensive cancer treatment with drug combination is widely exploited in the clinic but suffers from inconsistent pharmacokinetics among different therapeutic agents.To overcome it,the emerging nanomedicine offers an u...Intensive cancer treatment with drug combination is widely exploited in the clinic but suffers from inconsistent pharmacokinetics among different therapeutic agents.To overcome it,the emerging nanomedicine offers an unparalleled opportunity for encapsulating multiple drugs in a nano-carrier.Herein,a two-step super-assembled strategy was performed to unify the pharmacokinetics of a peptide and a small molecular compound.In this proof-of-concept study,the bioinformatics analysis firstly revealed the potential synergies towards hepatoma therapy for the associative inhibition of exportin 1(XPO1)and ataxia telangiectasia mutated-Rad3-related(ATR),and then a super-assembled nano-pill(gold nano drug carrier loaded AZD6738 and 97110 amino acids of apoptin(AP)(AA@G))was constructed through camouflaging AZD6738(ATR small-molecule inhibitor)-binding human serum albumin onto the AP-Au supramolecular nanoparticle.As expected,both in vitro and in vivo experiment results verified that the AA@G possessed extraordinary biocompatibility and enhanced therapeutic effect through inducing cell cycle arrest,promoting DNA damage and inhibiting DNA repair of hepatoma cell.This work not only provides a co-delivery strategy for intensive liver cancer treatment with the clinical translational potential,but develops a common approach to unify the pharmacokinetics of peptide and small-molecular compounds,thereby extending the scope of drugs for developing the advanced combination therapy.展开更多
Liver metastases(LMs)are common in lung cancer.Despite substantial advances in diagnosis and treatment,the survival rate of patients with LM remains low as the immune-suppressive microenvironment of the liver allows t...Liver metastases(LMs)are common in lung cancer.Despite substantial advances in diagnosis and treatment,the survival rate of patients with LM remains low as the immune-suppressive microenvironment of the liver allows tumor cells to evade the immune system.The impact of LMs on the outcomes of immune checkpoint inhibitors in patients with solid tumors has been the main focus of recent translational and clinical research.Growing evidence indicates that the hepatic microenvironment delivers paracrine and autocrine signals from non-parenchymal and parenchymal cells.Overall,these microenvironments create pre-and post-metastatic conditions for the progression of LMs.Herein,we reviewed the epidemiology,physiology,pathology and immunology,of LMs associated with non-small cell lung cancer and the role and potential targets of the liver microenvironment in LM in each phase of metastasis.Additionally,we reviewed the current treatment strategies and challenges that should be overcome in preclinical and clinical investigations.These approaches target liver elements as the basis for future clinical trials,including combinatorial interventions reported to resolve hepatic immune suppression,such as immunotherapy plus chemotherapy,immunotherapy plus radiotherapy,immunotherapy plus anti-angiogenesis therapy,and surgical resection.展开更多
目的综合分析多种局部治疗方案对原发性肝癌合并门静脉癌栓(PVTT)患者的疗效,并尝试找到最佳的治疗方案。方法计算机检索PubMed、Web of Science、Embase、Cochrane Library、中国知网、万方数据库等,对符合纳入标准的文献进行文献质量...目的综合分析多种局部治疗方案对原发性肝癌合并门静脉癌栓(PVTT)患者的疗效,并尝试找到最佳的治疗方案。方法计算机检索PubMed、Web of Science、Embase、Cochrane Library、中国知网、万方数据库等,对符合纳入标准的文献进行文献质量评价,提取数据后使用Stata 17.1软件进行Meta分析。结果本研究共纳入33篇文献,共计3441例原发性肝癌合并PVTT患者,治疗方式涉及肝动脉化疗栓塞(TACE)、放疗、Sorafenib、碘125放疗(^(125)I)、TACE+放疗、TACE+^(125)I、TACE+门静脉化疗(PVC)、TACE+Sorafenib、TACE+射频消融(RFA)、TACE+Apatinib、肝动脉灌注化疗(HAIC)+Sorafenib、TACE+HAIC共10种干预措施。网状Meta分析结果显示:在预后评价指标中,TACE+放疗、TACE+Sorafenib、TACE+PVC对原发性肝癌合并PVTT患者的客观缓解率(ORR)效果较好;对于患者总生存时间(OS),TACE+RFA、TACE+Sorafenib和TACE+^(125)I方案效果较好;对于患者1年生存率,TACE+^(125)I、TACE+PVC和TACE+RFA方案效果较好。结论在原发性肝癌合并PVTT患者的局部治疗方案中,基于TACE治疗的联合治疗方案相较于单一的局部治疗在预后中有更明显的获益。展开更多
Hepatocellular carcinoma(HCC)is the most common primary liver tumor and has been considered a very immunogenic tumor.The treatment with radiofrequency ablation(RFA)has been established as the standard ablative therapy...Hepatocellular carcinoma(HCC)is the most common primary liver tumor and has been considered a very immunogenic tumor.The treatment with radiofrequency ablation(RFA)has been established as the standard ablative therapy for early HCC,and is currently recognized as the main ablative tool for HCC tumors<5 cm in size;however,progression and local recurrence remain the main disadvantages of this approach.To solve this clinical problem,recent efforts were concentrated on multimodal treatment,combining different strategies,including the combination of RFA and immunotherapy.This article reviewed the combination treatment of RFA with immunotherapy and found that this treatment strategy leads to an increased response of anti-tumor T cells,significantly reduces the risk of recurrence and improves survival rates compared to RFA alone.This review highlighted scientific evidence that supports the current recommendations for pre-clinical studies,and discuss the need for further research on this topic.展开更多
基金Science and Technology Innovation Joint Fund Project of Fujian Province,No.2019Y9044Science and Technology Project of Quanzhou,No.2018Z155.
文摘The incidence and mortality of hepatocellular carcinoma have continued to increase over the last few years,and the medicine-based outlook of patients is poor.Given great ideas from the development of nanotechnology in medicine,especially the advantages in the treatments of liver cancer.Some engineering nanoparticles with active targeting,ligand modification,and passive targeting capacity achieve efficient drug delivery to tumor cells.In addition,the behavior of drug release is also applied to the drug loading nanosystem based on the tumor microenvironment.Considering clinical use of local treatment of liver cancer,in situ drug delivery of nanogels is also fully studied in orthotopic chemotherapy,radiotherapy,and ablation therapy.Furthermore,novel therapies including gene therapy,phototherapy,and immunotherapy are also applied as combined therapy for liver cancer.Engineering nonviral polymers to function as gene delivery vectors with increased efficiency and specificity,and strategies of co-delivery of therapeutic genes and drugs show great therapeutic effect against liver tumors,including drug-resistant tumors.Phototherapy is also applied in surgical procedures,chemotherapy,and immunotherapy.Combination strategies significantly enhance therapeutic effects and decrease side effects.Overall,the application of nanotechnology could bring a revolutionary change to the current treatment of liver cancer.
基金supported by the National Natural Science Foundation of China(Grant Nos.:81272488 and 81602802)the Shaanxi Province Innovation Capacity Support Program(Grant No.:2018TD-002).
文摘Intensive cancer treatment with drug combination is widely exploited in the clinic but suffers from inconsistent pharmacokinetics among different therapeutic agents.To overcome it,the emerging nanomedicine offers an unparalleled opportunity for encapsulating multiple drugs in a nano-carrier.Herein,a two-step super-assembled strategy was performed to unify the pharmacokinetics of a peptide and a small molecular compound.In this proof-of-concept study,the bioinformatics analysis firstly revealed the potential synergies towards hepatoma therapy for the associative inhibition of exportin 1(XPO1)and ataxia telangiectasia mutated-Rad3-related(ATR),and then a super-assembled nano-pill(gold nano drug carrier loaded AZD6738 and 97110 amino acids of apoptin(AP)(AA@G))was constructed through camouflaging AZD6738(ATR small-molecule inhibitor)-binding human serum albumin onto the AP-Au supramolecular nanoparticle.As expected,both in vitro and in vivo experiment results verified that the AA@G possessed extraordinary biocompatibility and enhanced therapeutic effect through inducing cell cycle arrest,promoting DNA damage and inhibiting DNA repair of hepatoma cell.This work not only provides a co-delivery strategy for intensive liver cancer treatment with the clinical translational potential,but develops a common approach to unify the pharmacokinetics of peptide and small-molecular compounds,thereby extending the scope of drugs for developing the advanced combination therapy.
基金supported by the National Natural Science Foundation of China(Nos.82202989 and 82003089)the Regional Innovation Cooperation Project of the Sichuan Science and Technology Program(No.2021YFQ0029)+4 种基金the China Postdoctoral Science Foundation(No.2022M722279)the Sichuan Science and Technology Program(No.2023YFS0163)the Postdoctoral Research Project of West China Hospital,Sichuan University,Chengdu,China(No.2021HXBH045)Fundamental Research Funds for the Central Universities(No.2022SCU12063)the Sichuan University Postdoctoral Interdisciplinary Innovation Fund(awarded to Lingling Zhu).
文摘Liver metastases(LMs)are common in lung cancer.Despite substantial advances in diagnosis and treatment,the survival rate of patients with LM remains low as the immune-suppressive microenvironment of the liver allows tumor cells to evade the immune system.The impact of LMs on the outcomes of immune checkpoint inhibitors in patients with solid tumors has been the main focus of recent translational and clinical research.Growing evidence indicates that the hepatic microenvironment delivers paracrine and autocrine signals from non-parenchymal and parenchymal cells.Overall,these microenvironments create pre-and post-metastatic conditions for the progression of LMs.Herein,we reviewed the epidemiology,physiology,pathology and immunology,of LMs associated with non-small cell lung cancer and the role and potential targets of the liver microenvironment in LM in each phase of metastasis.Additionally,we reviewed the current treatment strategies and challenges that should be overcome in preclinical and clinical investigations.These approaches target liver elements as the basis for future clinical trials,including combinatorial interventions reported to resolve hepatic immune suppression,such as immunotherapy plus chemotherapy,immunotherapy plus radiotherapy,immunotherapy plus anti-angiogenesis therapy,and surgical resection.
文摘目的综合分析多种局部治疗方案对原发性肝癌合并门静脉癌栓(PVTT)患者的疗效,并尝试找到最佳的治疗方案。方法计算机检索PubMed、Web of Science、Embase、Cochrane Library、中国知网、万方数据库等,对符合纳入标准的文献进行文献质量评价,提取数据后使用Stata 17.1软件进行Meta分析。结果本研究共纳入33篇文献,共计3441例原发性肝癌合并PVTT患者,治疗方式涉及肝动脉化疗栓塞(TACE)、放疗、Sorafenib、碘125放疗(^(125)I)、TACE+放疗、TACE+^(125)I、TACE+门静脉化疗(PVC)、TACE+Sorafenib、TACE+射频消融(RFA)、TACE+Apatinib、肝动脉灌注化疗(HAIC)+Sorafenib、TACE+HAIC共10种干预措施。网状Meta分析结果显示:在预后评价指标中,TACE+放疗、TACE+Sorafenib、TACE+PVC对原发性肝癌合并PVTT患者的客观缓解率(ORR)效果较好;对于患者总生存时间(OS),TACE+RFA、TACE+Sorafenib和TACE+^(125)I方案效果较好;对于患者1年生存率,TACE+^(125)I、TACE+PVC和TACE+RFA方案效果较好。结论在原发性肝癌合并PVTT患者的局部治疗方案中,基于TACE治疗的联合治疗方案相较于单一的局部治疗在预后中有更明显的获益。
文摘Hepatocellular carcinoma(HCC)is the most common primary liver tumor and has been considered a very immunogenic tumor.The treatment with radiofrequency ablation(RFA)has been established as the standard ablative therapy for early HCC,and is currently recognized as the main ablative tool for HCC tumors<5 cm in size;however,progression and local recurrence remain the main disadvantages of this approach.To solve this clinical problem,recent efforts were concentrated on multimodal treatment,combining different strategies,including the combination of RFA and immunotherapy.This article reviewed the combination treatment of RFA with immunotherapy and found that this treatment strategy leads to an increased response of anti-tumor T cells,significantly reduces the risk of recurrence and improves survival rates compared to RFA alone.This review highlighted scientific evidence that supports the current recommendations for pre-clinical studies,and discuss the need for further research on this topic.
