Tumor-targeting is becoming more and more important for cancer chemotherapy. Though many molecular-target drugs have been developed in the past two decades which shed some light on targeted tumor therapy,clinical resu...Tumor-targeting is becoming more and more important for cancer chemotherapy. Though many molecular-target drugs have been developed in the past two decades which shed some light on targeted tumor therapy,clinical results of those molecular-target drugs are not so encouraging especially for solid tumors, problems mostly relating to the heterogeneity and mutations of target molecules in human solid tumors. More general tumor-targeting strategy is thus anticipated. In this regard, the enhanced permeability and retention(EPR) effect which is a unique phenomenon of solid tumors based on the anatomical and pathophysiological nature of tumor blood vessels, is receiving more and more attentions. This EPR effect now served as a standard for tumor-targeted macromolecular anticancer therapy, namely nanomedicine. Many nanoplatforms have been developed as targeted drug delivery systems, including liposome, polymeric micelles, polymer conjugate, nanoparticles. Ample macromolecular drugs are now approved for clinical use or in clinical stage development, all of which by taking advantage of EPR effect, show superior in vivo pharmacokinetics and remarkable tumor selectivity, resulting in improved antitumor effects with less adverse effects. We thus believe EPR-based nanomedicine will be a solution for cancer in the future, whereas further consideration of factors involved in EPR effect and strategies to augment/improve EPR effect are warranted.展开更多
Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for L...Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21^(st) century.展开更多
Smart nanoparticles that respond to pathophysiological parameters,such as p H,GSH,and H2O2,have been developed with the huge and urgent demand for the high-efficient drug delivery systems(DDS)for cancer therapy.Herein...Smart nanoparticles that respond to pathophysiological parameters,such as p H,GSH,and H2O2,have been developed with the huge and urgent demand for the high-efficient drug delivery systems(DDS)for cancer therapy.Herein,cubic poly(ethylene glycol)(PEG)-modified mesoporous amorphous iron oxide(AFe)nanoparticles(AFe-PEG)have been successfully prepared as p H-stimulated drug carriers,which can combine doxorubicin(DOX)with a high loading capacity of 948 mg/g,forming a novel multifunctional AFe-PEG/DOX nanoparticulate DDS.In an acidic microenvironment,the AFe-PEG/DOX nanoparticles will not only release DOX efficiently,but also release Fe ions to catalyze the transformation of H2O2 to·OH,acting as fenton reagents.In vitro experimental results proved that the AFe-PEG/DOX nanoparticles can achieve combination of chemotherapeutic(CTT)and chemodynamic therapeutic(CDT)effects on Hela tumor cells.Furthermore,the intrinsic magnetism of AFePEG/DOX makes its cellular internalization efficiency be improved under an external magnetic field.Therefore,this work develops a new and promising magnetically targeted delivery and dual CTT/CDT therapeutic nano-medicine platform based on amorphous iron oxide.展开更多
As a targeted therapy, antiangiogenic treatment has been increasingly studied for advanced non-small cell lung cancer(NSCLC) and has proven effective for the treatment of advanced NSCLC. Bevacizumab, a monoclonal anti...As a targeted therapy, antiangiogenic treatment has been increasingly studied for advanced non-small cell lung cancer(NSCLC) and has proven effective for the treatment of advanced NSCLC. Bevacizumab, a monoclonal antibody targeting angiogenesis, is the only antiangiogenic agent approved for use in combination with first-line chemotherapy for non-squamous NSCLC. Small-molecule inhibitors targeting the tyrosine kinase receptor have also shown promise when combined with standard chemotherapeutic agents in patients with advanced NSCLC. However, unlike bevacizumab, not all other antiangiogenic agents show significant benefits when combined with chemotherapy. As for the failures of most other combinations, the combination schedule may be an important reason that has so far been overlooked in clinical trials. This article reviews the combination of angiogenic agents with chemotherapy in the treatment of NSCLC.展开更多
文摘Tumor-targeting is becoming more and more important for cancer chemotherapy. Though many molecular-target drugs have been developed in the past two decades which shed some light on targeted tumor therapy,clinical results of those molecular-target drugs are not so encouraging especially for solid tumors, problems mostly relating to the heterogeneity and mutations of target molecules in human solid tumors. More general tumor-targeting strategy is thus anticipated. In this regard, the enhanced permeability and retention(EPR) effect which is a unique phenomenon of solid tumors based on the anatomical and pathophysiological nature of tumor blood vessels, is receiving more and more attentions. This EPR effect now served as a standard for tumor-targeted macromolecular anticancer therapy, namely nanomedicine. Many nanoplatforms have been developed as targeted drug delivery systems, including liposome, polymeric micelles, polymer conjugate, nanoparticles. Ample macromolecular drugs are now approved for clinical use or in clinical stage development, all of which by taking advantage of EPR effect, show superior in vivo pharmacokinetics and remarkable tumor selectivity, resulting in improved antitumor effects with less adverse effects. We thus believe EPR-based nanomedicine will be a solution for cancer in the future, whereas further consideration of factors involved in EPR effect and strategies to augment/improve EPR effect are warranted.
基金J. Chad Brenner received funding from NIH (Grants No. U01DE025184 and P30: CA046592 S1)Andrew C. Birkeland and Rebecca Hoesli received support from University of Michigan Otolaryngology Resident Research (Grant No. T32DC005356)Megan L. Ludwig was supported by NIH (Grant No. T-32-GM007315)
文摘Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21^(st) century.
基金supported by the National Natural Science Foundation of China(No.51473152 and No.51573174)Scientific Research Foundation for Young Talents from Fujian Provincial Department of Education(No.JT180494)Scientific Research Platform Construction Project from Fujian Provincial Department of Science and Technology(No.2018H2002)。
文摘Smart nanoparticles that respond to pathophysiological parameters,such as p H,GSH,and H2O2,have been developed with the huge and urgent demand for the high-efficient drug delivery systems(DDS)for cancer therapy.Herein,cubic poly(ethylene glycol)(PEG)-modified mesoporous amorphous iron oxide(AFe)nanoparticles(AFe-PEG)have been successfully prepared as p H-stimulated drug carriers,which can combine doxorubicin(DOX)with a high loading capacity of 948 mg/g,forming a novel multifunctional AFe-PEG/DOX nanoparticulate DDS.In an acidic microenvironment,the AFe-PEG/DOX nanoparticles will not only release DOX efficiently,but also release Fe ions to catalyze the transformation of H2O2 to·OH,acting as fenton reagents.In vitro experimental results proved that the AFe-PEG/DOX nanoparticles can achieve combination of chemotherapeutic(CTT)and chemodynamic therapeutic(CDT)effects on Hela tumor cells.Furthermore,the intrinsic magnetism of AFePEG/DOX makes its cellular internalization efficiency be improved under an external magnetic field.Therefore,this work develops a new and promising magnetically targeted delivery and dual CTT/CDT therapeutic nano-medicine platform based on amorphous iron oxide.
文摘As a targeted therapy, antiangiogenic treatment has been increasingly studied for advanced non-small cell lung cancer(NSCLC) and has proven effective for the treatment of advanced NSCLC. Bevacizumab, a monoclonal antibody targeting angiogenesis, is the only antiangiogenic agent approved for use in combination with first-line chemotherapy for non-squamous NSCLC. Small-molecule inhibitors targeting the tyrosine kinase receptor have also shown promise when combined with standard chemotherapeutic agents in patients with advanced NSCLC. However, unlike bevacizumab, not all other antiangiogenic agents show significant benefits when combined with chemotherapy. As for the failures of most other combinations, the combination schedule may be an important reason that has so far been overlooked in clinical trials. This article reviews the combination of angiogenic agents with chemotherapy in the treatment of NSCLC.
