Metastasis and resistance are main causes to affect the outcome of the current anticancer therapies.Heat shock protein 90(Hsp90)as an ATP-dependent molecular chaperone takes important role in the tumor metastasis and ...Metastasis and resistance are main causes to affect the outcome of the current anticancer therapies.Heat shock protein 90(Hsp90)as an ATP-dependent molecular chaperone takes important role in the tumor metastasis and resistance.Targeting Hsp90 and downregulating its expression show promising in inhibiting tumor metastasis and resistance.In this study,a redox-responsive dual-drug nanocarrier was constructed for the effective delivery of a commonly used chemotherapeutic drug PTX,and a COAmodified 4-arm PEG polymer(4PSC)was synthesized.COA,an active component in oleanolic acid that exerts strong antitumor activity by downregulating Hsp90 expression,was used as a structural and functional element to endow 4PSC with redox responsiveness and Hsp90 inhibitory activity.Our results showed that 4PSC/PTX nanomicelles efficiently delivered PTX and COA to tumor locations without inducing systemic toxicity.By blocking the Hsp90 signaling pathway,4PSC significantly enhanced the antitumor effect of PTX,inhibiting tumor proliferation and invasiveness as well as chemotherapy-induced resistance in vitro.Remarkable results were further confirmed in vivo with two preclinical tumor models.These findings demonstrate that the COA-modified 4PSC drug delivery nanosystem provides a potential platform for enhancing the efficacy of chemotherapies.展开更多
Colon cancer is the fifth most common type of cancer in the world.Colon cancer develops when healthy cells in the lining of the colon or rectum alter and grow uncontrollably to form a mass known as a tumor.Despite maj...Colon cancer is the fifth most common type of cancer in the world.Colon cancer develops when healthy cells in the lining of the colon or rectum alter and grow uncontrollably to form a mass known as a tumor.Despite major medical improvements,colon cancer is still one of the leading causes of cancer-related mortality globally.One of the main issues of chemotherapy is toxicity related to conventional medicines.The targeted delivery systems are considered the safest and most effective by increasing the concentration of a therapeutic substance at the tumor site while decreasing it at other organs.Therefore,these delivery systems required lower doses for high therapeutic value with minimum side effects.The current review focuses on targeting therapeutic substances at the desired site using nanocarriers.Additionally,the diagnostic applications of nanocarriers in colorectal cancer are also discussed.展开更多
The increased level of chromosome instability in cancer cells,leading to aneuploidy and gross chromosomal rearrangements,is not only a driving force for oncogenesis but also can be the Achille’s heel of the disease s...The increased level of chromosome instability in cancer cells,leading to aneuploidy and gross chromosomal rearrangements,is not only a driving force for oncogenesis but also can be the Achille’s heel of the disease since many chemotherapies(CT)kill cells by inducing a non-tolerable rate of DNA damage.A wealth of published evidence showed that telomere stability can be more affected than the bulk of the genome by several conventional antineoplasic drugs.These results raise the interesting possibility that CT with genotoxic drugs preferentially target telomeres.In agreement with this view,accelerated shortening of telomere length has been described in blood lineage cells following high-dose CT(stem cell transplantation)or non-myeloablative CT.However,almost nothing is known on the consequences of this shortening in terms of telomere stability,senescence and on the development of second cancers or post-treatment aging-like syndromes in cancer survivors(cognitive defect,fertility impairment,etc.).In this article,we propose:(1)telomeres of cancer cells are preferential genomic targets of chemotherapies altering chromosome maintenance;(2)telomere functional parameters can be a surrogate marker of chemotherapy sensitivity and toxicity;(3)the use of anti-telomere molecule could greatly enhance the sensitivity to standards chemotherapies.展开更多
基金supported by the National Natural Science Foundation of China(Nos.3210110581373339)+6 种基金the 2021 Natural Science Foundation of Guangdong Province(Nos.2021A1515011367,China)the Southern Hospital Matching Fund(Nos.2013001,China)the High-Level university Academic Backbone and Training program in Guangzhou Medical University(Nos.B185004199,China)2022 City school joint funding project(Nos.202201020394,China)the 2018 Guangdong Key Discipline Construction Project of Pharmacy(Nos.Q185031010,China)the 2019 Undergraduate Laboratory Open Project(Nos.C195015003,China)Guangzhou Science and Technology Planning Project(Nos.202201010783,China)。
文摘Metastasis and resistance are main causes to affect the outcome of the current anticancer therapies.Heat shock protein 90(Hsp90)as an ATP-dependent molecular chaperone takes important role in the tumor metastasis and resistance.Targeting Hsp90 and downregulating its expression show promising in inhibiting tumor metastasis and resistance.In this study,a redox-responsive dual-drug nanocarrier was constructed for the effective delivery of a commonly used chemotherapeutic drug PTX,and a COAmodified 4-arm PEG polymer(4PSC)was synthesized.COA,an active component in oleanolic acid that exerts strong antitumor activity by downregulating Hsp90 expression,was used as a structural and functional element to endow 4PSC with redox responsiveness and Hsp90 inhibitory activity.Our results showed that 4PSC/PTX nanomicelles efficiently delivered PTX and COA to tumor locations without inducing systemic toxicity.By blocking the Hsp90 signaling pathway,4PSC significantly enhanced the antitumor effect of PTX,inhibiting tumor proliferation and invasiveness as well as chemotherapy-induced resistance in vitro.Remarkable results were further confirmed in vivo with two preclinical tumor models.These findings demonstrate that the COA-modified 4PSC drug delivery nanosystem provides a potential platform for enhancing the efficacy of chemotherapies.
文摘Colon cancer is the fifth most common type of cancer in the world.Colon cancer develops when healthy cells in the lining of the colon or rectum alter and grow uncontrollably to form a mass known as a tumor.Despite major medical improvements,colon cancer is still one of the leading causes of cancer-related mortality globally.One of the main issues of chemotherapy is toxicity related to conventional medicines.The targeted delivery systems are considered the safest and most effective by increasing the concentration of a therapeutic substance at the tumor site while decreasing it at other organs.Therefore,these delivery systems required lower doses for high therapeutic value with minimum side effects.The current review focuses on targeting therapeutic substances at the desired site using nanocarriers.Additionally,the diagnostic applications of nanocarriers in colorectal cancer are also discussed.
基金supported by National Natural Science Foundation of China(Grant Nos.81270433,81171846,81000875)Foundation for Young Scientist in Shanghai Municipal Health Bureau in China(Grant No.2010.24)Foundation for City Star of Science and Technology in Shanghai(Grant No.11QA1404400).
文摘The increased level of chromosome instability in cancer cells,leading to aneuploidy and gross chromosomal rearrangements,is not only a driving force for oncogenesis but also can be the Achille’s heel of the disease since many chemotherapies(CT)kill cells by inducing a non-tolerable rate of DNA damage.A wealth of published evidence showed that telomere stability can be more affected than the bulk of the genome by several conventional antineoplasic drugs.These results raise the interesting possibility that CT with genotoxic drugs preferentially target telomeres.In agreement with this view,accelerated shortening of telomere length has been described in blood lineage cells following high-dose CT(stem cell transplantation)or non-myeloablative CT.However,almost nothing is known on the consequences of this shortening in terms of telomere stability,senescence and on the development of second cancers or post-treatment aging-like syndromes in cancer survivors(cognitive defect,fertility impairment,etc.).In this article,we propose:(1)telomeres of cancer cells are preferential genomic targets of chemotherapies altering chromosome maintenance;(2)telomere functional parameters can be a surrogate marker of chemotherapy sensitivity and toxicity;(3)the use of anti-telomere molecule could greatly enhance the sensitivity to standards chemotherapies.
