Pancreatic ductal adenocarcinoma(PDAC)has one of the highest mortality rates among all cancer types.Its delayed diagnosis precludes curative resection,thus most of the current therapies against PDAC are based on chemo...Pancreatic ductal adenocarcinoma(PDAC)has one of the highest mortality rates among all cancer types.Its delayed diagnosis precludes curative resection,thus most of the current therapies against PDAC are based on chemo-and radiotherapy.Unfortunately,these strategies are insufficient to improve its poor prognosis.Despite the advances made in chemotherapy(e.g.nab-paclitaxel and gemcitabine),many patients with PDAC are unable to benefit from them due to the rapid development of drug resistance.Currently,more than 165 genes have been found to be implicated in drug resistance of pancreatic tumors,including different integrins,mucins,NF-κB,RAS and CXCR4.Moreover,drug resistance in PDAC is thought to be mediated by the modulation of miRNAs(e.g.miRNA-21,miRNA-145 and miRNA-155),which regulate genes that participate in cell proliferation,invasion and metastasis.Finally,cancer stem cells are intimately related to drug resistance in PDAC due to their ability to overexpress ABC genes-involved in drug transport-,and enzymes such as aldehyde dehydrogenases-implicated in cellular drug metabolism-and poly(ADP-ribose)polymerases-involved in drug-induced DNA damage repair.Understanding the mechanisms involved in drug resistance will contribute to the development of efficient therapeutic strategies and to improve the prognosis of patients with PDAC.展开更多
Pancreatic cancer(PC)continues to pose a major clinical challenge.There has been little improvement in patient survival over the past few decades,and it is projected to become the second leading cause of cancer mortal...Pancreatic cancer(PC)continues to pose a major clinical challenge.There has been little improvement in patient survival over the past few decades,and it is projected to become the second leading cause of cancer mortality by 2030.The dismal 5-year survival rate of less than 10%after the diagnosis is attributable to the lack of early symptoms,the absence of specific biomarkers for an early diagnosis,and the inadequacy of available chemotherapies.Most patients are diagnosed when the disease has already metastasized and cannot be treated.Cancer interception is vital,actively intervening in the malignization process before the development of a full-blown advanced tumor.An early diagnosis of PC has a dramatic impact on the survival of patients,and improved techniques are urgently needed to detect and evaluate this disease at an early stage.It is difficult to obtain tissue biopsies from the pancreas due to its anatomical position;however,liquid biopsies are readily available and can provide useful information for the diagnosis,prognosis,stratification,and follow-up of patients with PC and for the design of individually tailored treatments.The aim of this review was to provide an update of the latest advances in knowledge on the application of carbohydrates,proteins,cell-free nucleic acids,circulating tumor cells,metabo-lome compounds,exosomes,and platelets in blood as potential biomarkers for PC,focusing on their clinical relevance and potential for improving patient outcomes.展开更多
Paclitaxel （PTX）, one of the most effective cytotoxins for the treatment of breast and lung cancer, is limited by its severe side effects and low tumor selectivity. In this work hollow-poly（4-vinylpyridine） （holl...Paclitaxel （PTX）, one of the most effective cytotoxins for the treatment of breast and lung cancer, is limited by its severe side effects and low tumor selectivity. In this work hollow-poly（4-vinylpyridine） （hollow-p4VP） nanoparticles （NPs） have been used for the first time to generate PTX@p4VP NPs, employing a novel technique in which a gold core in the center of the NP is further oxidized to produce the hollow structure into which PTX molecules can be incorporated. The hollow-p4VP NPs exhibit good physicochemical properties and displayed excellent biocompatibility when tested on blood （no hemolysis） and cell cultures （no cytotoxicity）. Interestingly, PTX@p4VP NPs significantly increased PTX cytotoxicity in human lung （A-549） and breast （MCF-7） cancer cells with a significant reduction of PTX ICs0 （from 5.9 to 3.6 nM in A-549 and from 13.75 to 4.71 nM in MCF-7）. In addition, PTX@p4VP caused a decrease in volume of A-549 and MCF-7 multicellular tumor spheroids （MTS）, an in vitro system that mimics in vivo tumors, in comparison to free PTX. This increased antitumoral activity is accompanied by efficient cell internalization and increased apoptosis, especially in lung cancer MTS. Our results offer the first evidence that hollow- p4VP NPs can improve the antitumoral activity of PTX. This system can be used as a new nanoplatform to overcome the limitations of current breast and lung cancer treatments.展开更多
基金funded by grants from Instituto de Salud Carlos III (Grant No. DTS15/00201 and DTS17/00081)Junta de Andalucía (Grant No. PIN-0474-2016)
文摘Pancreatic ductal adenocarcinoma(PDAC)has one of the highest mortality rates among all cancer types.Its delayed diagnosis precludes curative resection,thus most of the current therapies against PDAC are based on chemo-and radiotherapy.Unfortunately,these strategies are insufficient to improve its poor prognosis.Despite the advances made in chemotherapy(e.g.nab-paclitaxel and gemcitabine),many patients with PDAC are unable to benefit from them due to the rapid development of drug resistance.Currently,more than 165 genes have been found to be implicated in drug resistance of pancreatic tumors,including different integrins,mucins,NF-κB,RAS and CXCR4.Moreover,drug resistance in PDAC is thought to be mediated by the modulation of miRNAs(e.g.miRNA-21,miRNA-145 and miRNA-155),which regulate genes that participate in cell proliferation,invasion and metastasis.Finally,cancer stem cells are intimately related to drug resistance in PDAC due to their ability to overexpress ABC genes-involved in drug transport-,and enzymes such as aldehyde dehydrogenases-implicated in cellular drug metabolism-and poly(ADP-ribose)polymerases-involved in drug-induced DNA damage repair.Understanding the mechanisms involved in drug resistance will contribute to the development of efficient therapeutic strategies and to improve the prognosis of patients with PDAC.
基金Junta de Andalucia,No.PC-0498-2017 and No.PC-0549-2017.
文摘Pancreatic cancer(PC)continues to pose a major clinical challenge.There has been little improvement in patient survival over the past few decades,and it is projected to become the second leading cause of cancer mortality by 2030.The dismal 5-year survival rate of less than 10%after the diagnosis is attributable to the lack of early symptoms,the absence of specific biomarkers for an early diagnosis,and the inadequacy of available chemotherapies.Most patients are diagnosed when the disease has already metastasized and cannot be treated.Cancer interception is vital,actively intervening in the malignization process before the development of a full-blown advanced tumor.An early diagnosis of PC has a dramatic impact on the survival of patients,and improved techniques are urgently needed to detect and evaluate this disease at an early stage.It is difficult to obtain tissue biopsies from the pancreas due to its anatomical position;however,liquid biopsies are readily available and can provide useful information for the diagnosis,prognosis,stratification,and follow-up of patients with PC and for the design of individually tailored treatments.The aim of this review was to provide an update of the latest advances in knowledge on the application of carbohydrates,proteins,cell-free nucleic acids,circulating tumor cells,metabo-lome compounds,exosomes,and platelets in blood as potential biomarkers for PC,focusing on their clinical relevance and potential for improving patient outcomes.
文摘Paclitaxel （PTX）, one of the most effective cytotoxins for the treatment of breast and lung cancer, is limited by its severe side effects and low tumor selectivity. In this work hollow-poly（4-vinylpyridine） （hollow-p4VP） nanoparticles （NPs） have been used for the first time to generate PTX@p4VP NPs, employing a novel technique in which a gold core in the center of the NP is further oxidized to produce the hollow structure into which PTX molecules can be incorporated. The hollow-p4VP NPs exhibit good physicochemical properties and displayed excellent biocompatibility when tested on blood （no hemolysis） and cell cultures （no cytotoxicity）. Interestingly, PTX@p4VP NPs significantly increased PTX cytotoxicity in human lung （A-549） and breast （MCF-7） cancer cells with a significant reduction of PTX ICs0 （from 5.9 to 3.6 nM in A-549 and from 13.75 to 4.71 nM in MCF-7）. In addition, PTX@p4VP caused a decrease in volume of A-549 and MCF-7 multicellular tumor spheroids （MTS）, an in vitro system that mimics in vivo tumors, in comparison to free PTX. This increased antitumoral activity is accompanied by efficient cell internalization and increased apoptosis, especially in lung cancer MTS. Our results offer the first evidence that hollow- p4VP NPs can improve the antitumoral activity of PTX. This system can be used as a new nanoplatform to overcome the limitations of current breast and lung cancer treatments.
