Lung cancer,highly prevalent and the leading cause of cancer-related death globally,persists as a significant challenge due to the lack of definitive tumor markers for early diagnosis and personalized therapeutic inte...Lung cancer,highly prevalent and the leading cause of cancer-related death globally,persists as a significant challenge due to the lack of definitive tumor markers for early diagnosis and personalized therapeutic interventions.Recently,extracellular vesicles(EVs),functioning as natural carriers for intercellular communication,have received increasing attention due to their ability to traverse biological barriers and deliver diverse biological cargoes,including cytosolic proteins,cell surface proteins,microRNA,lncRNA,circRNA,DNA,and lipids.EVs are increasingly recognized as a valuable resource for non-invasive liquid biopsy,as well as drug delivery platforms,and anticancer vaccines for precision medicine in lung cancer.Herein,given the diagnostic and therapeutic potential of tumor-associated EVs for lung cancer,we discuss this topic from a translational standpoint.We delve into the specific roles that EVs play in lung cancer carcinogenesis and offer a particular perspective on how advanced engineering technologies can overcome the current challenges and expedite and/or enhance the translation of EVs from laboratory research to clinical settings.展开更多
Circulating peptide is a potential source of biomarkers for cancer detection.However,the existence of large molecular weight proteins in plasma have a disastrous effect on circulating peptides isolating and detecting....Circulating peptide is a potential source of biomarkers for cancer detection.However,the existence of large molecular weight proteins in plasma have a disastrous effect on circulating peptides isolating and detecting.Herein,nanotrap fractionation following by mass spectrometry have been applied to quantify the levels of bradykinin (BK) and hydroxylated bradykinin (Hyp-BK) as a relative measure of KRAS-regulated prolyl-4-hydroxylase alpha-1 (P4HA1) which may serve as early diagnosis marker for pancreatic ductal adenocarcinoma (PDAC).We found that P4HA1 can be upregulated by KRASG12v,which is a PDAC driver mutation,using HPNE/KRAS and HPNE cells.And we revealed that P4HA1 is overexpressed in PDAC tumors,compared to normal and inflamed pancreatic tissues.RNA interference revealed that P4HA1 activity was primarily responsible for Hyp-BK production.Mass spectrometry analysis revealed that plasma Hyp-BK/BK ratio was higher in PDAC than pancreatitis patients and healthy controls,while the area under the receiver operating characteristic (ROC) curve (AUC) is 0.8209 (95%Cl,0.7269-0.9149).The Hyp-BK/BK association with PDAC was reproduced in another cohort,where this ratio was found to increase with advancing tumor stage.These novel findings paved the way for wider applications of Nanotrap coupled mass spectrometry as a powerful tool for revealing biosignatures from plasma.展开更多
Identification of epitopes targeted following virus infection or vaccination can guide vaccine design and development of therapeutic interventions targeting functional sites,but can be laborious.Herein,we employed pep...Identification of epitopes targeted following virus infection or vaccination can guide vaccine design and development of therapeutic interventions targeting functional sites,but can be laborious.Herein,we employed peptide microarrays to map linear peptide epitopes(LPEs)recognized following SARS-CoV-2 infetion and vaccination.LPEs detected by nonhuman primate(NHP)and patient IgMs after SARS-CoV-2 infection extensively overlapped,localized to functionally important virus regions,and aligned with reported neutralizing antibody binding sies.Similar LPE overlap occurred atfter infection and vaccination,with LPE clusters specifc to each stimulus,where strong and conserved LPEs mapping to sites known or likely to inhibit spike protein function.Vaccine-specifc LPEs tended to map to sites known or likely to be afected by structural changes induced by the proline substitutions in the mRNA vaccine's S protein.Mapping LPEs to regions of known functional importance in this manner may acelerate vaccine evaluation and discovery of targets for sile secific therapeutic interventions.展开更多
基金the US Department of Defense(W8IXWH1910926)National Institutes of Health(U01CA252965,R01AI144168,R01AI175618,R01HD090927,R01HD103511,R21NS130542,USA)Carol Lavin Bernick Faculty Award of Tulane University.
文摘Lung cancer,highly prevalent and the leading cause of cancer-related death globally,persists as a significant challenge due to the lack of definitive tumor markers for early diagnosis and personalized therapeutic interventions.Recently,extracellular vesicles(EVs),functioning as natural carriers for intercellular communication,have received increasing attention due to their ability to traverse biological barriers and deliver diverse biological cargoes,including cytosolic proteins,cell surface proteins,microRNA,lncRNA,circRNA,DNA,and lipids.EVs are increasingly recognized as a valuable resource for non-invasive liquid biopsy,as well as drug delivery platforms,and anticancer vaccines for precision medicine in lung cancer.Herein,given the diagnostic and therapeutic potential of tumor-associated EVs for lung cancer,we discuss this topic from a translational standpoint.We delve into the specific roles that EVs play in lung cancer carcinogenesis and offer a particular perspective on how advanced engineering technologies can overcome the current challenges and expedite and/or enhance the translation of EVs from laboratory research to clinical settings.
文摘Circulating peptide is a potential source of biomarkers for cancer detection.However,the existence of large molecular weight proteins in plasma have a disastrous effect on circulating peptides isolating and detecting.Herein,nanotrap fractionation following by mass spectrometry have been applied to quantify the levels of bradykinin (BK) and hydroxylated bradykinin (Hyp-BK) as a relative measure of KRAS-regulated prolyl-4-hydroxylase alpha-1 (P4HA1) which may serve as early diagnosis marker for pancreatic ductal adenocarcinoma (PDAC).We found that P4HA1 can be upregulated by KRASG12v,which is a PDAC driver mutation,using HPNE/KRAS and HPNE cells.And we revealed that P4HA1 is overexpressed in PDAC tumors,compared to normal and inflamed pancreatic tissues.RNA interference revealed that P4HA1 activity was primarily responsible for Hyp-BK production.Mass spectrometry analysis revealed that plasma Hyp-BK/BK ratio was higher in PDAC than pancreatitis patients and healthy controls,while the area under the receiver operating characteristic (ROC) curve (AUC) is 0.8209 (95%Cl,0.7269-0.9149).The Hyp-BK/BK association with PDAC was reproduced in another cohort,where this ratio was found to increase with advancing tumor stage.These novel findings paved the way for wider applications of Nanotrap coupled mass spectrometry as a powerful tool for revealing biosignatures from plasma.
基金supported by the Department of Defense(grant number W8IxwH19i0926)National Institute of Allergy and Infectious Diseases contract(grant number_HHSN2722017000331)+1 种基金National Institute of Child Health and Human Development grant(grant numbers R01HD090927 and R01HDi03511)National Center for Research Resources and the Ofice of Research Infrastructure Programs(grant numbers OD011104).
文摘Identification of epitopes targeted following virus infection or vaccination can guide vaccine design and development of therapeutic interventions targeting functional sites,but can be laborious.Herein,we employed peptide microarrays to map linear peptide epitopes(LPEs)recognized following SARS-CoV-2 infetion and vaccination.LPEs detected by nonhuman primate(NHP)and patient IgMs after SARS-CoV-2 infection extensively overlapped,localized to functionally important virus regions,and aligned with reported neutralizing antibody binding sies.Similar LPE overlap occurred atfter infection and vaccination,with LPE clusters specifc to each stimulus,where strong and conserved LPEs mapping to sites known or likely to inhibit spike protein function.Vaccine-specifc LPEs tended to map to sites known or likely to be afected by structural changes induced by the proline substitutions in the mRNA vaccine's S protein.Mapping LPEs to regions of known functional importance in this manner may acelerate vaccine evaluation and discovery of targets for sile secific therapeutic interventions.
