During lung cancer metastasis,tumor cells undergo epithelial-to-mesenchymal transition(EMT),enabling them to intravasate through the vascular barrier and enter the circulation before colonizing secondary sites.Here,a ...During lung cancer metastasis,tumor cells undergo epithelial-to-mesenchymal transition(EMT),enabling them to intravasate through the vascular barrier and enter the circulation before colonizing secondary sites.Here,a human in vitro microphysiological model of EMT-driven lung cancer intravasation-on-a-chip was developed and coupled with machine learning(ML)-assisted automatic identification and quantification of intravasation events.A robust EMT-inducing cocktail(EMT-IC)was formulated by augmenting macrophage-conditioned medium with transforming growth factor-β1.When introduced into microvascular networks(MVNs)in microfluidic devices,EMT-IC did not affect MVN stability and physiologically relevant barrier functions.To model lung cancer intravasation on-a-chip,EMT-IC was supplemented into co-cultures of lung tumor micromasses and MVNs.Wihin 24 h of exposure,EMT-IC facilitated the insertion of membrane protrusions of migratory A549 cells into microvascular structures,followed by successful intravasation.EMT-IC reduced key basement membrane and vascular junction proteins-laminin and VE-Cadherin-rendering vessel walls more permissive to intravasating cells.ML-assisted vessel segmentation combined with co-localization analysis to detect intravasation events confirmed that EMT induction significantly increased the number of intravasation events.Introducing metastatic(NCI-H1975)and non-metastatic(BEAS-2B)cell lines demonstrated that both,baseline intravasation potential and responsiveness to EMT-IC,are reflected in the metastatic predisposition of lung cancer cell lines,highlighting the model’s universal applicability and cell-specific sensitivity.The reproducible detection of intravasation events in the established model provides a physiologically relevant platform to study processes of cancer metastasis with high spatio-temporal resolution and short timeframe.This approach holds promise for improved drug development and informed personalized patient treatment plans.展开更多
Because of unavoidable complications of vasectomy, this study was undertaken to assess the efficacy and safety of male sterilization with a nonobstructive intravas device （IVD） implanted into the vas lumen by a mini...Because of unavoidable complications of vasectomy, this study was undertaken to assess the efficacy and safety of male sterilization with a nonobstructive intravas device （IVD） implanted into the vas lumen by a mini-surgical method compared with no-scalpel vasectomy （NSV）. IVDs were categorized into two types： IVD-B has a tail used for fixing to the vas deferens （fixed wing） whereas IVD-A does not. A multicenter prospective randomized controlled clinical trial was conducted in China. The study was comprised of 1459 male volunteers seeking vasectomy who were randomly assigned to the IVD-A （n = 487）, IVD-B （n = 485） or NSV （n = 487） groups and underwent operation. Follow-up included visits at the 3rd-6TM and 12~ postoperative months, The assessments of the subjects involved regular physical examinations （including general and andrological examinations） and semen analysis. The subjects＇ partners also underwent monitoring for pregnancy by monthly interviews regarding menstruation and if necessary, urine tests, There were no significant differences in pregnancy rates （0.65% for IVD-A, 0 for IVD-B and 0.21% for NSV） among the three groups （P 〉 0.05）. The cumulative rates of complications at the 12th postoperative month were zero, 0.9% and 1.7% in the three groups, respectively. In conclusion, IVD male sterilization exhibits a low risk of long-term adverse events and was found to be effective as a male sterilization method, similar to the NSV technique. IVD male sterilization is expected to be a novel contraceptive method.展开更多
基金supported by the research fund to the Center for Neuromusculoskeletal Restorative Medicine from Health@InnoHK program launched by Innovation and Technology Commission,the Government of the Hong Kong Special Administrative Region of the People’s Republic of China(AB),by the Health and Medical Research Fund(08191066,AB)a direct grant(4054732,AB)from the Faculty of Medicine,CUHK+1 种基金supported by the Lee Quo Wei and Lee Yick Hoi Lun Professorship in Tissue Engineering and Regenerative Medicine.A.J.receives a Walter Benjamin postdoctoral fellowship from the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation,Germany521343357).
文摘During lung cancer metastasis,tumor cells undergo epithelial-to-mesenchymal transition(EMT),enabling them to intravasate through the vascular barrier and enter the circulation before colonizing secondary sites.Here,a human in vitro microphysiological model of EMT-driven lung cancer intravasation-on-a-chip was developed and coupled with machine learning(ML)-assisted automatic identification and quantification of intravasation events.A robust EMT-inducing cocktail(EMT-IC)was formulated by augmenting macrophage-conditioned medium with transforming growth factor-β1.When introduced into microvascular networks(MVNs)in microfluidic devices,EMT-IC did not affect MVN stability and physiologically relevant barrier functions.To model lung cancer intravasation on-a-chip,EMT-IC was supplemented into co-cultures of lung tumor micromasses and MVNs.Wihin 24 h of exposure,EMT-IC facilitated the insertion of membrane protrusions of migratory A549 cells into microvascular structures,followed by successful intravasation.EMT-IC reduced key basement membrane and vascular junction proteins-laminin and VE-Cadherin-rendering vessel walls more permissive to intravasating cells.ML-assisted vessel segmentation combined with co-localization analysis to detect intravasation events confirmed that EMT induction significantly increased the number of intravasation events.Introducing metastatic(NCI-H1975)and non-metastatic(BEAS-2B)cell lines demonstrated that both,baseline intravasation potential and responsiveness to EMT-IC,are reflected in the metastatic predisposition of lung cancer cell lines,highlighting the model’s universal applicability and cell-specific sensitivity.The reproducible detection of intravasation events in the established model provides a physiologically relevant platform to study processes of cancer metastasis with high spatio-temporal resolution and short timeframe.This approach holds promise for improved drug development and informed personalized patient treatment plans.
文摘Because of unavoidable complications of vasectomy, this study was undertaken to assess the efficacy and safety of male sterilization with a nonobstructive intravas device （IVD） implanted into the vas lumen by a mini-surgical method compared with no-scalpel vasectomy （NSV）. IVDs were categorized into two types： IVD-B has a tail used for fixing to the vas deferens （fixed wing） whereas IVD-A does not. A multicenter prospective randomized controlled clinical trial was conducted in China. The study was comprised of 1459 male volunteers seeking vasectomy who were randomly assigned to the IVD-A （n = 487）, IVD-B （n = 485） or NSV （n = 487） groups and underwent operation. Follow-up included visits at the 3rd-6TM and 12~ postoperative months, The assessments of the subjects involved regular physical examinations （including general and andrological examinations） and semen analysis. The subjects＇ partners also underwent monitoring for pregnancy by monthly interviews regarding menstruation and if necessary, urine tests, There were no significant differences in pregnancy rates （0.65% for IVD-A, 0 for IVD-B and 0.21% for NSV） among the three groups （P 〉 0.05）. The cumulative rates of complications at the 12th postoperative month were zero, 0.9% and 1.7% in the three groups, respectively. In conclusion, IVD male sterilization exhibits a low risk of long-term adverse events and was found to be effective as a male sterilization method, similar to the NSV technique. IVD male sterilization is expected to be a novel contraceptive method.
