Early-stage brain metastasis of breast cancer(BMBC), due to the existence of an intact blood–brain barrier(BBB), is one of the deadliest neurologic complications. To improve the efficacy of chemotherapy for BMBC, a T...Early-stage brain metastasis of breast cancer(BMBC), due to the existence of an intact blood–brain barrier(BBB), is one of the deadliest neurologic complications. To improve the efficacy of chemotherapy for BMBC, a Trojan horse strategy-based nanocarrier has been developed by integrating the cell membrane of a brain-homing cancer cell and a polymeric drug depot. With the camouflage of a MDA-MB-231/Br cell membrane, doxorubicin-loaded poly(D, L-lactic-co-glycolic acid) nanoparticle(DOX-PLGA@CM) shows enhanced cellular uptake and boosted killing potency for MDA-MB-231/Br cells. Furthermore, DOX-PLGA@CM is equipped with naturally selected molecules for BBB penetration, as evidenced by its boosted capacity in entering the brain of both healthy and early-stage BMBC mouse models. Consequently, DOX-PLGA@CM effectively reaches the metastatic tumor lesions in the brain, slows down cancer progression, reduces tumor burden, and extends the survival time for the BMBC animal.Furthermore, the simplicity and easy scale-up of the design opens a new window for the treatment of BMBC and other brain metastatic cancers.展开更多
The Enhanced Complexity Model( ECM) developed previously has been further extended to produce a Motivationally Enhanced Complexity Model( MECM) which enables the degree of motivation,capability and opportunity of a hy...The Enhanced Complexity Model( ECM) developed previously has been further extended to produce a Motivationally Enhanced Complexity Model( MECM) which enables the degree of motivation,capability and opportunity of a hypothetical Trojan Horse author to be included in quantifying the relative plausibility of competing explanations for the existence of uncontested digital evidence.This new model has been applied to the case of the Trojan Horse defence( THD) against the possession of child pornography.Our results demonstrate that the THD in this case cannot be plausibly sustained unless it can be shown that an ‘off-theshelf'( OTS) Trojan Horse for this task is available and it is not detectable by the target computer,at the material time.展开更多
基金the National Institutes of Health(1R01AG054839-01A1,1R41CA254500-01A1,and 1R21CA252360-01)for financial support of the research。
文摘Early-stage brain metastasis of breast cancer(BMBC), due to the existence of an intact blood–brain barrier(BBB), is one of the deadliest neurologic complications. To improve the efficacy of chemotherapy for BMBC, a Trojan horse strategy-based nanocarrier has been developed by integrating the cell membrane of a brain-homing cancer cell and a polymeric drug depot. With the camouflage of a MDA-MB-231/Br cell membrane, doxorubicin-loaded poly(D, L-lactic-co-glycolic acid) nanoparticle(DOX-PLGA@CM) shows enhanced cellular uptake and boosted killing potency for MDA-MB-231/Br cells. Furthermore, DOX-PLGA@CM is equipped with naturally selected molecules for BBB penetration, as evidenced by its boosted capacity in entering the brain of both healthy and early-stage BMBC mouse models. Consequently, DOX-PLGA@CM effectively reaches the metastatic tumor lesions in the brain, slows down cancer progression, reduces tumor burden, and extends the survival time for the BMBC animal.Furthermore, the simplicity and easy scale-up of the design opens a new window for the treatment of BMBC and other brain metastatic cancers.
文摘The Enhanced Complexity Model( ECM) developed previously has been further extended to produce a Motivationally Enhanced Complexity Model( MECM) which enables the degree of motivation,capability and opportunity of a hypothetical Trojan Horse author to be included in quantifying the relative plausibility of competing explanations for the existence of uncontested digital evidence.This new model has been applied to the case of the Trojan Horse defence( THD) against the possession of child pornography.Our results demonstrate that the THD in this case cannot be plausibly sustained unless it can be shown that an ‘off-theshelf'( OTS) Trojan Horse for this task is available and it is not detectable by the target computer,at the material time.
