Molecular imaging has emerged as a new discipline in gastrointestinal endoscopy.This technology encompasses modalities that can visualize disease-specific morphological or functional tissue changes based on the molecu...Molecular imaging has emerged as a new discipline in gastrointestinal endoscopy.This technology encompasses modalities that can visualize disease-specific morphological or functional tissue changes based on the molecular signature of individual cells.Molecular imaging has several advantages including minimal damage to tissues,repetitive visualization,and utility for conducting quantitative analyses.Advancements in basic science coupled with endoscopy have made early detection of gastrointestinal cancer possible.Molecular imaging during gastrointestinal endoscopy requires thedevelopment of safe biomarkers and exogenous probes to detect molecular changes in cells with high specificity anda high signal-to-background ratio.Additionally,a high-resolution endoscope with an accurate wide-field viewing capability must be developed.Targeted endoscopic imaging is expected to improve early diagnosis and individual therapy of gastrointestinal cancer.展开更多
The epidermal growth factor receptor(EGFR)pathway plays an important role in the progression of colorectal cancer(CRC).Anti-EGFR drugs based on antibodies have been widely used for treating CRC through inducing the ce...The epidermal growth factor receptor(EGFR)pathway plays an important role in the progression of colorectal cancer(CRC).Anti-EGFR drugs based on antibodies have been widely used for treating CRC through inducing the cell death pathway.However,the majority of CRC patients will inevitably develop drug-resistance during anti-EGFR drug treatment,which is mainly caused by a point mutation in the KRAS oncogene.We developed a nanoliposomal(NL)particle containing the Cas9 protein and a single-guide RNA(sgRNA)complex(Cas9-RNP),for genomic editing of the KRAS mutation.The NL particle is composed of bio-compatible lipid compounds that can effectively encapsulate Cas9-RNP.By modifying the NL particle to include the appropriate antibody,it can specifically recognize EGFR expressing CRC and effectively deliver the gene-editing complexes.The conditions of NL treatment were optimized using a KRAS mutated CRC in vivo mouse model.Mice with KRAS-mutated CRC showed drug resistance against cetuximab,a therapeutic antibody drug.After treating the mice with the KRAS gene-editing NL particles,the implanted tumors showed a dramatic decrease in size.Our results demonstrated that this genomic editing complex has great potential as a therapeutic carrier system for the treatment of drug-resistant cancer caused by a point mutation.展开更多
基金Supported by The National Research Foundation of Korea grant funded by the Korea government No. 2010-0023295the Songeui Scholar Research grant funded by the Catholic University of Korea
文摘Molecular imaging has emerged as a new discipline in gastrointestinal endoscopy.This technology encompasses modalities that can visualize disease-specific morphological or functional tissue changes based on the molecular signature of individual cells.Molecular imaging has several advantages including minimal damage to tissues,repetitive visualization,and utility for conducting quantitative analyses.Advancements in basic science coupled with endoscopy have made early detection of gastrointestinal cancer possible.Molecular imaging during gastrointestinal endoscopy requires thedevelopment of safe biomarkers and exogenous probes to detect molecular changes in cells with high specificity anda high signal-to-background ratio.Additionally,a high-resolution endoscope with an accurate wide-field viewing capability must be developed.Targeted endoscopic imaging is expected to improve early diagnosis and individual therapy of gastrointestinal cancer.
基金This work was supported by the Industrial Strategic Technology Development Program(Project No.10047679)of the Ministry of Trade,Industry&Energy(MI,Republic of Korea)+1 种基金partially supported by the GRRC program of Gyeonggi province(GRRC 2016B02,Photonics-Medical Convergence Technology Research Center)was partly supported by grant(No.2019R1F1A1058879)from the National Foundation Research of Korea.
文摘The epidermal growth factor receptor(EGFR)pathway plays an important role in the progression of colorectal cancer(CRC).Anti-EGFR drugs based on antibodies have been widely used for treating CRC through inducing the cell death pathway.However,the majority of CRC patients will inevitably develop drug-resistance during anti-EGFR drug treatment,which is mainly caused by a point mutation in the KRAS oncogene.We developed a nanoliposomal(NL)particle containing the Cas9 protein and a single-guide RNA(sgRNA)complex(Cas9-RNP),for genomic editing of the KRAS mutation.The NL particle is composed of bio-compatible lipid compounds that can effectively encapsulate Cas9-RNP.By modifying the NL particle to include the appropriate antibody,it can specifically recognize EGFR expressing CRC and effectively deliver the gene-editing complexes.The conditions of NL treatment were optimized using a KRAS mutated CRC in vivo mouse model.Mice with KRAS-mutated CRC showed drug resistance against cetuximab,a therapeutic antibody drug.After treating the mice with the KRAS gene-editing NL particles,the implanted tumors showed a dramatic decrease in size.Our results demonstrated that this genomic editing complex has great potential as a therapeutic carrier system for the treatment of drug-resistant cancer caused by a point mutation.
