BACKGROUND Genomic profiling of tumors has contributed to the understanding of colorectal cancer(CRC), facilitating diagnosis, prognosis and selection of treatments,including targeted regimens. A report suggested that...BACKGROUND Genomic profiling of tumors has contributed to the understanding of colorectal cancer(CRC), facilitating diagnosis, prognosis and selection of treatments,including targeted regimens. A report suggested that a 19-gene-based risk classifier(TCA19) was a prognostic tool for patients with stage III CRC. The survival outcomes in patients with stage IV CRC are still poor and appropriate selection of targeted therapies and immunotherapies is challenging.AIM To assess clinical implication of TCA19 in patients with stage IV CRC, and to identify TCA19 with involvement in immune-oncology.METHODS A retrospective review of the medical records of 60 patients with stage IV CRC was conducted, assessing clinicopathological variables and progression-free survival(PFS). TCA19 gene expression was determined by quantitative polymerase chain reaction(qPCR) in matched normal and tumor tissues taken from the study cohort. Expression of potential immune-oncology regulatory proteins and targets was examined by immunohistochemistry(IHC), western blot, immunofluorescence staining in tissues from a validation cohort of 10 patients, and in CRC cell lines co-cultured with monocyte in vitro.RESULTS In the patients with TCA19 score higher than the median, the PFS rates of eight patients who received the targeted regimens were significantly higher than the PFS rates of four patients who received 5-fluorouracil-based regimen(P = 0.041).In multivariate analysis, expression of signaling lymphocytic activation molecule family, member 7(SLAMF7) and triggering receptor expressed on myeloid cells 1(TREM1) was associated with PFS in the 60-patient cohort. After checking another 10 validate set, the expression of the IHC, the level of real-time qPCR,and the level of western blot were lower for SLAMF7 and higher for TREM7 in primary and metastatic tumors than in normal tissues. In CRC cells expressing SLAMF7 that were co-cultured with a monocytic cell line, levels of CD 68 and CD73 were significantly lower at day 5 of co-culture than at day 0.CONCLUSION The TCA19 score might be prognostic for target-regimen-specific PFS in stage IV CRC. Down-regulation of SLAMF7 and up-regulation of TREM1 occur in primary and metastatic tumor tissues.展开更多
Cysteine(Cys)plays a pivotal role in many physiological and pathological processes,including detoxification and protein synthesis.The abnormal levels of Cys are linked to many diseases.In this study,a novel red-emitti...Cysteine(Cys)plays a pivotal role in many physiological and pathological processes,including detoxification and protein synthesis.The abnormal levels of Cys are linked to many diseases.In this study,a novel red-emitting off-on fluorescent probe Cys-TCF was masterly constructed for discriminative detection of Cys.After a series of experimental assessment,Cys-TCF displayed higher selectivity and sensitivity for Cys over other biothilols with a low detection limit(0.04μmol/L).More notably,the probe was also successfully applied to image Cys in live cells and live zebrafishes with low cytotoxicity.展开更多
The vicinal dithiol motif is widely present in proteins, and is critical for proteins’ structures and functions.In recent years, a variety of fluorescent probes with high specificity and outstanding optical propertie...The vicinal dithiol motif is widely present in proteins, and is critical for proteins’ structures and functions.In recent years, a variety of fluorescent probes with high specificity and outstanding optical properties for sensing protein vicinal dithiols have been developed. In this review, we summarized the fluorescent probes of protein vicinal dithiols in literature. These probes are classified into four types based on their acceptor sites, i.e., biarsenical probes, monoarsenical probes, dimaleimide probes and diacrylate probes.Through analyzing the properties of different probes, we expect that this review would help readers further understand the structural factors of these probes and provide the design strategy for novel fluorescent probes with improved properties.展开更多
基金Supported by The Basic Research Program of the Korea Science & Engineering Foundation,No.R01-2006-000-10021-0the Korea Health 21 R&D Project,Ministry of Health & Welfare No.A062254
基金Korea Research Foundation,No.2016R1E1A1A02919844 to Kim JC and No.2017R1A2B1009062 to Roh SAMinistry of Science,ICT,and Future Planning,Republic of Koreathe Asan Institute for Life Sciences,No.2016-710 to Lee JL
文摘BACKGROUND Genomic profiling of tumors has contributed to the understanding of colorectal cancer(CRC), facilitating diagnosis, prognosis and selection of treatments,including targeted regimens. A report suggested that a 19-gene-based risk classifier(TCA19) was a prognostic tool for patients with stage III CRC. The survival outcomes in patients with stage IV CRC are still poor and appropriate selection of targeted therapies and immunotherapies is challenging.AIM To assess clinical implication of TCA19 in patients with stage IV CRC, and to identify TCA19 with involvement in immune-oncology.METHODS A retrospective review of the medical records of 60 patients with stage IV CRC was conducted, assessing clinicopathological variables and progression-free survival(PFS). TCA19 gene expression was determined by quantitative polymerase chain reaction(qPCR) in matched normal and tumor tissues taken from the study cohort. Expression of potential immune-oncology regulatory proteins and targets was examined by immunohistochemistry(IHC), western blot, immunofluorescence staining in tissues from a validation cohort of 10 patients, and in CRC cell lines co-cultured with monocyte in vitro.RESULTS In the patients with TCA19 score higher than the median, the PFS rates of eight patients who received the targeted regimens were significantly higher than the PFS rates of four patients who received 5-fluorouracil-based regimen(P = 0.041).In multivariate analysis, expression of signaling lymphocytic activation molecule family, member 7(SLAMF7) and triggering receptor expressed on myeloid cells 1(TREM1) was associated with PFS in the 60-patient cohort. After checking another 10 validate set, the expression of the IHC, the level of real-time qPCR,and the level of western blot were lower for SLAMF7 and higher for TREM7 in primary and metastatic tumors than in normal tissues. In CRC cells expressing SLAMF7 that were co-cultured with a monocytic cell line, levels of CD 68 and CD73 were significantly lower at day 5 of co-culture than at day 0.CONCLUSION The TCA19 score might be prognostic for target-regimen-specific PFS in stage IV CRC. Down-regulation of SLAMF7 and up-regulation of TREM1 occur in primary and metastatic tumor tissues.
基金financial supports from the National Natural Science Foundation of China (Nos.21708017,21572093,21778028)Lanzhou University (the Fundamental Research Funds for the Central Universities,No.lzujbky-2018-64)Natural Science Foundation of Gansu Province (No.17JR5RA193)
文摘Cysteine(Cys)plays a pivotal role in many physiological and pathological processes,including detoxification and protein synthesis.The abnormal levels of Cys are linked to many diseases.In this study,a novel red-emitting off-on fluorescent probe Cys-TCF was masterly constructed for discriminative detection of Cys.After a series of experimental assessment,Cys-TCF displayed higher selectivity and sensitivity for Cys over other biothilols with a low detection limit(0.04μmol/L).More notably,the probe was also successfully applied to image Cys in live cells and live zebrafishes with low cytotoxicity.
基金financial supports from the National Natural Science Foundation of China (Nos. 21572093 & 21778028)the 111 Project
文摘The vicinal dithiol motif is widely present in proteins, and is critical for proteins’ structures and functions.In recent years, a variety of fluorescent probes with high specificity and outstanding optical properties for sensing protein vicinal dithiols have been developed. In this review, we summarized the fluorescent probes of protein vicinal dithiols in literature. These probes are classified into four types based on their acceptor sites, i.e., biarsenical probes, monoarsenical probes, dimaleimide probes and diacrylate probes.Through analyzing the properties of different probes, we expect that this review would help readers further understand the structural factors of these probes and provide the design strategy for novel fluorescent probes with improved properties.