:AIM To construct Hsp90 antisense RNAeukaryotic expression vector, transfect it intoSGC7901 and SGC7901/VCR of MDR-type humangastric cancer cell lines, HCC7402 of humanhepatic cancer and Eel09 of human esophagealcance...:AIM To construct Hsp90 antisense RNAeukaryotic expression vector, transfect it intoSGC7901 and SGC7901/VCR of MDR-type humangastric cancer cell lines, HCC7402 of humanhepatic cancer and Eel09 of human esophagealcancer cell lines, and to study the cell cycledistribution of the gene transected cells andtheir response to chemotherapeutic drugs.METHODS A I .03kb cDNA sequence of Hsp90Pwas obtained from the primary plasmid phHsp90by EcoR 1 and BamH I nuclease digestion andwas cloned to the EcoR 1 and BamH 1 site ofthe pcDNA by T4DNA ligase and an antisenseorientation of Hsp900 expression vector wasconstructed. The constructs were transfectedwith lipofectamine and positive clones wereselected with G418. The expression of RNA wasdetermined with dot blotting and RNaseprotection assay, and the expression of Hsp90protein determined with Western blot. Cell cycledistribution of the transfectants was analyzedwith flow cytometry, and the drug sensitivity ofthe transfectants to adriamycin (ADR ),vincrinstine (VCR ), mitomycin (MMC ) andcyclophosphamide (CTX ) with MTT andintracellular drug concentration of thetransfectants was determined with flowcytometry.RESULTS In EcoR 1 and BamH I restrictionanalysis, the size and the direction of the clonedsequence of Hsp900 remained what had beendesigned and the gene constructs were namedpcDNA-Hsp90. AH^SGC7901, AH^SGC7901/ VCR,AH-HCC7402 and AH-Eel09 cell clones allexpressed Hsp90 anti--sense RNA. Theexpression of Hsp90 was down--regulated in AHSGC7901, AH--SGC7901/ VCR, AH-HCC7402 andAH--Eel09 cell clones. Cell cycle distribution waschanged differently. In AH-SGC7901/ VCR andAH-Ec109 cells, G, phase cells were increased; Sphase and G, phase cells were decreased ascompared with their parental cell lines. In AHSGC7901 cell, G, phase cells were decreased, Qphase cells increased and S phase cells were notchanged, and in AH-HCC7402 cells G,, S and qphase cells remained unchanged as comparedwith their parental cell lines. The sensitivity ofAH--SGC7901, AH--SGC7901/ VCR, AH-HCC7402 andAH-Ec109 to chemotherapeutic drugs, thesensitivity ot AH--SGC7901/ VCR to ADR, VCR,MMC and CTX the sensitivity of AH-HCC7402 toADR and VCR, and the sensitivity of Eel09 toADR, VCR and CTX all increased as comparedwith their parental cell lines. The meanfluorescence intensity of ADR in AH--SGC7901,AH-SGC7901/ VCR, AH--HCC7402 and AH-Ec109was also significantly elevated (P< 0. 05).CONCLUSION Down-regulation of HsP90 couldchange cell cycle distribution and increase thedrug sensitivity of tumor cells.展开更多
O6-methylguanine-DNA methyltransferase (MGMT) plays an important role in repairing alkylated DNA. MGMT activity as well as cellular sensitivity to 1- ( 4- amino- 2-methyl-5-pyrimidinyl) methyl-3- ( 2-chloroethyl)-3-ni...O6-methylguanine-DNA methyltransferase (MGMT) plays an important role in repairing alkylated DNA. MGMT activity as well as cellular sensitivity to 1- ( 4- amino- 2-methyl-5-pyrimidinyl) methyl-3- ( 2-chloroethyl)-3-nitrosourea (ACNU) of 20 Chinese tumor cell strains were assayed. A linear response between MGMT activity and ACNU sensitivity (D10) was observed. The lower the MGMT activity In the cells, the more the sensitivity to ACNU killing. It suggested that assay of MGMT activity in tumor biopsy could be used as a guide to predict the effectiveness of ACNU treatment in chemotherapy of human cancer.展开更多
Tumor growth from a single transformed cancer cell up to a clinically apparent mass spans many spatial and temporal orders of magnitude. Implementation of cellular automata simulations of such tumor growth can be stra...Tumor growth from a single transformed cancer cell up to a clinically apparent mass spans many spatial and temporal orders of magnitude. Implementation of cellular automata simulations of such tumor growth can be straightforward but computing performance often counterbalances simplicity. Computationally convenient simulation times can be achieved by choosing appropriate data structures, memory and cell handling as well as domain setup. We propose a cellular automaton model of tumor growth with a domain that expands dynamically as the tumor population increases. We discuss memory access, data structures and implementation techniques that yield high-performance multi-scale Monte Carlo simulations of tumor growth. We discuss tumor properties that favor the proposed high-performance design and present simulation results of the tumor growth model. We estimate to which parameters the model is the most sensitive, and show that tumor volume depends on a number of parameters in a non-monotonic manner.展开更多
Objective：To investigate the association of the transportation characteristics of nolatrexed in tu-mor cells with its drug sensitivity. Methods: The sensitivity of 3 tumor cell lines, C6, SRS82 and LoVo, to nolatrexe...Objective：To investigate the association of the transportation characteristics of nolatrexed in tu-mor cells with its drug sensitivity. Methods: The sensitivity of 3 tumor cell lines, C6, SRS82 and LoVo, to nolatrexed were determined by growth inhibition study. After exposure to 20μmol/L nolatrexed at different time intervals ranging from 0 to 30 rain, or to nolatrexed at different concentrations ranging from 0 to 40μmol/L for 10 min, the intracellular drug concentration was measured using high-performance liquid chro-matography. Results: C6 was the most sensitive cell line among the three, with sensitivity 6.8-fold and 13.8-fold those of SRS-82 and LoVo cells respectively. Transportation of nolatrexed in the 3 cell lines were qualitatively similar, which rapidly achieved steady-state within 5 min, and linear relationship between the in-tracellular and extracellular drug concentration was observed. The intracellular steady-state level achieved in C6 was significantly higher than those in the other two cell lines, the latter having comparable levels. Con-clusion: Nolatrexed enters the cell very quickly and different transport capacities are involved in the genera-tion of varied sensitivity to nolatrexed in tumor cells.展开更多
A photoanode with Ga-doped ZnO nanorods has been prepared on F-doped SnO2 (FTO) coated glass substrate and its application in dye-sensitized solar cells (DSSCs) has been investigated. Ga-doped ZnO nanorods have been s...A photoanode with Ga-doped ZnO nanorods has been prepared on F-doped SnO2 (FTO) coated glass substrate and its application in dye-sensitized solar cells (DSSCs) has been investigated. Ga-doped ZnO nanorods have been synthesized by an electric-field-assisted wet chemical approach at 80?C. Under a direct current electric field, the nanorods predominantly grow on cathodes. The results of the X-ray photoelectron spectroscopy and photoluminescence verify that Ga dopant is successfully incorporated into the ZnO wurtzite lattice structure. Finally, employing Ga-doped ZnO nanorods with the length of ~5 μm as the photoanode of DSSCs, an overall energy conversion efficiency of 2.56% is achieved. The dramatically improved performance of Ga-doped ZnO based DSSCs compared with that of pure ZnO is due to the higher electron conductivity.展开更多
Since taking part as leading actors in driving the metastatic process,circulating tumor cells(CTCs)have displayed a wide range of potential applications in the cancer-related research field.Besides their well-proved p...Since taking part as leading actors in driving the metastatic process,circulating tumor cells(CTCs)have displayed a wide range of potential applications in the cancer-related research field.Besides their well-proved prognostic value,the role of CTCs in both predictive and diagnostics terms might be extremely informative about cancer properties and therefore highly helpful in the clinical decision-making process.Unfortunately,CTCs are scarcely released in the blood circulation and their counts vary a lot among different types of cancer,therefore CTC detection and consequent characterization are still highly challenging.In this context,in vitro CTC cultures could potentially offer a great opportunity to expand the number of tumor cells isolated at different stages of the disease and thus simplify the analysis of their biological and molecular features,allowing a deeper comprehension of the nature of neoplastic diseases.The aim of this review is to highlight the main attempts to establish in vitro CTC cultures from patients harboring different tumor types in order to highlight how powerful this practice could be,especially in optimizing the therapeutic strategies available in clinical practice and potentially preventing or contrasting the development of treatment resistance.展开更多
Cancer immunotherapy has become a promising strategy.However,the effectiveness of immunotherapy is restricted in"cold tumors"characterized with insufficient T cells intratumoral infiltration and failed T cel...Cancer immunotherapy has become a promising strategy.However,the effectiveness of immunotherapy is restricted in"cold tumors"characterized with insufficient T cells intratumoral infiltration and failed T cells priming.Herein,an on-demand integrated nano-engager(JOT-Lip)was developed to convert cold tumors to hot via"increased DNA damage and dual immune checkpoint inhibition"strategy.JOT-Lip was engineered by co-loading oxaliplatin(Oxa)and JQ1 into liposomes with T-cell immunoglobulin mucin-3 antibodies(Tim-3 mAb)coupled on the liposomal surface by metalloproteinase-2(MMP-2)-sensitive linker.JQ1 inhibited DNA repair to increase DNA damage and immunogenic cell death(ICD)of Oxa,thus promoting T cells intratumoral infiltration.In addition,JQ1 inhibited PD-1/PD-L1 pathway,achieving dual immune checkpoint inhibition combining with Tim-3 mAb,thus effectively promoting T cells priming.It is demonstrated that JOT-Lip not only increased DNA damage and promoted the release of damage-associated molecular patterns(DAMPs),but also enhanced T cells intratumoral infiltration and promoted T cell priming,which successfully converted cold tumors to hot and showed significant anti-tumor and anti-metastasis effects.Collectively,our study provides a rational design of an effective combination regimen and an ideal co-delivery system to convert cold tumors to hot,which holds great potential in clinical cancer chemoimmunotherapy.展开更多
目的通过生物信息学的方法构建头颈部鳞状细胞癌(HNSCC)血管生成相关基因(angiogenesis related genes,ARGs)预后模型,验证模型的预测价值。方法从UCSC Xena数据库下载头颈部鳞状细胞癌(TCGA-HNSCC)数据集,获取差异表达的ARGs,通过单因...目的通过生物信息学的方法构建头颈部鳞状细胞癌(HNSCC)血管生成相关基因(angiogenesis related genes,ARGs)预后模型,验证模型的预测价值。方法从UCSC Xena数据库下载头颈部鳞状细胞癌(TCGA-HNSCC)数据集,获取差异表达的ARGs,通过单因素Cox回归分析、蛋白互作网络(PPI)筛选预后相关核心ARGs,利用LASSO回归分析构建预后模型,分析高低风险组的预测效能,并使用GSE41613数据集进行验证。利用ESTIMATE算法对高低风险组进行免疫浸润分析,分析高低风险组免疫检查点基因表达的差异。对高低风险组进行药物敏感性分析。RT-qPCR验证PLAU、VEGF-C两个预后基因在舌鳞状细胞癌的表达情况。结果在TCGA-HNSCC中获得了414个差异表达的ARGs,基于14个ARGs构建了HNSCC预后模型。Kaplan-Meier生存曲线显示高风险组的生存时间低于低风险组(P<0.001),ROC曲线显示其有较高的预测价值(1年、3年、5年的AUC值分别为0.675、0.688、0.644),其预后价值在GSE41613数据集得到了验证。免疫浸润分析提示低风险组具有更高的免疫浸润评分,低风险组高表达免疫检查点基因。药物敏感性分析表明高低风险组对包括顺铂(cisplatin)、Tozasertib在内的多种药物的敏感性存在差异(P<0.05)。RT-qPCR结果显示PLAU、VEGF-C高表达于舌鳞状细胞癌(P<0.05)。结论由14个ARGs组成的HNSCC风险评分模型,可有效预测HNSCC患者的预后及对药物治疗的反应。展开更多
The analysis of circulating tumor cells(CTCs)allows a noninvasive method of“real-time liquid biopsy”from the blood samples of cancer patients for the diagnosis of early-stage cancer,prognosis,and monitoring therapeu...The analysis of circulating tumor cells(CTCs)allows a noninvasive method of“real-time liquid biopsy”from the blood samples of cancer patients for the diagnosis of early-stage cancer,prognosis,and monitoring therapeutic response.In this study,we develop a simple,inexpensive,and reliable method that utilizes a small molecule peptide,the asparagine-glycine-arginine(NGR),as a capture probe for the selective enrichment and isolation of circulating tumor cells(CTCs).The multiscale TiO_(2) nanofibers are obtained by electrospinning and calcination.Bovine serum albumin(BSA)is decorated onto TiO_(2) nanofiber surfaces to inhibit non-target cell adhesion,while NGR peptides are conjugated onto the TiO_(2)-BSA surface through the glutaraldehyde(GA)to specifically capture the target cells.The TiO_(2)-BSA-NGR substrate exhibits a high capture sensitivity and efficiency from the mimical blood samples with PC-3 cancer cells as low as 10 cells/mL.The TiO_(2) nanofiber substrate can be a promising strategy for the capture and enumeration of CTCs in cancer progression monitoring.展开更多
Circulating tumor cells(CTCs)have the potential to provide genetic information for heterogeneous tumors,which may be useful for monitoring disease progression and developing personalized therapies.However,the isolatio...Circulating tumor cells(CTCs)have the potential to provide genetic information for heterogeneous tumors,which may be useful for monitoring disease progression and developing personalized therapies.However,the isolation of CTCs for molecular analysis is challenging due to their extreme rarity and phenotypic heterogeneity,which hinders the transformation of CTCs into traditional clinical applications.In order to achieve clinically significant CTC detection,devices utilizing novel microfluidics and nanotechnology have been developed to achieve high sensitivity and specificity capture of CTCs.In this review,we discuss these newly developed devices for CTC capture and molecular characterization for early diagnosis and determining ideal treatment regimen to better manage these cancers clinically.In addition,the potential prognostic values of CTCs as treatment guidelines and that ultimately contribute to realize personalized treatment are also discussed.展开更多
基金Project supported by the National Natural Science Foundation of China,No.39570806National Excel1ent Youth Scientific Foundation,No.3952020.
文摘:AIM To construct Hsp90 antisense RNAeukaryotic expression vector, transfect it intoSGC7901 and SGC7901/VCR of MDR-type humangastric cancer cell lines, HCC7402 of humanhepatic cancer and Eel09 of human esophagealcancer cell lines, and to study the cell cycledistribution of the gene transected cells andtheir response to chemotherapeutic drugs.METHODS A I .03kb cDNA sequence of Hsp90Pwas obtained from the primary plasmid phHsp90by EcoR 1 and BamH I nuclease digestion andwas cloned to the EcoR 1 and BamH 1 site ofthe pcDNA by T4DNA ligase and an antisenseorientation of Hsp900 expression vector wasconstructed. The constructs were transfectedwith lipofectamine and positive clones wereselected with G418. The expression of RNA wasdetermined with dot blotting and RNaseprotection assay, and the expression of Hsp90protein determined with Western blot. Cell cycledistribution of the transfectants was analyzedwith flow cytometry, and the drug sensitivity ofthe transfectants to adriamycin (ADR ),vincrinstine (VCR ), mitomycin (MMC ) andcyclophosphamide (CTX ) with MTT andintracellular drug concentration of thetransfectants was determined with flowcytometry.RESULTS In EcoR 1 and BamH I restrictionanalysis, the size and the direction of the clonedsequence of Hsp900 remained what had beendesigned and the gene constructs were namedpcDNA-Hsp90. AH^SGC7901, AH^SGC7901/ VCR,AH-HCC7402 and AH-Eel09 cell clones allexpressed Hsp90 anti--sense RNA. Theexpression of Hsp90 was down--regulated in AHSGC7901, AH--SGC7901/ VCR, AH-HCC7402 andAH--Eel09 cell clones. Cell cycle distribution waschanged differently. In AH-SGC7901/ VCR andAH-Ec109 cells, G, phase cells were increased; Sphase and G, phase cells were decreased ascompared with their parental cell lines. In AHSGC7901 cell, G, phase cells were decreased, Qphase cells increased and S phase cells were notchanged, and in AH-HCC7402 cells G,, S and qphase cells remained unchanged as comparedwith their parental cell lines. The sensitivity ofAH--SGC7901, AH--SGC7901/ VCR, AH-HCC7402 andAH-Ec109 to chemotherapeutic drugs, thesensitivity ot AH--SGC7901/ VCR to ADR, VCR,MMC and CTX the sensitivity of AH-HCC7402 toADR and VCR, and the sensitivity of Eel09 toADR, VCR and CTX all increased as comparedwith their parental cell lines. The meanfluorescence intensity of ADR in AH--SGC7901,AH-SGC7901/ VCR, AH--HCC7402 and AH-Ec109was also significantly elevated (P< 0. 05).CONCLUSION Down-regulation of HsP90 couldchange cell cycle distribution and increase thedrug sensitivity of tumor cells.
文摘O6-methylguanine-DNA methyltransferase (MGMT) plays an important role in repairing alkylated DNA. MGMT activity as well as cellular sensitivity to 1- ( 4- amino- 2-methyl-5-pyrimidinyl) methyl-3- ( 2-chloroethyl)-3-nitrosourea (ACNU) of 20 Chinese tumor cell strains were assayed. A linear response between MGMT activity and ACNU sensitivity (D10) was observed. The lower the MGMT activity In the cells, the more the sensitivity to ACNU killing. It suggested that assay of MGMT activity in tumor biopsy could be used as a guide to predict the effectiveness of ACNU treatment in chemotherapy of human cancer.
文摘Tumor growth from a single transformed cancer cell up to a clinically apparent mass spans many spatial and temporal orders of magnitude. Implementation of cellular automata simulations of such tumor growth can be straightforward but computing performance often counterbalances simplicity. Computationally convenient simulation times can be achieved by choosing appropriate data structures, memory and cell handling as well as domain setup. We propose a cellular automaton model of tumor growth with a domain that expands dynamically as the tumor population increases. We discuss memory access, data structures and implementation techniques that yield high-performance multi-scale Monte Carlo simulations of tumor growth. We discuss tumor properties that favor the proposed high-performance design and present simulation results of the tumor growth model. We estimate to which parameters the model is the most sensitive, and show that tumor volume depends on a number of parameters in a non-monotonic manner.
基金Research Foundation of Guangdong Province (No. 99-Z-030-01)
文摘Objective：To investigate the association of the transportation characteristics of nolatrexed in tu-mor cells with its drug sensitivity. Methods: The sensitivity of 3 tumor cell lines, C6, SRS82 and LoVo, to nolatrexed were determined by growth inhibition study. After exposure to 20μmol/L nolatrexed at different time intervals ranging from 0 to 30 rain, or to nolatrexed at different concentrations ranging from 0 to 40μmol/L for 10 min, the intracellular drug concentration was measured using high-performance liquid chro-matography. Results: C6 was the most sensitive cell line among the three, with sensitivity 6.8-fold and 13.8-fold those of SRS-82 and LoVo cells respectively. Transportation of nolatrexed in the 3 cell lines were qualitatively similar, which rapidly achieved steady-state within 5 min, and linear relationship between the in-tracellular and extracellular drug concentration was observed. The intracellular steady-state level achieved in C6 was significantly higher than those in the other two cell lines, the latter having comparable levels. Con-clusion: Nolatrexed enters the cell very quickly and different transport capacities are involved in the genera-tion of varied sensitivity to nolatrexed in tumor cells.
文摘A photoanode with Ga-doped ZnO nanorods has been prepared on F-doped SnO2 (FTO) coated glass substrate and its application in dye-sensitized solar cells (DSSCs) has been investigated. Ga-doped ZnO nanorods have been synthesized by an electric-field-assisted wet chemical approach at 80?C. Under a direct current electric field, the nanorods predominantly grow on cathodes. The results of the X-ray photoelectron spectroscopy and photoluminescence verify that Ga dopant is successfully incorporated into the ZnO wurtzite lattice structure. Finally, employing Ga-doped ZnO nanorods with the length of ~5 μm as the photoanode of DSSCs, an overall energy conversion efficiency of 2.56% is achieved. The dramatically improved performance of Ga-doped ZnO based DSSCs compared with that of pure ZnO is due to the higher electron conductivity.
文摘Since taking part as leading actors in driving the metastatic process,circulating tumor cells(CTCs)have displayed a wide range of potential applications in the cancer-related research field.Besides their well-proved prognostic value,the role of CTCs in both predictive and diagnostics terms might be extremely informative about cancer properties and therefore highly helpful in the clinical decision-making process.Unfortunately,CTCs are scarcely released in the blood circulation and their counts vary a lot among different types of cancer,therefore CTC detection and consequent characterization are still highly challenging.In this context,in vitro CTC cultures could potentially offer a great opportunity to expand the number of tumor cells isolated at different stages of the disease and thus simplify the analysis of their biological and molecular features,allowing a deeper comprehension of the nature of neoplastic diseases.The aim of this review is to highlight the main attempts to establish in vitro CTC cultures from patients harboring different tumor types in order to highlight how powerful this practice could be,especially in optimizing the therapeutic strategies available in clinical practice and potentially preventing or contrasting the development of treatment resistance.
基金supported by National Natural Science Foundation of China(81974498 and 82173757)Translational Medicine Core Facility of Shandong UniversityPharmaceutical biology sharing platform of Shandong University for supporting the work。
文摘Cancer immunotherapy has become a promising strategy.However,the effectiveness of immunotherapy is restricted in"cold tumors"characterized with insufficient T cells intratumoral infiltration and failed T cells priming.Herein,an on-demand integrated nano-engager(JOT-Lip)was developed to convert cold tumors to hot via"increased DNA damage and dual immune checkpoint inhibition"strategy.JOT-Lip was engineered by co-loading oxaliplatin(Oxa)and JQ1 into liposomes with T-cell immunoglobulin mucin-3 antibodies(Tim-3 mAb)coupled on the liposomal surface by metalloproteinase-2(MMP-2)-sensitive linker.JQ1 inhibited DNA repair to increase DNA damage and immunogenic cell death(ICD)of Oxa,thus promoting T cells intratumoral infiltration.In addition,JQ1 inhibited PD-1/PD-L1 pathway,achieving dual immune checkpoint inhibition combining with Tim-3 mAb,thus effectively promoting T cells priming.It is demonstrated that JOT-Lip not only increased DNA damage and promoted the release of damage-associated molecular patterns(DAMPs),but also enhanced T cells intratumoral infiltration and promoted T cell priming,which successfully converted cold tumors to hot and showed significant anti-tumor and anti-metastasis effects.Collectively,our study provides a rational design of an effective combination regimen and an ideal co-delivery system to convert cold tumors to hot,which holds great potential in clinical cancer chemoimmunotherapy.
文摘目的通过生物信息学的方法构建头颈部鳞状细胞癌(HNSCC)血管生成相关基因(angiogenesis related genes,ARGs)预后模型,验证模型的预测价值。方法从UCSC Xena数据库下载头颈部鳞状细胞癌(TCGA-HNSCC)数据集,获取差异表达的ARGs,通过单因素Cox回归分析、蛋白互作网络(PPI)筛选预后相关核心ARGs,利用LASSO回归分析构建预后模型,分析高低风险组的预测效能,并使用GSE41613数据集进行验证。利用ESTIMATE算法对高低风险组进行免疫浸润分析,分析高低风险组免疫检查点基因表达的差异。对高低风险组进行药物敏感性分析。RT-qPCR验证PLAU、VEGF-C两个预后基因在舌鳞状细胞癌的表达情况。结果在TCGA-HNSCC中获得了414个差异表达的ARGs,基于14个ARGs构建了HNSCC预后模型。Kaplan-Meier生存曲线显示高风险组的生存时间低于低风险组(P<0.001),ROC曲线显示其有较高的预测价值(1年、3年、5年的AUC值分别为0.675、0.688、0.644),其预后价值在GSE41613数据集得到了验证。免疫浸润分析提示低风险组具有更高的免疫浸润评分,低风险组高表达免疫检查点基因。药物敏感性分析表明高低风险组对包括顺铂(cisplatin)、Tozasertib在内的多种药物的敏感性存在差异(P<0.05)。RT-qPCR结果显示PLAU、VEGF-C高表达于舌鳞状细胞癌(P<0.05)。结论由14个ARGs组成的HNSCC风险评分模型,可有效预测HNSCC患者的预后及对药物治疗的反应。
基金This work was financially supported by the National Natural Science Foundation of China(21904135,21575154,21775160)the Natural Science Foundation of Jiangsu Province(BK20180250)+2 种基金the Science Foundation of Jiangxi Province(20192ACB21033)the CAS International Cooperation Key program(121E32KYSB20170025)the Jiangsu Province Six Talent Peaks program and the CAS/SAFEA International Innovation Teams program.
文摘The analysis of circulating tumor cells(CTCs)allows a noninvasive method of“real-time liquid biopsy”from the blood samples of cancer patients for the diagnosis of early-stage cancer,prognosis,and monitoring therapeutic response.In this study,we develop a simple,inexpensive,and reliable method that utilizes a small molecule peptide,the asparagine-glycine-arginine(NGR),as a capture probe for the selective enrichment and isolation of circulating tumor cells(CTCs).The multiscale TiO_(2) nanofibers are obtained by electrospinning and calcination.Bovine serum albumin(BSA)is decorated onto TiO_(2) nanofiber surfaces to inhibit non-target cell adhesion,while NGR peptides are conjugated onto the TiO_(2)-BSA surface through the glutaraldehyde(GA)to specifically capture the target cells.The TiO_(2)-BSA-NGR substrate exhibits a high capture sensitivity and efficiency from the mimical blood samples with PC-3 cancer cells as low as 10 cells/mL.The TiO_(2) nanofiber substrate can be a promising strategy for the capture and enumeration of CTCs in cancer progression monitoring.
基金the National Natural Science Foundation of China(31800085)National Natural Science Foundation for Major Research Instruments(81527801)
文摘Circulating tumor cells(CTCs)have the potential to provide genetic information for heterogeneous tumors,which may be useful for monitoring disease progression and developing personalized therapies.However,the isolation of CTCs for molecular analysis is challenging due to their extreme rarity and phenotypic heterogeneity,which hinders the transformation of CTCs into traditional clinical applications.In order to achieve clinically significant CTC detection,devices utilizing novel microfluidics and nanotechnology have been developed to achieve high sensitivity and specificity capture of CTCs.In this review,we discuss these newly developed devices for CTC capture and molecular characterization for early diagnosis and determining ideal treatment regimen to better manage these cancers clinically.In addition,the potential prognostic values of CTCs as treatment guidelines and that ultimately contribute to realize personalized treatment are also discussed.
