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Li C, Li Y, Zhang Y, Zhao G, Wang Y, Wang H, Wang H, Xu R, Wei Q. Signal-enhanced electrochemiluminescence strategy using iron-based metal-organic frameworks modified with carboxylated Ru(II) complexes for neuron-specific enolase detection. Biosens Bioelectron 2022; 215:114605. [PMID: 35940004 DOI: 10.1016/j.bios.2022.114605] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 06/29/2022] [Accepted: 07/26/2022] [Indexed: 11/02/2022]
Abstract
The preparation of highly efficient electrochemiluminescence (ECL) illuminants is an effective method to improve the sensitivity and repeatability of ECL immunoassay. In this study, we prepared an ECL immunoassay for efficient and sensitive detection of neuron-specific enolase (NSE) by linking carboxylated Ru(bpy)32+ to an iron-based metal-organic framework (NH2-MIL-88 (Fe)) via an amide bond as an ECL signal probe. NH2-MIL-88 (Fe) possesses a large number of amino groups that can catalyze the co-reactant S2O82-, which generates abundant reaction intermediates SO4•- around Ru(dcbpy)32+, reduces the loss of material transport and energy transfer between SO4•- and Ru(dcbpy)32+, and significantly enhances the ECL signal. We used polyaniline-intercalating vanadium oxide (PVO) nanosheets as the substrates to capture NSE owing to the large specific surface area and extraordinary conductivity of the nanosheets. Similarly, PVO nanosheets also possess abundant amino groups, which can act as co-reaction promoters to catalyze the reaction of S2O82- to SO4•-, enhancing the ECL signal of the immunoassay. Therefore, we constructed a dual-enhanced ECL immunoassay with Ru(dcbpy)32+/NH2-MIL-88 (Fe) and PVO as the signal probe and substrate, respectively, which exhibited excellent sensitivity and selectivity for detecting NSE. This study offers an effective strategy for ultrasensitive detection of trace proteins using ECL immunoassays.
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Affiliation(s)
- Chenchen Li
- Provincial Key Laboratory of Rural Energy Engineering in Yunnan, Yunnan Normal University, Kunming, 650500, People's Republic of China; Collaborative Innovation Center for Green Chemical Manufacturing and Accurate Detection, Key Laboratory of Interfacial Reaction & Sensing Analysis in Universities of Shandong, School of Chemistry and Chemical Engineering, University of Jinan, Jinan, 250022, People's Republic of China
| | - Yunxiao Li
- Provincial Key Laboratory of Rural Energy Engineering in Yunnan, Yunnan Normal University, Kunming, 650500, People's Republic of China
| | - Yong Zhang
- Provincial Key Laboratory of Rural Energy Engineering in Yunnan, Yunnan Normal University, Kunming, 650500, People's Republic of China.
| | - Guanhui Zhao
- Collaborative Innovation Center for Green Chemical Manufacturing and Accurate Detection, Key Laboratory of Interfacial Reaction & Sensing Analysis in Universities of Shandong, School of Chemistry and Chemical Engineering, University of Jinan, Jinan, 250022, People's Republic of China.
| | - Yaoguang Wang
- Shandong Provincial Key Laboratory of Molecular Engineering, School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, People's Republic of China
| | - Huabin Wang
- Provincial Key Laboratory of Rural Energy Engineering in Yunnan, Yunnan Normal University, Kunming, 650500, People's Republic of China
| | - Huan Wang
- Collaborative Innovation Center for Green Chemical Manufacturing and Accurate Detection, Key Laboratory of Interfacial Reaction & Sensing Analysis in Universities of Shandong, School of Chemistry and Chemical Engineering, University of Jinan, Jinan, 250022, People's Republic of China
| | - Rui Xu
- Provincial Key Laboratory of Rural Energy Engineering in Yunnan, Yunnan Normal University, Kunming, 650500, People's Republic of China.
| | - Qin Wei
- Collaborative Innovation Center for Green Chemical Manufacturing and Accurate Detection, Key Laboratory of Interfacial Reaction & Sensing Analysis in Universities of Shandong, School of Chemistry and Chemical Engineering, University of Jinan, Jinan, 250022, People's Republic of China
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Yu X, Li Y, Li Y, Liu S, Wu Z, Dong H, Xu Z, Li X, Liu Q. An electrochemical amplification strategy based on the ferrocene functionalized cuprous oxide superparticles for the detection of NSE. Talanta 2022; 236:122865. [PMID: 34635247 DOI: 10.1016/j.talanta.2021.122865] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 09/04/2021] [Accepted: 09/08/2021] [Indexed: 10/20/2022]
Abstract
A sandwich-type electrochemical immunosensor was designed utilizing ferrocene-functionalized cuprous oxide superparticles (Au/Fc@CuxO SPs) as the signal label and graphene supported by hollow carbon balls (HCNs-GR) as the substrate. The CuxO SPs possess a superparticle structure with synergistic properties of isotropy and promising catalytic activity. Ferrocene (Fc) was deposited on the CuxO SPs to act as the electronic transmission medium. The Au/Fc@CuxO SPs played a pivotal role in improving the sensitivity of the immunosensor. The graphene supported by hollow carbon balls (HCNs-GR) was used to modify the electrode surface. The embedding of hollow carbon nanospheres (HCNs) reduced the decrease of the effective surface area caused by the stacking of graphene nanotubes. Meanwhile, the load of carbon balls further increases the surface area of graphene, enabled HCNs-GR to immobilize antibodies more effectively, improved the sensitivity of the immunosensor. The proposed immunosensor showed a linear range from 500 fg/mL to 100 ng/mL, with the detection limit to 25.7 fg/mL.
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Affiliation(s)
- Xiaodong Yu
- School of Chemical Engineering, Shandong University of Technology, Zibo, 255049, PR China
| | - Yueyun Li
- School of Chemical Engineering, Shandong University of Technology, Zibo, 255049, PR China.
| | - Yueyuan Li
- School of Chemical Engineering, Shandong University of Technology, Zibo, 255049, PR China
| | - Shanghua Liu
- School of Chemical Engineering, Shandong University of Technology, Zibo, 255049, PR China
| | - Zhanglei Wu
- School of Chemical Engineering, Shandong University of Technology, Zibo, 255049, PR China
| | - Hui Dong
- School of Chemical Engineering, Shandong University of Technology, Zibo, 255049, PR China
| | - Zhen Xu
- School of Chemical Engineering, Shandong University of Technology, Zibo, 255049, PR China
| | - Xinjin Li
- School of Chemical Engineering, Shandong University of Technology, Zibo, 255049, PR China
| | - Qing Liu
- School of Chemical Engineering, Shandong University of Technology, Zibo, 255049, PR China
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Serum midkine as non-invasive biomarker for detection and prognosis of non-small cell lung cancer. Sci Rep 2021; 11:14616. [PMID: 34272441 PMCID: PMC8285415 DOI: 10.1038/s41598-021-94272-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 07/07/2021] [Indexed: 11/09/2022] Open
Abstract
Lung cancer continues to be the leading cause for cancer-related deaths in men and women worldwide. Sufficient screening tools enabling early diagnosis are essential to improve patient outcomes. The aim of this study was to evaluate serum midkine (S-MK) both as a diagnostic and prognostic biomarker in non-small cell lung cancer (NSCLC). This single-center analysis included 59 NSCLC patients counting 30 squamous cell cancers and 29 adenocarcinomas. Preoperative S-MK concentration was determined using ELISA. Patients were followed up to five years. S-MK was found to be significantly overexpressed in patients with NSCLC compared to healthy controls (p < 0.001). The discriminative power of S-MK to differentiate NSCLC subjects from controls was fairly high with an area under the receiver operating characteristic curve of 0.83 (p < 0.001). Optimal sensitivity of 92% and reasonable specificity of 68% was reached at a threshold of 416 pg/ml S-MK. Patients with high S-MK concentration showed a significantly shorter overall survival compared to patients with low S-MK expression (p < 0.05). In conclusion, S-MK is overexpressed in patients with NSCLC and serves as an independent prognostic factor for overall survival. S-MK may thus be considered as an additional non-invasive biomarker not only for NSCLC screening but also for outcome prediction.
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Xu C, Liu W, Li L, Wang Y, Yuan Q. Serum tumour M2-pyruvate kinase as a biomarker for diagnosis and prognosis of early-stage non-small cell lung cancer. J Cell Mol Med 2021; 25:7335-7341. [PMID: 34255923 PMCID: PMC8335667 DOI: 10.1111/jcmm.16762] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Revised: 05/10/2021] [Accepted: 06/15/2021] [Indexed: 01/16/2023] Open
Abstract
Tumour M2-pyruvate kinase (TUM2-PK) is up-regulated in many human cancers. This study was to evaluate the clinical value of serum TUM2-PK in early-stage non-small cell lung cancer (NSCLC) patients. A total of 162 consecutive early-stage NSCLC patients were enrolled and followed up after tumour resection. Serum TUM2-PK level was detected by enzyme-linked immunosorbent assay (ELISA) in NSCLC patients, 50 benign pulmonary disease patients and 102 healthy controls. The TUM2-PK level in NSCLC patients was higher than that of healthy controls (P < .001) and benign pulmonary disease patients (P < .001). A threshold of 30 U/mL could be used to diagnose early-stage NSCLC with 71.6% sensitivity and 98.0% specificity. The 5-year overall survival rate in patients with high TUM2-PK level was lower than that of patients with low TUM2-PK level (P = .009). Multivariable Cox regression showed that high TUM2-PK level was an independent risk factor for overall survival (HR = 2.595, 95% CI: 1.231-5.474, P = .012). High serum TUM2-PK level could be a potential biomarker for diagnosis and prognosis of early-stage NSCLC patients.
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Affiliation(s)
- Chunhua Xu
- Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, China.,Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China
| | - Wei Liu
- Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, China.,Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China
| | - Li Li
- Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, China.,Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China
| | - Yuchao Wang
- Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, China.,Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China
| | - Qi Yuan
- Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, China.,Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China
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Analysis and interpretation of transcriptomic data obtained from extended Warburg effect genes in patients with clear cell renal cell carcinoma. Oncoscience 2015; 2:151-86. [PMID: 25859558 PMCID: PMC4381708 DOI: 10.18632/oncoscience.128] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2015] [Accepted: 02/17/2015] [Indexed: 12/22/2022] Open
Abstract
Background Many cancers adopt a metabolism that is characterized by the well-known Warburg effect (aerobic glycolysis). Recently, numerous attempts have been made to treat cancer by targeting one or more gene products involved in this pathway without notable success. This work outlines a transcriptomic approach to identify genes that are highly perturbed in clear cell renal cell carcinoma (CCRCC). Methods We developed a model of the extended Warburg effect and outlined the model using Cytoscape. Following this, gene expression fold changes (FCs) for tumor and adjacent normal tissue from patients with CCRCC (GSE6344) were mapped on to the network. Gene expression values with FCs of greater than two were considered as potential targets for treatment of CCRCC. Results The Cytoscape network includes glycolysis, gluconeogenesis, the pentose phosphate pathway (PPP), the TCA cycle, the serine/glycine pathway, and partial glutaminolysis and fatty acid synthesis pathways. Gene expression FCs for nine of the 10 CCRCC patients in the GSE6344 data set were consistent with a shift to aerobic glycolysis. Genes involved in glycolysis and the synthesis and transport of lactate were over-expressed, as was the gene that codes for the kinase that inhibits the conversion of pyruvate to acetyl-CoA. Interestingly, genes that code for unique proteins involved in gluconeogenesis were strongly under-expressed as was also the case for the serine/glycine pathway. These latter two results suggest that the role attributed to the M2 isoform of pyruvate kinase (PKM2), frequently the principal isoform of PK present in cancer: i.e. causing a buildup of glucose metabolites that are shunted into branch pathways for synthesis of key biomolecules, may not be operative in CCRCC. The fact that there was no increase in the expression FC of any gene in the PPP is consistent with this hypothesis. Literature protein data generally support the transcriptomic findings. Conclusions A number of key genes have been identified that could serve as valid targets for anti-cancer pharmaceutical agents. Genes that are highly over-expressed include ENO2, HK2, PFKP, SLC2A3, PDK1, and SLC16A1. Genes that are highly under-expressed include ALDOB, PKLR, PFKFB2, G6PC, PCK1, FBP1, PC, and SUCLG1.
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Qu S, Liu J, Luo J, Huang Y, Shi W, Wang B, Cai X. A rapid and highly sensitive portable chemiluminescent immunosensor of carcinoembryonic antigen based on immunomagnetic separation in human serum. Anal Chim Acta 2013; 766:94-9. [DOI: 10.1016/j.aca.2012.12.043] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2012] [Revised: 12/19/2012] [Accepted: 12/23/2012] [Indexed: 10/27/2022]
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Abstract
All forms of the neuropeptide gastrin-releasing peptide (GRP) are derived from the precursor proGRP1-125. Amidated GRP18-27, which together with amidated GRP1-27 was long thought to be the only biologically relevant product of the GRP gene, is involved in a multitude of physiological functions and acts as a mitogen, morphogen, and proangiogenic factor in certain cancers. Recently, GRP has been implicated in several psychiatric conditions, in the maintenance of circadian rhythm, in spinal transmission of the itch sensation, and in inflammation and wound repair. The actions of GRP are mediated by the GRP receptor. Over the last decade, nonamidated peptides derived from proGRP, such as the glycine-extended form GRP18-28 and recombinant and synthetic fragments from proGRP31-125, have been shown to be biologically active in a range of tissues and in cancer cell lines. While GRP18-28 acts via the GRP receptor, the identity of the receptor for proGRP31-125 and its fragments has not yet been established. Nonamidated fragments are also present in normal tissues and in various cancers. In fact, proGRP31-98 is the most sensitive serum biomarker in patients with small cell lung cancer and is a significant predictor of poor survival in patients with advanced prostate cancer.
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Affiliation(s)
- Joseph Ischia
- Department of Surgery, University of Melbourne, Austin Health, Melbourne, Victoria, Australia
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Congote LF. Monitoring insulin-like growth factors in HIV infection and AIDS. Clin Chim Acta 2005; 361:30-53. [PMID: 15970280 DOI: 10.1016/j.cccn.2005.05.001] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2005] [Revised: 05/05/2005] [Accepted: 05/06/2005] [Indexed: 01/09/2023]
Abstract
There is a close association between the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis, infection and immunity. Infection with the human immunodeficiency virus (HIV) is often associated with a decrease of the concentrations of IGF-I, IGF-II, IGF-binding protein 3 (IGFBP-3) and an increase of IGFBP-1 and -2. Many investigators have studied the relationship between the GH-IGF-I system and some of the most common characteristics of disease progression, such as decreased CD4 cell counts, weight loss and fat redistribution. Although conditions for restoration of thymic function and lymphopoiesis with GH or IGF-I are still not well defined, many studies led to the development of clinical trials on the therapeutic use of GH, IGF-I and GHRH for the treatment of weight loss or fat redistribution, two problems which persist despite the introduction of highly active antiretroviral therapy. Monitoring IGF-I concentrations during treatment with GH and GHRH is likely to become an essential component of their therapeutic use. IGF-I levels are the first indicator of treatment efficacy and can be used to monitor compliance. High levels of IGF-I are a warning sign for the increased risk of potential adverse effects, such as acromegalic-like symptoms or malignancy. This could lead to a reduction of the therapeutic dose or the temporary interruption of treatment until IGF levels reach a safe range. IGF-I levels are also likely to increase with other hormones used in HIV patients, such as erythropoietin for the treatment of anemia or anabolic androgens in HIV-infected women.
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Affiliation(s)
- Luis F Congote
- Endocrine Laboratory, Rm. L2.05, McGill University Health Centre, Montreal, Québec, Canada H3A 1A1.
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Zhang B, Chen JY, Chen DD, Wang GB, Shen P. Tumor type M2 pyruvate kinase expression in gastric cancer, colorectal cancer and controls. World J Gastroenterol 2004; 10:1643-6. [PMID: 15162541 PMCID: PMC4572770 DOI: 10.3748/wjg.v10.i11.1643] [Citation(s) in RCA: 54] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2003] [Revised: 10/04/2003] [Accepted: 10/07/2003] [Indexed: 12/15/2022] Open
Abstract
AIM Tumor formation is generally linked to an expansion of glycolytic phosphometabolite pools and aerobic glycolytic flux rates. To achieve this, tumor cells generally overexpress a special glycolytic isoenzyme, termed pyruvate kinase type M(2). The present study was designed to evaluate the use of a new tumor marker, tumor M(2)-PK, in discriminating gastrointestinal cancer patients from healthy controls, and to compare with the reference tumor markers CEA and CA72-4. METHODS The concentration of tumor M(2)-PK in body fluids could be quantitatively determined by a commercially available enzyme-linked immunosorbent assay (ELISA)-kit (ScheBo Tech, Giessen, Germany). By using this kit, the tumor M(2)-PK concentration was measured in EDTA-plasma of 108 patients. For the healthy blood donors a cut-off value of 15 U/mL was evaluated, which corresponded to 90% specificity. Overall 108 patients were included in this study, 54 patients had a histological confirmed gastric cancer, 54 patients colorectal cancer, and 20 healthy volunteers served as controls. RESULTS The cut-off value to discriminate patients from controls was established at 15 U/mL for tumor M(2)-PK. The mean tumor M(2)-PK concentration of gastric cancer was 26.937 U/mL. According to the TNM stage system, the mean tumor M(2)-PK concentration of stage I was 16.324 U/mL, of stage II 15.290 U/mL, of stage III 30.289 U/mL, of stage IV 127.31 U/mL, of non-metastasis 12.854 U/mL and of metastasis 35.711 U/mL. The mean Tumor M(2)-PK concentration of colorectal cancer was 30.588 U/mL. According to the Dukes stage system, the mean tumor M(2)-PK concentration of Dukes A was 16.638 U/mL, of Dukes B 22.070 U/mL, and of Dukes C 48.024 U/ml, of non-metastasis 19.501 U/mL, of metastasis 49.437 U/mL. The mean tumor M(2)-PK concentration allowed a significant discrimination of colorectal cancers (30.588 U/mL) from controls (10.965 U/mL) (P<0.01), and gastric cancer (26.937 U/mL) from controls (10.965 U/mL) (P<0.05). The overall sensitivity of tumor M(2)-PK for colorectal cancer was 68.52%, while that of CEA was 43.12%. In gastric cancer, tumor M(2)-PK showed a high sensitivity of 50.47%, while CA72-4 showed a sensitivity of 35.37%. CONCLUSION Tumor M(2)-PK has a higher sensitivity than markers CEA and CA72-4, and is a valuable tumor marker for the detection of gastrointestinal cancer.
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Affiliation(s)
- Bo Zhang
- Department of General Surgery, Affiliated Xiehe Hospital of Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
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