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Mohammed O, Gizaw ST, Degef M. Potential diagnostic, prognostic, and predictive biomarkers of gastric cancer. Health Sci Rep 2024; 7:e2261. [PMID: 39040881 PMCID: PMC11260885 DOI: 10.1002/hsr2.2261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 06/29/2024] [Accepted: 07/04/2024] [Indexed: 07/24/2024] Open
Abstract
Background Gastric cancer (GC), a malignant epithelial tumor, is the fourth leading cause of cancer-related death worldwide. Therapeutic strategies for GC, despite the biggest challenges, can significantly improve survival rates through early detection and effective screening methods. Aim To provide brief information on the necessity of multiple specific diagnostic, prognostic, and predictive markers for GC. Methods This review was conducted using a variety of search engines, including PubMed Central, Scopus, Web of Science, Google Scholar, and others. Results Some potential biomarkers that provide essential information include circulating tumor cells (CTCs), DNA methylation, claudin 18.2, fibroblast growth factor receptor 2 (FGFR2), long noncoding RNAs (lncRNAs), cell-free DNA (cfDNA), microRNAs, and serum pepsinogens. Conclusion Multiple tumor markers are essential for screening, tumor identification, staging, prognostic assessment, and monitoring recurrence after therapy due to the absence of a single tumor indicator for diagnosing, prognosticating, and predicting GC.
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Affiliation(s)
- Ousman Mohammed
- Department of Medical Laboratory SciencesCollege of Medicine and Health Sciences, Wollo UniversityDessieEthiopia
| | - Solomon Tebeje Gizaw
- Department of Medical BiochemistrySchool of Medicine, College of Health Sciences, AAUAddis AbabaEthiopia
| | - Maria Degef
- Department of Medical BiochemistrySchool of Medicine, College of Health Sciences, AAUAddis AbabaEthiopia
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2
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Marassi V, Giordani S, Placci A, Punzo A, Caliceti C, Zattoni A, Reschiglian P, Roda B, Roda A. Emerging Microfluidic Tools for Simultaneous Exosomes and Cargo Biosensing in Liquid Biopsy: New Integrated Miniaturized FFF-Assisted Approach for Colon Cancer Diagnosis. SENSORS (BASEL, SWITZERLAND) 2023; 23:9432. [PMID: 38067805 PMCID: PMC10708636 DOI: 10.3390/s23239432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Revised: 11/18/2023] [Accepted: 11/21/2023] [Indexed: 12/18/2023]
Abstract
The early-stage diagnosis of cancer is a crucial clinical need. The inadequacies of surgery tissue biopsy have prompted a transition to a less invasive profiling of molecular biomarkers from biofluids, known as liquid biopsy. Exosomes are phospholipid bilayer vesicles present in many biofluids with a biologically active cargo, being responsible for cell-to-cell communication in biological systems. An increase in their excretion and changes in their cargo are potential diagnostic biomarkers for an array of diseases, including cancer, and they constitute a promising analyte for liquid biopsy. The number of exosomes released, the morphological properties, the membrane composition, and their content are highly related to the physiological and pathological states. The main analytical challenge to establishing liquid biopsy in clinical practice is the development of biosensors able to detect intact exosomes concentration and simultaneously analyze specific membrane biomarkers and those contained in their cargo. Before analysis, exosomes also need to be isolated from biological fluids. Microfluidic systems can address several issues present in conventional methods (i.e., ultracentrifugation, size-exclusion chromatography, ultrafiltration, and immunoaffinity capture), which are time-consuming and require a relatively high amount of sample; in addition, they can be easily integrated with biosensing systems. A critical review of emerging microfluidic-based devices for integrated biosensing approaches and following the major analytical need for accurate diagnostics is presented here. The design of a new miniaturized biosensing system is also reported. A device based on hollow-fiber flow field-flow fractionation followed by luminescence-based immunoassay is applied to isolate intact exosomes and characterize their cargo as a proof of concept for colon cancer diagnosis.
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Affiliation(s)
- Valentina Marassi
- Department of Chemistry “G. Ciamician”, University of Bologna, 40126 Bologna, Italy; (V.M.); (S.G.); (A.P.); (A.Z.); (P.R.)
- National Institute of Biostructure and Biosystems (INBB), 00136 Rome, Italy; (A.P.); (C.C.)
- byFlow srl, 40129 Bologna, Italy
| | - Stefano Giordani
- Department of Chemistry “G. Ciamician”, University of Bologna, 40126 Bologna, Italy; (V.M.); (S.G.); (A.P.); (A.Z.); (P.R.)
| | - Anna Placci
- Department of Chemistry “G. Ciamician”, University of Bologna, 40126 Bologna, Italy; (V.M.); (S.G.); (A.P.); (A.Z.); (P.R.)
| | - Angela Punzo
- National Institute of Biostructure and Biosystems (INBB), 00136 Rome, Italy; (A.P.); (C.C.)
- Department of Biomedical and Neuromotor Sciences, University of Bologna, 40138 Bologna, Italy
| | - Cristiana Caliceti
- National Institute of Biostructure and Biosystems (INBB), 00136 Rome, Italy; (A.P.); (C.C.)
- Department of Biomedical and Neuromotor Sciences, University of Bologna, 40138 Bologna, Italy
- Interdepartmental Centre for Renewable Sources, Environment, Sea and Energy—CIRI FRAME, University of Bologna, 40131 Bologna, Italy
- Interdepartmental Centre for Industrial Agrofood Research—CIRI Agrofood, University of Bologna, 47521 Cesena, Italy
| | - Andrea Zattoni
- Department of Chemistry “G. Ciamician”, University of Bologna, 40126 Bologna, Italy; (V.M.); (S.G.); (A.P.); (A.Z.); (P.R.)
- National Institute of Biostructure and Biosystems (INBB), 00136 Rome, Italy; (A.P.); (C.C.)
- byFlow srl, 40129 Bologna, Italy
| | - Pierluigi Reschiglian
- Department of Chemistry “G. Ciamician”, University of Bologna, 40126 Bologna, Italy; (V.M.); (S.G.); (A.P.); (A.Z.); (P.R.)
- National Institute of Biostructure and Biosystems (INBB), 00136 Rome, Italy; (A.P.); (C.C.)
- byFlow srl, 40129 Bologna, Italy
| | - Barbara Roda
- Department of Chemistry “G. Ciamician”, University of Bologna, 40126 Bologna, Italy; (V.M.); (S.G.); (A.P.); (A.Z.); (P.R.)
- National Institute of Biostructure and Biosystems (INBB), 00136 Rome, Italy; (A.P.); (C.C.)
- byFlow srl, 40129 Bologna, Italy
| | - Aldo Roda
- Department of Chemistry “G. Ciamician”, University of Bologna, 40126 Bologna, Italy; (V.M.); (S.G.); (A.P.); (A.Z.); (P.R.)
- National Institute of Biostructure and Biosystems (INBB), 00136 Rome, Italy; (A.P.); (C.C.)
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Colorectal cancer-derived exosomes and modulation KRAS signaling. CLINICAL & TRANSLATIONAL ONCOLOGY : OFFICIAL PUBLICATION OF THE FEDERATION OF SPANISH ONCOLOGY SOCIETIES AND OF THE NATIONAL CANCER INSTITUTE OF MEXICO 2022; 24:2074-2080. [PMID: 35789981 DOI: 10.1007/s12094-022-02877-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Accepted: 06/13/2022] [Indexed: 10/17/2022]
Abstract
Colorectal cancer (CRC) is one of the most common cancers worldwide and one of the main causes of cancer-associated mortality. At the period of diagnosis, metastases to other tissues will be present in around 30% of CRC individuals. Individuals with CRC continue to have a poor prognosis despite advances in medication. There is a growing body of literature that CRC develops as a result of the aggregation of various mutations in tumor oncogenes or suppressor genes and that diagnosing cancer in its initial phases may assist in increasing the overall lifespan of individuals with the illness. On the other hand, tumor cells may discharge exosomes in response to oncogenic mutations. By Inhibiting signaling pathways, including the Kirsten rat sarcoma virus (KRAS) mechanism, which is important in a variety of cell activities, exosomes have been shown to cause colorectal cancer in animal studies. The purpose of this review was to summarize the latest discoveries on the modulation of KRAS signaling by exosomes extracted from colorectal cancer.
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Characterization of Extracellular vesicles isolated from different Liquid biopsies of uveal melanoma patients. J Circ Biomark 2022; 11:36-47. [PMID: 35784590 PMCID: PMC9238429 DOI: 10.33393/jcb.2022.2370] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 05/27/2022] [Indexed: 11/24/2022] Open
Abstract
Purpose: Uveal melanoma (UM) is the most common intraocular malignant tumor in adults. Extracellular vesicles (EVs) have been extensively studied as a biomarker to monitor disease in patients. The study of new biomarkers in melanoma patients could prevent metastasis by earlier diagnosis. In this study, we determined the proteomic profile of EVs isolated from aqueous humor (AH), vitreous humor (VH), and plasma from UM patients in comparison with cancer-free control patients. Methods: AH, VH and plasma were collected from seven patients with UM after enucleation; AH and plasma were collected from seven cancer-free patients with cataract (CAT; control group). EVs were isolated using the membrane-based affinity binding column method. Nanoparticle tracking analysis (NTA) was performed to determine the size and concentration of EVs. EV markers, CD63 and TSG101, were assessed by immunoblotting, and the EV proteome was characterized by mass spectrometry. Results: Mean EV concentration was higher in all analytes of UM patients compared to those in the CAT group. In the UM cohort, the mean concentration of EVs was significantly lower in AH and plasma than in VH. In contrast, the mean size and size distribution of EVs was invariably identical in all analyzed analytes and in both studied groups (UM vs. CAT). Mass spectrometry analyses from the different analytes from UM patients showed the presence of EV markers. Conclusion: EVs isolated from AH, VH, and plasma from patients with UM showed consistent profiles and support the use of blood to monitor UM patients as a noninvasive liquid biopsy.
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Yuksel B, Deveci Ozkan A, Aydın D, Betts Z. Evaluation of the antioxidative and genotoxic effects of sodium butyrate on breast cancer cells. Saudi J Biol Sci 2022; 29:1394-1401. [PMID: 35280546 PMCID: PMC8913555 DOI: 10.1016/j.sjbs.2021.12.061] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Revised: 12/23/2021] [Accepted: 12/28/2021] [Indexed: 02/06/2023] Open
Abstract
Oncogenic stimulation shows a rise in reactive oxygen species (ROS), and ROS can eventually induce carcinogenesis by causing DNA damage. In this context, this study aims to evaluate some biochemical and genotoxic changes in the control of cell death caused by NaBu (Sodium butyrate). treatment in breast cancer cells. NaBu’s impact on cell proliferation was determined via WST-1 assay. The lipid peroxidation (MDA), reduced glutathione (GSH), Nitric Oxide (NO), hydrogen peroxide (H2O2), and superoxide dismutase (SOD) enzyme levels were determined biochemically. NaBu-induced genotoxic damage was estimated via single-cell gel electrophoresis (SCGE). NaBu reduced cell viability and potentially induced GSH, but decreased SOD enzyme activity and the level of MDA and NO decreased also H2O2 decreased at different times and NaBu concentrations. Higher NaBu concentrations amplified DNA damage in MCF-7 cells compared to the control group. NaBu shows anticancer and genotoxic effects, especially through antioxidant enzymes, one of the oxidative stress parameters in breast cancer. However, the anticancer and genotoxic effects of NaBu is changed in the oxidative stress parameters with time and treatment concentration of NaBu in MCF-7 cells. Furthermore, his oxidative stress-dependent effect changes need to be clarified by further evaluation with molecular and more biochemical parameters.
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Manoochehri H, Asadi S, Tanzadehpanah H, Sheykhhasan M, Ghorbani M. CDC25A is strongly associated with colorectal cancer stem cells and poor clinical outcome of patients. GENE REPORTS 2021; 25:101415. [DOI: 10.1016/j.genrep.2021.101415] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Tieng FYF, Abu N, Nasir SN, Lee LH, Ab Mutalib NS. Liquid Biopsy-Based Colorectal Cancer Screening via Surface Markers of Circulating Tumor Cells. Diagnostics (Basel) 2021; 11:2136. [PMID: 34829483 PMCID: PMC8618170 DOI: 10.3390/diagnostics11112136] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 11/15/2021] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) is ranked second for cancer-related deaths worldwide with approximately half of the patients being diagnosed at the late stages. The untimely detection of CRC results in advancement to the metastatic stage and nearly 90% of cancer-related deaths. The early detection of CRC is crucial to decrease its overall incidence and mortality rates. The recent introduction of circulating tumor cells (CTCs) has enabled a less invasive sampling method from liquid biopsies, besides revealing key information toward CRC metastasis. The current gold standard for CTC identification is the CellSearch® system (Veridex). This first-generation instrumentation relies on a single cell surface marker (CSM) to capture and count CTCs. Detection of CTCs allows the identification of patients at risk for metastasis, whereas CTC enumeration could improve risk assessment, monitoring of systemic therapy, and detection of therapy resistance in advanced metastatic CRC. In this review, we compared the pros and cons between single CSM-based CTC enrichment techniques and multi-marker-based systems. We also highlighted the challenges faced in the routine implementation of CSM-dependent CTC detection methods in CRC screening, prediction, prognosis, disease monitoring, and therapy selection toward precision medicine, as well as the dwelling on post-CTC analysis and characterization methods.
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Affiliation(s)
- Francis Yew Fu Tieng
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (F.Y.F.T.); (N.A.); (S.N.N.)
| | - Nadiah Abu
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (F.Y.F.T.); (N.A.); (S.N.N.)
| | - Siti Nurmi Nasir
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (F.Y.F.T.); (N.A.); (S.N.N.)
| | - Learn-Han Lee
- Novel Bacteria and Drug Discovery Research Group, Microbiome and Bioresource Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University of Malaysia, Subang Jaya 47500, Selangor, Malaysia
| | - Nurul-Syakima Ab Mutalib
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (F.Y.F.T.); (N.A.); (S.N.N.)
- Novel Bacteria and Drug Discovery Research Group, Microbiome and Bioresource Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University of Malaysia, Subang Jaya 47500, Selangor, Malaysia
- Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia
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Bai SY, Li ML, Ren Y, Su XM. HDAC8-inhibitor PCI-34051-induced exosomes inhibit human bronchial smooth muscle cell proliferation via miR-381-3p mediated TGFB3. Pulm Pharmacol Ther 2021; 71:102096. [PMID: 34740750 DOI: 10.1016/j.pupt.2021.102096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 10/18/2021] [Accepted: 10/29/2021] [Indexed: 10/19/2022]
Abstract
The present study aimed to investigate the effects of PCI-34051-induced human bronchial epithelial cells (HBECs)-derived exosomes (PCI-Exo) on human bronchial smooth muscle cells (HBSMCs) and the key exosomal miRNAs involved in this process. Blank exosomes (Exo) and PCI-Exo were extracted from HBECs treated with PBS and PCI-34051, respectively. RNA-sequencing was performed to uncover the miRNA expression profile affected by PCI-Exo. The MTT, flow cytometry and TUNEL assays were performed to reveal the effect of PCI-34051 and PCI-Exo on the proliferation and apoptosis of HBSMCs. Western blotting and qRT-PCR were used for detecting protein and mRNA expression. A total of 25 exosomal miRNAs consisted of 17 down-regulated and eight up-regulated miRNAs were differentially expressed among PCI-Exo and Exo. Target genes of the exosomal miRNAs were mainly associated with signal transduction, cell adhesion, microRNAs in cancer, and ECM receptor interaction. miR-381-3p was identified as the most significant upregulated differential miRNA in PCI-Exo after qRT-PCR validation and could be transferred to HBSMCs by PCI-Exo. PCI-Exo treatment inhibited the proliferation but induced the apoptosis of HBSMCs. TGFβ3 was identified as a target gene of miR-381-3p which could directly bind to the 3'UTR of TGFβ3 mRNA. After transfecting the miR-381-3p mimic into HBSMCs, the proliferation inhibition and apoptosis rate of HBSMCs was significantly increased, and siTGFβ3 transfection showed similar effects. Moreover, miR-381-3p overexpression could not only decrease the expression of α-SMA, FN1 and collagen I but also increase that of E-cadherin in HBSMCs. Our findings suggested that PCI-Exo could hinder the proliferation and obviously induce the apoptosis of HBSMCs, and its mechanisms might partly be attributable to the reduction of TGFβ3 level by up-regulating exosomal miR-381-3p expression. These results may be vital for the treatment of lung related-diseases, especially asthma.
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Affiliation(s)
- Shi-Yao Bai
- Department of Pulmonary and Critical Care Medicine, Institute of Respiratory Diseases, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China
| | - Meng-Lu Li
- Department of Pulmonary and Critical Care Medicine, Institute of Respiratory Diseases, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China
| | - Yuan Ren
- Department of Pulmonary and Critical Care Medicine, Institute of Respiratory Diseases, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China
| | - Xin-Ming Su
- Department of Pulmonary and Critical Care Medicine, Institute of Respiratory Diseases, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
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Logozzi M, Mizzoni D, Di Raimo R, Giuliani A, Maggi M, Sciarra A, Fais S. Plasmatic Exosome Number and Size Distinguish Prostate Cancer Patients From Healthy Individuals: A Prospective Clinical Study. Front Oncol 2021; 11:727317. [PMID: 34745949 PMCID: PMC8564386 DOI: 10.3389/fonc.2021.727317] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Accepted: 09/28/2021] [Indexed: 12/12/2022] Open
Abstract
There is a urgent need for valuable strategy in early and less invasive diagnosis for cancer. Preliminary data have shown that the plasmatic levels of exosomes increase in cancer condition. This study investigates the relevance of plasmatic levels and size distribution of exosomes in 42 individuals with no signs of urological disease (CTR) as compared to 65 prostate cancer patients (PCa). It was used Nanoparticle Tracking Analysis (NTA), a highly reliable and sensitive method for exosomes characterization and quantification. The relation structure among the NTA-derived parameters was assessed by means of Principal Component Analysis, which allowed detecting the global discriminant power of NTA test in terms of Receiver Operating Characteristic (ROC) curve and the selection of cut-off thresholds. The results showed that PCa had significantly higher plasmatic levels of exosomes and that the exosomes were smaller in size as compared to the CTR; the values reached 89% sensitivity and 71% specificity, in distinguishing PCa from CTR. These results propose a new exosome-based non-invasive clinical approach for the clinical follow-up of prostate cancer undergoing surgical treatment; in addition this method may be developed as a new screening test for prostate cancer's early diagnosis. While this clinical study was performed in prostate cancer, it may represent a proof of concept extendable to virtually all cancers, as it is suggested by both pre-clinical evidence and clinical data obtained with different technical approaches.
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Affiliation(s)
- Mariantonia Logozzi
- Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
| | - Davide Mizzoni
- Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
| | - Rossella Di Raimo
- Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
| | - Alessandro Giuliani
- Environment and Health Department, Istituto Superiore di Sanità, Rome, Italy
| | - Martina Maggi
- Department of Urology, Policlinico Umberto I, Università La Sapienza, Rome, Italy
| | - Alessandro Sciarra
- Department of Urology, Policlinico Umberto I, Università La Sapienza, Rome, Italy
| | - Stefano Fais
- Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
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Qiu Z, Li Q, Lu Y, Wang Q. Clinical significance and prognostic value of circulating B10 cells in colorectal cancer. Asia Pac J Clin Oncol 2021; 18:e157-e162. [PMID: 34314570 DOI: 10.1111/ajco.13586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 02/14/2021] [Indexed: 12/01/2022]
Abstract
BACKGROUND B10 cells, a subset of regulatory B cells, can inhibit antitumor response and thus promote tumor development. This study explored the clinical meaning and prognostic value of circulating B10 cells in colorectal cancer (CRC). MATERIALS AND METHODS The proportion of B10 cells in peripheral blood in CRC patients and healthy controls was detected by multicolor flow cytometry. RESULTS The proportion of circulating B10 cells was remarkably elevated in CRC patients compared to normal controls (% of CD19+ B cells; 16.6% (IQR 6.0%) versus 9.0% (IQR 5.7%), p < 0.001). B10 cells proportion was associated with tumor size, depth of invasion, lymph node metastasis, and TNM stage in CRC. Kaplan-Meier analysis indicated that CRC patients with high B10 cells proportion suffered worse overall survival than those with low B10 cells proportion. Multivariate analysis revealed that the proportion of B10 cells was an independent prognostic indicator for CRC patients. CONCLUSION Our results indicate that the proportion of circulating B10 cells is an independent prognostic factor for patients with CRC and thus may help guide the clinical decision in CRC.
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Affiliation(s)
- Zhaoyan Qiu
- Department of General Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Qian Li
- Department of Engineering Physics, Tsinghua University, Beijing, China
| | - Yixun Lu
- Department of General Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Qian Wang
- Department of Anorectal Surgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou, China
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Bahrami A, Moradi Binabaj M, A Ferns G. Exosomes: Emerging modulators of signal transduction in colorectal cancer from molecular understanding to clinical application. Biomed Pharmacother 2021; 141:111882. [PMID: 34218003 DOI: 10.1016/j.biopha.2021.111882] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 06/10/2021] [Accepted: 06/28/2021] [Indexed: 12/15/2022] Open
Abstract
Exosomes are small cell derived membrane nano-vesicles that carry various components including lipids, proteins and nucleic acids. There is accumulating evidence that exosomes have a role in tumorigenesis, tumor invasiveness and metastasis. Furthermore, oncogene mutation may influence exosome release from tumor cells. Exosomes may induce colorectal cancer by altering signaling cascades such as the Wnt/β-catenin and KRAS pathways that are involved in cell proliferation, apoptosis, dissemination, angiogenesis, and drug resistance. The aim of this review was to overview recent findings evaluating the association between tumor cells-derived exosomes and their content in modulating signaling pathways in colorectal cancer.
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Affiliation(s)
- Afsane Bahrami
- Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran.
| | - Maryam Moradi Binabaj
- Non-Communicable Diseases Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran.
| | - Gordon A Ferns
- Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex BN1 9PH, UK
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12
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Li S, Yi M, Dong B, Tan X, Luo S, Wu K. The role of exosomes in liquid biopsy for cancer diagnosis and prognosis prediction. Int J Cancer 2021; 148:2640-2651. [PMID: 33180334 PMCID: PMC8049049 DOI: 10.1002/ijc.33386] [Citation(s) in RCA: 107] [Impact Index Per Article: 26.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 10/20/2020] [Accepted: 11/03/2020] [Indexed: 12/18/2022]
Abstract
Liquid biopsy is a revolutionary strategy in cancer diagnosis and prognosis prediction, which is used to analyze cancer cells or cancer-derived products through biofluids such as blood, urine and so on. Exosomes play a crucial role in mediating cell communication. A growing number of studies have reported that exosomes are involved in tumorigenesis, tumor growth, metastasis and drug resistance by delivering cargos including nucleic acids and protein. Thus, exosomes, as a new type of liquid biopsy, have the potential to be diagnostic or prognostic biomarkers. Herein, we elaborate on the current methods and introduce novel techniques for exosome isolation and characterization. Moreover, we elucidate the advantages of exosomes compared to other biological components in liquid biopsy and summarize the different exosomal biomarkers in cancer diagnosis and prognosis prediction.
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Affiliation(s)
- Shiyu Li
- Department of Oncology, Tongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Ming Yi
- Department of Oncology, Tongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Bing Dong
- Department of Medical OncologyThe Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalZhengzhouChina
| | - Ximin Tan
- Department of Oncology, Tongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Suxia Luo
- Department of Medical OncologyThe Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalZhengzhouChina
| | - Kongming Wu
- Department of Oncology, Tongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
- Department of Medical OncologyThe Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalZhengzhouChina
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13
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Mazouji O, Ouhajjou A, Incitti R, Mansour H. Updates on Clinical Use of Liquid Biopsy in Colorectal Cancer Screening, Diagnosis, Follow-Up, and Treatment Guidance. Front Cell Dev Biol 2021; 9:660924. [PMID: 34150757 PMCID: PMC8213391 DOI: 10.3389/fcell.2021.660924] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 03/30/2021] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common cancers worldwide, being the third most diagnosed in the world and the second deadliest. Solid biopsy provides an essential guide for the clinical management of patients with colorectal cancer; however, this method presents several limitations, in particular invasiveness, and cannot be used repeatedly. Recently, clinical research directed toward the use of liquid biopsy, as an alternative tool to solid biopsy, showed significant promise in several CRC clinical applications, as (1) detect CRC patients at early stage, (2) make treatment decision, (3) monitor treatment response, (4) predict relapses and metastases, (5) unravel tumor heterogeneity, and (6) detect minimal residual disease. The purpose of this short review is to describe the concept, the characteristics, the genetic components, and the technologies used in liquid biopsy in the context of the management of colorectal cancer, and finally we reviewed gene alterations, recently described in the literature, as promising potential biomarkers that may be specifically used in liquid biopsy tests.
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Affiliation(s)
- Omayma Mazouji
- GES-LCM2E, FPN, Mohamed First University, Oujda, Morocco
| | | | - Roberto Incitti
- Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia
| | - Hicham Mansour
- GES-LCM2E, FPN, Mohamed First University, Oujda, Morocco
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Yang X, Cai S, Shu Y, Deng X, Zhang Y, He N, Wan L, Chen X, Qu Y, Yu S. Exosomal miR-487a derived from m2 macrophage promotes the progression of gastric cancer. Cell Cycle 2021; 20:434-444. [PMID: 33522393 DOI: 10.1080/15384101.2021.1878326] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Tumor-associated macrophages contribute to cell growth, development, and metastasis in various cancers. However, the underlying mechanisms of M2 macrophage that modulate the progression of gastric cancer (GC) remain largely unknown. In this study, we detected the ratio of macrophages in GC tissues and found that the proportion of M2 macrophages was increased in GC tissues. We then co-cultured GC cells with M1 and M2 macrophages, respectively, and then assessed cell proliferation and tumorigenicity of GC cells by MTT and colony formation assay. The results indicated that M2 macrophages promoted the proliferation of GC cells, but M1 not. Besides, GW4869, an exosomes inhibitor, reduced the effects induced by M2 macrophage. Then, we isolated and identified exosomes derived from M1 and M2 macrophage, and confirmed that the exosomes could be taken up by GC cells. We demonstrated that M2 macrophage-exosomes could induce the proliferation and tumorigenesis in vitro and in vivo. Moreover, miR-487a was enriched in M2 macrophage-exosomes and further determined that miR-487a exert the functions by targeting TIA1. In conclusion, exosomal miR-487a derived from M2 macrophage promotes the proliferation and tumorigenesis in gastric cancer, and the novel findings might be helpful to the development of novel diagnostic and therapeutic methods in GC.
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Affiliation(s)
- Xuefeng Yang
- Department of Gastrointestinal Surgery, Affiliated Hospital of Zunyi Medical University , Zunyi, China.,Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zunyi Medical University , Zunyi, China
| | - Shuang Cai
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zunyi Medical University , Zunyi, China
| | - Yue Shu
- Key Laboratory of Brain Science, Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University , Zunyi, China
| | - Xun Deng
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zunyi Medical University , Zunyi, China
| | - Yuanwei Zhang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zunyi Medical University , Zunyi, China
| | - Nian He
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zunyi Medical University , Zunyi, China
| | - Lei Wan
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zunyi Medical University , Zunyi, China
| | - Xu Chen
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zunyi Medical University , Zunyi, China
| | - Yan Qu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zunyi Medical University , Zunyi, China
| | - Shouyang Yu
- Key Laboratory of Brain Science, Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University , Zunyi, China
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15
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Sharma A, Sharma KL, Bansal C, Kumar A. Updates on "Cancer Genomics and Epigenomics". World J Clin Oncol 2020; 11:890-897. [PMID: 33312884 PMCID: PMC7701914 DOI: 10.5306/wjco.v11.i11.890] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 07/03/2020] [Accepted: 08/01/2020] [Indexed: 02/06/2023] Open
Abstract
The field of "Cancer Genomics and Epigenomes" has been widely investigated for their involvement in cancer to understand the basic processes of different malignancies. The aggregation of genetic and epigenetic alterations also displays a wide range of heterogeneity making it quite necessary to develop personalized treatment strategies. The complex interplay between DNA methylation and chromatin dynamics in malignant cells is one of the major epigenetic mechanisms that lead to gene activation and repression. Hence, each tumor needs to be fully characterized to satisfy the ideas of personalized treatment strategies. The present article addresses various aspects of genome characterization methods and their potential role in the field of cancer genomics and epigenomics.
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Affiliation(s)
- Aarti Sharma
- Department of Surgical Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Kiran Lata Sharma
- Department of Pathology, Baylor College of Medicine, Houston, TX 77030, United States
| | - Cherry Bansal
- Department of Pathology, Era’s Medical College and Hospital, Lucknow 226003, India
| | - Ashok Kumar
- Department of Surgical Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
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Bahnassy AA, Abdel-Azim YA, Ezzat S, Abdellateif MS, Zekri ARN, Mohanad M, Salama A, Khaled H. The role of circulating tumor cells and K-ras mutations in patients with locally advanced rectal cancer: a prospective study. Mol Biol Rep 2020; 47:9645-9657. [PMID: 33174084 DOI: 10.1007/s11033-020-05973-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 11/03/2020] [Indexed: 12/24/2022]
Abstract
Rectal cancer is a common malignancy with a relatively poor prognosis. We assessed the possible prognostic and predictive role(s) of circulating tumor cells (CTCs) and K-ras mutations in locally advanced rectal carcinoma (LARC) patients. CTCs number and K-ras mutation status were assessed in the Peripheral blood and tumor tissue samples of 60 patients with LARC compared to control group (normal rectal mucosa). Data were correlated to relevant clinico-pathological features, response to treatment, disease free (DFS) and overall survival (OS) rates. K-ras mutations were present in 24/60 (40%) patients. Baseline CTCs (< 5 cells/7 ml blood) were detected in 23/60 (38.3%) patients, and 37 (61.7%) had baseline CTCs (≥ 5 cells/7 ml) blood (P = 0.071). Serial sampling showed a decrease in CTCs levels in 40 (66.7%) patients and increase in 20 (33.3%) patients (P = 0.01). Patients with K-ras mutations had a significantly poor response to treatment, with reduced DFS and OS rates (P = 0.001, 0.004, and 0.001; respectively). Similarly, decreased CTCs levels during treatment associated significantly with better pathological responses (P = 0.003). Multivariate analysis demonstrated that K-ras mutation and baseline CTCs are independent prognostic factors for DFS (P = 0.014 and 0.045; respectively) and OS (P = 0.002 and 0.045; respectively). The presence of mutant K-ras and baseline CTCs ≥ 5 cells associated significantly with poor pathological response, shorter DFS and OS rates compared to those with either K-ras mutation or CTCs ≥ 5 cells only (P = 0.014, 0.005 and 0.001, respectively). K-ras mutations, baseline and serial CTCs changes represent good prognostic and predictive factors for LARC patients.
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Affiliation(s)
- Abeer A Bahnassy
- Pathology Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt.
| | - Yasser A Abdel-Azim
- Department of Radiation Oncology, National Cancer Institute, Cairo University, Cairo, 11976, Egypt
| | - Somaya Ezzat
- Department of Radiation Oncology, National Cancer Institute, Cairo University, Cairo, 11976, Egypt
| | - Mona S Abdellateif
- Medical Biochemistry and Molecular Biology, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt
| | - Abdel-Rahman N Zekri
- Molecular Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt
| | - Marwa Mohanad
- Biochemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing, MISR University for Science and Technology, 6th October, 12945, Egypt
| | - Asmaa Salama
- Pathology Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt
| | - Hussein Khaled
- Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, 11976, Egypt
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17
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Vafaei S, Saeednejad Zanjani L, Habibi Shams Z, Naseri M, Fattahi F, Gheytanchi E, Alemrajabi M, Ebrahimi M, Madjd Z. Low expression of Talin1 is associated with advanced pathological features in colorectal cancer patients. Sci Rep 2020; 10:17786. [PMID: 33082414 PMCID: PMC7576823 DOI: 10.1038/s41598-020-74810-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 10/07/2020] [Indexed: 12/13/2022] Open
Abstract
To explore the proper prognostic markers for the likelihood of metastasis in CRC patients. Seventy-seven fresh CRC samples were collected to evaluate the mRNA level of the selected marker using Real-time PCR. Moreover, 648 formalin-fixed paraffin-embedded CRC tissues were gathered to evaluate protein expression by immunohistochemistry (IHC) on tissue microarrays. The results of Real-Time PCR showed that low expression of Talin1 was significantly associated with advanced TNM stage (p = 0.034) as well as gender (p = 0.029) in mRNA levels. Similarly, IHC results indicated that a low level of cytoplasmic expression of Talin1 was significantly associated with advanced TNM stage (p = 0.028) as well as gender (p = 0.009) in CRC patients. Moreover, decreased expression of cytoplasmic Talin1 protein was found to be a significant predictor of worse disease-specific survival (DSS) (p = 0.011) in the univariate analysis. In addition, a significant difference was achieved (p = 0.039) in 5-year survival rates of DSS: 65% for low, 72% for moderate, and 88% for high Talin1 protein expression. Observations showed that lower expression of Talin1 at both the gene and protein level may drive the disparity of CRC patients' outcomes via worse DSS and provide new insights into the development of progression indicators because of its correlation with increased tumor aggressiveness.
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Affiliation(s)
- Somayeh Vafaei
- Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Hemmat Street (Highway), Next To Milad Tower, Tehran, Iran
- Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
- Student Research Committee, Iran University of Medical Sciences, Tehran, Iran
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, 16635-148, Tehran, Iran
| | - Leili Saeednejad Zanjani
- Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Hemmat Street (Highway), Next To Milad Tower, Tehran, Iran
| | | | - Marzieh Naseri
- Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Hemmat Street (Highway), Next To Milad Tower, Tehran, Iran
- Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Fahimeh Fattahi
- Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Elmira Gheytanchi
- Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Hemmat Street (Highway), Next To Milad Tower, Tehran, Iran
| | - Mahdi Alemrajabi
- Firoozgar Clinical Research Development Center, Firoozgar Hospital (FCRDC), Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Marzieh Ebrahimi
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, 16635-148, Tehran, Iran.
| | - Zahra Madjd
- Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Hemmat Street (Highway), Next To Milad Tower, Tehran, Iran.
- Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
- Department of Pathology, Iran University of Medical Sciences, Tehran, Iran.
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18
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Exosomal miR-1246 and miR-155 as predictive and prognostic biomarkers for trastuzumab-based therapy resistance in HER2-positive breast cancer. Cancer Chemother Pharmacol 2020; 86:761-772. [PMID: 33068176 DOI: 10.1007/s00280-020-04168-z] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 10/06/2020] [Indexed: 12/21/2022]
Abstract
PURPOSE This study aimed to investigate the predictive and prognostic roles of circulating exosomal miRNAs in breast cancer treated with trastuzumab-based chemotherapy. METHODS Circulating exosomal miRNAs from trastuzumab-resistant (n = 4) and -sensitive (n = 4) patients were profiled using miRNA microarray. The predictive and prognostic roles of filtered miRNAs were validated in 107 early-stage and 68 metastatic patients treated with trastuzumab-based chemotherapy through receiver-operating characteristic (ROC) curve analysis, logistic regression and Cox proportional hazards regression analysis, and Kaplan-Meier survival analysis. RESULTS MiRNA microarray analysis revealed miR-1246 and miR-155 were the most up-regulated miRs in trastuzumab-resistant HER2-positive breast cancer patients, which were further validated in trastuzumab-resistant patient samples (n = 32) compared with trastuzumab sensitive ones (n = 36). MiR-1246 showed a ROC curve area of 0.750 with 78.1% sensitivity and 75% specificity in discriminating resistant from sensitive patients (p < 0.001), while miR-155 showed a ROC curve area of 0.877 with 68.8% sensitivity and 97.2% specificity (p < 0.001). Predictive factors and multivariate analysis showed that high levels of miR-1246 and miR-155 strongly predicted poor event-free survival (EFS) for early-stage patients, and poor progression-free survival (PFS) for metastatic patients. However, both miRNAs were revealed not to be associated with overall survival (OS). In addition, Kaplan-Meier survival analysis demonstrated that early-stage and metastatic patients with high expression of miR-1246 and miR-155 had poorer EFS or PFS, respectively, than those with decreased expression of both miRs. CONCLUSIONS This study demonstrated the valuable roles of circulating exosomal miR-1246 and miR-155 in distinguishing trastuzumab resistant from sensitive patients.
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Logozzi M, Mizzoni D, Di Raimo R, Fais S. Exosomes: A Source for New and Old Biomarkers in Cancer. Cancers (Basel) 2020; 12:E2566. [PMID: 32916840 PMCID: PMC7565506 DOI: 10.3390/cancers12092566] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 09/04/2020] [Accepted: 09/07/2020] [Indexed: 02/06/2023] Open
Abstract
Clinical oncology needs reliable tumor biomarkers to allow a follow-up of tumor patients who do not necessarily need invasive approaches. To date, the existing biomarkers are not sufficiently reliable, and many of them have generated more problems than facilitating the commitment of clinical oncologists. Over the last decades, a broad family of extracellular vesicles, with size ranging between micro to nano, has been raised as a new hope for potential sources of new tumor biomarkers. However, while knowledge in the field is increasing, we do not currently have definitive information allowing a clinical use of extracellular vesicles in cancer clinics. Recent evidence provides new perspective in clinical oncology, based on data showing that circulating nanovesicles called exosomes may represent a valuable source of tumor biomarkers. In this review, we discuss the existing clinical data supporting a key role of exosomes as a source of tumor biomarkers, including proteins and miRNAs, but also discuss the importance of the expression of known tumor biomarkers when expressed on exosomes.
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Affiliation(s)
| | | | | | - Stefano Fais
- Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy; (M.L.); (D.M.); (R.D.R.)
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20
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Quinchia J, Echeverri D, Cruz-Pacheco AF, Maldonado ME, Orozco J. Electrochemical Biosensors for Determination of Colorectal Tumor Biomarkers. MICROMACHINES 2020; 11:E411. [PMID: 32295170 PMCID: PMC7231317 DOI: 10.3390/mi11040411] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 03/13/2020] [Accepted: 03/17/2020] [Indexed: 12/15/2022]
Abstract
The accurate determination of specific tumor markers associated with cancer with non-invasive or minimally invasive procedures is the most promising approach to improve the long-term survival of cancer patients and fight against the high incidence and mortality of this disease. Quantification of biomarkers at different stages of the disease can lead to an appropriate and instantaneous therapeutic action. In this context, the determination of biomarkers by electrochemical biosensors is at the forefront of cancer diagnosis research because of their unique features such as their versatility, fast response, accurate quantification, and amenability for multiplexing and miniaturization. In this review, after briefly discussing the relevant aspects and current challenges in the determination of colorectal tumor markers, it will critically summarize the development of electrochemical biosensors to date to this aim, highlighting the enormous potential of these devices to be incorporated into the clinical practice. Finally, it will focus on the remaining challenges and opportunities to bring electrochemical biosensors to the point-of-care testing.
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Affiliation(s)
- Jennifer Quinchia
- Max Planck Tandem Group in Nanobioengineering, University of Antioquia, Complejo Ruta N, Calle 67 No. 52-20, Medellín 050010, Colombia; (J.Q.); (D.E.); (A.F.C.-P.)
| | - Danilo Echeverri
- Max Planck Tandem Group in Nanobioengineering, University of Antioquia, Complejo Ruta N, Calle 67 No. 52-20, Medellín 050010, Colombia; (J.Q.); (D.E.); (A.F.C.-P.)
| | - Andrés Felipe Cruz-Pacheco
- Max Planck Tandem Group in Nanobioengineering, University of Antioquia, Complejo Ruta N, Calle 67 No. 52-20, Medellín 050010, Colombia; (J.Q.); (D.E.); (A.F.C.-P.)
| | - María Elena Maldonado
- Grupo Impacto de los Componentes Alimentarios en la Salud, School of Dietetics and Human Nutrition, University of Antioquia, A.A. 1226, Medellín 050010, Colombia;
| | - Jahir Orozco
- Max Planck Tandem Group in Nanobioengineering, University of Antioquia, Complejo Ruta N, Calle 67 No. 52-20, Medellín 050010, Colombia; (J.Q.); (D.E.); (A.F.C.-P.)
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