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1
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Singh P, Chaturvedi R, Somvanshi P. Network-Based Integrative Analysis to Identify Key Genes and Corresponding Reporter Biomolecules for Triple-Negative Breast Cancer. Cancer Med 2025; 14:e70674. [PMID: 40287845 PMCID: PMC12034156 DOI: 10.1002/cam4.70674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 01/23/2025] [Accepted: 01/29/2025] [Indexed: 04/29/2025] Open
Abstract
BACKGROUND The malignant neoplasm of the TNBC is the leading cause of death among Indian women. Recent studies identified the global burden of TNBC affecting approximately more than 40 percent of all BC cases in women worldwide. The absence of expression of receptors such as ER, PR, and HER2 characterizes TNBC. OBJECTIVES Due to the lack of specific targets, standard treatment options for TNBC are limited. This integrative study aims to identify key genes and provide insights into the underlying molecular mechanisms of TNBC, which can potentially lead to the development of more effective therapeutic strategies. MATERIAL AND METHODOLOGY This study integrates PPI and WGCNA analysis of TNBC-related datasets (GSE52194 and GSE58135) to identify key genes. Subsequently, downstream analysis is conducted to explore potential therapeutic targets for TNBC. RESULTS The present study renders the potential 13 key genes (PLCG2, CXCL10, CDK1, STAT1, IL6, PLK1, CCNB1, AURKA, NDC80, EGFR, 1L1B, FN1, BUB1B), along with their associated 6 TFs and 20 miRNAs, as reporter biomolecules around which the most significant changes occur. There were some miRNAs hsa-mir-449b-5p, hsa-let-7b-5p, hsa-mir-26a-5p, hsa-mir-155-5p, hsa-mir-24-3p, hsa-mir-212-3p, hsa-mir-21-5p, hsa-mir-210-3p and hsa-mir-20a-5p whose association with other cancers and other BC subtypes have been reported but their association with TNBC need to be explored. Further, enrichment and cumulative survival analysis support the disease association of identified key genes with TNBC. CONCLUSION This integrative analysis could be regarded for experimental inspection as it provides the platform for future researchers in drug designing and biomarker discovery for TNBC diagnosis and treatment.
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Affiliation(s)
- Pooja Singh
- School of Computational & Sciences (SCIS)Jawaharlal Nehru UniversityNew DelhiIndia
| | - Rupesh Chaturvedi
- School of Biotechnology (SBT)Jawaharlal Nehru UniversityNew DelhiIndia
| | - Pallavi Somvanshi
- School of Computational & Sciences (SCIS)Jawaharlal Nehru UniversityNew DelhiIndia
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2
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Ożga K, Stepuch P, Maciejewski R, Sadok I. Promising Gastric Cancer Biomarkers-Focus on Tryptophan Metabolism via the Kynurenine Pathway. Int J Mol Sci 2025; 26:3706. [PMID: 40332338 PMCID: PMC12027761 DOI: 10.3390/ijms26083706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 04/08/2025] [Accepted: 04/10/2025] [Indexed: 05/08/2025] Open
Abstract
Currently, gastric cancer treatment remains an enormous challenge and requires a multidisciplinary approach. Globally, the incidence and prevalence of gastric cancer vary, with the highest rates found in East Asia, Central Europe, and Eastern Europe. Early diagnosis is critical for successful surgical removal of gastric cancer, but the disease often develops asymptomatically. Therefore, many cases are diagnosed at an advanced stage, resulting in poor survival. Metastatic gastric cancer also has a poor prognosis. Therefore, it is urgent to identify reliable molecular disease markers and develop an effective medical treatment for advanced stages of the disease. This review summarizes potential prognostic or predictive markers of gastric cancer. Furthermore, the role of tryptophan metabolites from the kynurenine pathway as prognostic, predictive, and diagnostic factors of gastric cancer is discussed, as this metabolic pathway is associated with tumor immune resistance.
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Affiliation(s)
- Kinga Ożga
- Department of Biomedicine and Environmental Research, Institute of Biological Sciences, Faculty of Medicine, Collegium Medicum, The John Paul II Catholic University of Lublin, Konstantynów 1J, 20-708 Lublin, Poland;
| | - Paweł Stepuch
- II Department of Oncological Surgery with Subdivision of Minimal Invasive Surgery, Center of Oncology of the Lublin Region St. Jana z Dukli, Jaczewskiego 7, 20-090 Lublin, Poland;
| | - Ryszard Maciejewski
- Faculty of Medicine, Collegium Medicum, The John Paul II Catholic University of Lublin, Konstantynów 1H, 20-708 Lublin, Poland;
| | - Ilona Sadok
- Department of Biomedical and Analytical Chemistry, Institute of Biological Sciences, Faculty of Medicine, Collegium Medicum, The John Paul II Catholic University of Lublin, Konstantynów 1J, 20-708 Lublin, Poland
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Khalili-Tanha G, Radisky ES, Radisky DC, Shoari A. Matrix metalloproteinase-driven epithelial-mesenchymal transition: implications in health and disease. J Transl Med 2025; 23:436. [PMID: 40217300 PMCID: PMC11992850 DOI: 10.1186/s12967-025-06447-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2025] [Accepted: 03/30/2025] [Indexed: 04/14/2025] Open
Abstract
Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells, defined by apical-basal polarity and tight intercellular junctions, acquire migratory and invasive properties characteristic of mesenchymal cells. Under normal conditions, EMT directs essential morphogenetic events in embryogenesis and supports tissue repair. When dysregulated, EMT contributes to pathological processes such as organ fibrosis, chronic inflammation, and cancer progression and metastasis. Matrix metalloproteinases (MMPs)-a family of zinc-dependent proteases that degrade structural components of the extracellular matrix-sit at the nexus of this transition by dismantling basement membranes, activating pro-EMT signaling pathways, and cleaving adhesion molecules. When normally regulated, MMPs promote balanced ECM turnover and support the cyclical remodeling necessary for proper development, wound healing, and tissue homeostasis. When abnormally regulated, MMPs drive excessive ECM turnover, thereby promoting EMT-related pathologies, including tumor progression and fibrotic disease. This review provides an integrated overview of the molecular mechanisms by which MMPs both initiate and sustain EMT under physiological and disease conditions. It discusses how MMPs can potentiate EMT through TGF-β and Wnt/β-catenin signaling, disrupt cell-cell junction proteins, and potentiate the action of hypoxia-inducible factors in the tumor microenvironment. It discusses how these pathologic processes remodel tissues during fibrosis, and fuel cancer cell invasion, metastasis, and resistance to therapy. Finally, the review explores emerging therapeutic strategies that selectively target MMPs and EMT, ranging from CRISPR/Cas-mediated interventions to engineered tissue inhibitors of metalloproteinases (TIMPs), and demonstrates how such approaches may suppress pathological EMT without compromising its indispensable roles in normal biology.
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Affiliation(s)
- Ghazaleh Khalili-Tanha
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Evette S Radisky
- Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, USA
| | - Derek C Radisky
- Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, USA
| | - Alireza Shoari
- Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, USA.
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Alshajrawi OM, Tengku Din TADAATD, Marzuki SSB, Maulidiani M, Mohd Rusli NARB, Badrol Hisham NFAB, Hui Ying L, Yahya MMB, Wan Azman WNB, Ramli RA, Wan Abdul Rahman WF. Exploring the complex relationship between metabolomics and breast cancer early detection (Review). Mol Clin Oncol 2025; 22:35. [PMID: 40083862 PMCID: PMC11905217 DOI: 10.3892/mco.2025.2830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Accepted: 10/08/2024] [Indexed: 03/16/2025] Open
Abstract
An overview of metabolomics in cancer research, focusing on the identification of biomarkers, pharmacological targets and therapeutic agents, is provided in the present review. The fundamentals of metabolomics, the role of metabolites in cancer emergence and the methods used in metabolomic analysis, are reviewed. The applications of metabolomics in cancer therapy and diagnostics, as well as the challenges encountered in metabolomic research, are discussed. Finally, the potential clinical uses of metabolomics in cancer research and its future possibilities are explored, emphasising the importance of non-invasive diagnostic and monitoring techniques. The present review highlights the significance of metabolite-based metabolomics as a specialised tool for illuminating disease processes and identifying treatment potentials. The malfunctioning of metabolomic pathways and metabolite accumulation or depletion is caused by metabolomics abnormalities. Metabolite signatures close to a subject's phenotypic informative dimension can be used to monitor therapies and disease prediction diagnosis and prognosis. Non-invasive diagnostic and monitoring techniques with high specificity and selectivity are urgently needed. Metabolite-based metabolomics is a specialised metabolic biomarker and pathway-analysis technique, illuminating the putative processes of numerous human illnesses and determining treatment potentials. Locating biochemical pathway modifications that are early warning signs of pathological malfunction and illness is possible by identifying functional biomarkers linked to phenotypic variance. Scientists generated numerous metabolomics profiles to disclose the underlying processes and metabolomics networks for therapeutic target research in biomedicine. The metabolomic analysis of the potential utility of metabolites as biomarkers for clinical events is summarised in the present review. The significance of metabolite-based metabolomics as a specialised tool for illuminating disease processes and identifying treatment potentials is highlighted.
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Affiliation(s)
- Omar Mahmoud Alshajrawi
- Department of Chemical Pathology, School of Medical Science, Health Campus, University Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia
| | | | - Shahira Sofea Binti Marzuki
- Department of Chemical Pathology, School of Medical Science, Health Campus, University Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia
| | - Maulidiani Maulidiani
- Faculty of Science and Marine Environment, University Malaysia Terengganu, Kuala Nerus, Terengganu 21030, Malaysia
| | | | | | - Lim Hui Ying
- Faculty of Science and Marine Environment, University Malaysia Terengganu, Kuala Nerus, Terengganu 21030, Malaysia
| | - Maya Mazuwin Binti Yahya
- Department of Surgery, School of Medical Science, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia
| | - Wan Norlina Binti Wan Azman
- Department of Chemical Pathology, School of Medical Science, Health Campus, University Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia
- Hospital University Sains Malaysia, Health Campus, University Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia
| | - Ras A. Ramli
- Faculty of Medicine, University Sultan Zainal Abidin, Kuala Terengganu, Terengganu 20400, Malaysia
| | - Wan Faiziah Wan Abdul Rahman
- Department of Pathology, School of Medical Science, Health Campus, University Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia
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Sheng J, Wang J, Ma T, He P. Relationship Between MIC-1, VEGF, and TGF-β1 and Clinicopathologic Stage and Lymph Node Metastasis in Gastric Cancer. Int J Gen Med 2025; 18:955-965. [PMID: 40007699 PMCID: PMC11853773 DOI: 10.2147/ijgm.s497572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 01/24/2025] [Indexed: 02/27/2025] Open
Abstract
Objective This research investigated the relationship between serum macrophage inhibitory cytokine-1 (MIC-1), vascular endothelial growth factor (VEGF), and transforming growth factor-β1 (TGF-β1) levels and clinicopathologic features, lymph node metastasis (LNM), and prognosis of gastric cancer (GC) patients. Methods The GC group (GC patients, 198 cases)) and healthy group (healthy people, 100 cases) were established. The relationship between serum MIC-1, VEGF, TGF-β1, and clinical and pathological features in GC patients was analyzed. GC patients were divided into a metastasis group (77 patients) and a non-metastasis group (121 patients) based on whether they had LNM. The factors influencing LNM in GC patients were identified. The predictive value of serum MIC-1, VEGF, and TGF-β1 for LNM in GC patients and the relationship between serum MIC-1, VEGF, TGF-β1 levels and prognosis were analyzed. Results MIC-1, VEGF, and TGF-β1 were higher in GC. Serum MIC-1, VEGF, and TGF-β1 levels were higher in GC patients with tumor diameter ≥ 3 cm, T stage of T3 and T4, low/moderate differentiation, and LNM. Multivariate Logistic regression analysis showed that TNM stage, tumor differentiation, and serum MIC-1, VEGF, and TGF-β1 levels were risk factors for LNM in GC patients. The ROC results indicated that the combination of serum MIC-1, VEGF, and TGF-β1 had the highest AUC for predicting LNM in GV patients. The median survival time of patients with low serum MIC-1, VEGF, and TGF-β1 was higher than that of patients with high serum MIC-1, VEGF, and TGF-β1 (26.13 months vs 19.24 months, 27.06 months vs 20.18 months, and 24.20 months vs 20.08 months). Conclusion The changes of serum MIC-1, VEGF and TGF-β1 levels are related to the clinicopathological characteristics of GC patients, and the elevated levels of these indices are independent risk factors affecting LNM and prognosis of GC patients.
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Affiliation(s)
- Jianyun Sheng
- General Surgery Department, The First People’s Hospital of Pingdingshan, Pingdingshan, Henan Province, 467000, People’s Republic of China
| | - Jieshi Wang
- General Surgery Department, The First People’s Hospital of Pingdingshan, Pingdingshan, Henan Province, 467000, People’s Republic of China
| | - Tengda Ma
- General Surgery Department, The First People’s Hospital of Pingdingshan, Pingdingshan, Henan Province, 467000, People’s Republic of China
| | - Peina He
- Pingdingshan University, Pingdingshan, Henan Province, 467000, People’s Republic of China
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Yousef Almulhim M. The efficacy of novel biomarkers for the early detection and management of acute kidney injury: A systematic review. PLoS One 2025; 20:e0311755. [PMID: 39879206 DOI: 10.1371/journal.pone.0311755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Accepted: 09/24/2024] [Indexed: 01/31/2025] Open
Abstract
Acute kidney injury (AKI) is a frequent clinical complication lacking early diagnostic tests and effective treatments. Novel biomarkers have shown promise for enabling earlier detection, risk stratification, and guiding management of AKI. We conducted a systematic review to synthesize evidence on the efficacy of novel biomarkers for AKI detection and management. Database searches yielded 17 relevant studies which were critically appraised. Key themes were biomarker efficacy in predicting AKI risk and severity before functional changes; potential to improve clinical management through earlier diagnosis, prognostic enrichment, and guiding interventions; emerging roles as therapeutic targets and prognostic tools; and ongoing challenges requiring further validation. Overall, novel biomarkers like neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cell cycle arrest markers ([TIMP-2] •[IGFBP7]) demonstrate capability for very early AKI prediction and accurate risk stratification. Their incorporation has potential to facilitate timely targeted interventions and personalized management. However, factors influencing biomarker performance, optimal cutoffs, cost-effectiveness, and impact on patient outcomes require robust validation across diverse settings before widespread implementation. Addressing these limitations through ongoing research can help translate novel biomarkers into improved detection, prognosis, and management of AKI in clinical practice.
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El Fil S, Uwishema O, Rizwan Ahmed A, Ratnani T, Rupani A, Mshaymesh S. Immunotherapy in gastrointestinal cancers: current strategies and future directions - a literature review. Ann Med Surg (Lond) 2025; 87:151-160. [PMID: 40109582 PMCID: PMC11918700 DOI: 10.1097/ms9.0000000000002757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 11/05/2024] [Indexed: 03/22/2025] Open
Abstract
Introduction The National Cancer Institute defines the disease of "cancer" as a group of disorders in which aberrant cells proliferate uncontrollably and have the potential to infiltrate neighboring tissues. It is well established that cancer remains a significant etiology contributing to worldwide mortality. Gastrointestinal (GI) neoplasms are a type of cancer that affects the digestive system and adds to the total cancer burden. Conventionally, several therapies have been employed, such as radiation and chemotherapy; nevertheless, their adverse effects have prompted the need for an improved therapeutic alternative. Immunotherapy thus became a notable medium of treatment for several malignancies, including tumors of the GI tract. Aim This comprehensive review seeks to provide insight on future directions and prospective therapies under development, as well as information regarding the present strategies utilized to mitigate one of the primary forms of cancer, GI cancer. Methods A detailed analysis of the existing literature on GI cancers has been conducted. Several databases were employed to gather this information, mainly PubMed/MEDLINE. Different aspects of the disease were considered when searching the databases to provide a comprehensive review of the current and future strategies being incorporated to mitigate the negative consequences of this disease. Results Many strategies are being used currently, and some are still under development. These comprise the usage of immune checkpoint inhibitors (ICIs), cytokine therapy, cancer vaccines, oncolytic viruses, and adoptive cell therapy. For instance, various monoclonal antibodies have been developed to inhibit the immunomodulatory effects of programmed death-1 and programmed death-1 ligand. There are also results of several clinical trials showing significant benefits and many changes are introduced to make the best of these strategies and minimize the challenges to group sizes. These challenges include overcoming the tumor's immunosuppressive environment, finding suitable predictive biomarkers, and reducing the adverse effects. Additionally, several novel immunotherapeutic approaches, such as chimeric antigen receptor T-cell (CAR-T) therapy, are being studied. In 2017, the US FDA approved the use of two CAR-T therapies, which marks a major milestone following extensive research and clinical trials. New approaches such as toll-like receptor-directed and helminth-based immunotherapies are being developed for the treatment of GI cancers as well. These therapies, along with targeted treatments, represent the future of immunotherapy in GI cancers. Conclusion Immunotherapy plays a significant role in the different types of GI cancers. However, optimizing these treatments will require overcoming barriers such as immune resistance, minimizing side effects, and improving the selection of patients through biomarkers. Continued research into these novel therapies and the mechanisms of immune modulation will be key to maximizing the therapeutic benefits of immunotherapy in the future.
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Affiliation(s)
- Serene El Fil
- Department of Research and Education, Oli Health Magazine Organization, Research and Education, Kigali, Rwanda
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon
| | - Olivier Uwishema
- Department of Research and Education, Oli Health Magazine Organization, Research and Education, Kigali, Rwanda
| | - Aisha Rizwan Ahmed
- Department of Research and Education, Oli Health Magazine Organization, Research and Education, Kigali, Rwanda
- Jinnah Medical and Dental College, Karachi, Pakistan
| | - Tanya Ratnani
- Department of Research and Education, Oli Health Magazine Organization, Research and Education, Kigali, Rwanda
- Chhattisgarh Institute of Medical Sciences, Bilaspur, India
| | - Ameen Rupani
- Department of Research and Education, Oli Health Magazine Organization, Research and Education, Kigali, Rwanda
- International Higher School of Medicine, Bishkek, Kyrgyzstan
| | - Sarah Mshaymesh
- Department of Research and Education, Oli Health Magazine Organization, Research and Education, Kigali, Rwanda
- Division of Natural Sciences, Faculty of Sciences, Haigazian University, Beirut, Lebanon
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Ge A, Chan C, Yang X. Exploring the Dark Matter of Human Proteome: The Emerging Role of Non-Canonical Open Reading Frame (ncORF) in Cancer Diagnosis, Biology, and Therapy. Cancers (Basel) 2024; 16:2660. [PMID: 39123386 PMCID: PMC11311765 DOI: 10.3390/cancers16152660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 07/21/2024] [Accepted: 07/24/2024] [Indexed: 08/12/2024] Open
Abstract
Cancer develops from abnormal cell growth in the body, causing significant mortalities every year. To date, potent therapeutic approaches have been developed to eradicate tumor cells, but intolerable toxicity and drug resistance can occur in treated patients, limiting the efficiency of existing treatment strategies. Therefore, searching for novel genes critical for cancer progression and therapeutic response is urgently needed for successful cancer therapy. Recent advances in bioinformatics and proteomic techniques have allowed the identification of a novel category of peptides encoded by non-canonical open reading frames (ncORFs) from historically non-coding genomic regions. Surprisingly, many ncORFs express functional microproteins that play a vital role in human cancers. In this review, we provide a comprehensive description of different ncORF types with coding capacity and technological methods in discovering ncORFs among human genomes. We also summarize the carcinogenic role of ncORFs such as pTINCR and HOXB-AS3 in regulating hallmarks of cancer, as well as the roles of ncORFs such as HOXB-AS3 and CIP2A-BP in cancer diagnosis and prognosis. We also discuss how ncORFs such as AKT-174aa and DDUP are involved in anti-cancer drug response and the underestimated potential of ncORFs as therapeutic targets.
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Affiliation(s)
| | | | - Xiaolong Yang
- Department of Pathology and Molecular Medicine, Queen’s University, Kingston, ON K7L 3N6, Canada; (A.G.); (C.C.)
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Jama M, Tabana Y, Barakat KH. Targeting cytotoxic lymphocyte antigen 4 (CTLA-4) in breast cancer. Eur J Med Res 2024; 29:353. [PMID: 38956700 PMCID: PMC11218087 DOI: 10.1186/s40001-024-01901-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 05/23/2024] [Indexed: 07/04/2024] Open
Abstract
Breast cancer (BC) has a high mortality rate and is one of the most common malignancies in the world. Initially, BC was considered non-immunogenic, but a paradigm shift occurred with the discovery of tumor-infiltrating lymphocytes (TILs) and regulatory T cells (Tregs) in the BC tumor microenvironment. CTLA-4 (Cytotoxic T-lymphocyte-associated protein 4) immunotherapy has emerged as a treatment option for BC, but it has limitations, including suboptimal antitumor effects and toxicity. Research has demonstrated that anti-CTLA-4 combination therapies, such as Treg depletion, cancer vaccines, and modulation of the gut microbiome, are significantly more effective than CTLA-4 monoclonal antibody (mAB) monotherapy. Second-generation CTLA-4 antibodies are currently being developed to mitigate immune-related adverse events (irAEs) and augment antitumor efficacy. This review examines anti-CTLA-4 mAB in BC, both as monotherapy and in combination with other treatments, and sheds light on ongoing clinical trials, novel CTLA-4 therapeutic strategies, and potential utility of biomarkers in BC.
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Affiliation(s)
- Maryam Jama
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada
| | - Yasser Tabana
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada
- Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
| | - Khaled H Barakat
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
- Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Canada.
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Mastronikolis NS, Kyrodimos E, Piperigkou Z, Spyropoulou D, Delides A, Giotakis E, Alexopoulou M, Bakalis NA, Karamanos NK. Matrix-based molecular mechanisms, targeting and diagnostics in oral squamous cell carcinoma. IUBMB Life 2024; 76:368-382. [PMID: 38168122 DOI: 10.1002/iub.2803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 11/22/2023] [Indexed: 01/05/2024]
Abstract
Oral squamous cell carcinoma (OSCC) is a head and neck cancer (HNC) with a high mortality rate. OSCC is developed in the oral cavity and it is triggered by many etiologic factors and can metastasize both regionally and distantly. Recent research advances in OSCC improved our understanding on the molecular mechanisms involved in and the initiation of OSCC metastasis. The key roles of the extracellular matrix (ECM) in OSCC are an emerging area of intensive research as the ECM macromolecular network is actively involved in events that regulate cellular morphological and functional properties, transcription and cell signaling mechanisms in invasion and metastasis. The provisional matrix that is formed by cancer cells is profoundly different in composition and functions as compared with the matrix of normal tissue. Fibroblasts are mainly responsible for matrix production and remodeling, but in cancer, the tumor matrix in the tumor microenvironment (TME) also originates from cancer cells. Even though extensive research has been conducted on the role of ECM in regulating cancer pathogenesis, its role in modulating OSCC is less elucidated since there are several issues yet to be fully understood. This critical review is focused on recent research as to present and discuss on the involvement of ECM macromolecular effectors (i.e., proteoglycans, integrins, matrix metalloproteinases) in OSCC development and progression.
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Affiliation(s)
- Nicholas S Mastronikolis
- Department of Otorhinolaryngology - Head and Neck Surgery, School of Medicine, University of Patras, Patras, Greece
| | - Efthymios Kyrodimos
- 1st Otolaryngology Department, School of Medicine, National & Kapodistrian University of Athens, 'Ippokrateion' General Hospital, Athens, Greece
| | - Zoi Piperigkou
- Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece
- Foundation for Research and Technology - Hellas (FORTH)/Institute of Chemical Engineering Sciences (ICE-HT), Patras, Greece
| | - Despoina Spyropoulou
- Department of Radiation Oncology, School of Medicine, University of Patras, Patras, Greece
| | - Alexander Delides
- 2nd Otolaryngology Department, School of Medicine, National & Kapodistrian University of Athens, 'Attikon' University Hospital, Athens, Greece
| | - Evangelos Giotakis
- 1st Otolaryngology Department, School of Medicine, National & Kapodistrian University of Athens, 'Ippokrateion' General Hospital, Athens, Greece
- Department of Radiation Oncology, School of Medicine, University of Patras, Patras, Greece
- 2nd Otolaryngology Department, School of Medicine, National & Kapodistrian University of Athens, 'Attikon' University Hospital, Athens, Greece
| | - Miranda Alexopoulou
- Department of Maxillofacial Surgery, University Hospital of Patras, Patras, Greece
| | - Nick A Bakalis
- Department of Nursing, University of Patras, Patras, Greece
| | - Nikos K Karamanos
- Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece
- Foundation for Research and Technology - Hellas (FORTH)/Institute of Chemical Engineering Sciences (ICE-HT), Patras, Greece
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Mehrab Mohseni M, Zamani H, Momeni M, Shirvani-Farsani Z. An update on the molecular mechanisms of ZFAS1 as a prognostic, diagnostic, or therapeutic biomarker in cancers. Discov Oncol 2024; 15:219. [PMID: 38856786 PMCID: PMC11164845 DOI: 10.1007/s12672-024-01078-x] [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: 01/05/2024] [Accepted: 06/04/2024] [Indexed: 06/11/2024] Open
Abstract
Zinc finger antisense 1 (ZFAS1), a newly discovered long noncoding RNA, is expressed in various tissues and organs and has been introduced an oncogenic gene in human malignancies. In various cancers, ZFAS1 regulates apoptosis, cell proliferation, the cell cycle, migration, translation, rRNA processing, and spliceosomal snRNP assembly; targets signaling cascades; and interacts with transcription factors via binding to key proteins and miRNAs, with conflicting findings on its effect on these processes. ZFAS1 is elevated in different types of cancer, like colorectal, colon, osteosarcoma, and gastric cancer. Considering the ZFAS1 expression pattern, it also has the potential to be a diagnostic or prognostic marker in various cancers. The current review discusses the mode of action of ZFAS1 in various human cancers and its regulation function related to chemoresistance comprehensively, as well as the potential role of ZFAS1 as an effective and noninvasive cancer-specific biomarker in tumor diagnosis, prognosis, and treatment. We expected that the current review could fill the current scientific gaps in the ZFAS1-related cancer causative mechanisms and improve available biomarkers.
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Affiliation(s)
- Mahdieh Mehrab Mohseni
- Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, IR, Iran
| | - Hedyeh Zamani
- Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, IR, Iran
| | - Mina Momeni
- Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, IR, Iran
| | - Zeinab Shirvani-Farsani
- Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, IR, Iran.
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Sieminska J, Miniewska K, Mroz R, Sierko E, Naumnik W, Kisluk J, Michalska-Falkowska A, Reszec J, Kozlowski M, Nowicki L, Moniuszko M, Kretowski A, Niklinski J, Ciborowski M, Godzien J. First insight about the ability of specific glycerophospholipids to discriminate non-small cell lung cancer subtypes. Front Mol Biosci 2024; 11:1379631. [PMID: 38725870 PMCID: PMC11079276 DOI: 10.3389/fmolb.2024.1379631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 04/05/2024] [Indexed: 05/12/2024] Open
Abstract
Introduction: Discrimination between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) subtypes in non-small cell lung cancer (NSCLC) patients is a significant challenge in oncology. Lipidomics analysis provides a promising approach for this differentiation. Methods: In an accompanying paper, we explored oxPCs levels in a cohort of 200 NSCLC patients. In this research, we utilized liquid chromatography coupled with mass spectrometry (LC-MS) to analyze the lipidomics profile of matching tissue and plasma samples from 25 NSCLC patients, comprising 11 ADC and 14 SCC cases. This study builds upon our previous findings, which highlighted the elevation of oxidised phosphatidylcholines (oxPCs) in NSCLC patients. Results: We identified eight lipid biomarkers that effectively differentiate between ADC and SCC subtypes using an untargeted approach. Notably, we observed a significant increase in plasma LPA 20:4, LPA 18:1, and LPA 18:2 levels in the ADC group compared to the SCC group. Conversely, tumour PC 16:0/18:2, PC 16:0/4:0; CHO, and plasma PC 16:0/18:2; OH, PC 18:0/20:4; OH, PC 16:0/20:4; OOH levels were significantly higher in the ADC group. Discussion: Our study is the first to report that plasma LPA levels can distinguish between ADC and SCC patients in NSCLC, suggesting a potential role for LPAs in NSCLC subtyping. This finding warrants further investigation into the mechanisms underlying these differences and their clinical implications.
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Affiliation(s)
- Julia Sieminska
- Metabolomics Laboratory, Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
| | - Katarzyna Miniewska
- Metabolomics Laboratory, Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
| | - Robert Mroz
- 2nd Department of Lung Diseases and Tuberculosis, Medical University of Bialystok, Bialystok, Poland
| | - Ewa Sierko
- Department of Oncology, Medical University of Bialystok, Bialystok, Poland
| | - Wojciech Naumnik
- 1st Department of Lung Diseases and Tuberculosis, Medical University of Bialystok, Bialystok, Poland
| | - Joanna Kisluk
- Department of Clinical Molecular Biology, Medical University of Bialystok, Bialystok, Poland
| | | | - Joanna Reszec
- Department of Medical Patomorphology, Medical University of Bialystok, Bialystok, Poland
| | - Miroslaw Kozlowski
- Department of Thoracic Surgery, Medical University of Bialystok, Bialystok, Poland
| | | | - Marcin Moniuszko
- Department of Allergology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
- Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland
| | - Adam Kretowski
- Metabolomics Laboratory, Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
- Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
| | - Jacek Niklinski
- Department of Clinical Molecular Biology, Medical University of Bialystok, Bialystok, Poland
| | - Michal Ciborowski
- Metabolomics Laboratory, Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
| | - Joanna Godzien
- Metabolomics Laboratory, Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
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Maulana AF, Maksum IP, Sriwidodo S, Rukayadi Y. Proposed molecular mechanism of non-competitive inhibition using molecular dynamics simulations between α-glucosidase enzyme and mangostin compound as antidiabetic. J Mol Model 2024; 30:136. [PMID: 38634946 DOI: 10.1007/s00894-024-05934-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 04/09/2024] [Indexed: 04/19/2024]
Abstract
CONTEXT Further understanding of the molecular mechanisms is necessary since it is important for designing new drugs. This study aimed to understand the molecular mechanisms involved in the design of drugs that are inhibitors of the α-glucosidase enzyme. This research aims to gain further understanding of the molecular mechanisms underlying antidiabetic drug design. The molecular docking process yielded 4 compounds with the best affinity energy, including γ-Mangostin, 1,6-dimethyl-ester-3-isomangostin, 1,3,6-trimethyl-ester-α-mangostin, and 3,6,7-trimethyl-ester-γ-mangostin. Free energy calculation with molecular mechanics with generalized born and surface area solvation indicated that the 3,6,7-trimethyl-γ-mangostin had a better free energy value compared to acarbose and simulated maltose together with 3,6,7-trimethyl-γ-mangostin compound. Based on the analysis of electrostatic, van der Waals, and intermolecular hydrogen interactions, 3,6,7-trimethyl-γ-mangostin adopts a noncompetitive inhibition mechanism, whereas acarbose adopts a competitive inhibition mechanism. Consequently, 3,6,7-trimethyl-ester-γ-mangostin, which is a derivative of γ-mangostin, can provide better activity in silico with molecular docking approaches and molecular dynamics simulations. METHOD This research commenced with retrieving protein structures from the RCSB database, generating the formation of ligands using the ChemDraw Professional software, conducting molecular docking with the Autodock Vina software, and performing molecular dynamics simulations using the Amber software, along with the evaluation of RMSD values and intermolecular hydrogen bonds. Free energy, electrostatic interactions, and Van der Waals interaction were calculated using MM/GBSA. Acarbose, used as a positive control, and maltose are simulated together with test compound that has the best free energy. The forcefields used for molecular dynamics simulations are ff19SB, gaff2, and tip3p.
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Affiliation(s)
- Ahmad Fariz Maulana
- Department of Chemistry, Faculty of Mathematics and Natural Sciences, Padjadjaran University, Jatinangor, Sumedang, 45363, Indonesia
| | - Iman Permana Maksum
- Department of Chemistry, Faculty of Mathematics and Natural Sciences, Padjadjaran University, Jatinangor, Sumedang, 45363, Indonesia.
| | - Sriwidodo Sriwidodo
- Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Padjadjaran University, Jatinangor, Sumedang, 45363, Indonesia
| | - Yaya Rukayadi
- Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia
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Zhang Z, Huang J, Li Y, Yan H, Xie J, Wang J, Zhao B. Global burden, risk factors, clinicopathological characteristics, molecular biomarkers and outcomes of microsatellite instability-high gastric cancer. Aging (Albany NY) 2024; 16:948-963. [PMID: 38224334 PMCID: PMC10817383 DOI: 10.18632/aging.205431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 12/06/2023] [Indexed: 01/16/2024]
Abstract
Microsatellite instability-high (MSI-H) has gained considerable interests since it was approved as a tumor-agnostic biomarker in immunotherapy. However, the reported characteristics of MSI-H gastric cancer (GC) are inconsistent due to the biological complexity. Here, we aim to clarify the prevalence, risk factors, clinicopathological/molecular features and outcomes of MSI-H GC though a comprehensive review on 43246 patients from 134 cohorts. Overall, the proportion of MSI-H GC was 14.5% (95% CI, 13.3%-15.8%). Patients with MSI-H GC were less likely to have Epstein-Barr virus infection. High incidences of MSI-H GC were associated with female, older age, lower gastric body, Lauren intestinal histology, WHO tubular and mucinous subtypes, and early disease stage. Additionally, patients with MSI-H GC harbored more KRAS mutation, PD-L1 positivity, CD8 overexpression, and higher TMB, but less HER2 positivity and TP53 mutation. When treated with conventional strategy, the 5-year survival rates in MSI-H patients (70.3%) and MSI-L/MSS patients (43.7%) were significantly different (p<0.001). Patients with MSI-H GC derived larger benefit from immunotherapy in term of overall survival (pInteraction<0.001) and objective response (pInteraction=0.02). Since the prevalence of MSI-H GC is relatively high and associated with distinct clinicopathological and molecular characteristics, MSI testing should be conducted during standard diagnostical activity. Moreover, giving MSI-H tumors are often diagnosed at early stage and have favorable outcomes, less aggressive treatment strategies may be considered in clinical practice. In summary, this panoramic review may assist in design and/or interpretation of clinical trials, provide references in drug development, and constitute complementary information in drafting the clinical practice guideline.
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Affiliation(s)
- Zhishan Zhang
- Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou 362000, China
| | - Jinyuan Huang
- Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou 362000, China
- The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325000, China
| | - Yingying Li
- Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou 362000, China
- The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325000, China
| | - Huimeng Yan
- Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou 362000, China
- The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325000, China
| | - Junxing Xie
- Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou 362000, China
| | - Jing Wang
- Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou 362000, China
| | - Bin Zhao
- Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou 362000, China
- The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325000, China
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Gajula SNR, Khairnar AS, Jock P, Kumari N, Pratima K, Munjal V, Kalan P, Sonti R. LC-MS/MS: A sensitive and selective analytical technique to detect COVID-19 protein biomarkers in the early disease stage. Expert Rev Proteomics 2023; 20:5-18. [PMID: 36919634 DOI: 10.1080/14789450.2023.2191845] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
Abstract
INTRODUCTION The COVID-19 outbreak has put enormous pressure on the scientific community to detect infection rapidly, identify the status of disease severity, and provide an immediate vaccine/drug for the treatment. Relying on immunoassay and a real-time reverse transcription polymerase chain reaction (rRT-PCR) led to many false-negative and false-positive reports. Therefore, detecting biomarkers is an alternative and reliable approach for determining the infection, its severity, and disease progression. Recent advances in liquid chromatography and mass spectrometry (LC-MS/MS) enable the protein biomarkers even at low concentrations, thus facilitating clinicians to monitor the treatment in hospitals. AREAS COVERED This review highlights the role of LC-MS/MS in identifying protein biomarkers and discusses the clinically significant protein biomarkers such as Serum amyloid A, Interleukin-6, C-Reactive Protein, Lactate dehydrogenase, D-dimer, cardiac troponin, ferritin, Alanine transaminase, Aspartate transaminase, gelsolin and galectin-3-binding protein in COVID-19, and their analysis by LC-MS/MS in the early stage. EXPERT OPINION Clinical doctors monitor significant biomarkers to understand, stratify, and treat patients according to disease severity. Knowledge of clinically significant COVID-19 protein biomarkers is critical not only for COVID-19 caused by the coronavirus but also to prepare us for future pandemics of other diseases in detecting by LC-MS/MS at the early stages.
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Affiliation(s)
- Siva Nageswara Rao Gajula
- Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Balanagar, India
| | - Ankita Sahebrao Khairnar
- Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Balanagar, India
| | - Pallavi Jock
- Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Balanagar, India
| | - Nikita Kumari
- Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Balanagar, India
| | - Kendre Pratima
- Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Balanagar, India
| | - Vijay Munjal
- Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Balanagar, India
| | - Pavan Kalan
- Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Balanagar, India
| | - Rajesh Sonti
- Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Balanagar, India
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Bodaghi A, Fattahi N, Ramazani A. Biomarkers: Promising and valuable tools towards diagnosis, prognosis and treatment of Covid-19 and other diseases. Heliyon 2023; 9:e13323. [PMID: 36744065 PMCID: PMC9884646 DOI: 10.1016/j.heliyon.2023.e13323] [Citation(s) in RCA: 81] [Impact Index Per Article: 40.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 01/21/2023] [Accepted: 01/26/2023] [Indexed: 01/31/2023] Open
Abstract
The use of biomarkers as early warning systems in the evaluation of disease risk has increased markedly in the last decade. Biomarkers are indicators of typical biological processes, pathogenic processes, or pharmacological reactions to therapy. The application and identification of biomarkers in the medical and clinical fields have an enormous impact on society. In this review, we discuss the history, various definitions, classifications, characteristics, and discovery of biomarkers. Furthermore, the potential application of biomarkers in the diagnosis, prognosis, and treatment of various diseases over the last decade are reviewed. The present review aims to inspire readers to explore new avenues in biomarker research and development.
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Affiliation(s)
- Ali Bodaghi
- Department of Chemistry, Tuyserkan Branch, Islamic Azad University, Tuyserkan, Iran
| | - Nadia Fattahi
- Department of Chemistry, University of Zanjan, Zanjan, 45371-38791, Iran,Trita Nanomedicine Research and Technology Development Center (TNRTC), Zanjan Health Technology Park, 45156-13191, Zanjan, Iran
| | - Ali Ramazani
- Department of Chemistry, University of Zanjan, Zanjan, 45371-38791, Iran,Department of Biotechnology, Research Institute of Modern Biological Techniques (RIMBT), University of Zanjan, Zanjan, 45371-38791, Iran,Corresponding author. Department of Chemistry, University of Zanjan, Zanjan, 45371-38791, Iran.;
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17
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Sobolewska-Włodarczyk A, Walecka-Kapica E, Włodarczyk M, Gąsiorowska A. Nutritional Status Indicators as a Predictor of Achieving Remission at Week 14 during Vedolizumab Therapy in Patients with Ulcerative Colitis: A Pilot Study. Nutrients 2023; 15:nu15010240. [PMID: 36615897 PMCID: PMC9824159 DOI: 10.3390/nu15010240] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 12/21/2022] [Accepted: 12/23/2022] [Indexed: 01/04/2023] Open
Abstract
Background: The loss of response or failure to achieve remission to vedolizumab in ulcerative colitis (UC) patients is currently a major clinical problem. Recently, Nutritional Risk Index (NRI), Controlling Nutritional Status (CONUT), and Malnutrition Universal Screening Tool (MUST) have been suggested as a new prognostic factor of UC activity. Here, we aimed at confirmation of hypotezis that NRI, CONUT and MUST may be used as inexpensive and efficient predictive biomarkers of response in UC patients treated with vedolizumab. Methods: This study was conducted in retrospective manner in 32 adult patients with UC of Caucasian origin (21 men and 11 women), who were qualified for 52-week therapy with vedolizumab and finished the 14-weeks from January 2020 to March 2022. Our study analyzed the 45 courses of vedolizumab therapy. Nutritional status indicators, i.e., the NRI, CONUT and MUST of each UC patient, were marked at the time of qualifying for biological treatment. Results: In our study, the MUST score was significantly lower in UC patients who positively achieved clinical remission at week 14 during vedolizumab induction therapy (0.33 ± 0.49 vs. 1.37 ± 0.83; p = 0.002). The analysis showed the lower baseline NRI and CONUT scores in patients with positive clinical remission at week 14 (NRI: 96.42 ± 4.29 vs. 101.41 ± 7.09; p = 0.024; CONUT: 1.00 ± 1.08 vs. 2.16 ± 1.46; p = 0.031). Conclusions: Nutritional status indicators (NRI, MUST and CONUT) may become valuable predictor of achieving remission at week 14 during vedolizumab therapy in UC patients.
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Affiliation(s)
| | - Ewa Walecka-Kapica
- Department of Gastroenterology, Medical University of Lodz, Pomorska Str. 251, 90-213 Lodz, Poland
| | - Marcin Włodarczyk
- Department of General and Oncological Surgery, Medical University of Lodz, Pomorska Str. 251, 90-213 Lodz, Poland
| | - Anita Gąsiorowska
- Department of Gastroenterology, Medical University of Lodz, Pomorska Str. 251, 90-213 Lodz, Poland
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Usman M, Beilerli A, Sufianov A, Kudryashov V, Ilyasova T, Balaev P, Danilov A, Lu H, Gareev I. Investigations into the impact of non-coding RNA on the sensitivity of gastric cancer to radiotherapy. Front Physiol 2023; 14:1149821. [PMID: 36909247 PMCID: PMC9998927 DOI: 10.3389/fphys.2023.1149821] [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: 01/23/2023] [Accepted: 02/16/2023] [Indexed: 02/26/2023] Open
Abstract
Non-coding RNAs (ncRNAs) are a newly discovered functional RNA different from messenger RNA, which can participate in regulating the occurrence and development of tumors. More and more research results show that ncRNAs can participate in the regulation of gastric cancer (GC) radiotherapy response, and its mechanism may be related to its effect on DNA damage repair, gastric cancer cell stemness, cell apoptosis, activation of epidermal growth factor receptor signaling pathway, etc. This article summarizes the relevant mechanisms of ncRNAs regulating the response to radiotherapy in gastric cancer, which will be directly important for the introduction of ncRNAs particularly microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) into clinical medicine as biomarkers and therapeutic targets.
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Affiliation(s)
- Muhammad Usman
- Department of Medical Imaging, Central Hospital Affiliated to Chongqing University of Technology, Chongqing, China
| | - Aferin Beilerli
- Department of Obstetrics and Gynecology, Tyumen State Medical University, Tyumen, Russia
| | - Albert Sufianov
- Department of Neurosurgery, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.,Department of Internal Diseases, Bashkir State Medical University, Ufa, Russia
| | - Valentin Kudryashov
- Gastric Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Tatiana Ilyasova
- Department of Internal Diseases, Bashkir State Medical University, Ufa, Russia
| | - Pavel Balaev
- Department of Oncology and Radiology, Ural State Medical University, Yekaterinburg, Russia
| | - Andrei Danilov
- Department of Clinical Pharmacology, Smolensk State Medical University, Smolensk, Russia
| | - Hong Lu
- Department of Medical Imaging, Central Hospital Affiliated to Chongqing University of Technology, Chongqing, China
| | - Ilgiz Gareev
- Educational and Scientific Institute of Neurosurgery, Рeoples' Friendship University of Russia (RUDN University), Moscow, Russia
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In Silico Study of Mangostin Compounds and Its Derivatives as Inhibitors of α-Glucosidase Enzymes for Anti-Diabetic Studies. BIOLOGY 2022; 11:biology11121837. [PMID: 36552346 PMCID: PMC9775444 DOI: 10.3390/biology11121837] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 12/02/2022] [Accepted: 12/12/2022] [Indexed: 12/24/2022]
Abstract
Diabetes is a chronic disease with a high mortality rate worldwide and can cause other diseases such as kidney damage, narrowing of blood vessels, and heart disease. The concomitant use of drugs such as metformin, sulfonylurea, miglitol, and acarbose may cause side effects with long-term administration. Therefore, natural ingredients are the best choice, considering that their long-term side effects are not significant. One of the compounds that can be used as a candidate antidiabetic is mangostin; however, information on the molecular mechanism needs to be further analyzed through molecular docking, simulating molecular dynamics, and testing the in silico antidiabetic potential. This study focused on modeling the protein structure, molecular docking, and molecular dynamics simulations and analyses. This process produces RMSD values, free energies, and intermolecular hydrogen bonding. Based on the analysis results, all molecular dynamics simulations can occur under physiological conditions, and γ-mangostin is the best among the test compounds.
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Liao T, Lu Y, Li W, Wang K, Zhang Y, Luo Z, Ju Y, Ouyang M. Construction and validation of a glycolysis-related lncRNA signature for prognosis prediction in Stomach Adenocarcinoma. Front Genet 2022; 13:794621. [PMID: 36313430 PMCID: PMC9614251 DOI: 10.3389/fgene.2022.794621] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 09/20/2022] [Indexed: 01/12/2024] Open
Abstract
Background: Glycolysis is closely related to the occurrence and progression of gastric cancer (GC). Currently, there is no systematic study on using the glycolysis-related long non-coding RNA (lncRNA) as a model for predicting the survival time in patients with GC. Therefore, it was essential to develop a signature for predicting the survival based on glycolysis-related lncRNA in patients with GC. Materials and methods: LncRNA expression profiles, containing 375 stomach adenocarcinoma (STAD) samples, were obtained from The Cancer Genome Atlas (TCGA) database. The co-expression network of lncRNA and glycolysis-related genes was used to identify the glycolysis-related lncRNAs. The Kaplan-Meier survival analysis and univariate Cox regression analysis were used to detect the glycolysis-related lncRNA with prognostic significance. Then, Bayesian Lasso-logistic and multivariate Cox regression analyses were performed to screen the glycolysis-related lncRNA with independent prognostic significance and to develop the risk model. Patients were assigned into the low- and high-risk cohorts according to their risk scores. A nomogram model was constructed based on clinical information and risk scores. Gene Set Enrichment Analysis (GSEA) was performed to visualize the functional and pathway enrichment analyses of the glycolysis-related lncRNA. Finally, the robustness of the results obtained was verified in an internal validation data set. Results: Seven glycolysis-related lncRNAs (AL353804.1, AC010719.1, TNFRSF10A-AS1, AC005586.1, AL355574.1, AC009948.1, and AL161785.1) were obtained to construct a risk model for prognosis prediction in the STAD patients using Lasso regression and multivariate Cox regression analyses. The risk score was identified as an independent prognostic factor for the patients with STAD [HR = 1.315, 95% CI (1.056-1.130), p < 0.001] via multivariate Cox regression analysis. Receiver operating characteristic (ROC) curves were drawn and the area under curve (AUC) values of 1-, 3-, and 5-year overall survival (OS) were calculated to be 0.691, 0.717, and 0.723 respectively. Similar results were obtained in the validation data set. In addition, seven glycolysis-related lncRNAs were significantly enriched in the classical tumor processes and pathways including cell adhesion, positive regulation of vascular endothelial growth factor, leukocyte transendothelial migration, and JAK_STAT signaling pathway. Conclusion: The prognostic prediction model constructed using seven glycolysis-related lncRNA could be used to predict the prognosis in patients with STAD, which might help clinicians in the clinical treatment for STAD.
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Affiliation(s)
- Tianyou Liao
- Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde Foshan), Foshan, Guangdong, China
| | - Yan Lu
- Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde Foshan), Foshan, Guangdong, China
| | - Wangji Li
- Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde Foshan), Foshan, Guangdong, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Kang Wang
- Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde Foshan), Foshan, Guangdong, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Yanxiang Zhang
- Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde Foshan), Foshan, Guangdong, China
| | - Zhentao Luo
- Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde Foshan), Foshan, Guangdong, China
| | - Yongle Ju
- Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde Foshan), Foshan, Guangdong, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Manzhao Ouyang
- Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde Foshan), Foshan, Guangdong, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
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Prevalence of Epstein-Barr Virus Infection and Mismatch Repair Protein Deficiency and the Correlation of Immune Markers in Tibetan Patients with Gastric Cancer. BIOMED RESEARCH INTERNATIONAL 2022; 2022:2684065. [PMID: 35734348 PMCID: PMC9208987 DOI: 10.1155/2022/2684065] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 05/13/2022] [Accepted: 05/24/2022] [Indexed: 11/23/2022]
Abstract
Background Gastric cancer (GC) is a major cause of cancer-related death in China. Immunotherapies based on PD-1/PD-L1 inhibitors have improved the survival of some patients with GC. Epstein–Barr virus (EBV) infection, mismatch repair (MMR) deficiency, and tumor immune microenvironment (TIME) markers (such as CD3, CD8, and PD-L1) may help to identify specific patients who will respond to PD-1/PD-L1 inhibitors. Considering racial heterogeneity, the pattern of TIME markers in Tibetan patients with GC is still unclear. We aimed to identify the prevalence of EBV infection and the MMR status and their association with immune markers in Tibetan GC to aid in patient selection for immunotherapy. Materials and Methods From 2001 to 2015, we retrospectively collected 120 tissue samples from consecutive Tibetan GC patients and constructed tissue microarrays. EBV infection was assessed by Epstein–Barr-encoded RNA (EBER) in situ hybridization, and MMR protein levels were measured. Immune markers (including CD3 and CD8) in intraepithelial, stromal, and total areas were detected by immunohistochemistry (IHC). PD-L1 expression was assessed by the combined positive score (CPS). We also analyzed the relationships of EBV infection and MMR status with immune markers. Results Of the 120 samples, 11 (9.17%) were EBV positive (+), and 6 (5%) were MMR deficient (dMMR). PD-L1 CPS ≥1% was found in 32.5% (39/120) of Tibetan GC patients. EBV infection was associated with higher numbers of CD3+ T cells (P < 0.05) and CD8+ T cells (P < 0.05) and higher PD-L1 expression (P < 0.05). For the limited number of dMMR patients, no significant relationship was observed between dMMR and TIME markers (P > 0.05). Conclusions In Tibetan GC patients, the rates of EBV infection, dMMR, and positive PD-L1 expression were 9.17%, 5%, and 32.5%, respectively. EBV infection was associated with the numbers of CD3+ T cells and CD8+ T cells and PD-L1 expression within the tumor. These markers may guide the selection of Tibetan GC patients for immunotherapy.
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22
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Khan MZI, Tam MSY, Azam Z, Law HKW. Proteomic profiling of metabolic proteins as potential biomarkers of radioresponsiveness for colorectal cancer. J Proteomics 2022; 262:104600. [DOI: 10.1016/j.jprot.2022.104600] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 04/25/2022] [Accepted: 05/01/2022] [Indexed: 12/24/2022]
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23
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Beyer K, Moris L, Lardas M, Haire A, Barletta F, Scuderi S, Molnar M, Herrera R, Rauf A, Campi R, Greco I, Shiranov K, Dabestani S, van den Broeck T, Arun S, Gacci M, Gandaglia G, Omar MI, MacLennan S, Roobol MJ, Farahmand B, Vradi E, Devecseri Z, Asiimwe A, Zong J, Maclennan SJ, Collette L, NDow J, Briganti A, Bjartell A, Van Hemelrijck M. Diagnostic and prognostic factors in patients with prostate cancer: a systematic review. BMJ Open 2022; 12:e058267. [PMID: 35379637 PMCID: PMC8981333 DOI: 10.1136/bmjopen-2021-058267] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVES As part of the PIONEER Consortium objectives, we have explored which diagnostic and prognostic factors (DPFs) are available in relation to our previously defined clinician and patient-reported outcomes for prostate cancer (PCa). DESIGN We performed a systematic review to identify validated and non-validated studies. DATA SOURCES MEDLINE, Embase and the Cochrane Library were searched on 21 January 2020. ELIGIBILITY CRITERIA Only quantitative studies were included. Single studies with fewer than 50 participants, published before 2014 and looking at outcomes which are not prioritised in the PIONEER core outcome set were excluded. DATA EXTRACTION AND SYNTHESIS After initial screening, we extracted data following the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of prognostic factor studies (CHARMS-PF) criteria and discussed the identified factors with a multidisciplinary expert group. The quality of the included papers was scored for applicability and risk of bias using validated tools such as PROBAST, Quality in Prognostic Studies and Quality Assessment of Diagnostic Accuracy Studies 2. RESULTS The search identified 6604 studies, from which 489 DPFs were included. Sixty-four of those were internally or externally validated. However, only three studies on diagnostic and seven studies on prognostic factors had a low risk of bias and a low risk concerning applicability. CONCLUSION Most of the DPFs identified require additional evaluation and validation in properly designed studies before they can be recommended for use in clinical practice. The PIONEER online search tool for DPFs for PCa will enable researchers to understand the quality of the current research and help them design future studies. ETHICS AND DISSEMINATION There are no ethical implications.
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Affiliation(s)
- Katharina Beyer
- Translational and Oncology Research (TOUR), King's College London, Faculty of Life Sciences and Medicine, London, UK
| | - Lisa Moris
- Department of Urology, University Hospitals Leuven, Leuven, Belgium
| | - Michael Lardas
- Department of Urology, Metropolitan Hospital, Athens, Greece
| | - Anna Haire
- Translational and Oncology Research (TOUR), King's College London, Faculty of Life Sciences and Medicine, London, UK
| | - Francesco Barletta
- Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Simone Scuderi
- Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
| | | | | | - Abdul Rauf
- Department of Urology, Mid Cheshire Hospitals, NHS Foundation Trust, Crewe, UK
| | - Riccardo Campi
- Department of Minimally Invasive and Robotic Urologic Surgery and Kidney Transplantation, University of Florence, Florence, Italy
| | - Isabella Greco
- Department of Minimally Invasive and Robotic Urologic Surgery and Kidney Transplantation, University of Florence, Florence, Italy
| | | | - Saeed Dabestani
- Dept. of Translational Medicine, Division of Urological Cancers, Lund University, Kristianstad Central Hospital, Malmo, Sweden
| | | | | | - Mauro Gacci
- Department of Minimally Invasive and Robotic Urologic Surgery and Kidney Transplantation, University of Florence, Florence, Italy
| | - Giorgio Gandaglia
- Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
| | | | | | - Monique J Roobol
- Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | | | | | | | | | - Jihong Zong
- Global Medical Affairs Oncology, Real World Evidence, Bayer HealthCare Pharmaceuticals Inc, Whippany, New Jersey, USA
| | | | | | - James NDow
- Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Alberto Briganti
- Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
- Department of Urology, University Vita e Salute-San Raffaele, Milan, Italy
| | - Anders Bjartell
- Department of Translational Medicine, Lund University, Malmö, Sweden
| | - Mieke Van Hemelrijck
- Translational and Oncology Research (TOUR), King's College London, Faculty of Life Sciences and Medicine, London, UK
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24
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Islam Khan MZ, Tam SY, Law HKW. Advances in High Throughput Proteomics Profiling in Establishing Potential Biomarkers for Gastrointestinal Cancer. Cells 2022; 11:973. [PMID: 35326424 PMCID: PMC8946849 DOI: 10.3390/cells11060973] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 03/05/2022] [Accepted: 03/08/2022] [Indexed: 12/24/2022] Open
Abstract
Gastrointestinal cancers (GICs) remain the most diagnosed cancers and accounted for the highest cancer-related death globally. The prognosis and treatment outcomes of many GICs are poor because most of the cases are diagnosed in advanced metastatic stages. This is primarily attributed to the deficiency of effective and reliable early diagnostic biomarkers. The existing biomarkers for GICs diagnosis exhibited inadequate specificity and sensitivity. To improve the early diagnosis of GICs, biomarkers with higher specificity and sensitivity are warranted. Proteomics study and its functional analysis focus on elucidating physiological and biological functions of unknown or annotated proteins and deciphering cellular mechanisms at molecular levels. In addition, quantitative analysis of translational proteomics is a promising approach in enhancing the early identification and proper management of GICs. In this review, we focus on the advances in mass spectrometry along with the quantitative and functional analysis of proteomics data that contributes to the establishment of biomarkers for GICs including, colorectal, gastric, hepatocellular, pancreatic, and esophageal cancer. We also discuss the future challenges in the validation of proteomics-based biomarkers for their translation into clinics.
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Affiliation(s)
| | | | - Helen Ka Wai Law
- Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China; (M.Z.I.K.); (S.Y.T.)
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25
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Experimental Nuclear Medicine Meets Tumor Biology. Pharmaceuticals (Basel) 2022; 15:ph15020227. [PMID: 35215337 PMCID: PMC8878163 DOI: 10.3390/ph15020227] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 02/01/2022] [Accepted: 02/04/2022] [Indexed: 02/01/2023] Open
Abstract
Personalized treatment of cancer patients demands specific and validated biomarkers for tumor diagnosis and therapy. The development and validation of such require translational preclinical models that recapitulate human diseases as accurately as possible. Moreover, there is a need for convergence of different (pre)clinical disciplines that openly share their knowledge and methodologies. This review sheds light on the differential perception of biomarkers and gives an overview of currently used models in tracer development and approaches for biomarker discovery.
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26
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Calogero A, Sagnelli C, Peluso G, Sica A, Candida M, Campanile S, Minieri G, Incollingo P, Creta M, Pelosio L, Tammaro V, Scotti A, Jamshidi A, Caggiano M, Sagnelli E, Dodaro CA, Carlomagno N, Santangelo M. Physical activity in elderly kidney transplant patients with multiple renal arteries. Minerva Med 2022; 113:119-127. [PMID: 32338484 DOI: 10.23736/s0026-4806.20.06573-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Kidney transplantation (KT) is the gold standard for treatment of patients with end-stage-renal disease. To expand the donor reserve, it is necessary to use marginal/suboptimal kidneys. METHODS We retrospectively evaluated the short/long-term outcome of 34 KT elderly patients who received allografts with vascular abnormalities (MRA group), in comparison with 34 KT patients who received a kidney with a single renal artery (SRA group) pair-matched by age, length of time on dialysis, comorbidity and donor age. RESULTS All participants completed the International Physical Activity Questionnaire at KT, and then 4, 8, and 12 weeks after transplantation. Our data indicate that kidney with vascular anatomical variants may be successfully transplanted, since the overall rate of surgical complications was 20.6% in the SRA group and 17.6% in the MRA group and that the 5-year survival rate after KT was 100% in both groups. CONCLUSIONS The data also underlined that individualized physical activity programs induced similar excellent results in both groups, improving physical capacities, arterial pressure, lipid metabolism, insulin sensitivity, quality of life and physical and mental status.
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Affiliation(s)
- Armando Calogero
- Unit of General Surgery and Transplant, Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
- Department of Nephrology, Urology, General Surgery and Kidney Transplants, Anesthesiology and Intensive Care, Federico II University, Naples, Italy
| | - Caterina Sagnelli
- Department of Mental Health and Public Medicine, Luigi Vanvitelli University of Campania, Naples, Italy -
| | - Gaia Peluso
- Unit of General Surgery and Transplant, Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
| | - Antonello Sica
- Department of Precision Medicine, Luigi Vanvitelli University of Campania, Naples, Italy
| | - Maria Candida
- Unit of General Surgery and Transplant, Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
| | - Silvia Campanile
- Unit of General Surgery and Transplant, Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
| | - Gianluca Minieri
- Unit of General Surgery and Transplant, Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
| | - Paola Incollingo
- Unit of General Surgery and Transplant, Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
| | - Massimiliano Creta
- Department of Nephrology, Urology, General Surgery and Kidney Transplants, Anesthesiology and Intensive Care, Federico II University, Naples, Italy
| | - Luigi Pelosio
- Unit of General Surgery and Transplant, Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
| | - Vincenzo Tammaro
- Unit of General Surgery and Transplant, Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
| | - Alessandro Scotti
- Unit of General Surgery and Transplant, Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
| | - Akbar Jamshidi
- Unit of General Surgery and Transplant, Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
| | - Marcello Caggiano
- Unit of General Surgery and Transplant, Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
| | - Evangelista Sagnelli
- Department of Precision Medicine, Luigi Vanvitelli University of Campania, Naples, Italy
| | - Concetta A Dodaro
- Unit of General Surgery and Transplant, Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
- Department of Nephrology, Urology, General Surgery and Kidney Transplants, Anesthesiology and Intensive Care, Federico II University, Naples, Italy
| | - Nicola Carlomagno
- Unit of General Surgery and Transplant, Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
| | - Michele Santangelo
- Unit of General Surgery and Transplant, Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
- Department of Nephrology, Urology, General Surgery and Kidney Transplants, Anesthesiology and Intensive Care, Federico II University, Naples, Italy
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27
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Weissenbacher A, Stone JP, Lo Faro ML, Hunter JP, Ploeg RJ, Coussios CC, Fildes JE, Friend PJ. Hemodynamics and Metabolic Parameters in Normothermic Kidney Preservation Are Linked With Donor Factors, Perfusate Cells, and Cytokines. Front Med (Lausanne) 2022; 8:801098. [PMID: 35083252 PMCID: PMC8784871 DOI: 10.3389/fmed.2021.801098] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Accepted: 12/08/2021] [Indexed: 12/29/2022] Open
Abstract
Kidney transplantation is the best renal-replacement option for most patients with end-stage renal disease. Normothermic machine preservation (NMP) of the kidney has been studied extensively during the last two decades and implemented in clinical trials. Biomarker research led to success in identifying molecules with diagnostic, predictive and therapeutic properties in chronic kidney disease. However, perfusate biomarkers and potential predictive mechanisms in NMP have not been identified yet. Twelve discarded human kidneys (n = 7 DBD, n = 5 DCD) underwent NMP for up to 24 h. Eight were perfused applying urine recirculation (URC), four with replacement of urine (UR) using Ringer's lactate. The aim of our study was to investigate biomarkers (NGAL, KIM-1, and L-FABP), cells and cytokines in the perfusate in context with donor characteristics, perfusate hemodynamics and metabolic parameters. Cold ischemia time did not correlate with any of the markers. Perfusates of DBD kidneys had a significantly lower number of leukocytes after 6 h of NMP compared to DCD. Arterial flow, pH, NGAL and L-FABP correlated with donor creatinine and eGFR. Arterial flow was higher in kidneys with lower perfusate lactate. Perfusate TNF-α was higher in kidneys with lower arterial flow. The cytokines IL-1β and GM-CSF decreased during 6 h of NMP. Kidneys with more urine output had lower perfusate KIM-1 levels. Median and 6-h values of lactate, arterial flow, pH, NGAL, KIM-1, and L-FABP correlated with each other indicating a 6-h period being applicable for kidney viability assessment. The study results demonstrate a comparable cytokine and cell profile in perfusates with URC and UR. In conclusion, clinically available perfusate and hemodynamic parameters correlate well with donor characteristics and measured biomarkers in a discarded human NMP model.
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Affiliation(s)
- Annemarie Weissenbacher
- Oxford Transplant Centre, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.,Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - John P Stone
- The ex-vivo Lab, Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.,The ex-vivo Research Centre Community Interest Company (CIC), Macclesfield, United Kingdom
| | - Maria Letizia Lo Faro
- Oxford Transplant Centre, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
| | - James P Hunter
- Oxford Transplant Centre, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
| | - Rutger J Ploeg
- Oxford Transplant Centre, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
| | | | - James E Fildes
- The ex-vivo Lab, Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.,The ex-vivo Research Centre Community Interest Company (CIC), Macclesfield, United Kingdom
| | - Peter J Friend
- Oxford Transplant Centre, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
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28
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Recent Developments in Clinical Plasma Proteomics—Applied to Cardiovascular Research. Biomedicines 2022; 10:biomedicines10010162. [PMID: 35052841 PMCID: PMC8773619 DOI: 10.3390/biomedicines10010162] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 01/05/2022] [Accepted: 01/12/2022] [Indexed: 01/27/2023] Open
Abstract
The human plasma proteome mirrors the physiological state of the cardiovascular system, a fact that has been used to analyze plasma biomarkers in routine analysis for the diagnosis and monitoring of cardiovascular diseases for decades. These biomarkers address, however, only a very limited subset of cardiovascular diseases, such as acute myocardial infarct or acute deep vein thrombosis, and clinical plasma biomarkers for the diagnosis and stratification cardiovascular diseases that are growing in incidence, such as heart failure and abdominal aortic aneurysm, do not exist and are urgently needed. The discovery of novel biomarkers in plasma has been hindered by the complexity of the human plasma proteome that again transforms into an extreme analytical complexity when it comes to the discovery of novel plasma biomarkers. This complexity is, however, addressed by recent achievements in technologies for analyzing the human plasma proteome, thereby facilitating the possibility for novel biomarker discoveries. The aims of this article is to provide an overview of the recent achievements in technologies for proteomic analysis of the human plasma proteome and their applications in cardiovascular medicine.
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29
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Smith BJ, Silva-Costa LC, Martins-de-Souza D. Human disease biomarker panels through systems biology. Biophys Rev 2021; 13:1179-1190. [PMID: 35059036 PMCID: PMC8724340 DOI: 10.1007/s12551-021-00849-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Accepted: 10/01/2021] [Indexed: 12/23/2022] Open
Abstract
As more uses for biomarkers are sought after for an increasing number of disease targets, single-target biomarkers are slowly giving way for biomarker panels. These panels incorporate various sources of biomolecular and clinical data to guarantee a higher robustness and power of separation for a clinical test. Multifactorial diseases such as psychiatric disorders show great potential for clinical use, assisting medical professionals during the analysis of risk and predisposition, disease diagnosis and prognosis, and treatment applicability and efficacy. More specific tests are also being developed to assist in ruling out, distinguishing between, and confirming suspicions of multifactorial diseases, as well as to predict which therapy option may be the best option for a given patient's biochemical profile. As more complex datasets are entering the field, involving multi-omic approaches, systems biology has stepped in to facilitate the discovery and validation steps during biomarker panel generation. Filtering biomolecules and clinical data, pre-validating and cross-validating potential biomarkers, generating final biomarker panels, and testing the robustness and applicability of those panels are all beginning to rely on machine learning and systems biology and research in this area will only benefit from advances in these approaches.
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Affiliation(s)
- Bradley J. Smith
- Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
| | - Licia C. Silva-Costa
- Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
| | - Daniel Martins-de-Souza
- Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Instituto Nacional de Biomarcadores Em Neuropsiquiatria (INBION), Conselho Nacional de Desenvolvimento Científico E Tecnológico, Sao Paulo, Brazil
- Experimental Medicine Research Cluster (EMRC), University of Campinas, Campinas, Brazil
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30
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Mehrabi SF, Ghatak S, Mehdawi LM, Topi G, Satapathy SR, Sjölander A. Brain-Derived Neurotrophic Factor, Neutrophils and Cysteinyl Leukotriene Receptor 1 as Potential Prognostic Biomarkers for Patients with Colon Cancer. Cancers (Basel) 2021; 13:cancers13215520. [PMID: 34771682 PMCID: PMC8583027 DOI: 10.3390/cancers13215520] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 10/12/2021] [Accepted: 10/28/2021] [Indexed: 01/24/2023] Open
Abstract
Simple Summary Colorectal cancer (CRC) is one of the most common type of cancer and the third leading cause of cancer-related death. CRC is associated with inflammatory bowel disease. We have earlier shown that high levels of the inflammatory receptor CysLT1 goes with poor prognosis for CRC patients. In this study, we found that high levels of neutrophils (CD66b) and brain-derived neurotropic factor (BDNF) goes with poor prognosis for colon cancer patient. We discovered a strong positive correlation between CysLT1, CD66b and BDNF. Our data support that these three proteins can be used as a combined biomarker for CC patients. Abstract The tumor microenvironment has been recognized as a complex network in which immune cells play an important role in cancer progression. We found significantly higher CD66b neutrophil expression in tumor tissue than in matched normal mucosa in the Malmö colon cancer (CC) cohort and poorer survival of stage I-III patients with high CD66b expression. Additionally, mice lacking CysLT1R expression (cysltr1−/−) produce less brain-derived neurotrophic factor (BDNF) compared to WT mice and Montelukast (a CysLT1R antagonist)-treated mice also reduced BDNF expression in a mouse xenograft model with human SW480 CC cells. CD66b and BDNF expression was significantly higher in patient tumor tissues than in the matched normal mucosa. The univariate Cox PH analysis yielded CD66b and BDNF as an independent predictor of overall survival, which was also found in the public TCGA-COAD dataset. We also discovered a strong positive correlation between CD66b, BDNF and CysLT1R expression in the Malmö CC cohort and in the TCGA-COAD dataset. Our data suggest that CD66b/BDNF/CysLT1R expression as a prognostic combined biomarker signature for CC patients.
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31
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Wong YK, Tse HF. Circulating Biomarkers for Cardiovascular Disease Risk Prediction in Patients With Cardiovascular Disease. Front Cardiovasc Med 2021; 8:713191. [PMID: 34660715 PMCID: PMC8517145 DOI: 10.3389/fcvm.2021.713191] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Accepted: 09/08/2021] [Indexed: 12/23/2022] Open
Abstract
Cardiovascular disease (CVD) is the leading cause of death globally. Risk assessment is crucial for identifying at-risk individuals who require immediate attention as well as to guide the intensity of medical therapy to reduce subsequent risk of CVD. In the past decade, many risk prediction models have been proposed to estimate the risk of developing CVD. However, in patients with a history of CVD, the current models that based on traditional risk factors provide limited power in predicting recurrent cardiovascular events. Several biomarkers from different pathophysiological pathways have been identified to predict cardiovascular events, and the incorporation of biomarkers into risk assessment may contribute to enhance risk stratification in secondary prevention. This review focuses on biomarkers related to cardiovascular and metabolic diseases, including B-type natriuretic peptide, high-sensitivity cardiac troponin I, adiponectin, adipocyte fatty acid-binding protein, heart-type fatty acid-binding protein, lipocalin-2, fibroblast growth factor 19 and 21, retinol-binding protein 4, plasminogen activator inhibitor-1, 25-hydroxyvitamin D, and proprotein convertase subtilisin/kexin type 9, and discusses the potential utility of these biomarkers in cardiovascular risk prediction among patients with CVD. Many of these biomarkers have shown promise in improving risk prediction of CVD. Further research is needed to assess the validity of biomarker and whether the strategy for incorporating biomarker into clinical practice may help to optimize decision-making and therapeutic management.
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Affiliation(s)
- Yuen-Kwun Wong
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
| | - Hung-Fat Tse
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.,Department of Medicine, Shenzhen Hong Kong University Hospital, Shenzhen, China.,Hong Kong-Guangdong Joint Laboratory on Stem Cell and Regenerative Medicine, The University of Hong Kong, Hong Kong, China.,Shenzhen Institutes of Research and Innovation, The University of Hong Kong, Hong Kong, China
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32
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Liu J, Chen Z, Li Y, Zhao W, Wu J, Zhang Z. PD-1/PD-L1 Checkpoint Inhibitors in Tumor Immunotherapy. Front Pharmacol 2021; 12:731798. [PMID: 34539412 PMCID: PMC8440961 DOI: 10.3389/fphar.2021.731798] [Citation(s) in RCA: 206] [Impact Index Per Article: 51.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 08/19/2021] [Indexed: 12/12/2022] Open
Abstract
Programmed death protein 1 (PD1) is a common immunosuppressive member on the surface of T cells and plays an imperative part in downregulating the immune system and advancing self-tolerance. Its ligand programmed cell death ligand 1 (PDL1) is overexpressed on the surface of malignant tumor cells, where it binds to PD1, inhibits the proliferation of PD1-positive cells, and participates in the immune evasion of tumors leading to treatment failure. The PD1/PDL1-based pathway is of great value in immunotherapy of cancer and has become an important immune checkpoint in recent years, so understanding the mechanism of PD1/PDL1 action is of great significance for combined immunotherapy and patient prognosis. The inhibitors of PD1/PDL1 have shown clinical efficacy in many tumors, for example, blockade of PD1 or PDL1 with specific antibodies enhances T cell responses and mediates antitumor activity. However, some patients are prone to develop drug resistance, resulting in poor treatment outcomes, which is rooted in the insensitivity of patients to targeted inhibitors. In this paper, we reviewed the mechanism and application of PD1/PDL1 checkpoint inhibitors in tumor immunotherapy. We hope that in the future, promising combination therapy regimens can be developed to allow immunotherapeutic tools to play an important role in tumor treatment. We also discuss the safety issues of immunotherapy and further reflect on the effectiveness of the treatment and the side effects it brings.
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Affiliation(s)
- Jinhua Liu
- Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.,College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Zichao Chen
- Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.,Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yaqun Li
- Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.,College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Wenjie Zhao
- Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - JiBiao Wu
- Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Zhen Zhang
- Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
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33
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Davey MG, Hynes SO, Kerin MJ, Miller N, Lowery AJ. Ki-67 as a Prognostic Biomarker in Invasive Breast Cancer. Cancers (Basel) 2021; 13:4455. [PMID: 34503265 PMCID: PMC8430879 DOI: 10.3390/cancers13174455] [Citation(s) in RCA: 128] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 08/31/2021] [Accepted: 09/01/2021] [Indexed: 12/12/2022] Open
Abstract
The advent of molecular medicine has transformed breast cancer management. Breast cancer is now recognised as a heterogenous disease with varied morphology, molecular features, tumour behaviour, and response to therapeutic strategies. These parameters are underpinned by a combination of genomic and immunohistochemical tumour factors, with estrogen receptor (ER) status, progesterone receptor (PgR) status, human epidermal growth factor receptor-2 (HER2) status, Ki-67 proliferation indices, and multigene panels all playing a contributive role in the substratification, prognostication and personalization of treatment modalities for each case. The expression of Ki-67 is strongly linked to tumour cell proliferation and growth and is routinely evaluated as a proliferation marker. This review will discuss the clinical utility, current pitfalls, and promising strategies to augment Ki-67 proliferation indices in future breast oncology.
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Affiliation(s)
- Matthew G. Davey
- Discipline of Surgery, The Lambe Institute for Translational Research, National University of Ireland, H91 YR71 Galway, Ireland; (M.J.K.); (N.M.); (A.J.L.)
- Department of Surgery, Galway University Hospitals, H91 YR71 Galway, Ireland
| | - Sean O. Hynes
- Department of Histopathology, National University of Ireland, H91 YR71 Galway, Ireland;
| | - Michael J. Kerin
- Discipline of Surgery, The Lambe Institute for Translational Research, National University of Ireland, H91 YR71 Galway, Ireland; (M.J.K.); (N.M.); (A.J.L.)
| | - Nicola Miller
- Discipline of Surgery, The Lambe Institute for Translational Research, National University of Ireland, H91 YR71 Galway, Ireland; (M.J.K.); (N.M.); (A.J.L.)
| | - Aoife J. Lowery
- Discipline of Surgery, The Lambe Institute for Translational Research, National University of Ireland, H91 YR71 Galway, Ireland; (M.J.K.); (N.M.); (A.J.L.)
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High-Throughput Sequencing Reveals the Differential MicroRNA Expression Profiles of Human Gastric Cancer SGC7901 Cell Xenograft Nude Mouse Models Treated with Traditional Chinese Medicine Si Jun Zi Tang Decoction. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:6119212. [PMID: 34457026 PMCID: PMC8387168 DOI: 10.1155/2021/6119212] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 07/14/2021] [Accepted: 08/04/2021] [Indexed: 12/14/2022]
Abstract
Objective. The present study aimed to investigate the potential mechanism underlying the antitumor effect of Si Jun Zi Tang (SJZT) decoction on gastric cancer. Methods. Twelve human gastric cancer SGC7901 cell xenograft nude mouse models were established. The mice were randomly divided into the Model group and SJZT group. SJZT exerted significant antitumor effects after 21 days of decoction administration. High-throughput sequencing was used to analyze the microRNA (miRNA) expression profiles of tumor tissues. Bioinformatics analysis was performed to provide further information regarding the differentially expressed miRNAs. Five representative differentially expressed miRNAs and four predicted target genes were further validated using quantitative real-time reverse transcription PCR (qRT-PCR). Results. We identified 33 miRNAs that were differentially expressed in the SJZT group compared with the Model group. Among them, 32 miRNAs were upregulated and 1 miRNA was downregulated. Bioinformatic analysis showed that most of miRNAs acted as tumor suppressors and their target genes participated in multiple signaling pathways, including the PI3K/Akt signaling pathway, microRNAs in cancer, and Wnt signaling pathway. The qRT-PCR result confirmed that miR-223-3p, miR-205-5p, miR-147b-3p, and miR-223-5p were overexpressed and their respective paired target genes FUT9, POU2F1, MUC4, and RAB14 mRNA were obviously downregulated in the SJZT group compared with those in the Model group. Network analysis revealed that miR-223-3p and miR-205-5p shared two targets POU2F1 (encoding POU class 2 homeobox 1) and FUT9 (encoding fucosyltransferase 9), suggesting they have a common role in certain pathways. Conclusion. This study provided novel insights into the anticancer mechanism of SJZT against gastric cancer, which might be partly related to the modulation of miRNA expression and their target pathways in tumors.
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Liu Z, Liang G, Zhan W. In situ Activatable Peptide-based Nanoprobes for Tumor Imaging. Chem Res Chin Univ 2021. [DOI: 10.1007/s40242-021-1181-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Bermúdez A, Arranz-Salas I, Mercado S, López-Villodres JA, González V, Ríus F, Ortega MV, Alba C, Hierro I, Bermúdez D. Her2-Positive and Microsatellite Instability Status in Gastric Cancer-Clinicopathological Implications. Diagnostics (Basel) 2021; 11:944. [PMID: 34070574 PMCID: PMC8228707 DOI: 10.3390/diagnostics11060944] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 05/19/2021] [Accepted: 05/21/2021] [Indexed: 12/24/2022] Open
Abstract
Gastric cancer (GC) is one of the leading causes of cancer-related death. The combination of new molecular classifications with clinicopathological data could contribute to the individualization of patients and to the development of new therapeutic strategies. We examined the various associations in two molecular types of GC: HER2-positive (human epidermal growth factor receptor 2) and microsatellite instability (MSI), assessing their influence on treatment and prognosis. A retrospective study of 142 GC patients was performed with molecular characterization through HER2 overexpression and DNA repair protein expression for MSI. The percentage of HER2-positive tumors was 13.4%, predominantly in men. Correlations were found with intestinal type, metastases, advanced stages and chemotherapy. Almost 75% of HER2-positive patients died. MSI occurred in 16.2%, associated with advanced age, female sex, distal location and intestinal type. These patients had few metastases and low stages. The percentage of deaths was higher among MSI patients who received perioperative chemotherapy. The determination of HER2 and MSI status in GC is important for their association with specific clinicopathological features and for their prognostic and predictive value.
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Affiliation(s)
- Ana Bermúdez
- Department of Anesthesiology, Nuestra Señora de Valme University Hospital, 41014 Seville, Spain;
| | - Isabel Arranz-Salas
- Department of Human Physiology, Human Histology, Anatomical Pathology and Physical Education, University of Malaga, 29010 Malaga, Spain; (I.A.-S.); (S.M.); (J.A.L.-V.); (M.V.O.); (C.A.)
- Unit of Anatomical Pathology, Virgen de la Victoria University Hospital, 29010 Malaga, Spain;
| | - Silvia Mercado
- Department of Human Physiology, Human Histology, Anatomical Pathology and Physical Education, University of Malaga, 29010 Malaga, Spain; (I.A.-S.); (S.M.); (J.A.L.-V.); (M.V.O.); (C.A.)
| | - Juan A. López-Villodres
- Department of Human Physiology, Human Histology, Anatomical Pathology and Physical Education, University of Malaga, 29010 Malaga, Spain; (I.A.-S.); (S.M.); (J.A.L.-V.); (M.V.O.); (C.A.)
| | - Virginia González
- Unit of Anatomical Pathology; Montilla Hospital, 14550 Montilla, Spain;
| | - Francisca Ríus
- Department of Public Health and Psychiatry, University of Malaga, 29010 Malaga, Spain;
| | - María V. Ortega
- Department of Human Physiology, Human Histology, Anatomical Pathology and Physical Education, University of Malaga, 29010 Malaga, Spain; (I.A.-S.); (S.M.); (J.A.L.-V.); (M.V.O.); (C.A.)
- Unit of Anatomical Pathology, Virgen de la Victoria University Hospital, 29010 Malaga, Spain;
| | - Carmen Alba
- Department of Human Physiology, Human Histology, Anatomical Pathology and Physical Education, University of Malaga, 29010 Malaga, Spain; (I.A.-S.); (S.M.); (J.A.L.-V.); (M.V.O.); (C.A.)
| | - Isabel Hierro
- Unit of Anatomical Pathology, Virgen de la Victoria University Hospital, 29010 Malaga, Spain;
| | - Diego Bermúdez
- Department of Human Physiology, Human Histology, Anatomical Pathology and Physical Education, University of Malaga, 29010 Malaga, Spain; (I.A.-S.); (S.M.); (J.A.L.-V.); (M.V.O.); (C.A.)
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Heat Shock Factor 1 as a Prognostic and Diagnostic Biomarker of Gastric Cancer. Biomedicines 2021; 9:biomedicines9060586. [PMID: 34064083 PMCID: PMC8224319 DOI: 10.3390/biomedicines9060586] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 05/18/2021] [Accepted: 05/19/2021] [Indexed: 01/09/2023] Open
Abstract
Identification of effective prognostic and diagnostic biomarkers is needed to improve the diagnosis and treatment of gastric cancer. Early detection of gastric cancer through diagnostic markers can help establish effective treatments. Heat shock factor 1 (HSF1), presented in this review, is known to be regulated by a broad range of transcription factors, including those characterized in various malignant tumors, including gastric cancer. Particularly, it has been demonstrated that HSF1 regulation in various cancers is correlated with different processes, such as cell death, proliferation, and metastasis. Due to the effect of HSF1 on the initiation, development, and progression of various tumors, it is considered as an important gene for understanding and treating tumors. Additionally, HSF1 exhibits high expression in various cancers, and its high expression adversely affects the prognosis of various cancer patients, thereby suggesting that it can be used as a novel, predictive, prognostic, and diagnostic biomarker for gastric cancer. In this review, we discuss the literature accumulated in recent years, which suggests that there is a correlation between the expression of HSF1 and prognosis of gastric cancer patients through public data. Consequently, this evidence also indicates that HSF1 can be established as a powerful biomarker for the prognosis and diagnosis of gastric cancer.
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Beyer K, Moris L, Lardas M, Haire A, Barletta F, Scuderi S, Vradi E, Gandaglia G, Omar MI, MacLennan S, Zong J, Farahmand B, Maclennan SJ, Devecseri Z, Asiimwe A, Collette L, Bjartell A, Ndow J, Briganti A, Van Hemelrijck M. Diagnostic and prognostic factors in patients with prostate cancer: a systematic review protocol. BMJ Open 2021; 11:e040531. [PMID: 33574142 PMCID: PMC7880102 DOI: 10.1136/bmjopen-2020-040531] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 12/22/2020] [Accepted: 01/07/2021] [Indexed: 01/08/2023] Open
Abstract
INTRODUCTION As part of the PIONEER (Prostate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe) Consortium, we will explore which diagnostic and prognostic factors (DPFs) are currently being researched to previously defined clinical and patient-reported outcomes for prostate cancer (PCa). METHODS AND ANALYSIS This research project will follow the following four steps: (1) a broad systematic literature review of DPFs for all stages of PCa, covering evidence from 2014 onwards; (2) discussion of systematic review findings by a multidisciplinary expert panel; (3) risk of bias assessment and applicability with Prediction model Risk Of Bias Assessment Tool criteria, Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and the Quality In Prognosis Studies tool (QUIPS) and (4) additional quantitative assessments if required. ETHICS AND DISSEMINATION We aim to develop an online tool to present the DPFs identified in this research and make them available across all stakeholders. There are no ethical implications.
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Affiliation(s)
- Katharina Beyer
- Translational Oncology and Urology Research (TOUR), King's College London, London, UK
| | - Lisa Moris
- Department of Urology, KU Leuven University Hospitals Leuven, Leuven, Flanders, Belgium
| | - Michael Lardas
- Department of Urology, Metropolitan Hospital Athens, Athens, Attike, Greece
| | - Anna Haire
- Translational Oncology and Urology Research (TOUR), King's College London, London, UK
| | - Francesco Barletta
- Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy
| | - Simone Scuderi
- Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy
| | - Eleni Vradi
- Medical Affairs and PV, Bayer Pharma AG, Berlin, Germany
| | - Giorgio Gandaglia
- Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy
| | - Muhammad Imran Omar
- Academic Urology Unit, Health Services Research Unit, University of Aberdeen, Aberdeen, Aberdeen, UK
| | - Steven MacLennan
- Academic Urology Unit, Health Services Research Unit, University of Aberdeen, Aberdeen, Aberdeen, UK
| | - Jihong Zong
- Epidemiology, Bayer U.S, Whippany, New Jersey, USA
| | | | - Sara J Maclennan
- Academic Urology Unit, Health Services Research Unit, University of Aberdeen, Aberdeen, Aberdeen, UK
| | | | - Alex Asiimwe
- Medical Affairs and PV, Bayer Pharma AG, Berlin, Germany
| | | | | | - James Ndow
- Guidelines Office, European Association of Urology, Arnhem, Netherlands
| | - Alberto Briganti
- Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy
- Department of Urology and Division of Experimental Oncology, Urological Research Institute, Vita-Salute University San Raffaele, RCCS San Raffaele Scientific Institute, Milan, Italy
| | - Mieke Van Hemelrijck
- Translational Oncology and Urology Research (TOUR), King's College London, London, UK
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Mechanism of tumour microenvironment in the progression and development of oral cancer. Mol Biol Rep 2021; 48:1773-1786. [PMID: 33492572 DOI: 10.1007/s11033-020-06054-6] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 12/01/2020] [Indexed: 01/19/2023]
Abstract
Oral cancer has been a major problem all across the globe, majorly in the developing countries. With a growing emphasis in the field of cancer research, the contribution of the tumour microenvironment has been gaining a lot of importance in identifying the role of components other than the tumour cells that cause the development of cancer, thus changing the outlook. The review will shed light on the studies that describe the role of microenvironment, its components as well as summarize the studies related to their mechanism in the progression of oral cancer. The literature for the review was derived mainly from Google Scholar and PubMed, in particular concentrating on the most recent papers published in 2019 and 2020, by using the keywords "Cancer, Oral Cancer, Metastasis, OSCC, Tumour microenvironment, CAFs, ECM, Cytokines, Hypoxia, Therapeutics targeting the microenvironment". The study provides insight into the world of micro-environmental regulation of oral cancer, the mechanism by which they interact and how to exploit it as a potential therapeutic haven for treating the disease. The components Cancer-Associated Fibroblasts (CAFs), Tumour-associated Macrophages (TAMs), Tumour-associated neutrophils (TANs), Hypoxic environment, myeloid-derived stem cells (MDSCs) and T regulatory (Tregs) cells and underlying mechanisms that control them will be the targets of study to understand the microenvironment.
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Shah A, Rauth S, Aithal A, Kaur S, Ganguly K, Orzechowski C, Varshney GC, Jain M, Batra SK. The Current Landscape of Antibody-based Therapies in Solid Malignancies. Am J Cancer Res 2021; 11:1493-1512. [PMID: 33391547 PMCID: PMC7738893 DOI: 10.7150/thno.52614] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Accepted: 10/21/2020] [Indexed: 02/06/2023] Open
Abstract
Over the past three decades, monoclonal antibodies (mAbs) have revolutionized the landscape of cancer therapy. Still, this benefit remains restricted to a small proportion of patients due to moderate response rates and resistance emergence. The field has started to embrace better mAb-based formats with advancements in molecular and protein engineering technologies. The development of a therapeutic mAb with long-lasting clinical impact demands a prodigious understanding of target antigen, effective mechanism of action, gene engineering technologies, complex interplay between tumor and host immune system, and biomarkers for prediction of clinical response. This review discusses the various approaches used by mAbs for tumor targeting and mechanisms of therapeutic resistance that is not only caused by the heterogeneity of tumor antigen, but also the resistance imposed by tumor microenvironment (TME), including inefficient delivery to the tumor, alteration of effector functions in the TME, and Fc-gamma receptor expression diversity and polymorphism. Further, this article provides a perspective on potential strategies to overcome these barriers and how diagnostic and prognostic biomarkers are being used in predicting response to mAb-based therapies. Overall, understanding these interdependent parameters can improve the current mAb-based formulations and develop novel mAb-based therapeutics for achieving durable clinical outcomes in a large subset of patients.
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Petersen EV, Chudakova DA, Skorova EY, Anikin V, Reshetov IV, Mynbaev OA. The Extracellular Matrix-Derived Biomarkers for Diagnosis, Prognosis, and Personalized Therapy of Malignant Tumors. Front Oncol 2020; 10:575569. [PMID: 33425730 PMCID: PMC7793707 DOI: 10.3389/fonc.2020.575569] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 11/10/2020] [Indexed: 01/18/2023] Open
Abstract
The tumor biomarkers already have proven clinical value and have become an integral part in cancer management and modern translational oncology. The tumor tissue microenvironment (TME), which includes extracellular matrix (ECM), signaling molecules, immune and stromal cells, and adjacent non-tumorous tissue, contributes to cancer pathogenesis. Thus, TME-derived biomarkers have many clinical applications. This review is predominately based on the most recent publications (manuscripts published in a last 5 years, or seminal publications published earlier) and fills a gap in the current literature on the cancer biomarkers derived from the TME, with particular attention given to the ECM and products of its processing and degradation, ECM-associated extracellular vesicles (EVs), biomechanical characteristics of ECM, and ECM-derived biomarkers predicting response to the immunotherapy. We discuss the clinical utility of the TME-incorporating three-dimensional in vitro and ex vivo cell culture models for personalized therapy. We conclude that ECM is a critical driver of malignancies and ECM-derived biomarkers should be included in diagnostics and prognostics panels of markers in the clinic.
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Affiliation(s)
- Elena V. Petersen
- Department of Molecular and Bio Physics, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
| | - Daria A. Chudakova
- School of Biological Sciences, University of Auckland, Auckland, New Zealand
| | - Ekaterina Yu. Skorova
- Department of Molecular and Bio Physics, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
| | - Vladimir Anikin
- Harefield Hospital, The Royal Brompton and Harefield Hospitals NHS Foundation Trust, Harefield, United Kingdom
- Department of Oncology and Reconstructive Surgery, Sechenov Medical University, Moscow, Russia
| | - Igor V. Reshetov
- Department of Molecular and Bio Physics, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
- Department of Oncology and Reconstructive Surgery, Sechenov Medical University, Moscow, Russia
| | - Ospan A. Mynbaev
- Department of Molecular and Bio Physics, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
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Gallo M, Ferrara L, Calogero A, Montesano D, Naviglio D. Relationships between food and diseases: What to know to ensure food safety. Food Res Int 2020; 137:109414. [DOI: 10.1016/j.foodres.2020.109414] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2020] [Revised: 05/21/2020] [Accepted: 06/04/2020] [Indexed: 02/07/2023]
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Jab1 promotes gastric cancer tumorigenesis via non-ubiquitin proteasomal degradation of p14ARF. Gastric Cancer 2020; 23:1003-1017. [PMID: 32458234 DOI: 10.1007/s10120-020-01087-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 05/16/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Jab1 has been reported to regulate various proteins in signal transduction pathways and be implicated in carcinogenesis or tumor progression. However, the precise role and molecular mechanism of Jab1 in gastric tumorigenesis have not yet been fully elucidated. METHODS Jab1 staining in gastric cancer tissues and paired non-cancerous tissues was measured using tissue microarray (TMA) technology. The impact of Jab1 on tumor growth in vivo was analyzed using xenotransplantation experiments in Balb/c mice. The expression of Jab1 and p14ARF in gastric cancer cells was analyzed by western blot and confocal immunofluorescence. CCK-8 and cell cycle experiment were used to evaluate the cell proliferation. Ubiquitination assay was performed to validate whether ubiquitination is involved in Jab1-mediated p14ARF degradation. RESULTS The expression level of protein p14ARF was inversely correlated with the protein level of Jab1. Then, we investigated the mechanism that how Jab1 induced p14ARF depletion. Mechanistic studies showed that Jab1 induced ubiquitin-independent proteasomal p14ARF degradation in gastric cancer cells. Our data demonstrated that Jab1 protein was a vital upstream negative modulation factor of p14ARF, and Jab1 could promote cell proliferation and tumor growth via inhibiting the expression of p14ARF in vivo and in vitro. Moreover, silencing Jab1 protein expression declined tumor growth and further increased the apoptosis rate of gastric cancer cells. In further studies of gastric cancer specimens, we found the increased level of Jab1 protein shortened the overall survival. CONCLUSION Jab1 is upstream of p14ARF and promote gastric cancer cell proliferation in vitro and in vivo. Furthermore, Jab1 decreased the expression of p14ARF though ubiquitination independent proteasomal degradation. Therefore, the connection of Jab1 and p14ARF may provide new methods for the treatment of gastric cancer.
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Erabi H, Okada G, Shibasaki C, Setoyama D, Kang D, Takamura M, Yoshino A, Fuchikami M, Kurata A, Kato TA, Yamawaki S, Okamoto Y. Kynurenic acid is a potential overlapped biomarker between diagnosis and treatment response for depression from metabolome analysis. Sci Rep 2020; 10:16822. [PMID: 33033336 PMCID: PMC7545168 DOI: 10.1038/s41598-020-73918-z] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 09/24/2020] [Indexed: 02/06/2023] Open
Abstract
Since optimal treatment at an early stage leads to remission of symptoms and recovery of function, putative biomarkers leading to early diagnosis and prediction of therapeutic responses are desired. The current study aimed to use a metabolomic approach to extract metabolites involved in both the diagnosis of major depressive disorder (MDD) and the prediction of therapeutic response for escitalopram. We compared plasma metabolites of MDD patients (n = 88) with those in healthy participants (n = 88) and found significant differences in the concentrations of 20 metabolites. We measured the Hamilton Rating Scale for Depression (HRSD) on 62 patients who completed approximately six-week treatment with escitalopram before and after treatment and found that kynurenic acid and kynurenine were significantly and negatively associated with HRSD reduction. Only one metabolite, kynurenic acid, was detected among 73 metabolites for overlapped biomarkers. Kynurenic acid was lower in MDD, and lower levels showed a better therapeutic response to escitalopram. Kynurenic acid is a metabolite in the kynurenine pathway that has been widely accepted as being a major mechanism in MDD. Overlapping biomarkers that facilitate diagnosis and prediction of the treatment response may help to improve disease classification and reduce the exposure of patients to less effective treatments in MDD.
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Affiliation(s)
- Hisayuki Erabi
- Department of Psychiatry and Neurosciences, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Go Okada
- Department of Psychiatry and Neurosciences, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Chiyo Shibasaki
- Department of Psychiatry and Neurosciences, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Daiki Setoyama
- Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Dongchon Kang
- Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Masahiro Takamura
- Department of Psychiatry and Neurosciences, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Atsuo Yoshino
- Department of Psychiatry and Neurosciences, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Manabu Fuchikami
- Department of Psychiatry and Neurosciences, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Akiko Kurata
- Department of Psychiatry and Neurosciences, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Takahiro A Kato
- Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Shigeto Yamawaki
- Department of Psychiatry and Neurosciences, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Yasumasa Okamoto
- Department of Psychiatry and Neurosciences, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
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Singh G, Yoshida EM, Rathi S, Marquez V, Kim P, Erb SR, Salh BS. Biomarkers for hepatocellular cancer. World J Hepatol 2020; 12:558-573. [PMID: 33033565 PMCID: PMC7522562 DOI: 10.4254/wjh.v12.i9.558] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 07/06/2020] [Accepted: 08/25/2020] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. If diagnosed early, curative treatment options such as surgical resection, loco-regional therapies, and liver transplantation are available to patients, increasing their chances of survival and improving their quality of life. Unfortunately, most patients are diagnosed with late stage HCC where only palliative treatment is available. Therefore, biomarkers which could detect HCC early with a high degree of sensitivity and specificity, may play a crucial role in the diagnosis and management of the disease. This review will aim to provide an overview of the different biomarkers of HCC comprising those used in the diagnosis of HCC in at risk populations, as well as others with potential for prognosis, risk predisposition and prediction of response to therapeutic intervention.
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Affiliation(s)
- Gurjot Singh
- Department of Medicine, University of British Columbia, Vancouver V5Z 1M9, Canada
| | - Eric M Yoshida
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver V5Z 1M9, Canada
| | - Sahaj Rathi
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver V5Z 1M9, Canada
| | - Vladimir Marquez
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver V5Z 1M9, Canada
| | - Peter Kim
- Division of Oncological Surgery, Department of Medicine, University of British Columbia, Vancouver V5Z 1M9, Canada
| | - Siegfried R Erb
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver V5Z 1M9, Canada
| | - Baljinder S Salh
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver V5Z 1M9, Canada
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Chiu CT, Wang PW, Asare-Werehene M, Tsang BK, Shieh DB. Circulating Plasma Gelsolin: A Predictor of Favorable Clinical Outcomes in Head and Neck Cancer and Sensitive Biomarker for Early Disease Diagnosis Combined with Soluble Fas Ligand. Cancers (Basel) 2020; 12:cancers12061569. [PMID: 32545773 PMCID: PMC7353036 DOI: 10.3390/cancers12061569] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 06/07/2020] [Accepted: 06/09/2020] [Indexed: 12/30/2022] Open
Abstract
Head and neck cancer (HNC) accounts for more than 330,000 cancer deaths annually worldwide. Despite late diagnosis being a major factor contributing to HNC mortality, no satisfactory biomarkers exist for early disease detection. Cytoplasmic gelsolin (cGSN) was discovered to predict disease progression in HNC and other malignancies, and circulating plasma gelsolin (pGSN) levels are significantly correlated with infectious and inflammatory disease prognoses. Here, the plasma levels of five candidate biomarkers (circulating pGSN, squamous cell carcinoma antigen, cytokeratin 19 fragment, soluble Fas, and soluble Fas ligand (sFasL)) in 202 patients with HNC and 45 healthy controls were measured using enzyme-linked immunosorbent assay or Millipore cancer multiplex assay. The results demonstrated that circulating pGSN levels were significantly lower in patients with HNC than in healthy controls. Moreover, circulating pGSN outperformed other candidate biomarkers as an independent diagnostic biomarker of HNC in both sensitivity (82.7%) and specificity (95.6%). Receiver operating characteristic curves indicated that combined pGSN and sFasL levels further augmented this sensitivity (90.6%) for early disease detection. Moreover, higher pGSN levels predicted improved prognosis at both 5-year overall survival and progression-free survival. In conclusion, circulating pGSN could be an independent predictor of favorable clinical outcomes and a novel biomarker for the early HNC detection in combination with sFasL.
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Affiliation(s)
- Chen-Tzu Chiu
- Institute of Basic Medical Sciences, National Cheng Kung University, Tainan 70101, Taiwan;
| | - Pei-Wen Wang
- Institute of Oral Medicine and Department of Stomatology, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan 70101, Taiwan;
- Center of Applied Nanomedicine, National Cheng Kung University, Tainan 70101, Taiwan
| | - Meshach Asare-Werehene
- Departments of Obstetrics & Gynecology and Cellular & Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8L6, Canada; (M.A.-W.); (B.K.T.)
- Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada
| | - Benjamin K. Tsang
- Departments of Obstetrics & Gynecology and Cellular & Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8L6, Canada; (M.A.-W.); (B.K.T.)
- Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada
| | - Dar-Bin Shieh
- Institute of Basic Medical Sciences, National Cheng Kung University, Tainan 70101, Taiwan;
- Institute of Oral Medicine and Department of Stomatology, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan 70101, Taiwan;
- Center of Applied Nanomedicine, National Cheng Kung University, Tainan 70101, Taiwan
- Center for Micro/Nano Science and Technology, National Cheng Kung University, Tainan 70101, Taiwan
- Correspondence: ; Tel.: +886-6-235-3535 (ext. 5899)
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Virgilio E, Giarnieri E, Giovagnoli MR, Montagnini M, Villani S, Proietti A, D'Urso R, Cardelli P, Balducci G, Cavallini M. Combined Analysis of Intragastric Malignant Exfoliation and Ca 72.4 Concentration in Stomach Adenocarcinoma: The "GL1 Ca 72.4" Parameter. Acta Cytol 2020; 64:563-571. [PMID: 32526755 DOI: 10.1159/000508019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2020] [Accepted: 04/15/2020] [Indexed: 12/24/2022]
Abstract
INTRODUCTION/OBJECTIVE Differently from other digestive malignancies, gastric cancer (GC) pathobiology is still little known and understood. Recently, cytopathology and molecular biology on gastric juice/gastric lavage (GJ/GL) of GC patients have provided novel and interesting results in terms of screening, diagnosis, prognosis, and therapy. However, entertaining cytologic examination and molecular test as a unified solo-run test is previously unreported. Our aim was to assess the new parameter "GL Ca 72.4" for GC patients. METHODS Between April 2012 and July 2013, GJ/GL obtained from 37 surgical GC patients were tested for the presence/absence (GL1/GL0) of exfoliated malignant cells along with the intragastric concentration of Ca 72.4 (normal value <6.49 ng/mL: Ca 72.4n; elevated level ≥6.49 ng/mL: Ca 72.4+). RESULTS At a median follow-up of 79.3 months, all the GC alive patients were "GL0 Ca 72.4n." The "GL1 Ca 72.4+" parameter, in comparison with GL0 Ca 72.4n, strongly correlated with deeper tumor invasion (p = 0.027), severe nodal metastasis (p = 0.012), worst metastatic node ratio (p = 0.041), higher number of metastatic lymph nodes (30 vs. 20 nodes, p = 0.014), angiolymphatic invasion (p = 0.044), advanced stage (p = 0.034), and adjuvant therapy (p = 0.044). The Kaplan-Meier model showed that GL1 Ca 72.4+ subjects had shorter overall survival (OS) than GL0 Ca 72.4n cases (9.7 vs. 43.2 months, respectively, p = 0.042). At univariate analysis, the GL1 Ca 72.4+ parameter resulted a significant prognostic factor for OS (p = 0.023). CONCLUSIONS The combined cyto-molecular parameter "GL1 Ca 72.4+" appears to be a strong indicator of aggressive tumor behavior and a significant prognostic factor of poor survival for GC patients.
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Affiliation(s)
- Edoardo Virgilio
- Department of Medical and Surgical Sciences and Translational Medicine, Sapienza University, St. Andrea Hospital, Rome, Italy,
| | - Enrico Giarnieri
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sapienza University, St. Andrea Hospital, Rome, Italy
| | - Maria Rosaria Giovagnoli
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sapienza University, St. Andrea Hospital, Rome, Italy
| | - Monica Montagnini
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sapienza University, St. Andrea Hospital, Rome, Italy
| | - Sandra Villani
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sapienza University, St. Andrea Hospital, Rome, Italy
| | - Antonella Proietti
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sapienza University, St. Andrea Hospital, Rome, Italy
| | - Rosaria D'Urso
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sapienza University, St. Andrea Hospital, Rome, Italy
| | - Patrizia Cardelli
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sapienza University, St. Andrea Hospital, Rome, Italy
| | - Genoveffa Balducci
- Department of Medical and Surgical Sciences and Translational Medicine, Sapienza University, St. Andrea Hospital, Rome, Italy
| | - Marco Cavallini
- Department of Medical and Surgical Sciences and Translational Medicine, Sapienza University, St. Andrea Hospital, Rome, Italy
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Wu Y, Li Y, Liu J, Chen M, Li W, Chen Y, Xu M. The diagnostic value of extracellular protein kinase A (ECPKA) in serum for gastric and colorectal cancer. Transl Cancer Res 2020; 9:3870-3878. [PMID: 35117754 PMCID: PMC8797401 DOI: 10.21037/tcr-20-764] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 04/24/2020] [Indexed: 01/26/2023]
Abstract
Background For the biomarkers of cancer, many chromosomal and genetic alterations have been examined as possible. However, some tumors do not display a clear molecular and genetic signature. While there are some cellular processes regulated by second messenger intracellular pathways indeed involved in carcinogenesis. The first intracellular second messenger was described as cyclic adenosine 3',5'-monophosphate (cAMP), and cAMP-dependent protein kinase (PKA) play a crucial role in several biological processes; The dysregulation of PKA-mediated signaling in several types of cancer should be investigated. More interesting, the alpha catalytic subunit of PKA (PKACα) could be secreted into the conditioned medium by different types of cancer cells, and it also existed in the serum of some cancer patients, defined as extracellular protein kinase A (ECPKA). Methods The levels of serum PKACα from healthy people, gastric cancer and colon cancer patients were detected by ELISA kits. Western blotting was used to detect the expression of PKACα in cancer tissue and the adjacent mucosa. Mann-Whitney test was applied to analyze the patients’ characteristics and serum PKACα. ROC analyses were performed to further evaluate the utility of PKACα in cancer diagnosis. The correlation of serum PKACα and T stage, age, and tumor markers were analyzed by Spearman rank and Pearson correlation analysis, respectively. Results There were significant differences of PKACα in serum between the volunteers and the gastric cancers (P<0.01), but not the colorectal cancers (P>0.05). ROC analyses evaluated the utility of PKACα for gastric cancer with 61.90% sensitivities and 87.50% specificities. The serum PKACα was correlated with tumor marker CA50, while there was no significant difference of PKACα expression between the gastric/colorectal cancer tissue and the adjacent mucosa. Conclusions The above results implied that PKACα levels might be a potential biomarker for the early screening of gastric cancers. Moreover, further research is still needed to investigate the role of secreted PKACα and the regulatory mechanism in tumor progression.
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Affiliation(s)
- Yan Wu
- Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Yafang Li
- Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Junqiang Liu
- Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, China
| | - Mengjiao Chen
- Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Wei Li
- The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
| | - Yongchang Chen
- Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Min Xu
- Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, China
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Rho GTPases in Gynecologic Cancers: In-Depth Analysis toward the Paradigm Change from Reactive to Predictive, Preventive, and Personalized Medical Approach Benefiting the Patient and Healthcare. Cancers (Basel) 2020; 12:cancers12051292. [PMID: 32443784 PMCID: PMC7281750 DOI: 10.3390/cancers12051292] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 05/12/2020] [Accepted: 05/13/2020] [Indexed: 12/24/2022] Open
Abstract
Rho guanosine triphospatases (GTPases) resemble a conserved family of GTP-binding proteins regulating actin cytoskeleton dynamics and several signaling pathways central for the cell. Rho GTPases create a so-called Ras-superfamily of GTPases subdivided into subgroups comprising at least 20 members. Rho GTPases play a key regulatory role in gene expression, cell cycle control and proliferation, epithelial cell polarity, cell migration, survival, and apoptosis, among others. They also have tissue-related functions including angiogenesis being involved in inflammatory and wound healing processes. Contextually, any abnormality in the Rho GTPase function may result in severe consequences at molecular, cellular, and tissue levels. Rho GTPases also play a key role in tumorigenesis and metastatic disease. Corresponding mechanisms include a number of targets such as kinases and scaffold/adaptor-like proteins initiating GTPases-related signaling cascades. The accumulated evidence demonstrates the oncogenic relevance of Rho GTPases for several solid malignancies including breast, liver, bladder, melanoma, testicular, lung, central nervous system (CNS), head and neck, cervical, and ovarian cancers. Furthermore, Rho GTPases play a crucial role in the development of radio- and chemoresistance e.g. under cisplatin-based cancer treatment. This article provides an in-depth overview on the role of Rho GTPases in gynecological cancers, highlights relevant signaling pathways and pathomechanisms, and sheds light on their involvement in tumor progression, metastatic spread, and radio/chemo resistance. In addition, insights into a spectrum of novel biomarkers and innovative approaches based on the paradigm shift from reactive to predictive, preventive, and personalized medicine are provided.
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50
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Baatar S, Bai T, Yokobori T, Gombodorj N, Nakazawa N, Ubukata Y, Kimura A, Kogure N, Sano A, Sohda M, Sakai M, Tumenjargal A, Ogata K, Kuwano H, Shirabe K, Saeki H. High RAD18 Expression is Associated with Disease Progression and Poor Prognosis in Patients with Gastric Cancer. Ann Surg Oncol 2020; 27:4360-4368. [PMID: 32356270 DOI: 10.1245/s10434-020-08518-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Indexed: 01/08/2023]
Abstract
BACKGROUND RAD18 plays an important role in DNA damage repair by inducing monoubiquitinated PCNA (mUB-PCNA) in both cancer and normal tissues. Previous studies have not determined the significance of RAD18 expression in clinical gastric cancer (GC) samples. Thus, this study aimed to clarify the expression and functional significance of RAD18 in GC. METHODS Overall, 96 resected GC samples were subjected to an immunohistochemical analysis of RAD18. GC cell lines were also subjected to functional RNA interference analyses of RAD18. RESULTS RAD18 expression was predominantly nuclear and was observed at higher levels in GC tissues than in normal tissues. In GC tissues, strong RAD18 expression was associated with progression of lymph node metastasis (p = 0.0001), lymphatic invasion (p = 0.0255), venous invasion (p < 0.0001), recurrence (p = 0.028), and disease stage (p = 0.0253). Moreover, GC patients with high tumor RAD18 expression had shorter overall survival (p = 0.0061) and recurrence-free survival durations (p = 0.035) than those with low tumor RAD18 expression. RAD18 knockdown inhibited GC proliferation and invasiveness and increased chemosensitivity by suppressing mUB-PCNA. CONCLUSIONS RAD18 expression may be a useful marker of progression and poor prognosis of GC. Moreover, therapeutic strategies that target RAD18 might be a novel chemosensitizer to eradicate the refractory GC.
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Affiliation(s)
- Seded Baatar
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan
| | - Tuya Bai
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan
| | - Takehiko Yokobori
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan. .,Research Program for Omics-Based Medical Science, Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research (GIAR), Maebashi, Japan.
| | - Navchaa Gombodorj
- Research Program for Omics-Based Medical Science, Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research (GIAR), Maebashi, Japan.,Department of Radiation Oncology, National Cancer Center of Mongolia, Ulaanbaatar, Mongolia
| | - Nobuhiro Nakazawa
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan
| | - Yasunari Ubukata
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan
| | - Akiharu Kimura
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan
| | - Norimichi Kogure
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan
| | - Akihiko Sano
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan
| | - Makoto Sohda
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan
| | - Makoto Sakai
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan
| | - Amartuvshin Tumenjargal
- Department of Bioimaging and Information Analysis, Graduate School of Medicine, Gunma University, Maebashi, Japan
| | - Kyoichi Ogata
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan
| | - Hiroyuki Kuwano
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan
| | - Ken Shirabe
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan
| | - Hiroshi Saeki
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan
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