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1
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Larue AEM, Atlasi Y. The epigenetic landscape in intestinal stem cells and its deregulation in colorectal cancer. Stem Cells 2024; 42:509-525. [PMID: 38597726 PMCID: PMC11177158 DOI: 10.1093/stmcls/sxae027] [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: 10/08/2023] [Accepted: 03/25/2024] [Indexed: 04/11/2024]
Abstract
Epigenetic mechanisms play a pivotal role in controlling gene expression and cellular plasticity in both normal physiology and pathophysiological conditions. These mechanisms are particularly important in the regulation of stem cell self-renewal and differentiation, both in embryonic development and within adult tissues. A prime example of this finely tuned epigenetic control is observed in the gastrointestinal lining, where the small intestine undergoes renewal approximately every 3-5 days. How various epigenetic mechanisms modulate chromatin functions in intestinal stem cells (ISCs) is currently an active area of research. In this review, we discuss the main epigenetic mechanisms that control ISC differentiation under normal homeostasis. Furthermore, we explore the dysregulation of these mechanisms in the context of colorectal cancer (CRC) development. By outlining the main epigenetic mechanisms contributing to CRC, we highlight the recent therapeutics development and future directions for colorectal cancer research.
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Affiliation(s)
- Axelle E M Larue
- Patrick G Johnston Centre for Cancer Research, Queen’s University Belfast, Belfast BT9 7AE, United Kingdom
| | - Yaser Atlasi
- Patrick G Johnston Centre for Cancer Research, Queen’s University Belfast, Belfast BT9 7AE, United Kingdom
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2
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Tajdari M, Peyrovinasab A, Bayanati M, Ismail Mahboubi Rabbani M, Abdolghaffari AH, Zarghi A. Dual COX-2/TNF-α Inhibitors as Promising Anti-inflammatory and Cancer Chemopreventive Agents: A Review. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH : IJPR 2024; 23:e151312. [PMID: 39830670 PMCID: PMC11742592 DOI: 10.5812/ijpr-151312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/11/2024] [Revised: 09/28/2024] [Accepted: 09/29/2024] [Indexed: 01/22/2025]
Abstract
Cyclooxygenases (COX) play a pivotal role in inflammation and are responsible for the production of prostaglandins (PGs). Two types of COXs have been identified as key biological targets for drug design: Constitutive COX-1 and inducible COX-2. Nonsteroidal anti-inflammatory drugs (NSAIDs) target COX-1, while selective COX-2 inhibitors are designed for COX-2. These COX isoforms are involved in multiple physiological and pathological pathways throughout the body. Overproduction of tumor necrosis factor-alpha (TNF-α) plays a role in COX-2's inflammatory activity. Tumor necrosis factor-alpha can contribute to cardiac fibrosis, heart failure, and various cancers by upregulating the COX-2/PGE2 axis. Therefore, suppressing COX activity has emerged as a potentially effective treatment for chronic inflammatory disorders and cancer. This review explores the mechanisms of TNF-α-induced COX-2/PGE2 expression, a significant pathophysiological feature of cancer development. Furthermore, we summarize chemical compounds with dual COX-2/TNF-α inhibitory actions, providing an overview of their structure-activity relationship. These insights may contribute to the development of new generations of dual-acting COX-2/TNF-α inhibitors with enhanced efficacy.
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Affiliation(s)
- Mobina Tajdari
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Amirreza Peyrovinasab
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Maryam Bayanati
- Department of Food Technology Research, National Nutrition, and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Amir Hossein Abdolghaffari
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Afshin Zarghi
- Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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3
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Esmaeili SA, Sahranavard S, Salehi A, Bagheri V. Selectively targeting cancer stem cells: Current and novel therapeutic strategies and approaches in the effective eradication of cancer. IUBMB Life 2021; 73:1045-1059. [PMID: 34184810 DOI: 10.1002/iub.2524] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 06/22/2021] [Accepted: 06/23/2021] [Indexed: 12/19/2022]
Abstract
Cancer stem cells (CSCs) are a subgroup of cells in malignant cancers, which possess self-renewal capacity, tumor-initiating capability, and pluripotency, as well as being responsible for tumor maintenance, metastasis, relapse, and chemoresistance. The treatment modalities previously established for cancer included surgery, chemotherapy, and radiotherapy. The majority of tumor cells of non-CSCs could be eradicated using conventional chemotherapy and radiotherapy. Therefore, novel and promising therapeutic strategies that selectively target CSCs are of great importance. In this review, we described different therapeutic strategies such as immunotherapy, metabolism-based therapeutic strategies, and additional potential therapeutic approaches (targeting microRNAs [miRNAs], histone deacetylase, and DNA methyl transferase) against CSCs. Taken together, due to the inefficiency of anticancer single therapies, targeting CSCs through their metabolism and using immunotherapy and miRNAs besides classical chemo- and radiotherapy may exert better therapeutic effects.
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Affiliation(s)
- Seyed-Alireza Esmaeili
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Immunology Department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Shamim Sahranavard
- Department of Traditional Pharmacy, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Astireh Salehi
- Biology Department, Islamic Azad University, Sanandaj, Iran
| | - Vahid Bagheri
- Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran
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4
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Moradi Sarabi M, Mohammadrezaei Khorramabadi R, Zare Z, Eftekhar E. Polyunsaturated fatty acids and DNA methylation in colorectal cancer. World J Clin Cases 2019; 7:4172-4185. [PMID: 31911898 PMCID: PMC6940323 DOI: 10.12998/wjcc.v7.i24.4172] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Revised: 11/27/2019] [Accepted: 12/13/2019] [Indexed: 02/05/2023] Open
Abstract
Colorectal cancer (CRC) has been designated a major global problem, especially due to its high prevalence in developed countries. CRC mostly occurs sporadically (75%-80%), and only 20%-25% of patients have a family history. Several processes are involved in the development of CRC such as a combination of genetic and epigenetic alterations. Epigenetic changes, including DNA methylation play a vital role in the progression of CRC. Complex interactions between susceptibility genes and environmental factors, such as a diet and sedentary lifestyle, lead to the development of CRC. Clinical and experimental studies have confirmed the beneficial effects of dietary polyunsaturated fatty acids (PUFAs) in preventing CRC. From a mechanistic viewpoint, it has been suggested that PUFAs are pleiotropic agents that alter chromatin remodeling, membrane structure and downstream cell signaling. Moreover, PUFAs can alter the epigenome via modulation of DNA methylation. In this review, we summarize recent investigations linking PUFAs and DNA methylation-associated CRC risk.
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Affiliation(s)
- Mostafa Moradi Sarabi
- Department of Biochemistry and Genetics, School of Medicine, Lorestan University of Medical Sciences, Khorramabad 381251698, Iran
| | - Reza Mohammadrezaei Khorramabadi
- Department of Biochemistry and Genetics, School of Medicine, Lorestan University of Medical Sciences, Khorramabad 381251698, Iran
| | - Zohre Zare
- Department of Pharmaceutics, School of Pharmacy, Lorestan University of Medical Sciences, Khorramabad 381251698, Iran
| | - Ebrahim Eftekhar
- Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas 7919915519, Iran
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5
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6
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Han ZQ, Liao H, Shi F, Chen XP, Hu HC, Tian MQ, Wang LH, Ying S. Inhibition of cyclooxygenase-2 sensitizes lung cancer cells to radiation-induced apoptosis. Oncol Lett 2017; 14:5959-5965. [PMID: 29113232 PMCID: PMC5661612 DOI: 10.3892/ol.2017.6940] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2016] [Accepted: 06/15/2017] [Indexed: 12/05/2022] Open
Abstract
Radiotherapy resistance is an enduring major setback in lung cancer therapy, and is responsible for a large proportion of treatment failures. In previous years, cyclooxygenase-2 (COX-2) has frequently been reported to promote tumor occurrence and development, suggesting a potential role in radiotherapy resistance. To investigate whether COX-2 inhibitors can be applied in radiosensitization, an MTT assay was performed to examine cell viability after X-ray radiation in the presence or absence of the specific COX-2 inhibitor Celecoxib. Cell apoptosis and cell cycle changes were also detected through laser confocal scanning microcopy and flow cytometry. X-ray treatment only caused mild cell death in lung cancer A549 cells. However, combination treatment using celecoxib and X-ray radiation exhibited improved inhibitory effects and significantly suppressed cell proliferation. Therefore, COX-2 inhibitors combined with radiotherapy can counteract radiation-induced high COX-2 expression, demonstrating that celecoxib can function as a radiosensitizer of lung cancer cells. It is therefore reasonable to predict COX-2 inhibitors to be potential clinical radiotherapy synergists.
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Affiliation(s)
- Zhi-Qiang Han
- Department of Respiratory Internal Medicine, People's Hospital of Quzhou City, Quzhou, Zhejiang 324000, P.R. China
| | - Hongwei Liao
- Institute of Respiratory Diseases, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China
| | - Feng Shi
- Department of Respiratory Internal Medicine, People's Hospital of Quzhou City, Quzhou, Zhejiang 324000, P.R. China
| | - Xiao-Ping Chen
- Department of Respiratory Internal Medicine, People's Hospital of Quzhou City, Quzhou, Zhejiang 324000, P.R. China
| | - Hua-Cheng Hu
- Department of Respiratory Internal Medicine, The Second Affiliated Hospital, Suzhou University, Suzhou, Jiangsu 215004, P.R. China
| | - Ming-Qing Tian
- Department of Respiratory Internal Medicine, People's Hospital of Quzhou City, Quzhou, Zhejiang 324000, P.R. China
| | - Li-Hua Wang
- Department of Respiratory Internal Medicine, People's Hospital of Quzhou City, Quzhou, Zhejiang 324000, P.R. China
| | - Songmin Ying
- Institute of Respiratory Diseases, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China
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7
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Li B, Lu Y, Yu L, Han X, Wang H, Mao J, Shen J, Wang B, Tang J, Li C, Song B. miR-221/222 promote cancer stem-like cell properties and tumor growth of breast cancer via targeting PTEN and sustained Akt/NF-κB/COX-2 activation. Chem Biol Interact 2017; 277:33-42. [PMID: 28844858 DOI: 10.1016/j.cbi.2017.08.014] [Citation(s) in RCA: 87] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Revised: 07/24/2017] [Accepted: 08/21/2017] [Indexed: 11/30/2022]
Abstract
MicroRNAs (miRNAs) play an important role in regulating cancer stem cell (CSC). Previous studies have shown that microRNA-221/222 (miR-221/222) cluster are involved in the propagation of breast cancer stem cell (BCSC), however, the underlying molecular mechanisms are still not fully understood. In this study, we found that miR-221/222 were overexpressed in highly aggressive breast cancer MDA-MB-231 cells, that are enriched in markers for epithelial-mesenchymal transition (EMT) and BCSCs, than in MCF-7 cells. Phosphatase and tensin homolog (PTEN) was confirmed to be the target of miR-221/222 in breast cancer cells. MiR-221/222 enhanced breast cancer cell growth, migration and invasion by downregulating PTEN. Importantly, both ectopic expression of miR-221/222 and PTEN knockdown increased the mammosphere formation capacity and the expression of the stemness marker ALDH1. MiR-221/222 lentivirus vector infected MCF-7 cells produced larger subcutaneous tumors, while shRNA vector of PTEN showed similar trend. Along with the downregulation of PTEN caused by miR-221/222 in the breast cancer cells and the xenograft tumor tissues, Akt phosphorylation (p-Akt), NF-κB p65 and phosphorylated p65 (p-p65), and cyclooxygenase-2 (COX-2) were all overexpressed compared to the negative control. Taken together, our findings indicate that miR-221/222 play a critical role in the propagation of BCSCs and tumor growth possibly through targeting PTEN, which in turn activating the Akt/NF-κB/COX-2 pathway. MiR-221/222 might represent the potential target of breast cancer therapy.
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Affiliation(s)
- Bailong Li
- Department of Pathology and Forensics, Dalian Medical University, No.9 West Section, Lvshun South Road, Dalian 116044, China; Department of Clinical Medicine, Grade 2013, Dalian Medical University, No. 9 West Section, Lvshun South Road, Dalian 116044, China
| | - Ying Lu
- Teaching Laboratory of Morphology, Dalian Medical University, No.9 West Section, Lvshun South Road, Dalian 116044, China
| | - Lihui Yu
- Department of Pathology and Forensics, Dalian Medical University, No.9 West Section, Lvshun South Road, Dalian 116044, China
| | - Xiaocui Han
- Department of Pathology and Forensics, Dalian Medical University, No.9 West Section, Lvshun South Road, Dalian 116044, China
| | - Honghai Wang
- Teaching Affairs Department, Dalian Medical University, No.9 West Section, Lvshun South Road, Dalian 116044, China
| | - Jun Mao
- Department of Pathology and Forensics, Dalian Medical University, No.9 West Section, Lvshun South Road, Dalian 116044, China
| | - Jie Shen
- Teaching Laboratory of Morphology, Dalian Medical University, No.9 West Section, Lvshun South Road, Dalian 116044, China
| | - Bo Wang
- Department of Pathology and Forensics, Dalian Medical University, No.9 West Section, Lvshun South Road, Dalian 116044, China
| | - Jianwu Tang
- Department of Pathology and Forensics, Dalian Medical University, No.9 West Section, Lvshun South Road, Dalian 116044, China
| | - Chunyan Li
- Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
| | - Bo Song
- Department of Pathology and Forensics, Dalian Medical University, No.9 West Section, Lvshun South Road, Dalian 116044, China; Teaching Laboratory of Morphology, Dalian Medical University, No.9 West Section, Lvshun South Road, Dalian 116044, China.
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8
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Jiménez P, Chueca E, Arruebo M, Strunk M, Solanas E, Serrano T, García-González MA, Lanas Á. CD24 Expression Is Increased in 5-Fluorouracil-Treated Esophageal Adenocarcinoma Cells. Front Pharmacol 2017; 8:321. [PMID: 28611669 PMCID: PMC5447731 DOI: 10.3389/fphar.2017.00321] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Accepted: 05/15/2017] [Indexed: 01/20/2023] Open
Abstract
The cancer stem cell (CSC) model suggests that there are subsets of cells within a tumor with increased proliferation and self-renewal capacity, which play a key role in therapeutic resistance. The importance of cyclooxygenase-2 (COX-2) in carcinogenesis has been previously established and the use of COX-2 inhibitors as celecoxib has been shown to exert antitumor effects. The present study investigated whether treatment of esophageal adenocarcinoma (EAC) cells with 5-fluorouracil (5-FU) or the growth of tumor spheres increased the proportion of CSCs and also if treatment with celecoxib was able to reduce the putative CSC markers in this tumor. OE19 and OE33 EAC cells surviving 5-FU exposure exhibited an increase in CSC markers CD24 and ABCG2 and also an increased resistance to apoptosis. EAC cell lines had the capacity to form multiple spheres displaying typical CSC functionalities such as self-renewal and increased CD24 levels. In addition, after the induction of differentiation, cancer cells reached levels of CD24 similar to those observed in the parental cells. Treatment with celecoxib alone or in combination with 5-FU also resulted in a reduction of CD24 expression. Moreover, celecoxib inhibited the growth of tumor spheres. These findings showing a reduction in CSC markers induced by celecoxib suggest that the COX-2 inhibitor might be a candidate for combined chemotherapy in the treatment of EAC. However, additional clinical and experimental studies are needed.
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Affiliation(s)
| | - Eduardo Chueca
- CIBERehdMadrid, Spain.,Instituto de Investigación Sanitaria Aragón (IIS Aragón)Zaragoza, Spain
| | - María Arruebo
- Instituto de Investigación Sanitaria Aragón (IIS Aragón)Zaragoza, Spain
| | - Mark Strunk
- Centro de Investigación Biomédica de Aragón, IACS Aragón, Instituto Aragonés de Ciencias de la Salud, Servicio de Secuenciación y Genómica FuncionalZaragoza, Spain
| | - Estela Solanas
- Instituto de Investigación Sanitaria Aragón (IIS Aragón)Zaragoza, Spain
| | - Trinidad Serrano
- Instituto de Investigación Sanitaria Aragón (IIS Aragón)Zaragoza, Spain.,Department of Gastroenterology, Hospital Clínico Universitario Lozano BlesaZaragoza, Spain
| | - María A García-González
- CIBERehdMadrid, Spain.,Instituto de Investigación Sanitaria Aragón (IIS Aragón)Zaragoza, Spain.,Instituto Aragonés de Ciencias de la Salud (IACS)Zaragoza, Spain
| | - Ángel Lanas
- CIBERehdMadrid, Spain.,Instituto de Investigación Sanitaria Aragón (IIS Aragón)Zaragoza, Spain.,Department of Gastroenterology, Hospital Clínico Universitario Lozano BlesaZaragoza, Spain.,Department of Medicine, University of ZaragozaZaragoza, Spain
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Abstract
Stems cells of the colon crypt are the origin of colon mature cells. Colorectal cancer cells are also suggested to originate from crypt stem cells undergoing a series of epigenetic and genetic alterations. Aberrant methylation plays important roles in early carcinogenesis and lead to altered gene expression and regulation, resulting in accumulation of damages to cell function and ultimately, malignant transformation. Aberrances in hypermethylation and hypomethylation act in different mechanism through the regulation of various genes during CSC carcinogenesis, and both of them play crucial roles in stem cell differentiation towards cancer cells. A large majority of epigenetic and genetic abnormalities that work coordinately in colorectal carcinogenesis are related to cell growth and division, indicating that the intrinsic abnormalities of CRC lie in dysregulation of basic cellular processes. Detection of abnormal methylation can be used in cancer screening and early detection, while reversal of aberrant methylation using drugs may have potential in cancer therapy. This review will provide an overview on the roles of aberrant methylation and a summary of genes that are affected during CRC carcinogenesis.
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Affiliation(s)
- Lele Song
- Department of Radiotherapy, The Chinese PLA 309th Hospital, No. 17, Heishanhu Road, Haidian District, Beijing, 100091, People's Republic of China.
- BioChain (Beijing) Science and Technology, Inc, Beijing, 100176, People's Republic of China.
| | - Yuemin Li
- Department of Radiotherapy, The Chinese PLA 309th Hospital, No. 17, Heishanhu Road, Haidian District, Beijing, 100091, People's Republic of China.
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10
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Westphalen CB, Quante M, Wang TC. Functional implication of Dclk1 and Dclk1-expressing cells in cancer. Small GTPases 2016; 8:164-171. [PMID: 27458755 DOI: 10.1080/21541248.2016.1208792] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Doublecortin like kinase protein 1 (Dclk1) is a microtubule-associated protein with C-terminal serine/threonine kinase domain. Originally designated Doublecortin and CaM kinase-like 1 protein (Dcamkl1) or KIAA0369, Dclk1 was first described as a marker for radial glia cells in the context of microtubule polymerization and neuronal migration, possibly contributing to early neurogenesis. Additionally, Dclk1 was proposed as a marker of quiescent gastrointestinal and pancreatic stem cells, but in recent years has been recognized as a marker for tuft cells in the gastrointestinal tract. While Dclk1+ tuft cells are now considered as niche or sensory cells in the normal gut, growing evidence supports a role for Dclk1 function in a variety of malignancies, modulating the activity of multiple key pathways, including Kras signaling. Here, we review the recent advances in understanding of the importance of Dclk1 function in tumorigenesis and cancer.
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Affiliation(s)
- C Benedikt Westphalen
- a Department of Internal Medicine III , Ludwig Maximilians University Munich , Munich , Germany
| | - Michael Quante
- b Department of Internal Medicine II , Klinikum rechts der Isar II, Technische Universität München , Munich , Germany
| | - Timothy C Wang
- c Divison of Digestive and Liver Disease , Columbia University Medical Center , New York , NY , USA.,d Herberg Irving Comprehensive Cancer Center , Columbia University Medical Center , New York , NY , USA
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11
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Angrisano T, Pero R, Brancaccio M, Coretti L, Florio E, Pezone A, Calabrò V, Falco G, Keller S, Lembo F, Avvedimento VE, Chiariotti L. Cyclical DNA Methylation and Histone Changes Are Induced by LPS to Activate COX-2 in Human Intestinal Epithelial Cells. PLoS One 2016; 11:e0156671. [PMID: 27253528 PMCID: PMC4890762 DOI: 10.1371/journal.pone.0156671] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2015] [Accepted: 05/18/2016] [Indexed: 01/26/2023] Open
Abstract
Bacterial lipopolysaccharide (LPS) induces release of inflammatory mediators both in immune and epithelial cells. We investigated whether changes of epigenetic marks, including selected histone modification and DNA methylation, may drive or accompany the activation of COX-2 gene in HT-29 human intestinal epithelial cells upon exposure to LPS. Here we describe cyclical histone acetylation (H3), methylation (H3K4, H3K9, H3K27) and DNA methylation changes occurring at COX-2 gene promoter overtime after LPS stimulation. Histone K27 methylation changes are carried out by the H3 demethylase JMJD3 and are essential for COX-2 induction by LPS. The changes of the histone code are associated with cyclical methylation signatures at the promoter and gene body of COX-2 gene.
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Affiliation(s)
- Tiziana Angrisano
- Dipartimento di Biologia, Università degli Studi di Napoli “Federico II”, Monte Sant'Angelo via Cintia 21, 80126 Naples, Italy
- * E-mail: (TA); (LC)
| | - Raffaela Pero
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, via S. Pansini, 5, 80131 Naples, Italy
- Istituto di Endocrinologia ed Oncologia Sperimentale C.N.R., via S. Pansini, 5, 80131 Naples, Italy
| | - Mariarita Brancaccio
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, via S. Pansini, 5, 80131 Naples, Italy
| | - Lorena Coretti
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, via S. Pansini, 5, 80131 Naples, Italy
- Istituto di Endocrinologia ed Oncologia Sperimentale C.N.R., via S. Pansini, 5, 80131 Naples, Italy
| | - Ermanno Florio
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, via S. Pansini, 5, 80131 Naples, Italy
- Istituto di Endocrinologia ed Oncologia Sperimentale C.N.R., via S. Pansini, 5, 80131 Naples, Italy
| | - Antonio Pezone
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, via S. Pansini, 5, 80131 Naples, Italy
- Istituto di Endocrinologia ed Oncologia Sperimentale C.N.R., via S. Pansini, 5, 80131 Naples, Italy
| | - Viola Calabrò
- Dipartimento di Biologia, Università degli Studi di Napoli “Federico II”, Monte Sant'Angelo via Cintia 21, 80126 Naples, Italy
| | - Geppino Falco
- Dipartimento di Biologia, Università degli Studi di Napoli “Federico II”, Monte Sant'Angelo via Cintia 21, 80126 Naples, Italy
| | - Simona Keller
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, via S. Pansini, 5, 80131 Naples, Italy
- Istituto di Endocrinologia ed Oncologia Sperimentale C.N.R., via S. Pansini, 5, 80131 Naples, Italy
| | - Francesca Lembo
- Dipartimento di Farmacia, Università degli Studi di Napoli “Federico II”, via D. Montesano 47, 80131 Naples, Italy
| | | | - Lorenzo Chiariotti
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, via S. Pansini, 5, 80131 Naples, Italy
- Istituto di Endocrinologia ed Oncologia Sperimentale C.N.R., via S. Pansini, 5, 80131 Naples, Italy
- * E-mail: (TA); (LC)
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12
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Takizawa N, Matsuzaki T, Yamamoto T, Mishima T, Miyasaka C, Tanaka S, Kinoshita H, Uemura Y, Yamada H, Matsuda T. Novel strategy for cystitis glandularis: Oral treatment with cyclooxygenase-2 inhibitor. Int J Urol 2016; 23:706-8. [PMID: 27238955 DOI: 10.1111/iju.13121] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2015] [Accepted: 04/07/2016] [Indexed: 12/23/2022]
Abstract
Cystitis glandularis, a proliferative disease of the bladder, is resistant to antibiotics, non-steroidal anti-inflammatory drugs, anti-allergy drugs and transurethral resection. Cystectomy or partial cystectomy is occasionally required for refractory cystitis glandularis. It has not been defined if cystitis glandularis is a premalignant lesion. We experienced a case of remission from cystitis glandularis after combination of oral treatment with selective cyclooxygenase-2 inhibitor, celecoxib and transurethral resection. Immunohistochemistry showed positive signals of cyclooxygenase-2 in the epithelium of pretreatment specimens, suggesting the pathophysiological role of cyclooxygenase-2 in cystitis glandularis. Here, we show the effectiveness of celecoxib against cystitis glandularis for the first time. Celecoxib could be one of the therapeutic strategies for cystitis glandularis.
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Affiliation(s)
- Nae Takizawa
- Department of Urology and Andrology, Kansai Medical University, Hirakata, Osaka, Japan
| | - Tomoaki Matsuzaki
- Department of Urology and Andrology, Kansai Medical University, Hirakata, Osaka, Japan
| | - Teppei Yamamoto
- Department of Urology and Andrology, Kansai Medical University, Hirakata, Osaka, Japan
| | - Takao Mishima
- Department of Urology and Andrology, Kansai Medical University, Hirakata, Osaka, Japan
| | - Chika Miyasaka
- Department of Pathology and Laboratory Medicine, Kansai Medical University, Hirakata, Osaka, Japan
| | - Susumu Tanaka
- Department of Anatomy and Cell Science, Kansai Medical University, Hirakata, Osaka, Japan
| | - Hidefumi Kinoshita
- Department of Urology and Andrology, Kansai Medical University, Hirakata, Osaka, Japan
| | - Yoshiko Uemura
- Department of Pathology and Laboratory Medicine, Kansai Medical University, Hirakata, Osaka, Japan
| | - Hisao Yamada
- Department of Anatomy and Cell Science, Kansai Medical University, Hirakata, Osaka, Japan
| | - Tadashi Matsuda
- Department of Urology and Andrology, Kansai Medical University, Hirakata, Osaka, Japan
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Cebola I, Custodio J, Muñoz M, Díez-Villanueva A, Paré L, Prieto P, Aussó S, Coll-Mulet L, Boscá L, Moreno V, Peinado MA. Epigenetics override pro-inflammatory PTGS transcriptomic signature towards selective hyperactivation of PGE2 in colorectal cancer. Clin Epigenetics 2015; 7:74. [PMID: 26207152 PMCID: PMC4512023 DOI: 10.1186/s13148-015-0110-4] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2015] [Accepted: 07/06/2015] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Misregulation of the PTGS (prostaglandin endoperoxide synthase, also known as cyclooxygenase or COX) pathway may lead to the accumulation of pro-inflammatory signals, which constitutes a hallmark of cancer. To get insight into the role of this signaling pathway in colorectal cancer (CRC), we have characterized the transcriptional and epigenetic landscapes of the PTGS pathway genes in normal and cancer cells. RESULTS Data from four independent series of CRC patients (502 tumors including adenomas and carcinomas and 222 adjacent normal tissues) and two series of colon mucosae from 69 healthy donors have been included in the study. Gene expression was analyzed by real-time PCR and Affymetrix U219 arrays. DNA methylation was analyzed by bisulfite sequencing, dissociation curves, and HumanMethylation450K arrays. Most CRC patients show selective transcriptional deregulation of the enzymes involved in the synthesis of prostanoids and their receptors in both tumor and its adjacent mucosa. DNA methylation alterations exclusively affect the tumor tissue (both adenomas and carcinomas), redirecting the transcriptional deregulation to activation of prostaglandin E2 (PGE2) function and blockade of other biologically active prostaglandins. In particular, PTGIS, PTGER3, PTGFR, and AKR1B1 were hypermethylated in more than 40 % of all analyzed tumors. CONCLUSIONS The transcriptional and epigenetic profiling of the PTGS pathway provides important clues on the biology of the tumor and its microenvironment. This analysis renders candidate markers with potential clinical applicability in risk assessment and early diagnosis and for the design of new therapeutic strategies.
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Affiliation(s)
- Inês Cebola
- />Institute of Predictive and Personalized Medicine of Cancer (IMPPC, Ctra Can Ruti, Cami de les Escoles, Badalona, 08916 Spain
- />Current address: Department of Medicine, Imperial College London, London, UK
| | - Joaquin Custodio
- />Institute of Predictive and Personalized Medicine of Cancer (IMPPC, Ctra Can Ruti, Cami de les Escoles, Badalona, 08916 Spain
- />Current address: Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
| | - Mar Muñoz
- />Institute of Predictive and Personalized Medicine of Cancer (IMPPC, Ctra Can Ruti, Cami de les Escoles, Badalona, 08916 Spain
| | - Anna Díez-Villanueva
- />Institute of Predictive and Personalized Medicine of Cancer (IMPPC, Ctra Can Ruti, Cami de les Escoles, Badalona, 08916 Spain
| | - Laia Paré
- />Unit of Biomarkers and Susceptibility, Cancer Prevention and Control Program, Catalan Institute of Oncology (ICO), IDIBELL and CIBERESP, Hospitalet de Llobregat, Barcelona Spain
| | - Patricia Prieto
- />Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid, Spain
| | - Susanna Aussó
- />Unit of Biomarkers and Susceptibility, Cancer Prevention and Control Program, Catalan Institute of Oncology (ICO), IDIBELL and CIBERESP, Hospitalet de Llobregat, Barcelona Spain
| | - Llorenç Coll-Mulet
- />Institute of Predictive and Personalized Medicine of Cancer (IMPPC, Ctra Can Ruti, Cami de les Escoles, Badalona, 08916 Spain
| | - Lisardo Boscá
- />Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid, Spain
| | - Victor Moreno
- />Unit of Biomarkers and Susceptibility, Cancer Prevention and Control Program, Catalan Institute of Oncology (ICO), IDIBELL and CIBERESP, Hospitalet de Llobregat, Barcelona Spain
- />Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain
| | - Miguel A. Peinado
- />Institute of Predictive and Personalized Medicine of Cancer (IMPPC, Ctra Can Ruti, Cami de les Escoles, Badalona, 08916 Spain
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Lu L, Zhang Q, Wu K, Chen X, Zheng Y, Zhu C, Wu J. Hepatitis C virus NS3 protein enhances cancer cell invasion by activating matrix metalloproteinase-9 and cyclooxygenase-2 through ERK/p38/NF-κB signal cascade. Cancer Lett 2014; 356:470-8. [PMID: 25305454 DOI: 10.1016/j.canlet.2014.09.027] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2014] [Revised: 09/06/2014] [Accepted: 09/22/2014] [Indexed: 12/17/2022]
Abstract
Hepatitis C virus (HCV) infection causes acute and chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). However, the mechanisms by which HCV causes the diseases are largely unknown. Here, we elucidated the effects of HCV on the invasion and migration of hepatoma cells, with the aim to reveal the mechanism by which HCV infection induces HCC. We initially showed that matrix metalloproteinase-9 (MMP-9) was elevated in the sera of HCV-infected patients, and demonstrated that HCV nonstructural protein 3 (NS3) activated MMP-9 transcription through nuclear factor-κB (NF-κB) by stimulating translocation of NF-κB from cytosol to the nucleus to enhance its binding to MMP-9 promoter. In addition, cyclooxygenase-2 (COX-2) and extracellular signal-regulated kinase (ERK1/2)/mitogen-activated protein kinase (p38) pathway were involved in HCV-activated MMP-9 expression. Moreover, NS3 enhanced hepatoma cell invasion and migration through MMP-9 and COX-2. Thus, this study provides new insights into the roles of HCV NS3, MMP-9 and COX-2 in regulating cancer cell invasion.
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Affiliation(s)
- Lili Lu
- State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China; Wuhan University of Science and Technology, Wuhan 430081, China
| | - Qi Zhang
- State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China
| | - Kailang Wu
- State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China
| | - Xi Chen
- State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China
| | - Yi Zheng
- State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China
| | - Chengliang Zhu
- State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China; Renmin Hospital, Wuhan University, Wuhan 430060, China
| | - Jianguo Wu
- State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
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Ash SA, Buggy DJ. Does regional anaesthesia and analgesia or opioid analgesia influence recurrence after primary cancer surgery? An update of available evidence. Best Pract Res Clin Anaesthesiol 2013; 27:441-56. [PMID: 24267550 DOI: 10.1016/j.bpa.2013.10.005] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Accepted: 10/07/2013] [Indexed: 12/12/2022]
Abstract
Cancer continues to be a key cause of morbidity and mortality worldwide and its overall incidence continues to increase. Anaesthetists are increasingly faced with the challenge of managing cancer patients, for surgical resection to debulk or excise the primary tumour, or for surgical emergencies in patients on chemotherapy or for the analgesic management of disease- or treatment-related chronic pain. Metastatic recurrence is a concern. Surgery and a number of perioperative factors are suspected to accelerate tumour growth and potentially increase the risk of metastatic recurrence. Retrospective analyses have suggested an association between anaesthetic technique and cancer outcomes, and anaesthetists have sought to ameliorate the consequences of surgical trauma and minimise the impact of anaesthetic interventions. Just how anaesthesia and analgesia impact cancer recurrence and consequent survival is very topical, as understanding the potential mechanisms and interactions has an impact on the anaesthetist's ability to contribute to the successful outcome of oncological interventions. The outcome of ongoing, prospective, randomized trials are awaited with interest.
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Affiliation(s)
- Simon A Ash
- Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland.
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