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Alkhaldy AA. Knowledge, attitudes, and practices toward colorectal cancer lifestyle risk factors among adults in Saudi Arabia. Front Nutr 2025; 12:1507563. [PMID: 40264557 PMCID: PMC12011586 DOI: 10.3389/fnut.2025.1507563] [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: 10/08/2024] [Accepted: 03/24/2025] [Indexed: 04/24/2025] Open
Abstract
Background Despite an apparent increase in early-onset colorectal cancer (CRC) in Saudi Arabia, with the majority of patients being diagnosed at an advanced disease stage, no previous assessment of the knowledge, attitudes, and practices (KAP) toward its dietary and lifestyle-related risk factors has been reported. The aim of this study was to investigate the KAP levels with respect to these risk factors for CRC and examine possible associations between the studied variables among the Saudi population. Methods This cross-sectional study involved 1,040 participants aged 18 years or older. Data were collected by convenience sampling via a self-administered online questionnaire in Saudi Arabia between June and December 2023. Results A majority of participants (77.8%) displayed low knowledge about the dietary and lifestyle-related risk factors for CRC, while only 22.2% possessed high knowledge. Similarly, 78.6% of participants exhibited negative attitudes toward these risk factors, with just 21.4% having positive attitudes. Furthermore, 75.0% of participants reported engaging in poor practices, leaving only 25.0% demonstrating good practices related to CRC risk factors. Conclusions The findings of this study indicate insufficient KAP levels toward dietary and lifestyle-related risk factors for CRC in Saudi Arabia, highlighting the urgent need for nationwide initiatives and programs to promote improved knowledge, attitudes, and practices and reduce the effect of the risk factors contributing to CRC.
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Affiliation(s)
- Areej Ali Alkhaldy
- Department of Clinical Nutrition, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
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Ghorbaninezhad F, Nour MA, Farzam OR, Saeedi H, Vanan AG, Bakhshivand M, Jafarlou M, Hatami-Sadr A, Baradaran B. The tumor microenvironment and dendritic cells: Developers of pioneering strategies in colorectal cancer immunotherapy? Biochim Biophys Acta Rev Cancer 2025; 1880:189281. [PMID: 39929377 DOI: 10.1016/j.bbcan.2025.189281] [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: 05/31/2024] [Revised: 01/25/2025] [Accepted: 02/04/2025] [Indexed: 02/13/2025]
Abstract
Colorectal cancer (CRC) is the world's third most frequent cancer, and both its incidence and fatality rates are rising. Despite various therapeutic approaches, neither its mortality rate nor its recurrence frequency has decreased significantly. Additionally, conventional treatment approaches, such as chemotherapy and radiotherapy, have several side effects and risks for patients with CRC. Accordingly, the need for alternative and effective treatments for CRC patients is critical. Immunotherapy that utilizes dendritic cells (DCs) harnesses the patient's immune system to combat cancer cells effectively. DCs are the most potent antigen-presenting cells (APCs), which play a vital role in generating anti-cancer T cell responses. A significant barrier to the immune system's ability to eliminate CRC is the establishment of a potent immunosuppressive tumor milieu by malignant cells. Since DCs are frequently defective in this milieu, the tumor setting significantly reduces the effectiveness of DC-based therapy. Determining central mechanisms contributing to tumor growth by unraveling and comprehending the interaction between CRC tumor milieu and DCs may lead to new therapeutic approaches. This study aims to review DC biology and discuss its role in T-cell-mediated anti-tumor immunity, as well as to highlight the immunosuppressive effects of the CRC tumor milieu on the function of DCs. We will also highlight the tumor microenvironment (TME)-related factors that interfere with DC function as a possible therapeutic target to enhance DC-based cell therapy efficacy.
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Affiliation(s)
- Farid Ghorbaninezhad
- Student Research Committee, Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Mina Afrashteh Nour
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Omid Rahbar Farzam
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hossein Saeedi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ahmad Ghorbani Vanan
- Student Research Committee, Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Mohammad Bakhshivand
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mahdi Jafarlou
- Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Behzad Baradaran
- Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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Wu Z, Hu Z, Li Q, Liu G, Oaknin A, Grau Bejar JF, Mills GB, Ma D, Sun C, Chen G. Molecular and clinical insights into early-onset endometrial cancer. Trends Cancer 2025:S2405-8033(25)00070-6. [PMID: 40133132 DOI: 10.1016/j.trecan.2025.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 02/24/2025] [Accepted: 03/04/2025] [Indexed: 03/27/2025]
Abstract
The global incidence of endometrial cancer is on the rise, marked by a notable surge in early-onset endometrial cancer (EOEC; age at diagnosis <50 years). By contrast to late-onset cases, EOEC displays distinct clinical, pathological, and molecular characteristics. The enhanced understanding of the disease's pathophysiology, enabling a more precise differentiation between low-risk and high-risk patients, could facilitate the establishment of risk-stratified treatments that preserve ovarian function and fertility in low-risk EOEC cases. In this review, we delve into the distinctive epidemiological, molecular, and clinical characteristics of EOEC, as well as early noninvasive screening and fertility preservation treatments.
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Affiliation(s)
- Zimeng Wu
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhe Hu
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qinlan Li
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Geyan Liu
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ana Oaknin
- Medical Oncology Service, Vall d'Hebron Institute of Oncology, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Juan Francisco Grau Bejar
- Medical Oncology Service, Vall d'Hebron Institute of Oncology, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | | | - Ding Ma
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chaoyang Sun
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Gang Chen
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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Sullivan JP, Jones MK. The Multifaceted Impact of Bioactive Lipids on Gut Health and Disease. Int J Mol Sci 2024; 25:13638. [PMID: 39769399 PMCID: PMC11728145 DOI: 10.3390/ijms252413638] [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: 12/02/2024] [Revised: 12/13/2024] [Accepted: 12/16/2024] [Indexed: 01/11/2025] Open
Abstract
Bioactive lipids have a multifaceted role in health and disease and are recognized to play an important part in gut immunity and disease conditions such as inflammatory bowel disease and colon cancer. Advancements in lipidomics, enabled by mass spectrometry and chromatographic techniques, have enhanced our understanding of lipid diversity and functionality. Bioactive lipids, including short-chain fatty acids, saturated fatty acids, omega-3 fatty acids, and sphingolipids, exhibit diverse effects on inflammation and immune regulation. Short-chain fatty acids like butyrate demonstrate anti-inflammatory properties, enhancing regulatory T cell function, gut barrier integrity, and epigenetic regulation, making them promising therapeutic targets for inflammatory bowel disease and colon cancer. Conversely, saturated fatty acids promote inflammation by disrupting gut homeostasis, triggering oxidative stress, and impairing immune regulation. Omega-3 lipids counteract these effects, reducing inflammation and supporting immune balance. Sphingolipids exhibit complex roles, modulating immune cell trafficking and inflammation. They can exert protective effects or exacerbate colitis depending on their source and context. Additionally, eicosanoids can also prevent pathology through prostaglandin defense against damage to epithelial barriers. This review underscores the importance of dietary lipids in shaping gut health and immunity and also highlights the potential use of lipids as therapeutic strategies for managing inflammatory conditions and cancer.
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Affiliation(s)
| | - Melissa K. Jones
- Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL 32611, USA;
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AlDoughaim M, AlSuhebany N, AlZahrani M, AlQahtani T, AlGhamdi S, Badreldin H, Al Alshaykh H. Cancer Biomarkers and Precision Oncology: A Review of Recent Trends and Innovations. Clin Med Insights Oncol 2024; 18:11795549241298541. [PMID: 39559827 PMCID: PMC11571259 DOI: 10.1177/11795549241298541] [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: 07/08/2024] [Accepted: 10/22/2024] [Indexed: 11/20/2024] Open
Abstract
The discovery of cancer-specific biomarkers has resulted in major advancements in the field of cancer diagnostics and therapeutics, therefore significantly lowering cancer-related morbidity and mortality. Cancer biomarkers can be generally classified as prognostic biomarkers that predict specific disease outcomes and predictive biomarkers that predict disease response to targeted therapeutic interventions. As research in the area of predictive biomarkers continues to grow, precision medicine becomes far more integrated in cancer treatment. This article presents a general overview on the most recent advancements in the area of cancer biomarkers, immunotherapy, artificial intelligence, and pharmacogenomics of the Middle East.
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Affiliation(s)
- Maha AlDoughaim
- College of Pharmacy, King Saud Bin Abdul Aziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia
| | - Nada AlSuhebany
- College of Pharmacy, King Saud Bin Abdul Aziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia
| | - Mohammed AlZahrani
- College of Pharmacy, King Saud Bin Abdul Aziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia
| | - Tariq AlQahtani
- College of Pharmacy, King Saud Bin Abdul Aziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia
| | - Sahar AlGhamdi
- College of Pharmacy, King Saud Bin Abdul Aziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia
| | - Hisham Badreldin
- College of Pharmacy, King Saud Bin Abdul Aziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia
| | - Hana Al Alshaykh
- Pharmaceutical Care Devision, King Faisal Specialist Hospital and Research Center (KFSHRC), Riyadh, Saudi Arabia
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Xu W, Liang X, Chen L, Hong W, Hu X. Biobanks in chronic disease management: A comprehensive review of strategies, challenges, and future directions. Heliyon 2024; 10:e32063. [PMID: 38868047 PMCID: PMC11168399 DOI: 10.1016/j.heliyon.2024.e32063] [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: 12/22/2023] [Revised: 05/27/2024] [Accepted: 05/28/2024] [Indexed: 06/14/2024] Open
Abstract
Biobanks, through the collection and storage of patient blood, tissue, genomic, and other biological samples, provide unique and rich resources for the research and management of chronic diseases such as cardiovascular diseases, diabetes, and cancer. These samples contain valuable cellular and molecular level information that can be utilized to decipher the pathogenesis of diseases, guide the development of novel diagnostic technologies, treatment methods, and personalized medical strategies. This article first outlines the historical evolution of biobanks, their classification, and the impact of technological advancements. Subsequently, it elaborates on the significant role of biobanks in revealing molecular biomarkers of chronic diseases, promoting the translation of basic research to clinical applications, and achieving individualized treatment and management. Additionally, challenges such as standardization of sample processing, information privacy, and security are discussed. Finally, from the perspectives of policy support, regulatory improvement, and public participation, this article provides a forecast on the future development directions of biobanks and strategies to address challenges, aiming to safeguard and enhance their unique advantages in supporting chronic disease prevention and treatment.
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Affiliation(s)
- Wanna Xu
- Shenzhen Center for Chronic Disease Control, Shenzhen Institute of Dermatology, Shenzhen, 518020, China
| | - Xiongshun Liang
- Shenzhen Center for Chronic Disease Control, Shenzhen Institute of Dermatology, Shenzhen, 518020, China
| | - Lin Chen
- Shenzhen Center for Chronic Disease Control, Shenzhen Institute of Dermatology, Shenzhen, 518020, China
| | - Wenxu Hong
- Shenzhen Center for Chronic Disease Control, Shenzhen Institute of Dermatology, Shenzhen, 518020, China
| | - Xuqiao Hu
- Shenzhen Center for Chronic Disease Control, Shenzhen Institute of Dermatology, Shenzhen, 518020, China
- Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology (Shenzhen People's Hospital), Shenzhen, China
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Lee J, Ogino S, Wang M. Weighting estimation in the cause-specific Cox regression with partially missing causes of failure. Stat Med 2024; 43:2575-2591. [PMID: 38659326 DOI: 10.1002/sim.10084] [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: 03/10/2023] [Revised: 02/25/2024] [Accepted: 04/05/2024] [Indexed: 04/26/2024]
Abstract
Complex diseases are often analyzed using disease subtypes classified by multiple biomarkers to study pathogenic heterogeneity. In such molecular pathological epidemiology research, we consider a weighted Cox proportional hazard model to evaluate the effect of exposures on various disease subtypes under competing-risk settings in the presence of partially or completely missing biomarkers. The asymptotic properties of the inverse and augmented inverse probability-weighted estimating equation methods are studied with a general pattern of missing data. Simulation studies have been conducted to demonstrate the double robustness of the estimators. For illustration, we applied this method to examine the association between pack-years of smoking before the age of 30 and the incidence of colorectal cancer subtypes defined by a combination of four tumor molecular biomarkers (statuses of microsatellite instability, CpG island methylator phenotype, BRAF mutation, and KRAS mutation) in the Nurses' Health Study cohort.
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Affiliation(s)
- Jooyoung Lee
- Department of Applied Statistics, Chung-Ang University, Seoul, Korea
| | - Shuji Ogino
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
- Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Eli and Edythe L Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
| | - Molin Wang
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
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8
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Lim SY, Ulaganathan V, Nallamuthu P, Gunasekaran B, Salvamani S. Dietary Patterns and Lifestyle Factors Associated with the Risk of Colorectal Cancer: A Hospital-Based Case-Control Study among Malaysians. Malays J Med Sci 2024; 31:212-234. [PMID: 38456114 PMCID: PMC10917583 DOI: 10.21315/mjms2024.31.1.18] [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: 01/09/2023] [Accepted: 06/16/2023] [Indexed: 03/09/2024] Open
Abstract
Background This study aimed to examine the association between dietary patterns, lifestyle factors, and colorectal cancer (CRC) risk among the Malaysian population. Methods We recruited 100 patients and 100 controls from two selected government hospitals. Principal component analysis was used to identify dietary patterns using a 123-item semiquantitative food frequency questionnaire. Tobacco smoking and alcohol consumption questionnaires were modified from the WHO STEPS Survey questionnaire. Physical activity levels were assessed using the revised Global Physical Activity questionnaire. Associations between dietary patterns, lifestyle factors and CRC risk were assessed using logistic regression with SPSS version 24.0. Results Three dietary patterns were derived from factor analysis: i) vegetables; ii) meat, seafood and processed food; and iii) grains and legumes. High vegetable diet intake was independently and significantly associated with an 81% decreased risk of CRC (odds ratio [OR]: 0.19; 95% confidence interval [CI]: 0.08, 0.46). Both recreational-related physical activity (OR: 2.04; 95% CI: 1.14, 3.64) and vigorous physical activity (OR: 2.06; 95% CI: 1.13, 3.74) are significantly associated with decreased risk of CRC. Increasing the number of cigarettes smoked (≥ 16 cigarettes) per day significantly increased the odds of developing CRC (OR: 2.58; 95% CI: 1.95, 6.75). The duration of alcohol consumption cessation was inversely associated with CRC risk (OR: 2.52; 95% CI: 2.30, 10.57). Conclusion The protective effects of a fruit and vegetable diet, and a healthy lifestyle can be used to develop interventions that help reduce the risk of CRC in the Malaysian population.
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Affiliation(s)
- Sook Yee Lim
- Faculty of Applied Sciences, UCSI University, Kuala Lumpur, Malaysia
| | | | | | | | - Shamala Salvamani
- Division of Applied Biomedical Science and Biotechnology, School of Health Sciences, International Medical University, Kuala Lumpur, Malaysia
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Hamasaki H. Effects of Tai Chi in diabetes patients: Insights from recent research. World J Diabetes 2024; 15:1-10. [PMID: 38313854 PMCID: PMC10835502 DOI: 10.4239/wjd.v15.i1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Revised: 12/10/2023] [Accepted: 12/28/2023] [Indexed: 01/12/2024] Open
Abstract
Tai Chi, a practice that combines elements of both exercise and mindfulness, offers a wide range of health benefits. The body of evidence concerning the impact of Tai Chi on diabetes has recently been growing. This editorial aims to provide a concise summary of the current state of evidence for Tai Chi's effects on individuals with type 2 diabetes (T2D). The review includes 3 randomized controlled trials (RCTs) and 5 systematic reviews and meta-analyses, all of which investigate the effectiveness of Tai Chi on various health outcomes in individuals with T2D. Tai Chi demonstrates a significant effect to enhance glycemic control, lower blood pressure, improve serum lipid profiles, reduce insulin resistance, positively influence obesity-related indices, and improve overall quality of life in individuals with T2D. However, it is noteworthy that recent RCTs have reported inconsistent findings regarding the effects of Tai Chi on glycemic control and insulin resistance. The author also delves into potential mechanisms by which Tai Chi may exert its influence on the human body. Finally, the editorial highlights the critical issues that warrant further exploration in the future.
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Affiliation(s)
- Hidetaka Hamasaki
- Department of Endocrinology and Metabolism, Internal Medicine, Hamasaki Clinic, Kagoshima 890-0046, Japan
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10
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Roshani M, Molavizadeh D, Sadeghi S, Jafari A, Dashti F, Mirazimi SMA, Ahmadi Asouri S, Rajabi A, Hamblin MR, Anoushirvani AA, Mirzaei H. Emerging roles of miR-145 in gastrointestinal cancers: A new paradigm. Biomed Pharmacother 2023; 166:115264. [PMID: 37619484 DOI: 10.1016/j.biopha.2023.115264] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 07/25/2023] [Accepted: 07/31/2023] [Indexed: 08/26/2023] Open
Abstract
Gastrointestinal (GI) carcinomas are a group of cancers affecting the GI tract and digestive organs, such as the gastric, liver, bile ducts, pancreas, small intestine, esophagus, colon, and rectum. MicroRNAs (miRNAs) are small functional non-coding RNAs (ncRNAs) which are involved in regulating the expression of multiple target genes; mainly at the post-transcriptional level, via complementary binding to their 3'-untranslated region (3'-UTR). Increasing evidence has shown that miRNAs have critical roles in modulating of various physiological and pathological cellular processes and regulating the occurrence and development of human malignancies. Among them, miR-145 is recognized for its anti-oncogenic properties in various cancers, including GI cancers. MiR-145 has been implicated in diverse biological processes of cancers through the regulation of target genes or signaling, including, proliferation, differentiation, tumorigenesis, angiogenesis, apoptosis, metastasis, and therapy resistance. In this review, we have summarized the role of miR-145 in selected GI cancers and also its downstream molecules and cellular processes targets, which could lead to a better understanding of the miR-145 in these cancers. In conclusion, we reveal the potential diagnostic, prognostic, and therapeutic value of miR-145 in GI cancer, and hope to provide new ideas for its application as a biomarker as well as a therapeutic target for the treatment of these cancer.
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Affiliation(s)
- Mohammad Roshani
- Internal Medicine and Gastroenterology, Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Danial Molavizadeh
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Sara Sadeghi
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Ameneh Jafari
- Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Dashti
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Seyed Mohammad Ali Mirazimi
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Sahar Ahmadi Asouri
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for BasicSciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Ali Rajabi
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, South Africa
| | - Ali Arash Anoushirvani
- Department of Internal Medicine, Firoozgar Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Hamed Mirzaei
- Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Internal Medicine, Firoozgar Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
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Ashrafizadeh M, Mohan CD, Rangappa S, Zarrabi A, Hushmandi K, Kumar AP, Sethi G, Rangappa KS. Noncoding RNAs as regulators of STAT3 pathway in gastrointestinal cancers: Roles in cancer progression and therapeutic response. Med Res Rev 2023; 43:1263-1321. [PMID: 36951271 DOI: 10.1002/med.21950] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2021] [Revised: 10/09/2022] [Accepted: 02/28/2023] [Indexed: 03/24/2023]
Abstract
Gastrointestinal (GI) tumors (cancers of the esophagus, gastric, liver, pancreas, colon, and rectum) contribute to a large number of deaths worldwide. STAT3 is an oncogenic transcription factor that promotes the transcription of genes associated with proliferation, antiapoptosis, survival, and metastasis. STAT3 is overactivated in many human malignancies including GI tumors which accelerates tumor progression, metastasis, and drug resistance. Research in recent years demonstrated that noncoding RNAs (ncRNAs) play a major role in the regulation of many signaling pathways including the STAT3 pathway. The major types of endogenous ncRNAs that are being extensively studied in oncology are microRNAs, long noncoding RNAs, and circular RNAs. These ncRNAs can either be tumor-promoters or tumor-suppressors and each one of them imparts their activity via different mechanisms. The STAT3 pathway is also tightly modulated by ncRNAs. In this article, we have elaborated on the tumor-promoting role of STAT3 signaling in GI tumors. Subsequently, we have comprehensively discussed the oncogenic as well as tumor suppressor functions and mechanism of action of ncRNAs that are known to modulate STAT3 signaling in GI cancers.
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Affiliation(s)
- Milad Ashrafizadeh
- Department of General Surgery and Institute of Precision Diagnosis and Treatment of Digestive System Tumors, Carson International Cancer Center, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong, China
- Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chakrabhavi D Mohan
- Department of Studies in Molecular Biology, University of Mysore, Manasagangotri, India
| | - Shobith Rangappa
- Adichunchanagiri Institute for Molecular Medicine, Adichunchanagiri University, Nagamangala Taluk, India
| | - Ali Zarrabi
- Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
- Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul, Sariyer, Turkey
| | - Kiavash Hushmandi
- Division of Epidemiology, Faculty of Veterinary Medicine, Department of Food Hygiene and Quality Control, University of Tehran, Tehran, Iran
| | - Alan Prem Kumar
- NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Gautam Sethi
- NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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Moslehian MS, Shabkhizan R, Asadi MR, Bazmani A, Mahdipour M, Haiaty S, Rahbarghazi R, Sakhinia E. Interaction of lncRNAs with mTOR in colorectal cancer: a systematic review. BMC Cancer 2023; 23:512. [PMID: 37280524 DOI: 10.1186/s12885-023-11008-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 05/25/2023] [Indexed: 06/08/2023] Open
Abstract
Colorectal cancer (CRC) is the third most widespread cancer and the fourth leading lethal disease among different societies. It is thought that CRC accounts for about 10% of all newly diagnosed cancer cases with high-rate mortality. lncRNAs, belonging to non-coding RNAs, are involved in varied cell bioactivities. Emerging data have confirmed a significant alteration in lncRNA transcription under anaplastic conditions. This systematic review aimed to assess the possible influence of abnormal mTOR-associated lncRNAs in the tumorigenesis of colorectal tissue. In this study, the PRISMA guideline was utilized based on the systematic investigation of published articles from seven databases. Of the 200 entries, 24 articles met inclusion criteria and were used for subsequent analyses. Of note, 23 lncRNAs were prioritized in association with the mTOR signaling pathway with up-regulation (79.16%) and down-regulation (20.84%) trends. Based on the obtained data, mTOR can be stimulated or inhibited during CRC by the alteration of several lncRNAs. Determining the dynamic activity of mTOR and relevant signaling pathways via lncRNAs can help us progress novel molecular therapeutics and medications.
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Affiliation(s)
- Marziyeh Sadat Moslehian
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Roya Shabkhizan
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Reza Asadi
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ahad Bazmani
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University Of Mashhad, Mashhad, Iran
| | - Mahdi Mahdipour
- Stem Cell Research Center, Tabriz University of Medical Sciences, Imam Reza St., Golgasht St, Tabriz, Iran
| | - Sanya Haiaty
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- Department of Biochemistry and Clinical Laboratories, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Reza Rahbarghazi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Imam Reza St., Golgasht St, Tabriz, Iran.
- Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Ebrahim Sakhinia
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- Tabriz Genetic Analysis Centre (TGAC), Tabriz University of Medical Sciences, Tabriz, Iran.
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13
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Baglaenko Y, Wagner C, Bhoj VG, Brodin P, Gershwin ME, Graham D, Invernizzi P, Kidd KK, Korsunsky I, Levy M, Mammen AL, Nizet V, Ramirez-Valle F, Stites EC, Williams MS, Wilson M, Rose NR, Ladd V, Sirota M. Making inroads to precision medicine for the treatment of autoimmune diseases: Harnessing genomic studies to better diagnose and treat complex disorders. CAMBRIDGE PRISMS. PRECISION MEDICINE 2023; 1:e25. [PMID: 38550937 PMCID: PMC10953750 DOI: 10.1017/pcm.2023.14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 04/21/2023] [Accepted: 04/25/2023] [Indexed: 06/13/2024]
Abstract
Precision Medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle. Autoimmune diseases are those in which the body's natural defense system loses discriminating power between its own cells and foreign cells, causing the body to mistakenly attack healthy tissues. These conditions are very heterogeneous in their presentation and therefore difficult to diagnose and treat. Achieving precision medicine in autoimmune diseases has been challenging due to the complex etiologies of these conditions, involving an interplay between genetic, epigenetic, and environmental factors. However, recent technological and computational advances in molecular profiling have helped identify patient subtypes and molecular pathways which can be used to improve diagnostics and therapeutics. This review discusses the current understanding of the disease mechanisms, heterogeneity, and pathogenic autoantigens in autoimmune diseases gained from genomic and transcriptomic studies and highlights how these findings can be applied to better understand disease heterogeneity in the context of disease diagnostics and therapeutics.
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Affiliation(s)
| | | | | | | | | | - Daniel Graham
- The Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Pietro Invernizzi
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), IRCCS Fondazione San Gerardo dei Tintori, Monza, Italy
| | - Kenneth K. Kidd
- Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA
| | | | - Michael Levy
- Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Andrew L. Mammen
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, USA
| | - Victor Nizet
- School of Medicine, University of California San Diego, San Diego, CA, USA
| | | | - Edward C. Stites
- Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA
| | | | - Michael Wilson
- Weill Institute for Neurosciences, Department of Neurology, UCSF, San Francisco, CA, USA
| | - Noel R. Rose
- Autoimmune Association, Clinton Township, MI, USA
| | | | - Marina Sirota
- Bakar Computational Health Sciences Institute, UCSF, San Francisco, CA, USA
- Department of Pediatrics, UCSF, San Francisco, CA, USA
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14
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Boughanem H, Kompella P, Tinahones FJ, Macias-Gonzalez M. An overview of vitamins as epidrugs for colorectal cancer prevention. Nutr Rev 2023; 81:455-479. [PMID: 36018754 DOI: 10.1093/nutrit/nuac065] [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: 11/13/2022] Open
Abstract
Gene expression altering epigenomic modifications such as DNA methylation, histone modification, and chromosome remodeling is crucial to regulating many biological processes. Several lifestyle factors, such as diet and natural, bioactive food compounds, such as vitamins, modify epigenetic patterns. However, epigenetic dysregulation can increase the risk of many diseases, including cancer. Various studies have provided supporting and contrasting evidence on the relationship between vitamins and cancer risk. Though there is a gap in knowledge about whether dietary vitamins can induce epigenetic modifications in the context of colorectal cancer (CRC), the possibility of using them as epidrugs for CRC treatment is being explored. This is promising because such studies might be informative about the most effective way to use vitamins in combination with DNA methyltransferase inhibitors and other approved therapies to prevent and treat CRC. This review summarizes the available epidemiological and observational studies involving dietary, circulating levels, and supplementation of vitamins and their relationship with CRC risk. Additionally, using available in vitro, in vivo, and human observational studies, the role of vitamins as potential epigenetic modifiers in CRC is discussed. This review is focused on the action of vitamins as modifiers of DNA methylation because aberrant DNA methylation, together with genetic alterations, can induce the initiation and progression of CRC. Although this review presents some studies with promising results, studies with better study designs are necessary. A thorough understanding of the underlying molecular mechanisms of vitamin-mediated epigenetic regulation of CRC genes can help identify effective therapeutic targets for CRC prevention and treatment.
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Affiliation(s)
- Hatim Boughanem
- are with the Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA), University of Malaga, Malaga, Spain.,are with the Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
| | - Pallavi Kompella
- are with the Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA), University of Malaga, Malaga, Spain.,is with the Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas, USA
| | - Francisco J Tinahones
- are with the Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA), University of Malaga, Malaga, Spain.,are with the Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
| | - Manuel Macias-Gonzalez
- are with the Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA), University of Malaga, Malaga, Spain.,are with the Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
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15
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Miro C, Docimo A, Barrea L, Verde L, Cernea S, Sojat AS, Marina LV, Docimo G, Colao A, Dentice M, Muscogiuri G. "Time" for obesity-related cancer: The role of the circadian rhythm in cancer pathogenesis and treatment. Semin Cancer Biol 2023; 91:99-109. [PMID: 36893964 DOI: 10.1016/j.semcancer.2023.03.003] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 02/21/2023] [Accepted: 03/06/2023] [Indexed: 03/09/2023]
Abstract
The circadian rhythm is regulated by an intrinsic time-tracking system, composed both of a central and a peripheral clock, which influences the cycles of activities and sleep of an individual over 24 h. At the molecular level, the circadian rhythm begins when two basic helix-loop-helix/Per-ARNT-SIM (bHLH-PAS) proteins, BMAL-1 and CLOCK, interact with each other to produce BMAL-1/CLOCK heterodimers in the cytoplasm. The BMAL-1/CLOCK target genes encode for the repressor components of the clock, cryptochrome (Cry1 and Cry2) and the Period proteins (Per1, Per2 and Per3). It has been recently demonstrated that the disruption of circadian rhythm is associated with an increased risk of developing obesity and obesity-related diseases. In addition, it has been demonstrated that the disruption of the circadian rhythm plays a key role in tumorigenesis. Further, an association between the circadian rhythm disruptions and an increased incidence and progression of several types of cancer (e.g., breast, prostate, colorectal and thyroid cancer) has been found. As the perturbation of circadian rhythm has adverse metabolic consequences (e.g., obesity) and at the same time tumor promoter functions, this manuscript has the aim to report how the aberrant circadian rhythms affect the development and prognosis of different types of obesity-related cancers (breast, prostate, colon rectal and thyroid cancer) focusing on both human studies and on molecular aspects.
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Affiliation(s)
- Caterina Miro
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", 80131 Naples, Italy
| | - Annamaria Docimo
- Dipartimento di Medicina Clinica e Chirurgia, Unità di Endocrinologia, Diabetologia ed Andrologia, Università Federico II, Naples, Italy
| | - Luigi Barrea
- Dipartimento di Scienze Umanistiche, Università Telematica Pegaso, 80143 Naples, Italy
| | - Ludovica Verde
- Department of Public Health, University of Federico II, 80131 Naples, Italy
| | - Simona Cernea
- George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mures/Internal Medicine I, Târgu Mureş, Romania; Diabetes, Nutrition and Metabolic Diseases Outpatient Unit, Emergency County Clinical Hospital, Târgu Mureş, Romania
| | - Antoan Stefan Sojat
- National Centre for Infertility and Endocrinology of Gender, Clinic for Endocrinology Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, Serbia
| | - Ljiljana V Marina
- National Centre for Infertility and Endocrinology of Gender, Clinic for Endocrinology Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, Serbia
| | - Giovanni Docimo
- Department of Medical and Advanced Surgical Sciences, University of Campania "Luigi Vanvitelli", 80131 Naples, Italy
| | - Annamaria Colao
- Dipartimento di Medicina Clinica e Chirurgia, Unità di Endocrinologia, Diabetologia ed Andrologia, Università Federico II, Naples, Italy; UNESCO Chair "Education for Health and Sustainable Development", University of Naples "Federico II", Naples, Italy
| | - Monica Dentice
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", 80131 Naples, Italy
| | - Giovanna Muscogiuri
- Dipartimento di Medicina Clinica e Chirurgia, Unità di Endocrinologia, Diabetologia ed Andrologia, Università Federico II, Naples, Italy; UNESCO Chair "Education for Health and Sustainable Development", University of Naples "Federico II", Naples, Italy.
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16
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Jardim SR, de Souza LMP, de Souza HSP. The Rise of Gastrointestinal Cancers as a Global Phenomenon: Unhealthy Behavior or Progress? INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:3640. [PMID: 36834334 PMCID: PMC9962127 DOI: 10.3390/ijerph20043640] [Citation(s) in RCA: 50] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 02/09/2023] [Accepted: 02/13/2023] [Indexed: 06/18/2023]
Abstract
The overall burden of cancer is rapidly increasing worldwide, reflecting not only population growth and aging, but also the prevalence and spread of risk factors. Gastrointestinal (GI) cancers, including stomach, liver, esophageal, pancreatic, and colorectal cancers, represent more than a quarter of all cancers. While smoking and alcohol use are the risk factors most commonly associated with cancer development, a growing consensus also includes dietary habits as relevant risk factors for GI cancers. Current evidence suggests that socioeconomic development results in several lifestyle modifications, including shifts in dietary habits from local traditional diets to less-healthy Western diets. Moreover, recent data indicate that increased production and consumption of processed foods underlies the current pandemics of obesity and related metabolic disorders, which are directly or indirectly associated with the emergence of various chronic noncommunicable conditions and GI cancers. However, environmental changes are not restricted to dietary patterns, and unhealthy behavioral features should be analyzed with a holistic view of lifestyle. In this review, we discussed the epidemiological aspects, gut dysbiosis, and cellular and molecular characteristics of GI cancers and explored the impact of unhealthy behaviors, diet, and physical activity on developing GI cancers in the context of progressive societal changes.
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Affiliation(s)
- Silvia Rodrigues Jardim
- Division of Worker’s Health, Universidade Federal do Rio de Janeiro, Rio de Janeiro 22290-140, RJ, Brazil
| | - Lucila Marieta Perrotta de Souza
- Departamento de Clínica Médica, Hospital Universitário, Universidade Federal do Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco 255, Ilha do Fundão, Rio de Janeiro 21941-913, RJ, Brazil
| | - Heitor Siffert Pereira de Souza
- Departamento de Clínica Médica, Hospital Universitário, Universidade Federal do Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco 255, Ilha do Fundão, Rio de Janeiro 21941-913, RJ, Brazil
- D’Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro 30, Botafogo, Rio de Janeiro 22281-100, RJ, Brazil
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17
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Wu JY, Shao Y, Huang CZ, Wang ZL, Zhang HQ, Fu Z. Genetic variants in the calcium signaling pathway participate in the pathogenesis of colorectal cancer through the tumor microenvironment. Front Oncol 2023; 13:992326. [PMID: 36824126 PMCID: PMC9941622 DOI: 10.3389/fonc.2023.992326] [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: 07/12/2022] [Accepted: 01/18/2023] [Indexed: 02/10/2023] Open
Abstract
Background Cancer risk is influenced by calcium signaling in intracellular and intercellular signaling pathways. However, the relationship between the calcium signaling pathway and colorectal cancer risk remains unknown. We aim to evaluate the role of genetic variants in calcium signaling pathway genes in colorectal cancer risk through the tumor microenvironment. Methods An analysis of genetic variants in the calcium signaling pathway was conducted using a case-control study that included 1150 colorectal cancer patients and 1342 non-cancer patients. Using the regression model, we assessed whether single-nucleotide polymorphisms (SNPs) increase the risk of colorectal cancer. We also performed a dual luciferase reporter gene assay using HCT116 cell lines and DLD1 cell lines to demonstrate the regulatory relationship between SNP and candidate risk gene. We evaluated the expression of candidate risk gene in different populations. In addition, we also evaluated candidate risk gene and 22 immune cells correlation studies. Results There was a significant association between the PDE1C rs12538364 T allele and colorectal cancer risk [odds ratio (OR) = 1.57, 95% confidence interval (CI) = 1.30 - 1.90, P = 3.07 × 10-6, P FDR = 0.004]. Mutation of intron region rs1538364 C to T locus reduces promoter activity of PDE1C in DLD1 and HCT116 cell lines (P < 0.05). We identified that PDE1C is significantly down-regulated in colorectal cancer, closely associated with 22 immune cells. Finally, we found that PDE1C could be the biomarker for individual immunotherapy of colorectal cancer. Conclusion According to our findings, PDE1C may be a key factor contributing to colorectal cancer, thus improving individual immunotherapy for the disease. The potential mechanism by which polymorphisms in the calcium signaling pathway genes may participate in the pathogenesis of colorectal cancer through the tumor microenvironment.
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Affiliation(s)
- Jing-Yu Wu
- The General Surgery Laboratory, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yu Shao
- The General Surgery Laboratory, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Chang-Zhi Huang
- The General Surgery Laboratory, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zhen-Ling Wang
- The General Surgery Laboratory, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hong-Qiang Zhang
- The General Surgery Laboratory, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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18
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Dai W, Yang J, Liu X, Mei Q, Peng W, Hu X. Anti-colorectal cancer of Ardisia gigantifolia Stapf. and targets prediction via network pharmacology and molecular docking study. BMC Complement Med Ther 2023; 23:4. [PMID: 36624500 PMCID: PMC9827653 DOI: 10.1186/s12906-022-03822-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Accepted: 12/09/2022] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Ardisia gigantifolia Stapf. (AGS), a Chinese folk medicine widely grows in the south of China and several studies reported that AGS could inhibit the proliferation of breast cancer, liver cancer, and bladder cancer cell lines. However, little is known about its anti-colorectal cancer (CRC) efficiency. METHODS In the present study, a combination of MTT assay, network pharmacological analysis, bioinformatics, molecular docking, and molecular dynamics simulation study was used to investigate the active ingredients, and targets of AGS against CRC, as well as the potential mechanism. RESULTS MTT assay showed that three kinds of fractions from AGS, including the n-butanol extract (NBAGS), ethyl acetate fraction (EAAGS), and petroleum ether fraction (PEAGS) significantly inhibited the proliferation of CRC cells, with the IC50 values of 197.24, 264.85, 15.45 µg/mL on HCT116 cells, and 523.6, 323.59, 150.31 µg/mL on SW620 cells, respectively. Eleven active ingredients, including, 11-O-galloylbergenin, 11-O-protocatechuoylbergenin, 11-O-syringylbergenin, ardisiacrispin B, bergenin, epicatechin-3-gallate, gallic acid, quercetin, stigmasterol, stigmasterol-3-o-β-D-glucopyranoside were identified. A total of 173 targets related to the bioactive components and 21,572 targets related to CRC were picked out through database searching. Based on the crossover targets of AGS and CRC, a protein-protein interaction network was built up by the String database, from which it was concluded that the core targets would be SRC, MAPK1, ESR1, HSP90AA1, MAPK8. Besides, GO analysis showed that the numbers of biological process, cellular component, and molecular function of AGS against CRC were 1079, 44, and 132, respectively, and KEGG pathway enrichment indicated that 96 signaling pathways in all would probably be involved in AGS against CRC, among which MAPK signaling pathway, lipid, and atherosclerosis, proteoglycans in cancer, prostate cancer, adherens junction would probably be the major pathways. The docking study verified that AGS had multiple ingredients and multiple targets against CRC. Molecular dynamics (MD) simulation analysis showed that the binding would be stable via forming hydrogen bonds. CONCLUSION Our study showed that AGS had good anti-CRC potency with the characteristics of multi-ingredients, -targets, and -signaling pathways.
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Affiliation(s)
- Weibo Dai
- grid.411866.c0000 0000 8848 7685Pharmacology Laboratory, Zhongshan Hospital, Guangzhou University of Chinese Medicine, 528401 Zhongshan, PR China
| | - Jing Yang
- grid.411866.c0000 0000 8848 7685Pharmacology Laboratory, Zhongshan Hospital, Guangzhou University of Chinese Medicine, 528401 Zhongshan, PR China ,Zhongshan Torch Development Zone People’s Hospital, 528401 Zhongshan, PR China
| | - Xin Liu
- grid.411866.c0000 0000 8848 7685Pharmacology Laboratory, Zhongshan Hospital, Guangzhou University of Chinese Medicine, 528401 Zhongshan, PR China
| | - Quanxi Mei
- Shenzhen Baoan Authentic TCM Therapy Hospital, 518101 Shenzhen, PR China
| | - Weijie Peng
- grid.411866.c0000 0000 8848 7685Pharmacology Laboratory, Zhongshan Hospital, Guangzhou University of Chinese Medicine, 528401 Zhongshan, PR China
| | - Xianjing Hu
- grid.410560.60000 0004 1760 3078Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, 523808 Dongguan, PR China
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19
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Jafari M, Laraqui A, Baba W, Benmokhtar S, Zaitouni SE, Ali AA, Bounaim A, Moujahid M, Tanz R, Mahfoud T, Sbitti Y, Annaz HE, Abi R, Tagajdid MR, Kochri SE, Lahlou IA, Hsaini HE, Belayachi L, Benjouad A, Ichou M, En-Nya A, Ennibi K. Prevalence and patterns of mutations in RAS/RAF/MEK/ERK/MAPK signaling pathway in colorectal cancer in North Africa. BMC Cancer 2022; 22:1142. [PMID: 36344948 PMCID: PMC9639273 DOI: 10.1186/s12885-022-10235-w] [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: 04/13/2022] [Accepted: 10/11/2022] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Our review discuss (i) the findings from analyzed data that have examined KRAS, NRAS and BRAF mutations in patients with colorectal cancer (CRC) in North Africa and to compare its prevalence with that shown in other populations and (ii) the possible role of dietary and lifestyle factors with CRC risk. METHODS: Using electronic databases, a systematic literature search was performed for the KRAS, NRAS, and BRAF mutations in CRC patients from Morocco, Tunisia, Algeria and Lybia. RESULTS: Seventeen studies were identified through electronic searches with six studies conducted in Morocco, eight in Tunisia, two in Algeria, and one in Libya. A total of 1843 CRC patients were included 576 (31.3%) in Morocco, 641 (34.8%) in Tunisia, 592 (32.1%) in Algeria, and 34 (1.8%) in Libya. Overall, the average age of patients was 52.7 years old. Patients were predominantly male (56.6%). The mutation rates of KRAS, NRAS and BRAF were 46.4%, 3.2% and 3.5% of all patients, respectively. A broad range of reported KRAS mutation frequencies have been reported in North Africa countries. The KRAS mutation frequency was 23.9% to 51% in Morocco, 23.1% to 68.2% in Tunisia, 31.4% to 50% in Algeria, and 38.2% in Libya. The G12D was the most frequently identified KRAS exon 2 mutations (31.6%), followed by G12V (25.4%), G13D (15.5%), G12C (10.2%), G12A (6.9%), and G12S (6.4%). G12R, G13V, G13C and G13R are less than 5%. There are important differences among North Africa countries. In Morocco and Tunisia, there is a higher prevalence of G12D mutation in KRAS exon 2 (≈50%). The most frequently mutation type in KRAS exon 3 was Q61L (40%). A59T and Q61E mutations were also found. In KRAS exon 4, the most common mutation was A146T (50%), followed by K117N (33.3%), A146P (8.3%) and A146V (8.3%). CONCLUSION KRAS mutated CRC patients in North Africa have been identified with incidence closer to the European figures. Beside established anti-CRC treatment, better understanding of the causality of CRC can be established by combining epidemiology and genetic/epigenetic on CRC etiology. This approach may be able to significantly reduce the burden of CRC in North Africa.
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Affiliation(s)
- Meryem Jafari
- Sequencing Unit, Laboratory of Virology, Center of Virology, Infectious and Tropical Diseases, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco.
- Laboratory of Biology of Human Pathologies, Department of Biology, Faculty of Sciences, Genomic Center of Human Pathologies, Mohammed V University in Rabat, Rabat, Morocco.
| | - Abdelilah Laraqui
- Sequencing Unit, Laboratory of Virology, Center of Virology, Infectious and Tropical Diseases, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Walid Baba
- Sequencing Unit, Laboratory of Virology, Center of Virology, Infectious and Tropical Diseases, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
- Laboratory of Biology of Human Pathologies, Department of Biology, Faculty of Sciences, Genomic Center of Human Pathologies, Mohammed V University in Rabat, Rabat, Morocco
| | - Soukaina Benmokhtar
- Laboratory of Biology of Human Pathologies, Department of Biology, Faculty of Sciences, Genomic Center of Human Pathologies, Mohammed V University in Rabat, Rabat, Morocco
| | - Sara El Zaitouni
- Laboratory of Biology of Human Pathologies, Department of Biology, Faculty of Sciences, Genomic Center of Human Pathologies, Mohammed V University in Rabat, Rabat, Morocco
| | - Abdelmounaim Ait Ali
- Department of Digestive Surgery, Faculty of Medicine and Pharmacy, Mohammed V Military Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Ahmed Bounaim
- Department of Digestive Surgery, Faculty of Medicine and Pharmacy, Mohammed V Military Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Mountassir Moujahid
- Department of Digestive Surgery, Faculty of Medicine and Pharmacy, Mohammed V Military Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Rachid Tanz
- Department of Medical Oncology, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Tarik Mahfoud
- Department of Medical Oncology, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Yassir Sbitti
- Department of Medical Oncology, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Hicham El Annaz
- Sequencing Unit, Laboratory of Virology, Center of Virology, Infectious and Tropical Diseases, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Rachid Abi
- Sequencing Unit, Laboratory of Virology, Center of Virology, Infectious and Tropical Diseases, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Mohamed Rida Tagajdid
- Sequencing Unit, Laboratory of Virology, Center of Virology, Infectious and Tropical Diseases, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Safae El Kochri
- Sequencing Unit, Laboratory of Virology, Center of Virology, Infectious and Tropical Diseases, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Idriss Amine Lahlou
- Sequencing Unit, Laboratory of Virology, Center of Virology, Infectious and Tropical Diseases, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Houda El Hsaini
- International Faculty of Dental Medicine, College of Health Sciences, International University in Rabat, Rabat, Morocco
| | - Lamiae Belayachi
- International Faculty of Dental Medicine, College of Health Sciences, International University in Rabat, Rabat, Morocco
| | - Abdelaziz Benjouad
- International Faculty of Dental Medicine, College of Health Sciences, International University in Rabat, Rabat, Morocco
| | - Mohammed Ichou
- Department of Medical Oncology, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
| | - Amina En-Nya
- Laboratory of Biology of Human Pathologies, Department of Biology, Faculty of Sciences, Genomic Center of Human Pathologies, Mohammed V University in Rabat, Rabat, Morocco
| | - Khalid Ennibi
- Sequencing Unit, Laboratory of Virology, Center of Virology, Infectious and Tropical Diseases, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
- Center of Virology, Infectious and Tropical Diseases, Faculty of Medicine and Pharmacy, Mohammed V Military Teaching Hospital, Mohammed V University in Rabat, Rabat, Morocco
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20
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Zhang W, Zhang J, Liu T, Xing J, Zhang H, Wang D, Tang D. Bidirectional effects of intestinal microbiota and antibiotics: a new strategy for colorectal cancer treatment and prevention. J Cancer Res Clin Oncol 2022; 148:2387-2404. [PMID: 35661254 DOI: 10.1007/s00432-022-04081-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 05/19/2022] [Indexed: 12/24/2022]
Abstract
PURPOSE Colorectal cancer (CRC) is the third most common cancer worldwide, and its incidence and mortality rates are increasing every year. The intestinal microbiota has been called the "neglected organ" and there is growing evidence that the intestinal microbiota and its metabolites can be used in combination with immunotherapy, radiotherapy and chemotherapy to greatly enhance the treatment of colorectal cancer and to address some of the side effects and adverse effects of these therapies. Antibiotics have great potential to eliminate harmful microbiota, control infection, and reduce colorectal cancer side effects. However, the use of antibiotics has been a highly controversial issue, and numerous retrospective studies have shown that the use of antibiotics affects the effectiveness of treatment (especially immunotherapy). Understanding the bi-directional role of the gut microbiota and antibiotics will further enhance our research into the diagnosis and treatment of cancer. METHODS We searched the "PubMed" database and selected the following keywords "intestinal microbiota, antibiotics, treatment, prevention, colorectal cancer". In this review, we discuss the role of the intestinal microbiota in immunotherapy, radiotherapy, chemotherapy, diagnosis, and prevention of CRC. We also conclude that the intestinal microbiota and antibiotics work together to promote the treatment of CRC through a bidirectional effect. RESULTS We found that the intestinal microbiota plays a key role in promoting immunotherapy, chemotherapy, radiotherapy, diagnosis and prevention of CRC. In addition, gut microbiota and antibiotic interactions could be a new strategy for CRC treatment. CONCLUSION The bi-directional role of the intestinal microbiota and antibiotics plays a key role in the prevention, diagnosis, and treatment of colorectal cancer.
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Affiliation(s)
- Wenjie Zhang
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Jie Zhang
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Tian Liu
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Juan Xing
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Huan Zhang
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Daorong Wang
- Department of General Surgery, Institute of General Surgery, Clinical Medical College, Northern Jiangsu Province Hospital, Yangzhou University, Yangzhou, 225001, China
| | - Dong Tang
- Department of General Surgery, Institute of General Surgery, Clinical Medical College, Northern Jiangsu Province Hospital, Yangzhou University, Yangzhou, 225001, China.
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21
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Mahmod AI, Haif SK, Kamal A, Al-Ataby IA, Talib WH. Chemoprevention effect of the Mediterranean diet on colorectal cancer: Current studies and future prospects. Front Nutr 2022; 9:924192. [PMID: 35990343 PMCID: PMC9386380 DOI: 10.3389/fnut.2022.924192] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Accepted: 07/18/2022] [Indexed: 12/11/2022] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer and the second most deadly cancer worldwide. Nevertheless, more than 70% of CRC cases are resulted from sporadic tumorigenesis and are not inherited. Since adenoma-carcinoma development is a slow process and may take up to 20 years, diet-based chemoprevention could be an effective approach in sporadic CRC. The Mediterranean diet is an example of a healthy diet pattern that consists of a combination of nutraceuticals that prevent several chronic diseases and cancer. Many epidemiological studies have shown the correlation between adherence to the Mediterranean diet and low incidence of CRC. The goal of this review is to shed the light on the anti-inflammatory and anti-colorectal cancer potentials of the natural bioactive compounds derived from the main foods in the Mediterranean diet.
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Affiliation(s)
- Asma Ismail Mahmod
- Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman, Jordan
| | - Shatha Khaled Haif
- Department of Pharmacy, Princess Sarvath Community College, Amman, Jordan
| | - Ayah Kamal
- Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman, Jordan
| | - Israa A Al-Ataby
- Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman, Jordan
| | - Wamidh H Talib
- Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman, Jordan
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22
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Plant-Derived Bioactive Compounds in Colorectal Cancer: Insights from Combined Regimens with Conventional Chemotherapy to Overcome Drug-Resistance. Biomedicines 2022; 10:biomedicines10081948. [PMID: 36009495 PMCID: PMC9406120 DOI: 10.3390/biomedicines10081948] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 07/25/2022] [Accepted: 08/08/2022] [Indexed: 11/21/2022] Open
Abstract
Acquired drug resistance represents a major clinical problem and one of the biggest limitations of chemotherapeutic regimens in colorectal cancer. Combination regimens using standard chemotherapeutic agents, together with bioactive natural compounds derived from diet or plants, may be one of the most valuable strategies to overcome drug resistance and re-sensitize chemoresistant cells. In this review, we highlight the effect of combined regimens based on conventional chemotherapeutics in conjunction with well-tolerated plant-derived bioactive compounds, mainly curcumin, resveratrol, and EGCG, with emphasis on the molecular mechanisms associated with the acquired drug resistance.
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23
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Wang F, Ugai T, Haruki K, Wan Y, Akimoto N, Arima K, Zhong R, Twombly TS, Wu K, Yin K, Chan AT, Giannakis M, Nowak JA, Meyerhardt JA, Liang L, Song M, Smith‐Warner SA, Zhang X, Giovannucci EL, Willett WC, Ogino S. Healthy and unhealthy plant-based diets in relation to the incidence of colorectal cancer overall and by molecular subtypes. Clin Transl Med 2022; 12:e893. [PMID: 35998061 PMCID: PMC9398226 DOI: 10.1002/ctm2.893] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 04/30/2022] [Accepted: 05/09/2022] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Plant-based foods have been recommended for health. However, not all plant foods are healthy, and little is known about the association between plant-based diets and specific molecular subtypes of colorectal cancer (CRC). We examined the associations of healthy and unhealthy plant-based diets with the incidence of CRC and its molecular subtypes. METHODS While 123 773 participants of the Nurses' Health Study and the Health Professionals Follow-up Study had been followed up (3 143 158 person-years), 3077 of them had developed CRC. Healthy and unhealthy plant-based diet indices (hPDI and uPDI, respectively) were calculated using repeated food frequency questionnaire data. We determined the tumoural status of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and BRAF and KRAS mutations. RESULTS Higher hPDI was associated with lower CRC incidence (multivariable hazard ratio [HR] comparing extreme quartiles, 0.86, 95% confidence interval [CI]: 0.77, 0.96; P-trend = .04), whereas higher uPDI was associated with higher CRC incidence (multivariable HR comparing extreme quartiles, 1.16, 95% CI: 1.04, 1.29; P-trend = .005). The association of hPDI significantly differed by KRAS status (P-heterogeneity = .003) but not by other tumour markers. The hPDI was associated with lower incidence of KRAS-wildtype CRC (multivariable HR comparing extreme quartiles, 0.74, 95% CI: 0.57, 0.96; P-trend = .004) but not KRAS-mutant CRC (P-trend = .22). CONCLUSIONS While unhealthy plant-based diet enriched with refined grains and sugar is associated with higher CRC incidence, healthy plant-based diet rich in whole grains, fruits and vegetables is associated with lower incidence of CRC, especially KRAS-wildtype CRC.
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The Tissue-Associated Microbiota in Colorectal Cancer: A Systematic Review. Cancers (Basel) 2022; 14:cancers14143385. [PMID: 35884445 PMCID: PMC9317273 DOI: 10.3390/cancers14143385] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 07/05/2022] [Accepted: 07/08/2022] [Indexed: 11/28/2022] Open
Abstract
Simple Summary Growing evidence shows a close relationship between the microbiome and colorectal cancer, but most studies analyze fecal samples. However, solid information on the microbial community that is present locally in the intestinal tumor tissues is lacking. Therefore, the aim of this systematic review was to compile evidence on the relationship between tissue-associated microbiota and colorectal cancer. Among 5080 screened publications, 39 were eligible and included in the analysis. Despite the heterogeneity in methodologies and reporting between studies, 12 groups of bacteria with strong positive and 18 groups of bacteria with strong negative associations with colorectal cancer were identified. Such knowledge may ultimately be used in novel strategies that aim to prevent, detect, and treat colorectal cancer in the upcoming years. Abstract The intestinal microbiome is associated with colorectal cancer. Although the mucosal microbiota better represents an individual’s local microbiome, studies on the colorectal cancer microbiota mainly reflect knowledge obtained from fecal samples. This systematic review aimed to summarize the current evidence on the relationship between the mucosal-associated bacterial microbiota and colorectal cancer. Searches were conducted in PubMed and Web of Science databases for publications comparing the mucosal microbiome of colorectal cancer patients with that of healthy controls, or with that of non-cancerous mucosal tissues. The primary outcomes were differences in microbial diversity and taxonomy. The Newcastle-Ottawa Scale was used to assess the quality of the included studies. Of the 5080 studies identified, 39 were eligible and included in the systematic review. No consistent results were identified for the α- and β-diversity, due to high heterogeneity in reporting and to differences in metrics and statistical approaches, limiting study comparability. Qualitative synthesis of microbial taxonomy identified 12 taxa with strong positive and 18 taxa with strong negative associations with colorectal cancer. Fusobacterium, Campylobacter, Parvimonas, Peptostreptococcus, Streptococcus, and Granulicatella were defined as enriched in colorectal cancer. Despite the methodological limitations of the studies, consistent evidence on bacterial taxa associated with colorectal cancer was identified. Prospective studies in large and well-characterized patient populations will be crucial to validate these findings.
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25
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Screening colonoscopy similarly prevented distal and proximal colorectal cancer; A prospective study among 55-69-year-olds. J Clin Epidemiol 2022; 149:118-126. [DOI: 10.1016/j.jclinepi.2022.05.024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 05/18/2022] [Accepted: 05/30/2022] [Indexed: 11/23/2022]
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26
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Jothimani G, Bhatiya M, Pathak S, Paul S, Banerjee A. Tumor Suppressor microRNAs in Gastrointestinal Cancers: A Mini-Review. RECENT ADVANCES IN INFLAMMATION & ALLERGY DRUG DISCOVERY 2022; 16:5-15. [PMID: 35670340 DOI: 10.2174/2772270816666220606112727] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 03/04/2022] [Accepted: 03/18/2022] [Indexed: 01/17/2023]
Abstract
BACKGROUND Gastrointestinal (GI) cancer is associated with a group of cancers affecting the organs in the GI tract, with a high incidence and mortality rate. This type of cancer development involves a series of molecular events that arise by the dysregulation of gene expressions and microRNAs (miRNAs). OBJECTIVES This mini-review focuses on elucidating the mechanism of tumor suppressor miRNA-mediated oncogenic gene silencing, which may contribute to a better understanding of miRNA-mediated gene expression regulation of cell cycle, proliferation, invasion, and apoptosis in GI cancers. In this review, the biological significance of tumor suppressor miRNAs involved in gastrointestinal cancers is briefly explained. METHODS The articles were searched with the keywords 'miRNA', 'gastrointestinal cancers', 'esophageal cancer', 'gastric cancer', 'colorectal cancer', 'pancreatic cancer', 'liver cancer', and 'gall bladder cancer' from the Google Scholar and PubMed databases. A total of 71 research and review articles have been collected and referred for this study. RESULTS This review summarises recent research enhancing the effectiveness of miRNAs as novel prognostic, diagnostic, and therapeutic markers for GI cancer treatment strategies. The expression pattern of various miRNAs has been dysregulated in GI cancers, which are associated with proliferation, cell cycle regulation, apoptosis, migration, and invasion. CONCLUSION The role of tumor suppressor miRNAs in the negative regulation of oncogenic gene expression was thoroughly explained in this review. Its potential role as a microRNA therapeutic candidate is also discussed. Profiling and regulating tumor suppressor miRNA expression in gastrointestinal cancers using miRNA mimics could be used as a prognostic, diagnostic, and therapeutic marker, as well as an elucidating molecular therapeutic approach to tumor suppression.
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Affiliation(s)
- Ganesan Jothimani
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai, India
| | - Meenu Bhatiya
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai, India
| | - Surajit Pathak
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai, India
| | - Sujay Paul
- Tecnologico de Monterrey, School of Engineering and Sciences, Campus Queretaro, Av. Epigmenio Gonzalez, No. 500 Fracc. San Pablo, Querétaro CP 76130, Mexico
| | - Antara Banerjee
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai, India
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27
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Zhao C, Chen H, Min K. CircCDC6 restrains tumor growth and glycolysis energy metabolism in colorectal cancer via regulating miR-3187-3p and downstream PRKAA2. J Bioenerg Biomembr 2022; 54:163-174. [PMID: 35438362 DOI: 10.1007/s10863-022-09938-3] [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: 02/14/2022] [Accepted: 04/05/2022] [Indexed: 11/26/2022]
Abstract
The aberrant downregulation of circCDC6 in colorectal cancer (CRC) was previously identified by circRNA microarray analysis. However, the detailed role of circCDC6 in CRC is still lacking. We thus investigated the function of circCDC6 in CRC. The expression of circCDC6, miR-3187-3p and PRKAA2 mRNA was checked by real-time quantitative PCR (RT-qPCR). Cell growth was evaluated by MTT, EdU and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Glycolysis was evaluated by glycolysis stress test and lactic acid level. The expression of PRKAA2, HK2 and LDHA proteins was checked by western blotting. The potential binding between miR-3187-3p and circCDC6 or PRKAA2 was confirmed by dual-luciferase reporter assay, RIP assay and pull-down assay. Xenograft model was established in nude mice. CircCDC6 showed poor expression in CRC tumor samples and cells. CircCDC6 ectopic expression repressed CRC cell proliferation, survival and glycolysis energy metabolism. MiR-3187-3p was targeted by circCDC6, and miR-3187-3p depletion also repressed CRC cell growth and glycolysis. PRKAA2 was a downstream target of circCDC6/miR-3187-3p pathway, and circCDC6 upregulated PRKAA2 expression via targeting miR-3187-3p. PRKAA2 knockdown rescued the functional effects of circCDC6 ectopic expression. CircCDC6 overexpression in vivo impeded tumor development in animal models. CircCDC6, acting as a tumor inhibitor, repressed tumor growth and glycolysis metabolism in CRC via targeting the miR-3187-3p/PRKAA2 axis, which partly clarified the role of circCDC6 in CRC.
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Affiliation(s)
- Chunxiang Zhao
- Department of Gastrointestinal Surgery, Wuhan First Hospital, No.215 Zhongshan Avenue, Qiaokou District, Wuhan City, 430000, Hubei Province, China
| | - Hong Chen
- Department of Gastrointestinal Surgery, Wuhan First Hospital, No.215 Zhongshan Avenue, Qiaokou District, Wuhan City, 430000, Hubei Province, China
| | - Kai Min
- Department of Gastrointestinal Surgery, Wuhan First Hospital, No.215 Zhongshan Avenue, Qiaokou District, Wuhan City, 430000, Hubei Province, China.
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28
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Lin Y, Kong DX, Zhang YN. Does the Microbiota Composition Influence the Efficacy of Colorectal Cancer Immunotherapy? Front Oncol 2022; 12:852194. [PMID: 35463305 PMCID: PMC9023803 DOI: 10.3389/fonc.2022.852194] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 03/07/2022] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is the second most common malignancy globally, and many people with CRC suffer the fate of death. Due to the importance of CRC and its negative impact on communities, treatment strategies to control it or increase patient survival are being studied. Traditional therapies, including surgery and chemotherapy, have treated CRC patients. However, with the advancement of science, we are witnessing the emergence of novel therapeutic approaches such as immunotherapy for CRC treatment, which have had relatively satisfactory clinical outcomes. Evidence shows that gastrointestinal (GI) microbiota, including various bacterial species, viruses, and fungi, can affect various biological events, regulate the immune system, and even treat diseases like human malignancies. CRC has recently shown that the gut microorganism pattern can alter both antitumor and pro-tumor responses, as well as cancer immunotherapy. Of course, this is also true of traditional therapies because it has been revealed that gut microbiota can also reduce the side effects of chemotherapy. Therefore, this review summarized the effects of gut microbiota on CRC immunotherapy.
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Affiliation(s)
- Yan Lin
- Health Management Center, Department of General Practice, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, China
- *Correspondence: Yan Lin, ; You-Ni Zhang,
| | - De-Xia Kong
- Health Management Center, Department of General Practice, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, China
| | - You-Ni Zhang
- Department of Laboratory Medicine, Tiantai People’s Hospital, Taizhou, China
- *Correspondence: Yan Lin, ; You-Ni Zhang,
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29
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Ugai T, Väyrynen JP, Lau MC, Borowsky J, Akimoto N, Väyrynen SA, Zhao M, Zhong R, Haruki K, Dias Costa A, Fujiyoshi K, Arima K, Wu K, Chan AT, Cao Y, Song M, Fuchs CS, Wang M, Lennerz JK, Ng K, Meyerhardt JA, Giannakis M, Nowak JA, Ogino S. Immune cell profiles in the tumor microenvironment of early-onset, intermediate-onset, and later-onset colorectal cancer. Cancer Immunol Immunother 2022; 71:933-942. [PMID: 34529108 PMCID: PMC8924022 DOI: 10.1007/s00262-021-03056-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Accepted: 09/07/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND Despite heightened interest in early-onset colorectal cancer (CRC) diagnosed before age 50, little is known on immune cell profiles of early-onset CRC. It also remains to be studied whether CRCs diagnosed at or shortly after age 50 are similar to early-onset CRC. We therefore hypothesized that immune cell infiltrates in CRC tissue might show differential heterogeneity patterns between three age groups (< 50 "early onset," 50-54 "intermediate onset," ≥ 55 "later onset"). METHODS We examined 1,518 incident CRC cases with available tissue data, including 35 early-onset and 73 intermediate-onset cases. To identify immune cells in tumor intraepithelial and stromal areas, we developed three multiplexed immunofluorescence assays combined with digital image analyses and machine learning algorithms, with the following markers: (1) CD3, CD4, CD8, CD45RO (PTPRC), and FOXP3 for T cells; (2) CD68, CD86, IRF5, MAF, and MRC1 (CD206) for macrophages; and (3) ARG1, CD14, CD15, CD33, and HLA-DR for myeloid cells. RESULTS Although no comparisons between age groups showed statistically significant differences at the stringent two-sided α level of 0.005, compared to later-onset CRC, early-onset CRC tended to show lower levels of tumor-infiltrating lymphocytes (P = 0.013), intratumoral periglandular reaction (P = 0.025), and peritumoral lymphocytic reaction (P = 0.044). Compared to later-onset CRC, intermediate-onset CRC tended to show lower densities of overall macrophages (P = 0.050), M1-like macrophages (P = 0.062), CD14+HLA-DR+ cells (P = 0.015), and CD3+CD4+FOXP3+ cells (P = 0.039). CONCLUSIONS This hypothesis-generating study suggests possible differences in histopathologic lymphocytic reaction patterns, macrophages, and regulatory T cells in the tumor microenvironment by age at diagnosis.
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Affiliation(s)
- Tomotaka Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Juha P Väyrynen
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
- Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, Finland
| | - Mai Chan Lau
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA
| | - Jennifer Borowsky
- Conjoint Gastroenterology Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
| | - Naohiko Akimoto
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA
| | - Sara A Väyrynen
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Melissa Zhao
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA
| | - Rong Zhong
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Koichiro Haruki
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA
| | - Andressa Dias Costa
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA
| | - Kenji Fujiyoshi
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA
| | - Kota Arima
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA
| | - Kana Wu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Andrew T Chan
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Yin Cao
- Division of Public Health Sciences, Department of Surgery, Washington University in St. Louis, St. Louis, MO, USA
- Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA
- Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Mingyang Song
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
| | - Charles S Fuchs
- Yale Cancer Center, New Haven, CT, USA
- Department of Medicine, Yale School of Medicine, New Haven, CT, USA
- Smilow Cancer Hospital, New Haven, CT, USA
- Genentech, South San Francisco, CA, USA
| | - Molin Wang
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Jochen K Lennerz
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Kimmie Ng
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Jeffrey A Meyerhardt
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Marios Giannakis
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Jonathan A Nowak
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, MA, 02115, USA.
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
- Broad Institute of MIT and Harvard, Cambridge, MA, USA.
- Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA, USA.
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30
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Gadaleta E, Thorn GJ, Ross-Adams H, Jones LJ, Chelala C. Field cancerization in breast cancer. J Pathol 2022; 257:561-574. [PMID: 35362092 PMCID: PMC9322418 DOI: 10.1002/path.5902] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 03/23/2022] [Accepted: 03/29/2022] [Indexed: 11/30/2022]
Abstract
Breast cancer affects one in seven women worldwide during their lifetime. Widespread mammographic screening programs and education campaigns allow for early detection of the disease, often during its asymptomatic phase. Current practice in treatment and recurrence monitoring is based primarily on pathological evaluations but can also encompass genomic evaluations, both of which focus on the primary tumor. Although breast cancer is one of the most studied cancers, patients still recur at a rate of up to 15% within the first 10 years post‐surgery. Local recurrence was originally attributed to tumor cells contaminating histologically normal (HN) tissues beyond the surgical margin, but advances in technology have allowed for the identification of distinct aberrations that exist in the peri‐tumoral tissues themselves. One leading theory to explain this phenomenon is the field cancerization theory. Under this hypothesis, tumors arise from a field of molecularly altered cells that create a permissive environment for malignant evolution, which can occur with or without morphological changes. The traditional histopathology paradigm dictates that molecular alterations are reflected in the tissue phenotype. However, the spectrum of inter‐patient variability of normal breast tissue may obfuscate recognition of a cancerized field during routine diagnostics. In this review, we explore the concept of field cancerization focusing on HN peri‐tumoral tissues: we present the pathological and molecular features of field cancerization within these tissues and discuss how the use of peri‐tumoral tissues can affect research. Our observations suggest that pathological and molecular evaluations could be used synergistically to assess risk and guide the therapeutic management of patients. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Affiliation(s)
- Emanuela Gadaleta
- Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK
| | - Graeme J Thorn
- Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK
| | - Helen Ross-Adams
- Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK
| | - Louise J Jones
- Centre for Tumour Biology Barts Cancer Institute, Queen Mary University of London, London, UK
| | - Claude Chelala
- Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK
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31
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Yuan C, Zhao X, Wangmo D, Alshareef D, Gates TJ, Subramanian S. Tumor models to assess immune response and tumor-microbiome interactions in colorectal cancer. Pharmacol Ther 2022; 231:107981. [PMID: 34480964 PMCID: PMC8844062 DOI: 10.1016/j.pharmthera.2021.107981] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 08/20/2021] [Accepted: 08/24/2021] [Indexed: 02/07/2023]
Abstract
Despite significant advances over the past 2 decades in preventive screening and therapy aimed at improving patient survival, colorectal cancer (CRC) remains the second most common cause of cancer death in the United States. The average 5-year survival rate of CRC patients with positive regional lymph nodes is only 40%, while less than 5% of patients with distant metastases survive beyond 5 years. There is a critical need to develop novel therapies that can improve overall survival in patients with poor prognoses, particularly since 60% of them are diagnosed at an advanced stage. Pertinently, immune checkpoint blockade therapy has dramatically changed how we treat CRC patients with microsatellite-instable high tumors. Furthermore, accumulating evidence shows that changes in gut microbiota are associated with the regulation of host antitumor immune response and cancer progression. Appropriate animal models are essential to deciphering the complex mechanisms of host antitumor immune response and tumor-gut microbiome metabolic interactions. Here, we discuss various mouse models of colorectal cancer that are developed to address key questions on tumor immune response and tumor-microbiota interactions. These CRC models will also serve as resourceful tools for effective preclinical studies.
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Affiliation(s)
- Ce Yuan
- Department of Surgery, University of Minnesota, Minneapolis, MN 55455, United States of America
| | - Xianda Zhao
- Department of Surgery, University of Minnesota, Minneapolis, MN 55455, United States of America
| | - Dechen Wangmo
- Department of Surgery, University of Minnesota, Minneapolis, MN 55455, United States of America; Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, United States of America
| | - Duha Alshareef
- Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, United States of America
| | - Travis J Gates
- Department of Surgery, University of Minnesota, Minneapolis, MN 55455, United States of America; Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, United States of America
| | - Subbaya Subramanian
- Department of Surgery, University of Minnesota, Minneapolis, MN 55455, United States of America; Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, United States of America; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, United States of America.
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32
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Seely KD, Morgan AD, Hagenstein LD, Florey GM, Small JM. Bacterial Involvement in Progression and Metastasis of Colorectal Neoplasia. Cancers (Basel) 2022; 14:1019. [PMID: 35205767 PMCID: PMC8870662 DOI: 10.3390/cancers14041019] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 02/14/2022] [Accepted: 02/15/2022] [Indexed: 02/06/2023] Open
Abstract
While the gut microbiome is composed of numerous bacteria, specific bacteria within the gut may play a significant role in carcinogenesis, progression, and metastasis of colorectal carcinoma (CRC). Certain microbial species are known to be associated with specific cancers; however, the interrelationship between bacteria and metastasis is still enigmatic. Mounting evidence suggests that bacteria participate in cancer organotropism during solid tumor metastasis. A critical review of the literature was conducted to better characterize what is known about bacteria populating a distant site and whether a tumor depends upon the same microenvironment during or after metastasis. The processes of carcinogenesis, tumor growth and metastatic spread in the setting of bacterial infection were examined in detail. The literature was scrutinized to discover the role of the lymphatic and venous systems in tumor metastasis and how microbes affect these processes. Some bacteria have a potent ability to enhance epithelial-mesenchymal transition, a critical step in the metastatic cascade. Bacteria also can modify the microenvironment and the local immune profile at a metastatic site. Early targeted antibiotic therapy should be further investigated as a measure to prevent metastatic spread in the setting of bacterial infection.
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Affiliation(s)
- Kevin D. Seely
- College of Osteopathic Medicine, Rocky Vista University, Ivins, UT 84738, USA; (A.D.M.); (L.D.H.)
| | - Amanda D. Morgan
- College of Osteopathic Medicine, Rocky Vista University, Ivins, UT 84738, USA; (A.D.M.); (L.D.H.)
| | - Lauren D. Hagenstein
- College of Osteopathic Medicine, Rocky Vista University, Ivins, UT 84738, USA; (A.D.M.); (L.D.H.)
| | - Garrett M. Florey
- College of Osteopathic Medicine, Rocky Vista University, Parker, CO 80134, USA;
| | - James M. Small
- Department of Biomedical Sciences, Rocky Vista University, Parker, CO 80134, USA;
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Nunna S, Huang YP, Rasa M, Krepelova A, Annunziata F, Adam L, Käppel S, Hsu MH, Neri F. Characterization of Novel α-Mangostin and Paeonol Derivatives With Cancer-Selective Cytotoxicity. Mol Cancer Ther 2022; 21:257-270. [PMID: 34789561 PMCID: PMC9398122 DOI: 10.1158/1535-7163.mct-20-0787] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 04/22/2021] [Accepted: 11/03/2021] [Indexed: 01/07/2023]
Abstract
α-Mangostin (aMan) and Paeonol (Pae) have shown anticancer and anti-inflammatory properties. However, these two natural compounds have no clinical value because of their low solubility and low membrane permeability. In this study, we screened chemically synthesized derivatives from these two natural compounds as potential novel chemicals that increase cancer cell cytotoxicity over nontransformed human cells. We found that two derivative compounds, named α-Mangostin-1 (aMan1) and Paeonol-1 (Pae1) more efficiently and more specifically induced cytotoxicity in HCT116, HT29, and SW48 colorectal cancer cell lines than the parental compounds. Both aMan1 and Pae1 arrested HCT116 cells in the G1 phase and HT29 and SW48 cells in the G2-M phase of the cell cycle. Both aMan1 and Pae1 induced apoptosis in human colorectal cancer cells, through a caspase-dependent mechanism. aMan1 and Pae1 induced selective transcriptional responses in colorectal cancer cells involving genes related to metabolic stress and DNA damage response signaling pathways. Finally, experiments on primary colon organoids showed that both derivatives were able to kill cancer-derived organoids without affecting the viability of organoids derived from healthy tissue, where the parental compounds and the currently used chemotherapeutic drug irinotecan failed. In conclusion, our findings expand the knowledge of natural compound derivatives as anticancer agents and open new avenues of research in the derivation of lead compounds aimed at developing novel chemotherapeutic drugs for colorectal cancer treatment that selectively target cancer, but not healthy cells.
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Affiliation(s)
- Suneetha Nunna
- Leibniz-Institute on Ageing - Fritz-Lipmann-Institute (FLI), Jena, Germany
| | - Ying-Pei Huang
- Leibniz-Institute on Ageing - Fritz-Lipmann-Institute (FLI), Jena, Germany.,Nuclear Science & Technology Development Center, National Tsing Hua University, Hsinchu, Taiwan
| | - Mahdi Rasa
- Leibniz-Institute on Ageing - Fritz-Lipmann-Institute (FLI), Jena, Germany
| | - Anna Krepelova
- Leibniz-Institute on Ageing - Fritz-Lipmann-Institute (FLI), Jena, Germany
| | | | - Lisa Adam
- Leibniz-Institute on Ageing - Fritz-Lipmann-Institute (FLI), Jena, Germany
| | - Sandra Käppel
- Leibniz-Institute on Ageing - Fritz-Lipmann-Institute (FLI), Jena, Germany
| | - Ming-Hua Hsu
- Department of Chemistry, National Changhua University of Education, Changhua, Taiwan, ROC.,Department of Medical and Applied Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Francesco Neri
- Leibniz-Institute on Ageing - Fritz-Lipmann-Institute (FLI), Jena, Germany.,Corresponding Author: Francesco Neri, Epigenetics group, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, 07745, Germany. E-mail:
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Zhang Y, Yu H, Guo Z. Circ_KIAA1199 inhibits MSI1 degradation by targeting miR-34c-5p to drive the malignant cell behaviors and tumor growth of colorectal cancer. Anticancer Drugs 2022; 33:e134-e144. [PMID: 34387591 DOI: 10.1097/cad.0000000000001164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Circular RNAs (circRNAs) are important regulators that drive or inhibit cancer initiation and development. Here, we identified the expression and function of a circRNA, circ_KIAA1199, in colorectal cancer (CRC). The expression levels of circ_KIAA1199, microRNA-34c-5p (miR-34c-5p) and Musashi RNA-binding protein 1 (MSI1) mRNA were detected by quantitative real-time PCR. Cell proliferative capacity was assessed by colony formation assay, EdU assay and MTT assay. Cell apoptosis was determined by flow cytometry assay. Cell migration and cell invasion were investigated by transwell assay. The expression of MSI1 protein and proliferation, migration-related markers was detected by western blot. The relationship between miR-34c-5p and circ_KIAA1199 or MSI1 was verified by dual-luciferase reporter assay. Animal models were constructed to ascertain the role of circ_KIAA1199 in vivo. The expression of circ_KIAA1199 was elevated in CRC. Circ_KIAA1199 downregulation suppressed CRC cell proliferation, survival, migration and invasion. MiR-34c-5p was a target of circ_KIAA1199. The effects of circ_KIAA1199 downregulation were reversed by miR-34c-5p deficiency. In addition, MSI1 was a target of circ_KIAA1199, and the inhibitory effects of miR-34c-5p restoration on CRC cell proliferation, survival, migration and invasion were reversed by MSI1 overexpression. Circ_KIAA1199 positively regulated MSI1 expression by targeting miR-34c-5p. Moreover, circ_KIAA1199 knockdown blocked tumor growth in animal models. Circ_KIAA1199 functioned as an oncogene to drive the malignant development of CRC by activating MSI1 via competitively targeting miR-34c-5p.
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Affiliation(s)
- Yanbo Zhang
- Department of General Surgery, Liaocheng People's Hospital, Liaocheng City, Shandong Province, China
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35
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Zhao L, Grimes SM, Greer SU, Kubit M, Lee H, Nadauld L, Ji H. Characterization of the consensus mucosal microbiome of colorectal cancer. NAR Cancer 2021; 3:zcab049. [PMID: 34988460 PMCID: PMC8693571 DOI: 10.1093/narcan/zcab049] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2021] [Revised: 11/18/2021] [Accepted: 12/08/2021] [Indexed: 12/13/2022] Open
Abstract
Dysbioisis is an imbalance of an organ's microbiome and plays a role in colorectal cancer pathogenesis. Characterizing the bacteria in the microenvironment of a cancer through genome sequencing has advantages compared to culture-based profiling. However, there are notable technical and analytical challenges in characterizing universal features of tumor microbiomes. Colorectal tumors demonstrate microbiome variation among different studies and across individual patients. To address these issues, we conducted a computational study to determine a consensus microbiome for colorectal cancer, analyzing 924 tumors from eight independent RNA-Seq data sets. A standardized meta-transcriptomic analysis pipeline was established with quality control metrics. Microbiome profiles across different cohorts were compared and recurrently altered microbial shifts specific to colorectal cancer were determined. We identified cancer-specific set of 114 microbial species associated with tumors that were found among all investigated studies. Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria were among the four most abundant phyla for the colorectal cancer microbiome. Member species of Clostridia were depleted and Fusobacterium nucleatum was one of the most enriched bacterial species in tumors. Associations between the consensus species and specific immune cell types were noted. Our results are available as a web data resource for other researchers to explore (https://crc-microbiome.stanford.edu).
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Affiliation(s)
- Lan Zhao
- Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
| | - Susan M Grimes
- Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
| | - Stephanie U Greer
- Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
| | - Matthew Kubit
- Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
| | - HoJoon Lee
- Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
| | - Lincoln D Nadauld
- Intermountain Precision Genomics Program, Intermountain Healthcare, Saint George, UT 84790, USA
| | - Hanlee P Ji
- Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
- Stanford Genome Technology Center, Stanford University, Palo Alto, CA 94304, USA
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36
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Hu LF, Lan HR, Huang D, Li XM, Jin KT. Personalized Immunotherapy in Colorectal Cancers: Where Do We Stand? Front Oncol 2021; 11:769305. [PMID: 34888246 PMCID: PMC8649954 DOI: 10.3389/fonc.2021.769305] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 10/26/2021] [Indexed: 12/17/2022] Open
Abstract
Colorectal cancer (CRC) is the second leading cause of cancer death in the world. Immunotherapy using monoclonal antibodies, immune-checkpoint inhibitors, adoptive cell therapy, and cancer vaccines has raised great hopes for treating poor prognosis metastatic CRCs that are resistant to the conventional therapies. However, high inter-tumor and intra-tumor heterogeneity hinder the success of immunotherapy in CRC. Patients with a similar tumor phenotype respond differently to the same immunotherapy regimen. Mutation-based classification, molecular subtyping, and immunoscoring of CRCs facilitated the multi-aspect grouping of CRC patients and improved immunotherapy. Personalized immunotherapy using tumor-specific neoantigens provides the opportunity to consider each patient as an independent group deserving of individualized immunotherapy. In the recent decade, the development of sequencing and multi-omics techniques has helped us classify patients more precisely. The expansion of such advanced techniques along with the neoantigen-based immunotherapy could herald a new era in treating heterogeneous tumors such as CRC. In this review article, we provided the latest findings in immunotherapy of CRC. We elaborated on the heterogeneity of CRC patients as a bottleneck of CRC immunotherapy and reviewed the latest advances in personalized immunotherapy to overcome CRC heterogeneity.
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Affiliation(s)
- Li-Feng Hu
- Department of Colorectal Surgery, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, China
| | - Huan-Rong Lan
- Department of Breast and Thyroid Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China
| | - Dong Huang
- Department of Colorectal Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China
| | - Xue-Min Li
- Department of Hepatobiliary Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China
| | - Ke-Tao Jin
- Department of Colorectal Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China
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Sikavi DR, Nguyen LH, Haruki K, Ugai T, Ma W, Wang DD, Thompson KN, Yan Y, Branck T, Wilkinson JE, Akimoto N, Zhong R, Lau MC, Mima K, Kosumi K, Morikawa T, Rimm EB, Garrett WS, Izard J, Cao Y, Song M, Huttenhower C, Ogino S, Chan AT. The Sulfur Microbial Diet and Risk of Colorectal Cancer by Molecular Subtypes and Intratumoral Microbial Species in Adult Men. Clin Transl Gastroenterol 2021; 12:e00338. [PMID: 34333506 PMCID: PMC8323793 DOI: 10.14309/ctg.0000000000000338] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Accepted: 03/05/2021] [Indexed: 01/22/2023] Open
Abstract
INTRODUCTION We recently described the sulfur microbial diet, a pattern of intake associated with increased gut sulfur-metabolizing bacteria and incidence of distal colorectal cancer (CRC). We assessed whether this risk differed by CRC molecular subtypes or presence of intratumoral microbes involved in CRC pathogenesis (Fusobacterium nucleatum and Bifidobacterium spp.). METHODS We performed Cox proportional hazards modeling to examine the association between the sulfur microbial diet and incidence of overall and distal CRC by molecular and microbial subtype in the Health Professionals Follow-Up Study (1986-2012). RESULTS We documented 1,264 incident CRC cases among 48,246 men, approximately 40% of whom had available tissue data. After accounting for multiple hypothesis testing, the relationship between the sulfur microbial diet and CRC incidence did not differ by subtype. However, there was a suggestion of an association by prostaglandin synthase 2 (PTGS2) status with a multivariable adjusted hazard ratio for highest vs lowest tertile of sulfur microbial diet scores of 1.31 (95% confidence interval: 0.99-1.74, Ptrend = 0.07, Pheterogeneity = 0.04) for PTGS2-high CRC. The association of the sulfur microbial diet with distal CRC seemed to differ by the presence of intratumoral Bifidobacterium spp. with an adjusted hazard ratio for highest vs lowest tertile of sulfur microbial diet scores of 1.65 (95% confidence interval: 1.14-2.39, Ptrend = 0.01, Pheterogeneity = 0.03) for Bifidobacterium-negative distal CRC. We observed no apparent heterogeneity by other tested molecular markers. DISCUSSION Greater long-term adherence to the sulfur microbial diet could be associated with PTGS2-high and Bifidobacterium-negative distal CRC in men. Additional studies are needed to further characterize the role of gut microbial sulfur metabolism and CRC.
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Affiliation(s)
- Daniel R. Sikavi
- Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Long H. Nguyen
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Koichiro Haruki
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Tomotaka Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Wenjie Ma
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Dong D. Wang
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Kelsey N. Thompson
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
| | - Yan Yan
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Tobyn Branck
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Jeremy E. Wilkinson
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Naohiko Akimoto
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Rong Zhong
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Mai Chan Lau
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Kosuke Mima
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Keisuke Kosumi
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Teppei Morikawa
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Eric B. Rimm
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Wendy S. Garrett
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
- Department of Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Jacques Izard
- Department of Food Science and Technology, University of Nebraska, Lincoln, Nebraska, USA
- Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Yin Cao
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, Missouri, USA
- Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, Missouri, USA
| | - Mingyang Song
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Curtis Huttenhower
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
- Department of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
- Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, Massachusetts, USA
| | - Andrew T. Chan
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
- Department of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
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Dai J, Nishi A, Tran N, Yamamoto Y, Dewey G, Ugai T, Ogino S. Revisiting social MPE: an integration of molecular pathological epidemiology and social science in the new era of precision medicine. Expert Rev Mol Diagn 2021; 21:869-886. [PMID: 34253130 DOI: 10.1080/14737159.2021.1952073] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Molecular pathological epidemiology (MPE) is an integrative transdisciplinary area examining the relationships between various exposures and pathogenic signatures of diseases. In line with the accelerating advancements in MPE, social science and its health-related interdisciplinary areas have also developed rapidly. Accumulating evidence indicates the pathological role of social-demographic factors. We therefore initially proposed social MPE in 2015, which aims to elucidate etiological roles of social-demographic factors and address health inequalities globally. With the ubiquity of molecular diagnosis, there are ample opportunities for researchers to utilize and develop the social MPE framework. AREAS COVERED Molecular subtypes of breast cancer have been investigated rigorously for understanding its etiologies rooted from social factors. Emerging evidence indicates pathogenic heterogeneity of neurological disorders such as Alzheimer's disease. Presenting specific patterns of social-demographic factors across different molecular subtypes should be promising for advancing the screening, prevention, and treatment strategies of those heterogeneous diseases. This article rigorously reviewed literatures investigating differences of race/ethnicity and socioeconomic status across molecular subtypes of breast cancer and Alzheimer's disease to date. EXPERT OPINION With advancements of the multi-omics technologies, we foresee a blooming of social MPE studies, which can address health disparities, advance personalized molecular medicine, and enhance public health.
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Affiliation(s)
- Jin Dai
- Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, California, United States
| | - Akihiro Nishi
- Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, California, United States.,California Center for Population Research, University of California, Los Angeles, CA United States
| | - Nathan Tran
- Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, California, United States
| | - Yasumasa Yamamoto
- Graduate School of Advanced Integrated Studies in Human Survivability, Kyoto University, Sakyo-ku, Kyoto Japan
| | - George Dewey
- Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, California, United States
| | - Tomotaka Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, United States.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, United States.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States.,Cancer Immunology Program, Dana-Farber Harvard Cancer Center, Boston, Massachusetts, United States.,Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, United States
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39
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Guz M, Jeleniewicz W, Malm A, Korona-Glowniak I. A Crosstalk between Diet, Microbiome and microRNA in Epigenetic Regulation of Colorectal Cancer. Nutrients 2021; 13:2428. [PMID: 34371938 PMCID: PMC8308570 DOI: 10.3390/nu13072428] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 07/09/2021] [Accepted: 07/13/2021] [Indexed: 02/07/2023] Open
Abstract
A still growing interest between human nutrition in relation to health and disease states can be observed. Dietary components shape the composition of microbiota colonizing our gastrointestinal tract which play a vital role in maintaining human health. There is a strong evidence that diet, gut microbiota and their metabolites significantly influence our epigenome, particularly through the modulation of microRNAs. These group of small non-coding RNAs maintain cellular homeostasis, however any changes leading to impaired expression of miRNAs contribute to the development of different pathologies, including neoplastic diseases. Imbalance of intestinal microbiota due to diet is primary associated with the development of colorectal cancer as well as other types of cancers. In the present work we summarize current knowledge with particular emphasis on diet-microbiota-miRNAs axis and its relation to the development of colorectal cancer.
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Affiliation(s)
- Małgorzata Guz
- Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin, Poland;
| | - Witold Jeleniewicz
- Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin, Poland;
| | - Anna Malm
- Department of Pharmaceutical Microbiology, Medical University of Lublin, 20-093 Lublin, Poland; (A.M.); (I.K.-G.)
| | - Izabela Korona-Glowniak
- Department of Pharmaceutical Microbiology, Medical University of Lublin, 20-093 Lublin, Poland; (A.M.); (I.K.-G.)
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Sun Y, Zhang Z, Zheng CQ, Sang LX. Mucosal lesions of the upper gastrointestinal tract in patients with ulcerative colitis: A review. World J Gastroenterol 2021; 27:2963-2978. [PMID: 34168401 PMCID: PMC8192286 DOI: 10.3748/wjg.v27.i22.2963] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 03/10/2021] [Accepted: 04/21/2021] [Indexed: 02/06/2023] Open
Abstract
Ulcerative colitis (UC) is a chronic, nonspecific, relapsing inflammatory bowel disease. The colorectum is considered the chief target organ of UC, whereas upper gastrointestinal (UGI) tract manifestations are infrequent. Recently, emerging evidence has suggested that UC presents complications in esophageal, stomachic, and duodenal mucosal injuries. However, UC-related UGI tract manifestations are varied and frequently silenced or concealed. Moreover, the endoscopic and microscopic characteristics of UGI tract complicated with UC are nonspecific. Therefore, UGI involvement may be ignored by many clinicians. In addition, no standard criteria have been established for patients with UC who should undergo fibrogastroduodenoscopy. Furthermore, specific treatment recommendations may be needed for patients with UC-associated UGI lesions. Herein, we review the esophageal, gastric, and duodenal mucosal lesions of the UC-associated UGI tract, as well as the potential pathogenesis and therapy.
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Affiliation(s)
- Yan Sun
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| | - Zhe Zhang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| | - Chang-Qing Zheng
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| | - Li-Xuan Sang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
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Aldaya MM, Ibañez FC, Domínguez-Lacueva P, Murillo-Arbizu MT, Rubio-Varas M, Soret B, Beriain MJ. Indicators and Recommendations for Assessing Sustainable Healthy Diets. Foods 2021; 10:999. [PMID: 34063236 PMCID: PMC8147455 DOI: 10.3390/foods10050999] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 04/28/2021] [Accepted: 04/30/2021] [Indexed: 12/12/2022] Open
Abstract
Research coupling human nutrition and sustainability concerns is a rapidly developing field, which is essential to guide governments' policies. This critical and comprehensive review analyzes indicators and approaches to "sustainable healthy diets" published in the literature since this discipline's emergence a few years ago, identifying robust gauges and highlighting the flaws of the most commonly used models. The reviewed studies largely focus on one or two domains such as greenhouse gas emissions or water use, while overlooking potential impact shifts to other sectors or resources. The present study covers a comprehensive set of indicators from the health, environmental and socio-economic viewpoints. This assessment concludes that in order to identify the best food option in sustainability assessments and nutrition analysis of diets, some aspects such as the classification and disaggregation of food groups, the impacts of the rates of local food consumption and seasonality, preservation methods, agrobiodiversity and organic food and different production systems, together with consequences for low-income countries, require further analysis and consideration.
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Affiliation(s)
- Maite M. Aldaya
- Institute on Innovation & Sustainable Development in the Food Chain (IS-FOOD), Public University of Navarra (UPNA), Jerónimo de Ayanz Building, Arrosadia Campus, 31006 Pamplona, Spain; (F.C.I.); (M.T.M.-A.); (B.S.); (M.J.B.)
| | - Francisco C. Ibañez
- Institute on Innovation & Sustainable Development in the Food Chain (IS-FOOD), Public University of Navarra (UPNA), Jerónimo de Ayanz Building, Arrosadia Campus, 31006 Pamplona, Spain; (F.C.I.); (M.T.M.-A.); (B.S.); (M.J.B.)
| | | | - María Teresa Murillo-Arbizu
- Institute on Innovation & Sustainable Development in the Food Chain (IS-FOOD), Public University of Navarra (UPNA), Jerónimo de Ayanz Building, Arrosadia Campus, 31006 Pamplona, Spain; (F.C.I.); (M.T.M.-A.); (B.S.); (M.J.B.)
| | - Mar Rubio-Varas
- Institute for Advanced Research in Business and Economics (INARBE), Public University of Navarra (UPNA), Jerónimo de Ayanz Building, Arrosadia Campus, 31006 Pamplona, Spain;
| | - Beatriz Soret
- Institute on Innovation & Sustainable Development in the Food Chain (IS-FOOD), Public University of Navarra (UPNA), Jerónimo de Ayanz Building, Arrosadia Campus, 31006 Pamplona, Spain; (F.C.I.); (M.T.M.-A.); (B.S.); (M.J.B.)
| | - María José Beriain
- Institute on Innovation & Sustainable Development in the Food Chain (IS-FOOD), Public University of Navarra (UPNA), Jerónimo de Ayanz Building, Arrosadia Campus, 31006 Pamplona, Spain; (F.C.I.); (M.T.M.-A.); (B.S.); (M.J.B.)
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Akimoto N, Zhao M, Ugai T, Zhong R, Lau MC, Fujiyoshi K, Kishikawa J, Haruki K, Arima K, Twombly TS, Zhang X, Giovannucci EL, Wu K, Song M, Chan AT, Cao Y, Meyerhardt JA, Ng K, Giannakis M, Väyrynen JP, Nowak JA, Ogino S. Tumor Long Interspersed Nucleotide Element-1 (LINE-1) Hypomethylation in Relation to Age of Colorectal Cancer Diagnosis and Prognosis. Cancers (Basel) 2021; 13:2016. [PMID: 33922024 PMCID: PMC8122644 DOI: 10.3390/cancers13092016] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/17/2021] [Accepted: 04/18/2021] [Indexed: 12/12/2022] Open
Abstract
Evidence indicates the pathogenic role of epigenetic alterations in early-onset colorectal cancers diagnosed before age 50. However, features of colorectal cancers diagnosed at age 50-54 (hereafter referred to as "intermediate-onset") remain less known. We hypothesized that tumor long interspersed nucleotide element-1 (LINE-1) hypomethylation might be increasingly more common with decreasing age of colorectal cancer diagnosis. In 1356 colorectal cancers, including 28 early-onset and 66 intermediate-onset cases, the tumor LINE-1 methylation level measured by bisulfite-PCR-pyrosequencing (scaled 0 to 100) showed a mean of 63.6 (standard deviation (SD) 10.1). The mean tumor LINE-1 methylation level decreased with decreasing age (mean 64.7 (SD 10.4) in age ≥70, 62.8 (SD 9.4) in age 55-69, 61.0 (SD 10.2) in age 50-54, and 58.9 (SD 12.0) in age <50; p < 0.0001). In linear regression analysis, the multivariable-adjusted β coefficient (95% confidence interval (CI)) (vs. age ≥70) was -1.38 (-2.47 to -0.30) for age 55-69, -2.82 (-5.29 to -0.34) for age 50-54, and -4.54 (-8.24 to -0.85) for age <50 (Ptrend = 0.0003). Multivariable-adjusted hazard ratios (95% CI) for LINE-1 methylation levels of ≤45, 45-55, and 55-65 (vs. >65) were 2.33 (1.49-3.64), 1.39 (1.05-1.85), and 1.29 (1.02-1.63), respectively (Ptrend = 0.0005). In conclusion, tumor LINE-1 hypomethylation is increasingly more common with decreasing age of colorectal cancer diagnosis, suggesting a role of global DNA hypomethylation in colorectal cancer arising in younger adults.
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Affiliation(s)
- Naohiko Akimoto
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (N.A.); (M.Z.); (T.U.); (R.Z.); (M.C.L.); (K.F.); (J.K.); (K.H.); (K.A.); (T.S.T.); (J.A.N.)
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo 1138602, Japan
| | - Melissa Zhao
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (N.A.); (M.Z.); (T.U.); (R.Z.); (M.C.L.); (K.F.); (J.K.); (K.H.); (K.A.); (T.S.T.); (J.A.N.)
| | - Tomotaka Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (N.A.); (M.Z.); (T.U.); (R.Z.); (M.C.L.); (K.F.); (J.K.); (K.H.); (K.A.); (T.S.T.); (J.A.N.)
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston 02115, MA, USA; (E.L.G.); (K.W.)
| | - Rong Zhong
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (N.A.); (M.Z.); (T.U.); (R.Z.); (M.C.L.); (K.F.); (J.K.); (K.H.); (K.A.); (T.S.T.); (J.A.N.)
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston 02115, MA, USA; (E.L.G.); (K.W.)
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Mai Chan Lau
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (N.A.); (M.Z.); (T.U.); (R.Z.); (M.C.L.); (K.F.); (J.K.); (K.H.); (K.A.); (T.S.T.); (J.A.N.)
| | - Kenji Fujiyoshi
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (N.A.); (M.Z.); (T.U.); (R.Z.); (M.C.L.); (K.F.); (J.K.); (K.H.); (K.A.); (T.S.T.); (J.A.N.)
| | - Junko Kishikawa
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (N.A.); (M.Z.); (T.U.); (R.Z.); (M.C.L.); (K.F.); (J.K.); (K.H.); (K.A.); (T.S.T.); (J.A.N.)
| | - Koichiro Haruki
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (N.A.); (M.Z.); (T.U.); (R.Z.); (M.C.L.); (K.F.); (J.K.); (K.H.); (K.A.); (T.S.T.); (J.A.N.)
| | - Kota Arima
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (N.A.); (M.Z.); (T.U.); (R.Z.); (M.C.L.); (K.F.); (J.K.); (K.H.); (K.A.); (T.S.T.); (J.A.N.)
| | - Tyler S. Twombly
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (N.A.); (M.Z.); (T.U.); (R.Z.); (M.C.L.); (K.F.); (J.K.); (K.H.); (K.A.); (T.S.T.); (J.A.N.)
| | - Xuehong Zhang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA; (X.Z.); (A.T.C.)
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA;
| | - Edward L. Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston 02115, MA, USA; (E.L.G.); (K.W.)
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA; (X.Z.); (A.T.C.)
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA;
| | - Kana Wu
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston 02115, MA, USA; (E.L.G.); (K.W.)
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA; (X.Z.); (A.T.C.)
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA;
| | - Mingyang Song
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA;
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Andrew T. Chan
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA; (X.Z.); (A.T.C.)
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
| | - Yin Cao
- Division of Public Health Sciences, Department of Surgery, Washington University in St. Louis, St. Louis, MO 63110, USA;
- Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA
- Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Jeffrey A. Meyerhardt
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; (J.A.M.); (K.N.); (M.G.)
| | - Kimmie Ng
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; (J.A.M.); (K.N.); (M.G.)
| | - Marios Giannakis
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; (J.A.M.); (K.N.); (M.G.)
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Juha P. Väyrynen
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (N.A.); (M.Z.); (T.U.); (R.Z.); (M.C.L.); (K.F.); (J.K.); (K.H.); (K.A.); (T.S.T.); (J.A.N.)
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; (J.A.M.); (K.N.); (M.G.)
- Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, 90220 Oulu, Finland
| | - Jonathan A. Nowak
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (N.A.); (M.Z.); (T.U.); (R.Z.); (M.C.L.); (K.F.); (J.K.); (K.H.); (K.A.); (T.S.T.); (J.A.N.)
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; (N.A.); (M.Z.); (T.U.); (R.Z.); (M.C.L.); (K.F.); (J.K.); (K.H.); (K.A.); (T.S.T.); (J.A.N.)
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston 02115, MA, USA; (E.L.G.); (K.W.)
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA 02215, USA
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Fang N, Ding GW, Ding H, Li J, Liu C, Lv L, Shi YJ. Research Progress of Circular RNA in Gastrointestinal Tumors. Front Oncol 2021; 11:665246. [PMID: 33937077 PMCID: PMC8082141 DOI: 10.3389/fonc.2021.665246] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 03/15/2021] [Indexed: 01/17/2023] Open
Abstract
circular RNA (circRNA) is a closed ring structure formed by cyclic covalent bonds connecting the 5’-end and 3’-end of pre-mRNA. circRNA is widely distributed in eukaryotic cells. Recent studies have shown that circRNA is involved in the pathogenesis and development of multiple types of diseases, including tumors. circRNA is specifically expressed in tissues. And the stability of circRNA is higher than that of linear RNA, which can play biological roles through sponge adsorption of miRNA, interaction with RNA binding protein, regulation of gene transcription, the mRNA and protein translation brake, and translation of protein and peptides. These characteristics render circRNAs as biomarkers and therapeutic targets of tumors. Gastrointestinal tumors are common malignancies worldwide, which seriously threaten human health. In this review, we summarize the generation and biological characteristics of circRNA, molecular regulation mechanism and related effects of circRNA in gastrointestinal tumors.
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Affiliation(s)
- Na Fang
- Department of Oncology, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China
| | - Guo-Wen Ding
- Department of Thoracic and Cardiovascular Surgery, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China
| | - Hao Ding
- Department of Respiratory, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China
| | - Juan Li
- Department of Oncology, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China
| | - Chao Liu
- Department of Thoracic and Cardiovascular Surgery, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China
| | - Lu Lv
- Department of Thoracic and Cardiovascular Surgery, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China
| | - Yi-Jun Shi
- Department of Thoracic and Cardiovascular Surgery, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China
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Genua F, Raghunathan V, Jenab M, Gallagher WM, Hughes DJ. The Role of Gut Barrier Dysfunction and Microbiome Dysbiosis in Colorectal Cancer Development. Front Oncol 2021; 11:626349. [PMID: 33937029 PMCID: PMC8082020 DOI: 10.3389/fonc.2021.626349] [Citation(s) in RCA: 74] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Accepted: 03/12/2021] [Indexed: 02/06/2023] Open
Abstract
Accumulating evidence indicates that breakdown of the+ protective mucosal barrier of the gut plays a role in colorectal cancer (CRC) development. Inflammation and oxidative stress in the colonic epithelium are thought to be involved in colorectal carcinogenesis and the breakdown of the integrity of the colonic barrier may increase the exposure of colonocytes to toxins from the colonic milieu, enhancing inflammatory processes and release of Reactive Oxygen Species (ROS). The aetiological importance of the gut microbiome and its composition - influenced by consumption of processed meats, red meats and alcoholic drinks, smoking, physical inactivity, obesity - in CRC development is also increasingly being recognized. The gut microbiome has diverse roles, such as in nutrient metabolism and immune modulation. However, microbial encroachment towards the colonic epithelium may promote inflammation and oxidative stress and even translocation of species across the colonic lumen. Recent research suggests that factors that modify the above mechanisms, e.g., obesity and Western diet, also alter gut microbiota, degrade the integrity of the gut protective barrier, and expose colonocytes to toxins. However, it remains unclear how obesity, lifestyle and metabolic factors contribute to gut-barrier integrity, leading to metabolic disturbance, colonocyte damage, and potentially to CRC development. This review will discuss the interactive roles of gut-barrier dysfunction, microbiome dysbiosis, and exposure to endogenous toxins as another mechanism in CRC development, and how biomarkers of colonic mucosal barrier function may provide avenues for disease, prevention and detection.
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Affiliation(s)
- Flavia Genua
- Cancer Biology and Therapeutics Laboratory, Conway Institute, School of Biomedical and Biomolecular Sciences, University College Dublin, Dublin, Ireland
| | - Vedhika Raghunathan
- College of Literature, Sciences, and the Arts, University of Michigan, Ann Arbor, MI, United States
| | - Mazda Jenab
- Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - William M. Gallagher
- Cancer Biology and Therapeutics Laboratory, Conway Institute, School of Biomedical and Biomolecular Sciences, University College Dublin, Dublin, Ireland
| | - David J. Hughes
- Cancer Biology and Therapeutics Laboratory, Conway Institute, School of Biomedical and Biomolecular Sciences, University College Dublin, Dublin, Ireland
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Akimoto N, Ugai T, Zhong R, Hamada T, Fujiyoshi K, Giannakis M, Wu K, Cao Y, Ng K, Ogino S. Rising incidence of early-onset colorectal cancer - a call to action. Nat Rev Clin Oncol 2021; 18:230-243. [PMID: 33219329 PMCID: PMC7994182 DOI: 10.1038/s41571-020-00445-1] [Citation(s) in RCA: 374] [Impact Index Per Article: 93.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/14/2020] [Indexed: 02/07/2023]
Abstract
The incidence of early-onset colorectal cancer (CRC), which occurs in individuals <50 years of age, has been increasing worldwide and particularly in high-income countries. The reasons for this increase remain unknown but plausible hypotheses include greater exposure to potential risk factors, such as a Western-style diet, obesity, physical inactivity and antibiotic use, especially during the early prenatal to adolescent periods of life. These exposures can not only cause genetic and epigenetic alterations in colorectal epithelial cells but also affect the gut microbiota and host immunity. Early-onset CRCs have differential clinical, pathological and molecular features compared with later-onset CRCs. Certain existing resources can be utilized to elucidate the aetiology of early-onset CRC and inform the development of effective prevention, early detection and therapeutic strategies; however, additional life-course cohort studies spanning childhood and young adulthood, integrated with prospective biospecimen collections, omics biomarker analyses and a molecular pathological epidemiology approach, are needed to better understand and manage this disease entity. In this Perspective, we summarize our current understanding of early-onset CRC and discuss how we should strategize future research to improve its prevention and clinical management.
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Affiliation(s)
- Naohiko Akimoto
- Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo, Japan
| | - Tomotaka Ugai
- Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Rong Zhong
- Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China
| | - Tsuyoshi Hamada
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kenji Fujiyoshi
- Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Department of Surgery, Kurume University, Kurume, Japan
| | - Marios Giannakis
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Kana Wu
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Yin Cao
- Division of Public Health Sciences, Department of Surgery, Washington University in St. Louis, St. Louis, MO, USA
- Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA
- Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Kimmie Ng
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Shuji Ogino
- Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
- Broad Institute of MIT and Harvard, Cambridge, MA, USA.
- Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA, USA.
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Zhou E, Rifkin S. Colorectal Cancer and Diet: Risk Versus Prevention, Is Diet an Intervention? Gastroenterol Clin North Am 2021; 50:101-111. [PMID: 33518157 DOI: 10.1016/j.gtc.2020.10.012] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Colorectal cancer is the third most common cause of cancer in men and women in the world. Epidemiologic research approximates that half of colon cancer risk is preventable by modifiable risk factors, including diet. This article reviews prior studies involving certain food items and their relation to colorectal cancer, to elucidate whether diet can be a potential intervention.
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Affiliation(s)
- Elinor Zhou
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 431, Baltimore, MD, USA.
| | - Samara Rifkin
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, 1150 West Medical Center Drive, 6520 MSRB1, Ann Arbor, MI, USA
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Liao Z, Nie H, Wang Y, Luo J, Zhou J, Ou C. The Emerging Landscape of Long Non-Coding RNAs in Colorectal Cancer Metastasis. Front Oncol 2021; 11:641343. [PMID: 33718238 PMCID: PMC7947863 DOI: 10.3389/fonc.2021.641343] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 01/29/2021] [Indexed: 12/11/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common gastrointestinal cancers, with extremely high rates of morbidity and mortality. The main cause of death in CRC is distant metastasis; it affects patient prognosis and survival and is one of the key challenges in the treatment of CRC. Long non-coding RNAs (lncRNAs) are a group of non-coding RNA molecules with more than 200 nucleotides. Abnormal lncRNA expression is closely related to the occurrence and progression of several diseases, including cancer. Recent studies have shown that numerous lncRNAs play pivotal roles in the CRC metastasis, and reversing the expression of these lncRNAs through artificial means can reduce the malignant phenotype of metastatic CRC to some extent. This review summarizes the major mechanisms of lncRNAs in CRC metastasis and proposes lncRNAs as potential therapeutic targets for CRC and molecular markers for early diagnosis.
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Affiliation(s)
- Zhiming Liao
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
| | - Hui Nie
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
| | - Yutong Wang
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
| | - Jingjing Luo
- Teaching and Research Room of Biochemistry and Molecular Biology, Medical School of Hunan University of Traditional Chinese Medicine, Changsha, China
| | - Jianhua Zhou
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Chunlin Ou
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
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Ye DX, Wang SS, Huang Y, Wang XJ, Chi P. USP43 directly regulates ZEB1 protein, mediating proliferation and metastasis of colorectal cancer. J Cancer 2021; 12:404-416. [PMID: 33391437 PMCID: PMC7738986 DOI: 10.7150/jca.48056] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 09/06/2020] [Indexed: 12/18/2022] Open
Abstract
Colorectal cancer is one of the most common malignant tumors of the digestive tract. In this study, we had examined the biological role of USP43 in colorectal cancer. USP43 protein and mRNA abundance in clinical tissues and five cell lines were analyzed with quantitative real-time PCR test (qRT-PCR) and western blot. USP43 overexpression treated DLD1 cells and USP43 knockdown treated SW480 cells were used to study cell proliferation, migration, colony formation, invasion, and the expression of epithelial-mesenchymal transformation (EMT) biomarkers. Moreover, ubiquitination related ZEB1 degradation was studied with qRT-PCR and western blot. The relationships between USP43 and ZEB1 were investigated with western blot, co-immunoprecipitation, migration, and invasion. USP43 was highly expressed in colorectal cancer tissues. USP43 overexpression and knockdown treatments could affect cell proliferation, colony formation, migration, invasion, and the expression of EMT associated biomarkers. Moreover, USP43 can regulate ZEB1 degradation through ubiquitination pathway. USP43 could promote the proliferation, migration, and invasion of colorectal cancer. Meanwhile, USP43 can deubiquitinate and stabilize the ZEB1 protein, which plays an important role in the function of colorectal cancer.
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Affiliation(s)
- Dao-Xiong Ye
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, China
| | - Si-Si Wang
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, China
| | - Ying Huang
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, China
| | - Xiao-Jie Wang
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, China
| | - Pan Chi
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, China
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Abstract
INTRODUCTION The aim of this study was to provide the most comprehensive and up-to-date evidence on the association between cigarette smoking and colorectal cancer (CRC) risk. METHODS We conducted a systematic review and meta-analysis of epidemiological studies on the association between cigarette smoking and CRC risk published up to September 2018. We calculated relative risk (RR) of CRC according to smoking status, intensity, duration, pack-years, and time since quitting, with a focus on molecular subtypes of CRC. RESULTS The meta-analysis summarizes the evidence from 188 original studies. Compared with never smokers, the pooled RR for CRC was 1.14 (95% confidence interval [CI] 1.10-1.18) for current smokers and 1.17 (95% CI 1.15-1.20) for former smokers. CRC risk increased linearly with smoking intensity and duration. Former smokers who had quit smoking for more than 25 years had significantly decreased risk of CRC compared with current smokers. Smoking was strongly associated with the risk of CRC, characterized by high CpG island methylator phenotype (RR 1.42; 95% CI 1.20-1.67; number of studies [n] = 4), BRAF mutation (RR 1.63; 95% CI 1.23-2.16; n = 4), or high microsatellite instability (RR 1.56; 95% CI 1.32-1.85; n = 8), but not characterized by KRAS (RR 1.04; 95% CI 0.90-1.20; n = 5) or TP53 (RR 1.13; 95% CI 0.99-1.29; n = 5) mutations. DISCUSSION Cigarette smoking increases the risk of CRC in a dose-dependent manner with intensity and duration, and quitting smoking reduces CRC risk. Smoking greatly increases the risk of CRC that develops through the microsatellite instability pathway, characterized by microsatellite instability-high, CpG island methylator phenotype positive, and BRAF mutation.
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Beck M, Baranger M, Moufok-Sadoun A, Bersuder E, Hinkel I, Mellitzer G, Martin E, Marisa L, Duluc I, de Reynies A, Gaiddon C, Freund JN, Gross I. The atypical cadherin MUCDHL antagonizes colon cancer formation and inhibits oncogenic signaling through multiple mechanisms. Oncogene 2020; 40:522-535. [PMID: 33188295 DOI: 10.1038/s41388-020-01546-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 10/12/2020] [Accepted: 10/28/2020] [Indexed: 01/24/2023]
Abstract
Cadherins form a large and pleiotropic superfamily of membranous proteins sharing Ca2+-binding repeats. While the importance of classic cadherins such as E- or N-cadherin for tumorigenesis is acknowledged, there is much less information about other cadherins that are merely considered as tissue-specific adhesion molecules. Here, we focused on the atypical cadherin MUCDHL that stood out for its unusual features and unique function in the gut. Analyses of transcriptomic data sets (n > 250) established that MUCDHL mRNA levels are down-regulated in colorectal tumors. Importantly, the decrease of MUCDHL expression is more pronounced in the worst-prognosis subset of tumors and is associated with decreased survival. Molecular characterization of the tumors indicated a negative correlation with proliferation-related processes (e.g., nucleic acid metabolism, DNA replication). Functional genomic studies showed that the loss of MUCDHL enhanced tumor incidence and burden in intestinal tumor-prone mice. Extensive structure/function analyses revealed that the mode of action of MUCDHL goes beyond membrane sequestration of ß-catenin and targets through its extracellular domain key oncogenic signaling pathways (e.g., EGFR, AKT). Beyond MUCDHL, this study illustrates how the loss of a gene critical for the morphological and functional features of mature cells contributes to tumorigenesis by dysregulating oncogenic pathways.
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Affiliation(s)
- Marine Beck
- Université de Strasbourg, Inserm, IRFAC UMR-S1113, 67200, Strasbourg, France
| | - Mathilde Baranger
- Université de Strasbourg, Inserm, IRFAC UMR-S1113, 67200, Strasbourg, France
| | - Ahlam Moufok-Sadoun
- Université de Strasbourg, Inserm, IRFAC UMR-S1113, 67200, Strasbourg, France
| | - Emilie Bersuder
- Université de Strasbourg, Inserm, IRFAC UMR-S1113, 67200, Strasbourg, France
| | - Isabelle Hinkel
- Université de Strasbourg, Inserm, IRFAC UMR-S1113, 67200, Strasbourg, France
| | - Georg Mellitzer
- Université de Strasbourg, Inserm, IRFAC UMR-S1113, 67200, Strasbourg, France
| | - Elisabeth Martin
- Université de Strasbourg, Inserm, IRFAC UMR-S1113, 67200, Strasbourg, France
| | | | - Isabelle Duluc
- Université de Strasbourg, Inserm, IRFAC UMR-S1113, 67200, Strasbourg, France
| | | | - Christian Gaiddon
- Université de Strasbourg, Inserm, IRFAC UMR-S1113, 67200, Strasbourg, France
| | - Jean-Noel Freund
- Université de Strasbourg, Inserm, IRFAC UMR-S1113, 67200, Strasbourg, France
| | - Isabelle Gross
- Université de Strasbourg, Inserm, IRFAC UMR-S1113, 67200, Strasbourg, France.
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