|
1
|
Li WB, Li J, Yu W, Gao JH. Short-term efficacy of laparoscopic radical resection for colorectal cancer and risk of unplanned reoperation after surgery. World J Gastrointest Surg 2025; 17:102442. [DOI: 10.4240/wjgs.v17.i4.102442] [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: 01/08/2025] [Revised: 02/11/2025] [Accepted: 03/07/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND Surgery is the first choice of treatment for patients with colorectal cancer. Traditional open surgery imparts great damage to the body of the patient and can easily cause adverse stress reactions. With the continuous development of medical technology, laparoscopic minimally invasive surgery has shown great advantages for the treatment of patients with celiac disease.
AIM To investigate the short-term efficacy of laparoscopic radical surgery and traditional laparotomy for the treatment of colorectal cancer, and the differences in the risk analysis of unplanned reoperation after operation.
METHODS As the research subjects, this study selected 100 patients with colorectal cancer who received surgical treatment at the Yulin First Hospital from January 2018 to January 2022. Among them, 50 patients who underwent laparoscopic radical resection were selected as the research group and 50 patients who underwent traditional laparotomy were selected as the control group. Data pertaining to clinical indexes, gastrointestinal hormones, nutrition indexes, the levels of inflammatory factors, quality of life, Visual Analog Scale score, and the postoperative complications of the two groups of patients before and after treatment were collected, and the therapeutic effects in the two groups were analyzed and compared.
RESULTS Compared with the control group, perioperative bleeding, peristalsis recovery time, and hospital stays were significantly shorter in the research group. After surgery, the levels of gastrin (GAS) and motilin (MTL) were decreased in both groups, and the fluctuation range of GAS and MTL observed in the research group was significantly lower than that recorded in the control group. The hemoglobin (Hb) levels increased after surgery, and the level of Hb in the research group was significantly higher compared with the control group. After the operation, the expression levels of tumor necrosis factor-α, interleukin-6, and C-reactive protein and the total incidence of complications were significantly lower in the research group compared with the control group. One year after the operation, the quality of life of the two groups was greatly improved, with the quality of life in the research group being significantly better.
CONCLUSION Laparoscopy was effective for colorectal surgery by reducing the occurrence of complications and inflammatory stress reaction; moreover, the quality of life of patients was significantly improved, which warrants further promotion.
Collapse
Affiliation(s)
- Wen-Bin Li
- Department of General Surgery, Yulin First Hospital, Yulin 719000, Shaanxi Province, China
| | - Jiang Li
- Department of General Surgery, Yulin First Hospital, Yulin 719000, Shaanxi Province, China
| | - Wei Yu
- Department of General Surgery, Yulin First Hospital, Yulin 719000, Shaanxi Province, China
| | - Jian-Hua Gao
- Department of General Surgery, Yulin First Hospital, Yulin 719000, Shaanxi Province, China
| |
Collapse
|
|
2
|
Chalif J, Goldstein N, Mehra Y, Spakowicz D, Chambers LM. The Role of the Microbiome in Cancer Therapies: Current Evidence and Future Directions. Hematol Oncol Clin North Am 2025; 39:269-294. [PMID: 39856008 DOI: 10.1016/j.hoc.2024.12.005] [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] [Indexed: 01/27/2025]
Abstract
The microbiome is essential for maintaining human health and is also a key factor in the development and progression of various diseases, including cancer. Growing evidence has highlighted the microbiome's significant impact on cancer development, progression, and treatment outcomes. As research continues to unfold, the microbiome and its modulation stand out as a promising frontier in cancer research and therapy. This review highlights current literature on the interplay between various cancer treatment modalities and human microbiotas, focusing on how the microbiome may affect treatment efficacy and toxicity and its potential as a therapeutic target to enhance future outcomes.
Collapse
Affiliation(s)
- Julia Chalif
- Division of Gynecologic Oncology, The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | - Naomi Goldstein
- Division of Obstetrics & Gynecology, The Ohio State University, Columbus, OH, USA
| | - Yogita Mehra
- Department of Medical Oncology, The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | - Dan Spakowicz
- Department of Medical Oncology, The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | - Laura M Chambers
- Division of Gynecologic Oncology, The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Columbus, OH, USA.
| |
Collapse
|
|
3
|
Gu C, Sha G, Zeng B, Cao H, Cao Y, Tang D. Therapeutic potential of fecal microbiota transplantation in colorectal cancer based on gut microbiota regulation: from pathogenesis to efficacy. Therap Adv Gastroenterol 2025; 18:17562848251327167. [PMID: 40104324 PMCID: PMC11915259 DOI: 10.1177/17562848251327167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 02/24/2025] [Indexed: 03/20/2025] Open
Abstract
Colorectal cancer (CRC) remains a leading cause of cancer-related deaths worldwide, with its progression intricately linked to gut microbiota dysbiosis. Disruptions in microbial homeostasis contribute to tumor initiation, immune suppression, and inflammation, establishing the microbiota as a key therapeutic target. Fecal microbiota transplantation (FMT) has emerged as a transformative approach to restore microbial balance, enhance immune responses, and reshape the tumor microenvironment. This review explores the mechanisms underlying FMT's therapeutic potential, evaluates its advantages over other microbiota-based interventions, and addresses challenges such as donor selection, safety concerns, and treatment standardization. Looking forward, the integration of FMT into personalized CRC therapies requires robust clinical trials and the identification of predictive biomarkers to optimize its efficacy and safety.
Collapse
Affiliation(s)
- Chen Gu
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China
| | - Gengyu Sha
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China
| | - Binbin Zeng
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China
| | - Herong Cao
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China
| | - Yibo Cao
- The Second School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Dong Tang
- Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou University, Yangzhou 225000, China
- The Yangzhou Clinical College of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, 221000, China
- Department of General Surgery, Institute of General Surgery, Northern Jiangsu People's Hospital, Yangzhou University, Yangzhou, 225000, China
- Northern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Nanjing, 210000, China
| |
Collapse
|
|
4
|
McDonnell KJ. Operationalizing Team Science at the Academic Cancer Center Network to Unveil the Structure and Function of the Gut Microbiome. J Clin Med 2025; 14:2040. [PMID: 40142848 PMCID: PMC11943358 DOI: 10.3390/jcm14062040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Revised: 02/28/2025] [Accepted: 03/05/2025] [Indexed: 03/28/2025] Open
Abstract
Oncologists increasingly recognize the microbiome as an important facilitator of health as well as a contributor to disease, including, specifically, cancer. Our knowledge of the etiologies, mechanisms, and modulation of microbiome states that ameliorate or promote cancer continues to evolve. The progressive refinement and adoption of "omic" technologies (genomics, transcriptomics, proteomics, and metabolomics) and utilization of advanced computational methods accelerate this evolution. The academic cancer center network, with its immediate access to extensive, multidisciplinary expertise and scientific resources, has the potential to catalyze microbiome research. Here, we review our current understanding of the role of the gut microbiome in cancer prevention, predisposition, and response to therapy. We underscore the promise of operationalizing the academic cancer center network to uncover the structure and function of the gut microbiome; we highlight the unique microbiome-related expert resources available at the City of Hope of Comprehensive Cancer Center as an example of the potential of team science to achieve novel scientific and clinical discovery.
Collapse
Affiliation(s)
- Kevin J McDonnell
- Center for Precision Medicine, Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA
| |
Collapse
|
|
5
|
Xia S, Ma L, Li H, Li Y, Yu L. Prevalence of enterotoxigenic Bacteroides fragilis in patients with colorectal cancer: a systematic review and meta-analysis. Front Cell Infect Microbiol 2025; 15:1525609. [PMID: 40125515 PMCID: PMC11926129 DOI: 10.3389/fcimb.2025.1525609] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Accepted: 02/19/2025] [Indexed: 03/25/2025] Open
Abstract
Introduction The gut microbiome, specifically enterotoxigenic Bacteroides fragilis (ETBF), has been reported to play a role in colorectal cancer development. We aimed to conduct a systematic review and meta-analysis of published studies to compare the prevalence of ETBF in patients with colorectal cancer and healthy controls as well as in various stages of colorectal cancer. Methods PubMed, EMBASE, and The Cochrane Library were systematically searched for studies published until May 2024. We utilized studies either comparing the prevalence of ETBF in patients with colorectal cancer and healthy control or examining its prevalence across different stages of colorectal cancer. The prevalence of ETBF colonization in biological samples from individuals with colorectal cancer compared to that in healthy controls or adjacent normal tissue as well as the association between the prevalence of ETBF and various stages of colorectal cancer were plotted using a random-effect or fixed-effect model. Results Fourteen relevant articles were identified. Meta-analyses revealed that patients with colorectal cancer had a higher likelihood of having ETBF than healthy controls (odds ratio [OR]: 2.54, 95% confidence interval [CI]: 1.63-3.98, I2 = 55%). Additionally, ETBF detection was lower in stage I/II than in stage III/IV colorectal cancer (OR: 0.61, 95% CI: 0.41-0.91, I2 = 41%). Discussion The prevalence of ETBF was consistently higher in the tissue and fecal samples of patients with colorectal cancer than in those of controls. A difference in ETBF prevalence between stage I/II and stage III/IV colorectal cancer was noted, but further analysis revealed that the conclusion is unreliable. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD 42024548325.
Collapse
Affiliation(s)
- Shijun Xia
- Department of Anus & Intestine Surgery, Shenzhen Hospital (Fu Tian) of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Lijuan Ma
- Department of Anus & Intestine Surgery, Shenzhen Traditional Chinese Medicine Anorectal Hospital (Fu tian), Shenzhen, China
| | - Hui Li
- State Key Laboratory of Traditional Chinese Medicine Syndrome/Research Group of Standardization of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China
| | - Yue Li
- Department of Anus & Intestine Surgery, Shenzhen Hospital (Fu Tian) of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Linchong Yu
- Department of Anus & Intestine Surgery, Shenzhen Hospital (Fu Tian) of Guangzhou University of Chinese Medicine, Shenzhen, China
| |
Collapse
|
|
6
|
Zhang C, Wang Y, Cheng L, Cao X, Liu C. Gut microbiota in colorectal cancer: a review of its influence on tumor immune surveillance and therapeutic response. Front Oncol 2025; 15:1557959. [PMID: 40110192 PMCID: PMC11919680 DOI: 10.3389/fonc.2025.1557959] [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: 01/09/2025] [Accepted: 02/14/2025] [Indexed: 03/22/2025] Open
Abstract
Colorectal cancer (CRC) poses a significant global health burden, with gut microbiota emerging as a crucial modulator of CRC pathogenesis and therapeutic outcomes. This review synthesizes current evidence on the influence of gut microbiota on tumor immune surveillance and responses to immunotherapies and chemotherapy in CRC. We highlight the role of specific microbial taxa in promoting or inhibiting tumor growth and the potential of microbiota-based biomarkers for predicting treatment efficacy. The review also discusses the implications of microbiota modulation strategies, including diet, probiotics, and fecal microbiota transplantation, for personalized CRC management. By critically evaluating the literature, we aim to provide a comprehensive understanding of the gut microbiota's dual role in CRC and to inform future research directions in this field.
Collapse
Affiliation(s)
- Chunlei Zhang
- Department of Colorectal and Anus Surgery, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
| | - Yong Wang
- Department of Hepatobiliary Surgery, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
| | - Lei Cheng
- Department of Colorectal and Anus Surgery, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
| | - Xiansheng Cao
- Department of Gastrointestinal Surgery, Hernia and Abdominal Wall Surgery I, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
| | - Chunyuan Liu
- Department of Colorectal and Anus Surgery, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
| |
Collapse
|
|
7
|
Ullah H, Arbab S, Chang C, Bibi S, Muhammad N, Rehman SU, Suleman, Ullah I, Hassan IU, Tian Y, Li K. Gut microbiota therapy in gastrointestinal diseases. Front Cell Dev Biol 2025; 13:1514636. [PMID: 40078367 PMCID: PMC11897527 DOI: 10.3389/fcell.2025.1514636] [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: 10/21/2024] [Accepted: 02/03/2025] [Indexed: 03/14/2025] Open
Abstract
The human gut microbiota, consisting of trillions of microorganisms, plays a crucial role in gastrointestinal (GI) health and disease. Dysbiosis, an imbalance in microbial composition, has been linked to a range of GI disorders, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, and colorectal cancer. These conditions are influenced by the interactions between the gut microbiota, the host immune system, and the gut-brain axis. Recent research has highlighted the potential for microbiome-based therapeutic strategies, such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary modifications, to restore microbial balance and alleviate disease symptoms. This review examines the role of gut microbiota in the pathogenesis of common gastrointestinal diseases and explores emerging therapeutic approaches aimed at modulating the microbiome. We discuss the scientific foundations of these interventions, their clinical effectiveness, and the challenges in their implementation. The review underscores the therapeutic potential of microbiome-targeted treatments as a novel approach to managing GI disorders, offering personalized and alternative options to conventional therapies. As research in this field continues to evolve, microbiome-based interventions hold promise for improving the treatment and prevention of gastrointestinal diseases.
Collapse
Affiliation(s)
- Hanif Ullah
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials, Nursing Key Laboratory of Sichuan Province, West China Hospital, West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Safia Arbab
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, China
| | - Chengting Chang
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials, Nursing Key Laboratory of Sichuan Province, West China Hospital, West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Saira Bibi
- Department of Zoology Hazara University Manshera, Dhodial, Pakistan
| | - Nehaz Muhammad
- Hebei Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology, Hebei Collaborative Innovation Center for Eco-Environment, College of Life Sciences, Hebei Normal University, Shijiazhuang, Hebei, China
| | - Sajid Ur Rehman
- School of Public Health and Emergency Management, School of Medicine, Southern University of Science and Technology, Shenzhen, China
| | - Suleman
- Department of Zoology, Government Post Graduate Collage, Swabi, Pakistan
- Higher Education Department, Civil Secretariat Peshawar, Peshawar, Pakistan
| | - Irfan Ullah
- Department of Biotechnology and Genetics Engineering, Hazara University, Manshera, Pakistan
| | - Inam Ul Hassan
- Department of Microbiology, Hazara University Manshera, Manshera, Pakistan
| | - Yali Tian
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials, Nursing Key Laboratory of Sichuan Province, West China Hospital, West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Ka Li
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials, Nursing Key Laboratory of Sichuan Province, West China Hospital, West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| |
Collapse
|
|
8
|
Darnindro N, Abdullah M, Sukartini N, Rumende CM, Pitarini A, Nursyirwan SA, Fauzi A, Makmun D, Nelwan EJ, Shatri H, Rinaldi I, Tanadi C. Differences in diversity and composition of mucosa-associated colonic microbiota in colorectal cancer and non-colorectal cancer in Indonesia. World J Gastroenterol 2025; 31:100051. [PMID: 39991683 PMCID: PMC11755252 DOI: 10.3748/wjg.v31.i7.100051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 12/05/2024] [Accepted: 12/23/2024] [Indexed: 01/20/2025] Open
Abstract
BACKGROUND Colorectal cancer is the third most common malignancy and the fourth leading cause of cancer-related deaths worldwide. Several studies have shown an association between gut microbiota and colorectal cancer. Gut microbiota is unique and can be influenced by geographic factors and habits. This study aimed to determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer. AIM To determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer in Indonesia. METHODS This case-control study included 59 subjects (35 colorectal cancer patients and 24 non-colorectal cancer patients indicated for colonoscopy at Dr. Cipto Mangunkusumo Gastrointestinal Endoscopy Center and Fatmawati Hospital. Microbiota examination was performed using 16S rRNA sequencing. Bioinformatics analysis was performed using the wf-metagenomics pipeline from EPI2Me-Labs (Oxford Nanopore Technologies platform). RESULTS Patients with colorectal cancer had a higher median index value on the Shannon index (3.28 vs 2.82, P > 0.05) and a lower value on the Simpson index (0.050 vs 0.060, P > 0.05). Significant differences in beta diversity were observed at the genus (P = 0.002) and species levels (P = 0.001). Firmicutes, Proteobacteria, Bacteroidetes, and Fusobacteria were the dominant phyla. The genera Bacteroides, Campylobacter, Peptostreptococcus, and Parvimonas were found more frequently in colorectal cancer, while Faecalibacterium, Haemophilus, and Phocaeicola were more frequently found in non-colorectal cancer. The relative abundance of Fusobacterium nucleatum, Bacteroides fragilis, Enterococcus faecalis, Campylobacter hominis, and Enterococcus faecalis species was significantly elevated in patients with colorectal cancer. Meanwhile, Faecalibacterium prausnitzii, Faecalibacterium duncaniae, and Prevotella copri were more commonly found in non-colorectal cancer. CONCLUSION Patients with colorectal cancer exhibit distinct differences in the composition and diversity of their colonic mucosal microbiota compared to those with non-colorectal cancer. This study was reviewed and approved by the Ethics Committee of Faculty of Medicine, Universitas Indonesia (No. KET-1517/UN2.F1/ETIK/PPM.00.02/2023).
Collapse
Affiliation(s)
- Nikko Darnindro
- Division of Gastroenterology, Pancreatobiliary and Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
- Division of Gastrohepatology, Department of Internal Medicine, Fatmawati General Hospital, Jakarta 12430, Indonesia
| | - Murdani Abdullah
- Division of Gastroenterology, Pancreatobiliary and Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
- Human Cancer Research Center, IMERI Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
| | - Ninik Sukartini
- Department of Clinical Pathology, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Cleopas M Rumende
- Division of Respirology and Critical Care, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Amanda Pitarini
- Division of Gastroenterology, Pancreatobiliary and Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Saskia A Nursyirwan
- Division of Gastroenterology, Pancreatobiliary and Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Achmad Fauzi
- Division of Gastroenterology, Pancreatobiliary and Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Dadang Makmun
- Division of Gastroenterology, Pancreatobiliary and Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Erni J Nelwan
- Division of Tropical Medicine and Infectious Disease, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Hamzah Shatri
- Division of Psychosomatic and Palliative Medicine, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Ikhwan Rinaldi
- Division of Haematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Caroline Tanadi
- School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta 14440, Indonesia
| |
Collapse
|
|
9
|
Pratikna AM, Rivai MI, Suswita R, Putra AE, Rachman IA, Suchitra A. The effect of tumor resection on intestinal microbiota dysbiosis in patients with right-sided colon cancer. Ann Coloproctol 2025; 41:47-56. [PMID: 40044111 PMCID: PMC11894938 DOI: 10.3393/ac.2024.00346.0049] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 09/23/2024] [Accepted: 10/04/2024] [Indexed: 03/14/2025] Open
Abstract
PURPOSE This study aimed to determine the effect of tumor resection on dysbiosis of the intestinal microbiota in patients with right-sided colon cancer. METHODS This study utilized a longitudinal design to explore the outcomes of patients diagnosed with right-sided colon cancer who underwent surgical resection at Dr. M. Djamil General Hospital from July to December 2023. We excluded patients with a documented history of comorbidities, specifically those affecting the digestive system. To compare the microbiota (genus and phylum) between patients with right-sided colon cancer and the control group, we conducted bivariate analyses using the independent t-test or Mann-Whitney test. Furthermore, we employed the dependent t-test or Wilcoxon test to assess changes in the dysbiosis of the microbiota (genus and phylum) before and after resection. A P-value of <0.05 was considered statistically significant. RESULTS This study included a total of 21 patients diagnosed with right-sided colon cancer. In the control group, Bacteroidetes constituted the highest proportion of intestinal microbiota, accounting for 56.34%. Prior to tumor resection, the intestinal microbiota of patients exhibited Proteobacteria as the predominant phylum, representing 52.97%. Following tumor resection, Bacteroidetes remained the most prevalent, comprising 50.9% of the intestinal microbiota. Significant variations in the levels of Proteobacteria, Verrucomicrobia, and Cyanobacteria/Chloroplast were observed in the intestinal microbiota of patients with right-sided colorectal cancer before and after tumor excision (all P=0.001). CONCLUSIONS The microbiome of patients with right-sided colorectal cancer differed significantly from that of the control group. However, following tumor resection, the microbiome composition of these patients became more similar to that observed in the control group.
Collapse
Affiliation(s)
| | - M. Iqbal Rivai
- Department of Surgery, Dr. M. Djamil General Hospital, Universitas Andalas, Padang, Indonesia
| | - Rini Suswita
- Department of Surgery, Dr. M. Djamil General Hospital, Universitas Andalas, Padang, Indonesia
| | - Andani Eka Putra
- Department of Microbiology, Universitas Andalas, Padang, Indonesia
| | - Irwan Abdul Rachman
- Department of Surgery, Dr. M. Djamil General Hospital, Universitas Andalas, Padang, Indonesia
| | - Avit Suchitra
- Department of Surgery, Dr. M. Djamil General Hospital, Universitas Andalas, Padang, Indonesia
| |
Collapse
|
|
10
|
Delle Cave D. Advances in Molecular Mechanisms and Therapeutic Strategies in Colorectal Cancer: A New Era of Precision Medicine. Int J Mol Sci 2025; 26:346. [PMID: 39796202 PMCID: PMC11719900 DOI: 10.3390/ijms26010346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Revised: 12/19/2024] [Accepted: 12/20/2024] [Indexed: 01/13/2025] Open
Abstract
Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality worldwide [...].
Collapse
Affiliation(s)
- Donatella Delle Cave
- Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso', National Research Council CNR, 80131 Naples, Italy
| |
Collapse
|
|
11
|
Yang S, Hao S, Ye H, Zhang X. Crosstalk between gut microbiota and cancer chemotherapy: current status and trends. Discov Oncol 2024; 15:833. [PMID: 39715958 DOI: 10.1007/s12672-024-01704-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 12/13/2024] [Indexed: 12/25/2024] Open
Abstract
BACKGROUND Chemotherapy is crucial in the management of tumors, but challenges such as chemoresistance and adverse reactions frequently lead to therapeutic delays or even premature cessation. A growing body of research underscores a profound connection between the gut microbiota (GM) and cancer chemotherapy (CC). This paper aims to pinpoint highly influential publications and monitor the current landscape and evolving trends within the realm of GM/CC research. METHODS On October 1st, 2024, a comprehensive search for GM/CC publications spanning the past 20 years from 2004 to 2023 was conducted utilizing the Web of Science Core Collection (WoSCC). The scope encompassed both articles and reviews, and the data was subsequently extracted. To gain insights into the evolution and dynamics of this research field, we employed bibliometric analysis tools such as the Bibliometrix R package, VOSviewer, and Microsoft Excel to visualize and analyze various dimensions, including prominent journals, leading authors, esteemed institutions, contributing countries/regions, highly cited papers, and frequently occurring keywords. RESULTS A total of 888 papers were obtained. The number of publications about GM/CC studies has increased gradually. China and the United States published the largest number of papers. The INSERM was in the leading position in publishers. The most productive authors were Zitvogel L from France. Cancers had the largest number of papers. Citation analysis explained the historical evolution and breakthroughs in GM/CC research. Highly cited papers and common keywords illustrated the status and trends of GM/CC research. Four clusters were identified, and the hot topics included the role of the GM in the efficacy and toxicity of CC, the targeting of the GM to improve the outcome of CC, the mechanism by which the GM affects CC, and the correlation of the GM with carcinogenesis and cancer therapy. Metabolism, GM-derived metabolites, tumor microenvironment, immunity, intestinal barrier, tumor microbiota and Fusobacterium nucleatum may become the new hotspots and trends of GM/CC research. CONCLUSION This study analyzed global publications and bibliometric characteristics of the links between GM and CC, identified highly cited papers in GM/CC, provided insight into the status, hotspots, and trends of global GM/CC research, and showed that the GM can be used to predict the efficacy and toxicity of CC and modifying the GM can improve the outcomes of chemotherapeutics, which may inform clinical researchers of future directions.
Collapse
Affiliation(s)
- Shanshan Yang
- Department of Traditional Chinese Medicine, Peking University First Hospital, Beijing, China
| | - Shaodong Hao
- Spleen-Stomach Department, Fangshan Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Hui Ye
- Department of Traditional Chinese Medicine, Peking University First Hospital, Beijing, China.
| | - Xuezhi Zhang
- Department of Traditional Chinese Medicine, Peking University First Hospital, Beijing, China.
| |
Collapse
|
|
12
|
Nguyen DK, Kang MJ, Oh SJ, Park HJ, Kim SH, Yu JH, Lee Y, Lee HS, Yang JW, Seo Y, Ahn JS, Kim HS. Parvimonas micra-polarized M2-like tumor-associated macrophages accelerate colorectal cancer development via IL-8 secretion. Anim Cells Syst (Seoul) 2024; 29:24-34. [PMID: 39777026 PMCID: PMC11703389 DOI: 10.1080/19768354.2024.2442401] [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: 08/16/2024] [Revised: 10/27/2024] [Accepted: 11/29/2024] [Indexed: 01/11/2025] Open
Abstract
Parvimonas micra (Pm), a periodontal pathogen, has been implicated in the impairment of anti-tumor responses in colorectal cancer (CRC). The tumor microenvironment in CRC involves tumor-associated macrophages (TAMs), which are pivotal in modulating tumor-associated immune responses. The polarization of TAMs towards an M2-like phenotype promotes CRC progression by suppressing the immune system. However, the mechanisms by which Pm affects the progression of CRC remain inadequately elucidated. In this study, we explored the impact of Pm infection on CRC cell characteristics, including proliferation, chemoresistance, migration, and macrophage polarization. We found that Pm-infected THP-1-derived macrophages exhibited elevated interleukin-10 levels, a well-established M2 marker. Conditioned media from Pm-treated THP-1 cells significantly enhanced CRC cell proliferation, cisplatin resistance, and migration, and interleukin-8 was identified as a key factor. Consistent with the in vitro results, an azoxymethane/dextran sodium sulfate mouse model treated with oral Pm showed accelerated CRC tumor growth. These results offer mechanistic insights into the influence of Pm infection on tumor microenvironment in CRC through M2-like macrophage polarization. The identified pathways may serve as potential targets for therapeutic interventions for CRC.
Collapse
Affiliation(s)
- Dang Khoa Nguyen
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan, Republic of Korea
| | - Min-Jung Kang
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
| | - Su-Jeong Oh
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan, Republic of Korea
| | - Hee-Jeong Park
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan, Republic of Korea
| | - Seong Hui Kim
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan, Republic of Korea
| | - Jeong Hyun Yu
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan, Republic of Korea
| | - Yunji Lee
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan, Republic of Korea
| | - Hyeon Seo Lee
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan, Republic of Korea
| | - Ji Won Yang
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
| | - Yoojin Seo
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
| | - Ji-Su Ahn
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
| | - Hyung-Sik Kim
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan, Republic of Korea
| |
Collapse
|
|
13
|
Guzowska M, Dziendzikowska K, Kopiasz Ł, Gajewska M, Wilczak J, Harasym J, Czerwińska M, Gromadzka-Ostrowska J. Oat Beta-Glucans Modulate the Gut Microbiome, Barrier Function, and Immune Responses in an In Vivo Model of Early-Stage Colorectal Cancer. Int J Mol Sci 2024; 25:13586. [PMID: 39769349 PMCID: PMC11677220 DOI: 10.3390/ijms252413586] [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: 11/20/2024] [Revised: 12/10/2024] [Accepted: 12/16/2024] [Indexed: 01/04/2025] Open
Abstract
Oat beta-glucans (OBGs) are known for their beneficial effects on gut health, including anti-inflammatory and prebiotic effects. The aim of this study was to evaluate the impact of two doses (1% or 3% w/w) of dietary low-molar-mass OBG supplementation on colorectal cancer (CRC) development, immune cell profiles, intestinal barrier protein expression, and microbiota composition in a rat model of CRC induced by azoxymethane (AOM). Microbiome analysis revealed significant differences between the control and CRC groups. OBG supplementation influenced microbial diversity and abundance, particularly increasing the population of beneficial bacteria, such as Lachnospiraceae and Ruminococcaceae, associated with butyrate production. However, higher doses of OBG (3%) led to a decrease in butyrate-producing bacteria and a shift toward higher levels of Akkermansia muciniphila and Enterococcus faecalis. Immune cell profiling showed a higher percentage of T lymphocytes (CD3+) in rats fed a diet supplemented with 3% OBG, both in the intraepithelial (IEL) and lamina propria lymphocytes (LPLs). Immunohistochemical analysis of the large intestine revealed a significantly elevated expression of intestinal barrier proteins, i.e., claudin 3 and 4 in rats receiving 1% OBG, while claudin 7 expression was reduced in early-stage CRC. Gene expression analysis also revealed a significant downregulation of Cldn1 in CRC rats. These findings suggest that dietary OBG supplementation modulates the gut microbiota, immune response, and intestinal barrier integrity, with potential implications for nutritional CRC development prevention and treatment strategies.
Collapse
Affiliation(s)
- Magdalena Guzowska
- Department of Physiological Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-776 Warsaw, Poland; (M.G.); (J.W.)
| | - Katarzyna Dziendzikowska
- Department of Dietetics, Institute of Human Nutrition Sciences, Warsaw University of Life Sciences, 02-776 Warsaw, Poland; (Ł.K.); (M.C.); (J.G.-O.)
| | - Łukasz Kopiasz
- Department of Dietetics, Institute of Human Nutrition Sciences, Warsaw University of Life Sciences, 02-776 Warsaw, Poland; (Ł.K.); (M.C.); (J.G.-O.)
| | - Małgorzata Gajewska
- Department of Physiological Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-776 Warsaw, Poland; (M.G.); (J.W.)
| | - Jacek Wilczak
- Department of Physiological Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-776 Warsaw, Poland; (M.G.); (J.W.)
| | - Joanna Harasym
- Department of Biotechnology and Food Analysis, Wroclaw University of Economics and Business, 53-345 Wroclaw, Poland;
| | - Malwina Czerwińska
- Department of Dietetics, Institute of Human Nutrition Sciences, Warsaw University of Life Sciences, 02-776 Warsaw, Poland; (Ł.K.); (M.C.); (J.G.-O.)
| | - Joanna Gromadzka-Ostrowska
- Department of Dietetics, Institute of Human Nutrition Sciences, Warsaw University of Life Sciences, 02-776 Warsaw, Poland; (Ł.K.); (M.C.); (J.G.-O.)
| |
Collapse
|
|
14
|
Rong J, Chen X, Li Z, Li B, Sun Y, Miao Y. Dysregulation of saliva and fecal microbiota as novel biomarkers of colorectal cancer. Front Oncol 2024; 14:1498328. [PMID: 39743994 PMCID: PMC11688226 DOI: 10.3389/fonc.2024.1498328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 12/02/2024] [Indexed: 01/04/2025] Open
Abstract
The aim of this study was to investigate the biomarkers of salivary and fecal microbiota in Colorectal cancer (CRC). Initially, the study scrutinized the microbial community composition disparities among groups. Utilizing Lasso analysis, it sifted through operational taxonomic units (OTUs) to pinpoint distinctive features. Subsequently, by intersecting feature OTUs across groups, it curated a set of core-shared OTUs and devised a corresponding network. Concluding with functional enrichment analysis, the research delved into the divergent biological functions of these microbial communities within the studied groups. Analysis revealed higher bacterial diversity in saliva compared to feces, with distinct differences at both phylum and genus levels. Feces primarily contained Firmicutes, while saliva was dominated by Bacteroidetes and Proteobacteria. Notably, Escherichia-Shigella and Fusobacterium in feces and Streptococcus in saliva showed increasing abundance from average to adenoma to colorectal cancer. Specific dominant flora was identified within and between groups, including CRC and adenomas across different stages. Seventeen core shared OTUs were identified, and networks of shared OTUs were constructed for each group. Functional enrichment analysis highlighted distinct microbial community functions among the groups. This study's findings on characteristic OTUs in saliva and fecal samples offer valuable insights for distinguishing between healthy individuals, adenoma patients, and those with colorectal cancer. This study identified distinctive OTUs in saliva and feces to distinguish between healthy individuals, adenoma patients, and those with CRC, offering a valuable diagnostic reference.
Collapse
Affiliation(s)
- Jiamei Rong
- Yan’an Hospital Affiliated To Kunming Medical University, Kunming, Yunnan, China
| | - Xiaocui Chen
- Affiliated Hospital of Panzhihua University, Panzhihua, Sichuan, China
| | - Zhangqin Li
- Department of Gastroenterology, First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Bona Li
- Department of Gastroenterology, First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yang Sun
- Department of Gastroenterology, First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yinglei Miao
- Department of Gastroenterology, First Affiliated Hospital of Kunming Medical University, Kunming, China
| |
Collapse
|
|
15
|
Pedrosa LDF, de Vos P, Fabi JP. From Structure to Function: How Prebiotic Diversity Shapes Gut Integrity and Immune Balance. Nutrients 2024; 16:4286. [PMID: 39770907 PMCID: PMC11678351 DOI: 10.3390/nu16244286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 12/06/2024] [Accepted: 12/11/2024] [Indexed: 01/11/2025] Open
Abstract
The microbiota stability, diversity, and composition are pillars for an efficient and beneficial symbiotic relationship between its host and itself. Microbial dysbiosis, a condition where a homeostatic bacterial community is disturbed by acute or chronic events, is a predisposition for many diseases, including local and systemic inflammation that leads to metabolic syndrome, diabetes, and some types of cancers. Classical dysbiosis occurs in the large intestine. During this period, pathogenic strains can multiply, taking advantage of the compromised environment. This overgrowth triggers an exaggerated inflammatory response from the human immune system due to the weakened integrity of the intestinal barrier. Such inflammation can also directly influence higher polyp formation and/or tumorigenesis. Prebiotics can be instrumental in preventing or correcting dysbiosis. Prebiotics are molecules capable of serving as substrates for fermentation processes by gut microorganisms. This can promote returning the intestinal environment to homeostasis. Effective prebiotics are generally specific oligo- and polysaccharides, such as FOS or inulin. However, the direct effects of prebiotics on intestinal epithelial and immune cells must also be taken into consideration. This interaction happens with diverse prebiotic nondigestible carbohydrates, and they can inhibit or decrease the inflammatory response. The present work aims to elucidate and describe the different types of prebiotics, their influence, and their functionalities for health, primarily focusing on their ability to reduce and control inflammation in the intestinal epithelial barrier, gut, and systemic environments.
Collapse
Affiliation(s)
- Lucas de Freitas Pedrosa
- Department of Food Science and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-000, SP, Brazil;
- Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands;
| | - Paul de Vos
- Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands;
| | - João Paulo Fabi
- Department of Food Science and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-000, SP, Brazil;
- Food and Nutrition Research Center (NAPAN), University of São Paulo, São Paulo 05508-000, SP, Brazil
- Food Research Center (FoRC), CEPID-FAPESP (Research, Innovation, and Dissemination Centers), São Paulo 05508-080, SP, Brazil
- Food Research Center (FoRC), CEPIX-USP, University of São Paulo, São Paulo 05508-000, SP, Brazil
| |
Collapse
|
|
16
|
Li M, Zhang J, Jia L, Su L, Zhang Y, Zheng Z, Shen H, Chang J. Supportive care needs and associated factors among caregivers of elderly patients with gastrointestinal cancer: an exploratory study. BMC Nurs 2024; 23:877. [PMID: 39623407 PMCID: PMC11613536 DOI: 10.1186/s12912-024-02544-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Accepted: 11/21/2024] [Indexed: 12/06/2024] Open
Abstract
BACKGROUND Gastrointestinal cancers, including gastric and colorectal cancers, are major contributors to cancer-related morbidity and mortality worldwide, placing significant burdens on patients and their informal caregivers. This study aims to evaluate the level of supportive needs among informal caregivers of patients with gastrointestinal cancer and to identify key factors influencing these needs. METHODS We conducted a descriptive survey involving 335 informal caregivers of patients with gastrointestinal cancer at a large hospital in Shanghai, China, from September 2023 to April 2024. Multivariate linear regression analysis was employed to examine potential factors affecting supportive needs, including demographic information, caregiver burden, and self-efficacy. RESULTS The average supportive needs score among the 335 caregivers was 113.59 ± 52.97. This score was positively correlated with caregiver burden (r = 0.363, P < 0.001), self-efficacy (r = 0.224, P < 0.001), and patients' Karnofsky Performance Status (KPS) score (r = 0.119, P < 0.05). Multivariate regression analysis revealed that the care experience, duration of caregiving, relationship (sibling), self-efficacy, caregiver burden, KPS score of patients, treatment duration of patients, and cancer type of patients were significant factors influencing the supportive care needs of caregivers for elderly gastrointestinal cancer patients (P < 0.05). CONCLUSION Informal caregivers of elderly patients with gastrointestinal cancer often have increased levels of supportive needs. Clinical practice should include comprehensive assessments of these needs and the development of targeted interventions to improve caregiving skills and reduce caregiver burden, thereby enhancing the quality of life for both caregivers and patients.
Collapse
Affiliation(s)
- Mengxue Li
- School of Nursing, Shanghai Jiao Tong University, 85 Wu Jin Road, Hongkou District, Shanghai, 200001, China
| | - Jie Zhang
- Department of Nursing, Shanghai General Hospital, Shanghai, 201620, China
| | - Lei Jia
- Department of Nursing, Shanghai General Hospital, Shanghai, 201620, China
| | - Liqing Su
- Department of Nursing, Stomatological Hospital of Xiamen Medical College, Xiamen, 361008, China
| | - Yumeng Zhang
- School of Nursing, Shanghai Jiao Tong University, 85 Wu Jin Road, Hongkou District, Shanghai, 200001, China
| | - Ziyi Zheng
- School of Nursing, Shanghai Jiao Tong University, 85 Wu Jin Road, Hongkou District, Shanghai, 200001, China
| | - Huili Shen
- Department of Medical Services, Shanghai General Hospital, Shanghai, 200080, China
| | - Jian Chang
- School of Nursing, Shanghai Jiao Tong University, 85 Wu Jin Road, Hongkou District, Shanghai, 200001, China.
- Department of Nursing, Shanghai General Hospital, Shanghai, 200080, China.
| |
Collapse
|
|
17
|
Kumar A, Pramanik J, Batta K, Bamal P, Gaur M, Rustagi S, Prajapati BG, Bhattacharya S. Impact of metallic nanoparticles on gut microbiota modulation in colorectal cancer: A review. CANCER INNOVATION 2024; 3:e150. [PMID: 39398260 PMCID: PMC11467490 DOI: 10.1002/cai2.150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 06/03/2024] [Accepted: 07/05/2024] [Indexed: 10/15/2024]
Abstract
Colorectal cancer (CRC) is the third most prevalent cancer. Ongoing research aims to uncover the causes of CRC, with a growing focus on the role of gut microbiota (GM) in carcinogenesis. The GM influences CRC development, progression, treatment efficacy, and therapeutic toxicities. For example, Fusobacterium nucleatum and Escherichia coli can regulate microbial gene expression through the incorporation of human small noncode RNA and potentially contribute to cancer progression. Metallic nanoparticles (MNPs) have both negative and positive impacts on GM, depending on their type. Several studies state that titanium dioxide may increase the diversity, richness, and abundance of probiotics bacteria, whereas other studies demonstrate dose-dependent GM dysbiosis. The MNPs offer cytotoxicity through the modulation of MAPK signaling pathways, NF-kB signaling pathways, PI3K/Akt signaling pathways, extrinsic signaling pathways, intrinsic apoptosis, and cell cycle arrest at G1, G2, or M phase. MNPs enhance drug delivery, enable targeted therapy, and may restore GM. However, there is a need to conduct well-designed clinical trials to assess the toxicity, safety, and effectiveness of MNPs-based CRC therapies.
Collapse
Affiliation(s)
- Akash Kumar
- Department of Food TechnologySRM University, Delhi NCRSonepatIndia
- MMICT & BM (Hotel Management), Maharishi Markandeshwar (Deemed to be University)MullanaIndia
| | - Jhilam Pramanik
- Department of Food TechnologyWilliam Carey UniversityShillongIndia
| | - Kajol Batta
- Department of Food TechnologyITM UniversityGwaliorIndia
| | - Pooja Bamal
- Department of Food TechnologyChaudhary Devi Lal UniversitySirsaIndia
| | - Mukesh Gaur
- Department of Food TechnologyGuru Jambheshwar University of Science and TechnologyHisarIndia
| | - Sarvesh Rustagi
- School of Applied and Life SciencesUttaranchal UniversityDehradunIndia
| | - Bhupendra G. Prajapati
- Shree S. K. Patel College of Pharmaceutical Education and ResearchGanpat UniversityMehsanaIndia
| | - Sankha Bhattacharya
- Department of PharmaceuticsSchool of Pharmacy & Technology Management, SVKM'S NMIMS Deemed‐to‐be UniversityShirpurMaharashtraIndia
| |
Collapse
|
|
18
|
Hong BY, Chhaya A, Robles A, Cervantes J, Tiwari S. The role of Fusobacterium nucleatum in the pathogenesis of colon cancer. J Investig Med 2024; 72:819-827. [PMID: 39175147 DOI: 10.1177/10815589241277829] [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] [Indexed: 08/24/2024]
Abstract
Previously, many studies have reported changes in the gut microbiota of patients with colorectal cancer (CRC). While CRC is a well-described disease, the relationship between its development and features of the intestinal microbiome is still being understood. Evidence linking Fusobacterium nucleatum enrichment in colorectal tumor tissue has prompted the elucidation of various molecular mechanisms and tumor-promoting attributes. In this review we highlight various aspects of our understanding of the relationship between the development of CRC and the alteration of intestinal microbiome, focusing specifically on the role of F. nucleatum. As the amount of F. nucleatum DNA in CRC tissue is associated with shorter survival, it may potentially serve as a prognostic biomarker, and most importantly may open the door for a role in CRC treatment.
Collapse
Affiliation(s)
- Bo-Young Hong
- Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA
| | - Ajay Chhaya
- Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, USA
| | - Alejandro Robles
- Department of Internal Medicine, Division of Gastroenterology, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA
| | - Jorge Cervantes
- Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA
| | - Sangeeta Tiwari
- Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, USA
- Biomedical Research Center, University of Texas at El Paso, El Paso, TX, USA
| |
Collapse
|
|
19
|
Gharib E. Closing Editorial: Colorectal Cancer-A Molecular Genetics Perspective. Int J Mol Sci 2024; 25:12604. [PMID: 39684316 DOI: 10.3390/ijms252312604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Accepted: 11/21/2024] [Indexed: 12/18/2024] Open
Abstract
Colorectal cancer (CRC) remains a significant global health challenge, ranking third in incidence and second in mortality among all cancers [...].
Collapse
Affiliation(s)
- Ehsan Gharib
- Département de Chimie et Biochimie, Université de Moncton, Moncton, NB E1A 3E9, Canada
- Atlantic Cancer Research Institute, Moncton, NB E1C 8X3, Canada
| |
Collapse
|
|
20
|
Xu Y, Wu X, Li Y, Liu X, Fang L, Jiang Z. Probiotics and the Role of Dietary Substrates in Maintaining the Gut Health: Use of Live Microbes and Their Products for Anticancer Effects against Colorectal Cancer. J Microbiol Biotechnol 2024; 34:1933-1946. [PMID: 39210613 PMCID: PMC11540615 DOI: 10.4014/jmb.2403.03056] [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: 03/27/2024] [Revised: 07/19/2024] [Accepted: 07/28/2024] [Indexed: 09/04/2024]
Abstract
The gut microbiome is an important and the largest endocrine organ linked to the microbes of the GI tract. The bacterial, viral and fungal communities are key regulators of the health and disease status in a host at hormonal, neurological, immunological, and metabolic levels. The useful microbes can compete with microbes exhibiting pathogenic behavior by maintaining resistance against their colonization, thereby maintaining eubiosis. As diagnostic tools, metagenomic, proteomic and genomic approaches can determine various microbial markers in clinic for early diagnosis of colorectal cancer (CRC). Probiotics are live non-pathogenic microorganisms such as lactic acid bacteria, Bifidobacteria, Firmicutes and Saccharomyces that can help maintain eubiosis when administered in appropriate amounts. In addition, the type of dietary intake contributes substantially to the composition of gut microbiome. The use of probiotics has been found to exert antitumor effects at preclinical levels and promote the antitumor effects of immunotherapeutic drugs at clinical levels. Also, modifying the composition of gut microbiota by Fecal Microbiota Transplantation (FMT), and using live lactic acid producing bacteria such as Lactobacillus, Bifidobacteria and their metabolites (termed postbiotics) can contribute to immunomodulation of the tumor microenvironment. This can lead to tumor-preventive effects at early stages and antitumor effects after diagnosis of CRC. To conclude, probiotics are presumably found to be safe to use in humans and are to be studied further to promote their appliance at clinical levels for management of CRC.
Collapse
Affiliation(s)
- Yi Xu
- Phase I Clinical Cancer Trial Center, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, 222002, P.R. China
| | - Xiahui Wu
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang 222002, P.R. China
- Department of Oncology, The First People’s Hospital of Lianyungang, Lianyungang 222002, P.R. China
| | - Yan Li
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang 222002, P.R. China
- Department of Oncology, The First People’s Hospital of Lianyungang, Lianyungang 222002, P.R. China
| | - Xuejie Liu
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang 222002, P.R. China
- Department of Oncology, The First People’s Hospital of Lianyungang, Lianyungang 222002, P.R. China
| | - Lijian Fang
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang 222002, P.R. China
- Department of Oncology, The First People’s Hospital of Lianyungang, Lianyungang 222002, P.R. China
| | - Ziyu Jiang
- Phase I Clinical Cancer Trial Center, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, 222002, P.R. China
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang 222002, P.R. China
- Department of Oncology, The First People’s Hospital of Lianyungang, Lianyungang 222002, P.R. China
| |
Collapse
|
|
21
|
Halawa M, Newman PM, Aderibigbe T, Carabetta VJ. Conjugated therapeutic proteins as a treatment for bacteria which trigger cancer development. iScience 2024; 27:111029. [PMID: 39635133 PMCID: PMC11615139 DOI: 10.1016/j.isci.2024.111029] [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] [Indexed: 12/07/2024] Open
Abstract
In recent years, an increasing amount of research has focused on the intricate and complex correlation between bacterial infections and the development of cancer. Some studies even identified specific bacterial species as potential culprits in the initiation of carcinogenesis, which generated a great deal of interest in the creation of innovative therapeutic strategies aimed at addressing both the infection and the subsequent risk of cancer. Among these strategies, there has been a recent emergence of the use of conjugated therapeutic proteins, which represent a highly promising avenue in the field of cancer therapeutics. These proteins offer a dual-targeting approach that seeks to effectively combat both the bacterial infection and the resulting malignancies that may arise because of such infections. This review delves into the landscape of conjugated therapeutic proteins that have been intricately designed with the purpose of specifically targeting bacteria that have been implicated in the induction of cancer.
Collapse
Affiliation(s)
- Mohamed Halawa
- Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ 08103, USA
| | - Precious M. Newman
- Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ 08103, USA
| | - Tope Aderibigbe
- Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ 08103, USA
| | - Valerie J. Carabetta
- Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ 08103, USA
| |
Collapse
|
|
22
|
Mohammadpour S, Torshizi Esfahani A, Sarpash S, Vakili F, Zafarjafarzadeh N, Mashaollahi A, Pardakhtchi A, Nazemalhosseini-Mojarad E. Hippo Signaling Pathway in Colorectal Cancer: Modulation by Various Signals and Therapeutic Potential. Anal Cell Pathol (Amst) 2024; 2024:5767535. [PMID: 39431199 PMCID: PMC11489006 DOI: 10.1155/2024/5767535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 07/07/2024] [Accepted: 08/19/2024] [Indexed: 10/22/2024] Open
Abstract
Colorectal cancer (CRC) stands as a significant global health issue, marked by elevated occurrence and mortality statistics. Despite the availability of various treatments, including chemotherapy, radiotherapy, and targeted therapy, CRC cells often exhibit resistance to these interventions. As a result, it is imperative to identify the disease at an earlier stage and enhance the response to treatment by acquiring a deeper comprehension of the processes driving tumor formation, aggressiveness, metastasis, and resistance to therapy. The Hippo pathway plays a critical role in facilitating the initiation of tumorigenesis and frequently experiences disruption within CRC because of genetic mutations and modified expression in its fundamental constituents. Targeting upstream regulators or core Hippo pathway components may provide innovative therapeutic strategies for modulating Hippo signaling dysfunction in CRC. To advance novel therapeutic techniques for CRC, it is imperative to grasp the involvement of the Hippo pathway in CRC and its interaction with alternate signaling pathways, noncoding RNAs, gut microbiota, and the immune microenvironment. This review seeks to illuminate the function and control of the Hippo pathway in CRC, ultimately aiming to unearth innovative therapeutic methodologies for addressing this ailment.
Collapse
Affiliation(s)
- Somayeh Mohammadpour
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Torshizi Esfahani
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - SeyedKasra Sarpash
- Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Fatemeh Vakili
- Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Nikta Zafarjafarzadeh
- Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Amirhesam Mashaollahi
- Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Ali Pardakhtchi
- Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Ehsan Nazemalhosseini-Mojarad
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
23
|
Jin S, Zhong W, Li B, Wang K, Lai D. Multidimensional analysis of the impact of Gemmatimonas, Rhodothermus, and Sutterella on drug and treatment response in colorectal cancer. Front Cell Infect Microbiol 2024; 14:1457461. [PMID: 39439901 PMCID: PMC11493733 DOI: 10.3389/fcimb.2024.1457461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Accepted: 09/19/2024] [Indexed: 10/25/2024] Open
Abstract
Background Colorectal cancer is the third most prevalent cancer across the globe. Despite a diversity of treatment methods, the recurrence and mortality rates of the disease remain high. Recent studies have revealed a close association of the gut microbiota with the occurrence, development, treatment response, and prognosis of colorectal cancer. Objective This study aims to integrate transcriptome and microbiome data to identify colorectal cancer subtypes associated with different gut microbiota and evaluate their roles in patient survival prognosis, tumor microenvironment (TME), and drug treatment response. Methods An integrated analysis of microbiome data was conducted on samples of colorectal cancer from public databases. Based on this, two tumor subtypes (C1 and C2) closely associated with patient survival prognosis were identified and a risk score model was constructed. The survival status, clinical parameters, immune scores, and other features were analyzed in-depth, and the sensitivity of various potential drugs was examined. Results A thorough examination of microbiome information obtained from colorectal cancer patients led to the identification of two primary tumor clusters (C1 and C2), exhibiting notable variations in survival outcomes. Patients with the C1 subtype were closely associated with better prognosis, while those with the C2 subtype had higher gut microbial richness and poorer survival prognosis. A predictive model utilizing the microbiome data was developed to accurately forecast the survival outcome of patients with colorectal cancer. The TME scores provided a biological basis for risk assessment in high-risk (similar to the C2 subtype) patient cohorts. Evaluation of the sensitivity of different subtypes to various potential drugs, indicated the critical importance of personalized treatment. Further analysis showed good potential of the developed risk-scoring model in predicting immune checkpoint functions and treatment response of patients, which may be crucial in guiding the selection of immunotherapy strategies for patients with colorectal cancer. Conclusion This study, through a comprehensive analysis of colorectal cancer microbiome, immune microenvironment, and drug sensitivity, enhances the current understanding of the multidimensional interactions of colorectal cancer and provides important clinical indications for improving future treatment strategies. The findings offer a new perspective on improving treatment response and long-term prognosis of patients with CRC through the regulation of microbiota or the utilization of biomarkers provided by it.
Collapse
Affiliation(s)
- Shaowen Jin
- Department of Gastrointestinal Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Wa Zhong
- Department of Gastrointestinal Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Bo Li
- Department of Orthopedics, Beijing Luhe Hospital, Capital Medical University, Beijing, China
| | - Kaimei Wang
- Department of Pediatrics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Dongming Lai
- Department of Gastrointestinal Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
- Department of Gastrointestinal Surgery, Shenshan Medical Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Shanwei, China
| |
Collapse
|
|
24
|
Bachelle SV, Bah SY, Addo RT, Bediako-Bowan AAA, Egyir B, Tsatsu SE, Dzudzor B, Amarh V. Genomic analysis of Enterobacteriaceae from colorectal cancer patients at a tertiary hospital in Ghana: a case-control study. Sci Rep 2024; 14:23195. [PMID: 39369124 PMCID: PMC11455924 DOI: 10.1038/s41598-024-74299-3] [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: 07/12/2024] [Accepted: 09/25/2024] [Indexed: 10/07/2024] Open
Abstract
Colorectal cancer (CRC) is a severe gastrointestinal cancer and a leading cause of cancer-related deaths in Ghana. The potential role of gut Enterobacteriaceae in the increasing incidence of CRC in Ghana is yet to be thoroughly investigated. In this study, Enterobacteriaceae from CRC patients and healthy control participants were analyzed by whole genome sequencing to identify genomic features that are associated with CRC. Socio-demographic data showed a significant association between age and alcohol consumption and CRC. Escherichia coli was the most abundant Enterobacteriaceae isolated from the study participants and they were predominantly intestinal commensals. Escherichia coli isolates belonging to phylogroup D encoded the highest number of virulence genes. The agn43 and int genes were widespread in Escherichia coli isolates from the CRC patients. Multilocus sequence types of potentially pathogenic Escherichia coli from the CRC patients also encoded genes involved in aggregation, adherence and biofilm formation. The ampC2 and ampH antimicrobial resistance genes were also widespread in the genome of the Escherichia coli isolates. This study highlights the virulence tendencies of Escherichia coli from CRC patients and their ability to transfer virulence determinants to other Enterobacteriaceae residing in the gut.
Collapse
Affiliation(s)
- Sarah V Bachelle
- Department of Medical Biochemistry, University of Ghana Medical School, Korle-Bu, Accra, Ghana
| | - Saikou Y Bah
- School of Infection & Immunity, University of Glasgow, Glasgow, UK
| | - Richmond T Addo
- Central Laboratory, Korle-Bu Teaching Hospital, Korle-Bu, Accra, Ghana
| | - Antoinette A A Bediako-Bowan
- Department of Surgery, University of Ghana Medical School, Korle-Bu, Accra, Ghana
- Department of Surgery, Korle-Bu Teaching Hospital, Korle-Bu, Accra, Ghana
| | - Beverly Egyir
- Bacteriology Department, Noguchi Memorial Institute for Medical Research, Accra, Ghana
| | - Sandra E Tsatsu
- Department of Surgery, University of Ghana Medical School, Korle-Bu, Accra, Ghana
- Department of Surgery, Korle-Bu Teaching Hospital, Korle-Bu, Accra, Ghana
| | - Bartholomew Dzudzor
- Department of Medical Biochemistry, University of Ghana Medical School, Korle-Bu, Accra, Ghana.
| | - Vincent Amarh
- Department of Medical Biochemistry, University of Ghana Medical School, Korle-Bu, Accra, Ghana.
| |
Collapse
|
|
25
|
Fadel MG, Zonoobi E, Rodríguez-Luna MR, Mishima K, Ris F, Diana M, Vahrmeijer AL, Perretta S, Ashrafian H, Fehervari M. Efficacy and Safety of Fluorescence-Guided Surgery Compared to Conventional Surgery in the Management of Colorectal Cancer: A Systematic Review and Meta-Analysis. Cancers (Basel) 2024; 16:3377. [PMID: 39409997 PMCID: PMC11476237 DOI: 10.3390/cancers16193377] [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: 07/31/2024] [Revised: 09/09/2024] [Accepted: 09/24/2024] [Indexed: 10/20/2024] Open
Abstract
BACKGROUND The use of fluorescence agents and imaging systems is a promising adjunct in the surgical management of colorectal cancer. This systematic review and meta-analysis aimed to assess the safety and efficacy of fluorescence-guided surgery in the management of colorectal cancer, with a comparison to conventional (non-fluorescence-guided) surgery. METHODS A literature search of MEDLINE, Embase, Emcare, and CINAHL databases was performed for studies that reported data on the outcomes of fluorescence-guided surgery, with or without a comparison group undergoing conventional surgery, for colorectal cancer between January 2000 and January 2024. A meta-analysis was performed using random-effect models, and between-study heterogeneity was assessed. RESULTS 35 studies of 3217 patients with colorectal cancer were included: 26 studies (964 patients) reported on fluorescence-guided surgery and 9 studies (2253 patients) reported on fluorescence versus conventional surgery. The weighted mean of the cancer detection rate of fluorescence-guided surgery was 71% (95% CI 0.55-0.85), with no significant difference in lymph node yield ratio (WMD -0.04; 95% CI -0.10-0.02; p = 0.201) between fluorescence and conventional surgery groups. There was a significantly lower blood loss (WMD -4.38; 95% CI -7.05--1.70; p = 0.001) and complication rate (WMD -0.04; 95% CI -0.07-0.00; p = 0.027) in the fluorescence-guided surgery group, with a potentially lower anastomotic leak rate (WMD -0.05; 95% CI -0.10-0.01; p = 0.092). CONCLUSIONS Fluorescence-guided surgery is a safe and effective approach in the management of colorectal cancer, potentially reducing blood loss and complications. Further randomised controlled trials are required comparing fluorescence-guided surgery with conventional surgery to determine its prognostic benefit and where it should precisely fit within the management pathway of colorectal cancer.
Collapse
Affiliation(s)
- Michael G. Fadel
- Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, UK
- Department of General Surgery, Chelsea and Westminster Hospital, London SW10 9NH, UK
| | - Elham Zonoobi
- Edinburgh Molecular Imaging Limited, Nine Edinburgh Bioquarter, Edinburgh EH16 4UX, UK
- Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | | | - Kohei Mishima
- Research Institute Against Digestive Cancer (IRCAD), 67000 Strasbourg, France
| | - Frédéric Ris
- Department of Surgery, University Hospital of Geneva, 1205 Geneva, Switzerland
- Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland
| | - Michele Diana
- Department of Surgery, University Hospital of Geneva, 1205 Geneva, Switzerland
- Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland
- ICube Laboratory, Photonics Instrumentation for Health, 67034 Strasbourg, France
| | | | - Silvana Perretta
- Research Institute Against Digestive Cancer (IRCAD), 67000 Strasbourg, France
- IHU-Strasbourg, Institute of Image-Guided Surgery, 67000 Strasbourg, France
- Department of Digestive and Endocrine Surgery, University of Strasbourg, 67081 Strasbourg, France
| | - Hutan Ashrafian
- Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, UK
| | - Matyas Fehervari
- Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, UK
- Department of Gastrointestinal Surgery, Maidstone and Tunbridge Wells NHS Trust, Tunbridge Wells TN2 4QJ, UK
| |
Collapse
|
|
26
|
Guo Z, Lei Y, Wang Q. Chinese expert consensus on standard technical specifications for a gut microecomics laboratory (Review). Exp Ther Med 2024; 28:403. [PMID: 39234587 PMCID: PMC11372251 DOI: 10.3892/etm.2024.12692] [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: 03/21/2024] [Accepted: 07/11/2024] [Indexed: 09/06/2024] Open
Abstract
The intestinal microbiota is a complex ecosystem that not only affects various physiological functions, such as metabolism, inflammation and the immune response, but also has an important effect on the development of tumors and response to treatment. The detection of intestinal flora enables the timely identification of disease-related flora abnormalities, which has significant implications for both disease prevention and treatment. In the field of basic and clinical research targeting gut microbiome, there is a need to recognize and understand the laboratory assays for gut microbiomics. Currently, there is no unified standard for the experimental procedure, quality management and report interpretation of intestinal microbiome assay technology. In order to clarify the process, the Tumor and Microecology Committee of China Anti-Cancer Association and the Tumor and Microecology Committee of Hubei Provincial Immunology Society organized relevant experts to discuss and put forward the standard technical specifications for gut microecomics laboratories, which provides a basis for further in-depth research in the field of intestinal microecomics.
Collapse
Affiliation(s)
- Zhi Guo
- Department of Hematology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, Guangdong 518052, P.R. China
- Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Medical College, Wuhan University of Science and Technology, Wuhan, Hubei 430065, P.R. China
| | - Yumeng Lei
- Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Medical College, Wuhan University of Science and Technology, Wuhan, Hubei 430065, P.R. China
| | - Qiang Wang
- Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Medical College, Wuhan University of Science and Technology, Wuhan, Hubei 430065, P.R. China
| |
Collapse
|
|
27
|
Xia Y, Duan L, Zhang XL, Niu YJ, Ling X. Integrated analysis of gut microbiota and metabolomic profiling in colorectal cancer metastasis. ENVIRONMENTAL TOXICOLOGY 2024; 39:4467-4478. [PMID: 38483004 DOI: 10.1002/tox.24228] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 02/28/2024] [Accepted: 03/04/2024] [Indexed: 10/24/2024]
Abstract
Colorectal cancer (CRC) is characterized by its heterogeneity and complex metastatic mechanisms, presenting significant challenges in treatment and prognosis. This study aimed to unravel the intricate interplay between the gut microbiota and metabolic alterations associated with CRC metastasis. By employing high-throughput sequencing and advanced metabolomic techniques, we identified distinct patterns in the gut microbiome and fecal metabolites across different CRC metastatic sites. The differential gene analysis highlighted significant enrichment in biological processes related to immune response and extracellular matrix organization, with key genes playing roles in the complement and clotting cascades, and staphylococcus aureus infections. Protein-protein interaction networks further elucidated the potential mechanisms driving CRC spread, emphasizing the importance of extracellular vesicles and the PPAR signaling pathway in tumor metastasis. Our comprehensive microbiota analysis revealed a relatively stable alpha diversity across groups but identified specific bacterial genera associated with metastatic stages. Metabolomic profiling using OPLS-DA models unveiled distinct metabolic signatures, with differential metabolites enriched in pathways crucial for cancer metabolism and immune modulation. Integrative analysis of the gut microbiota and metabolic profiles highlighted significant correlations, suggesting a complex interplay that may influence CRC progression and metastasis. These findings offer novel insights into the microbial and metabolic underpinnings of CRC metastasis, paving the way for innovative diagnostic and therapeutic strategies targeting the gut microbiome and metabolic pathways.
Collapse
Affiliation(s)
- Yang Xia
- The First Clinical Medicine of Lanzhou University, Lanzhou, China
- Department of Hematology, The First People's Hospital of Lanzhou, Lanzhou, China
| | - Ling Duan
- The First Clinical Medicine of Lanzhou University, Lanzhou, China
- Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, China
| | - Xin-Lian Zhang
- Department of Hematology, The First People's Hospital of Lanzhou, Lanzhou, China
| | - Yu-Juan Niu
- Department of Hematology, The First People's Hospital of Lanzhou, Lanzhou, China
| | - Xiaoling Ling
- The First Clinical Medicine of Lanzhou University, Lanzhou, China
- Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, China
| |
Collapse
|
|
28
|
Kamal R, Awasthi A, Paul P, Mir MS, Singh SK, Dua K. Novel drug delivery systems in colorectal cancer: Advances and future prospects. Pathol Res Pract 2024; 262:155546. [PMID: 39191194 DOI: 10.1016/j.prp.2024.155546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 08/10/2024] [Accepted: 08/14/2024] [Indexed: 08/29/2024]
Abstract
Colorectal cancer (CRC) is an abnormal proliferation of cells within the colon and rectum, leading to the formation of polyps and disruption of mucosal functions. The disease development is influenced by a combination of factors, including inflammation, exposure to environmental mutagens, genetic alterations, and impairment in signaling pathways. Traditional treatments such as surgery, radiation, and chemotherapy are often used but have limitations, including poor solubility and permeability, treatment resistance, side effects, and post-surgery issues. Novel Drug Delivery Systems (NDDS) have emerged as a superior alternative, offering enhanced drug solubility, precision in targeting cancer cells, and regulated drug release. Thereby addressing the shortcomings of conventional therapies and showing promise for more effective CRC management. The present review sheds light on the pathogenesis, signaling pathways, biomarkers, conventional treatments, need for NDDS, and application of NDDS against CRC. Additionally, clinical trials, ongoing clinical trials, marketed formulations, and patents on CRC are also covered in the present review.
Collapse
Affiliation(s)
- Raj Kamal
- Department of Quality Assurance, ISF College of Pharmacy, Moga, Punjab 142001, India; School of Pharmacy, Desh Bhagat University, Mandi Gobindgarh, Punjab 147301, India
| | - Ankit Awasthi
- Department of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab 142001, India; Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India.
| | - Priyanka Paul
- Department of Pharmaceutical Science, PCTE Group of Institute, Ludhiana, Punjab, India
| | - Mohammad Shabab Mir
- School of Pharmacy, Desh Bhagat University, Mandi Gobindgarh, Punjab 147301, India
| | - Sachin Kumar Singh
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia
| | - Kamal Dua
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia; Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW 2007, Australia
| |
Collapse
|
|
29
|
Guo J, Meng F, Hu R, Chen L, Chang J, Zhao K, Ren H, Liu Z, Hu P, Wang G, Tai J. Inhibition of the NF-κB/HIF-1α signaling pathway in colorectal cancer by tyrosol: a gut microbiota-derived metabolite. J Immunother Cancer 2024; 12:e008831. [PMID: 39343509 PMCID: PMC11440206 DOI: 10.1136/jitc-2024-008831] [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] [Accepted: 09/08/2024] [Indexed: 10/01/2024] Open
Abstract
BACKGROUND The development and progression of colorectal cancer (CRC) are influenced by the gut environment, much of which is modulated by microbial-derived metabolites. Although some research has been conducted on the gut microbiota, there have been limited empirical investigations on the role of the microbial-derived metabolites in CRC. METHODS In this study, we used LC-MS and 16S rRNA sequencing to identify gut microbiome-associated fecal metabolites in patients with CRC and healthy controls. Moreover, we examined the effects of Faecalibacterium prausnitzii and tyrosol on CRC by establishing orthotopic and subcutaneous tumor mouse models. Additionally, we conducted in vitro experiments to investigate the mechanism through which tyrosol inhibits tumor cell growth. RESULTS Our study revealed changes in the gut microbiome and metabolome that are linked to CRC. We observed that Faecalibacterium prausnitzii, a bacterium known for its multiple anti-CRC properties, is significantly more abundant in the intestines of healthy individuals than in those of individuals with CRC. In mouse tumor models, our study illustrated that Faecalibacterium prausnitzii has the ability to inhibit tumor growth by reducing inflammatory responses and enhancing tumor immunity. Additionally, research investigating the relationship between CRC-associated features and microbe-metabolite interactions revealed a correlation between Faecalibacterium prausnitzii and tyrosol, both of which are less abundant in the intestines of tumor patients. Tyrosol demonstrated antitumor activity in vivo and specifically targeted CRC cells without affecting intestinal epithelial cells in cell experiments. Moreover, tyrosol treatment effectively reduced the levels of reactive oxygen species (ROS) and inflammatory cytokines in MC38 cells. Western blot analysis further revealed that tyrosol inhibited the activation of the NF-κB and HIF-1 signaling pathways. CONCLUSIONS This study investigated the relationship between CRC development and changes in the gut microbiota and microbial-derived metabolites. Specifically, the intestinal metabolite tyrosol exhibits antitumor effects by inhibiting HIF-1α/NF-κB signaling pathway activation, leading to a reduction in the levels of ROS and inflammatory factors. These findings indicate that manipulating the gut microbiota and its metabolites could be a promising approach for preventing and treating CRC and could provide insights for the development of anticancer drugs.
Collapse
Affiliation(s)
- Jian Guo
- Department of Colorectal&anal surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China
| | - Fanqi Meng
- Department of Colorectal&anal surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Ruixue Hu
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China
| | - Lei Chen
- Department of Colorectal&anal surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Jiang Chang
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China
| | - Ke Zhao
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China
| | - Honglin Ren
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China
| | - Zengshan Liu
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China
| | - Pan Hu
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China
| | - Guangyi Wang
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China
| | - Jiandong Tai
- Department of Colorectal&anal surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China
| |
Collapse
|
|
30
|
Arrè V, Balestra F, Scialpi R, Dituri F, Donghia R, Coletta S, Stabile D, Bianco A, Vincenti L, Fedele S, Shen C, Pettinato G, Scavo MP, Giannelli G, Negro R. Inorganic Polyphosphate Promotes Colorectal Cancer Growth via TRPM8 Receptor Signaling Pathway. Cancers (Basel) 2024; 16:3326. [PMID: 39409946 PMCID: PMC11476407 DOI: 10.3390/cancers16193326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Revised: 09/24/2024] [Accepted: 09/26/2024] [Indexed: 10/20/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is characterized by a pro-inflammatory microenvironment and features high-energy-supply molecules that assure tumor growth. A still less studied macromolecule is inorganic polyphosphate (iPolyP), a high-energy linear polymer that is ubiquitous in all forms of life. Made up of hundreds of repeated orthophosphate units, iPolyP is essential for a wide variety of functions in mammalian cells, including the regulation of proliferative signaling pathways. Some evidence has suggested its involvement in carcinogenesis, although more studies need to be pursued. Moreover, iPolyP regulates several homeostatic processes in animals, spanning from energy metabolism to blood coagulation and tissue regeneration. RESULTS In this study, we tested the role of iPolyP on CRC proliferation, using in vitro and ex vivo approaches, in order to evaluate its effect on tumor growth. We found that iPolyP is significantly increased in tumor tissues, derived from affected individuals enrolled in this study, compared to the corresponding peritumoral counterparts. In addition, iPolyP signaling occurs through the TRPM8 receptor, a well-characterized Na+ and Ca2+ ion channel often overexpressed in CRC and linked with poor prognosis, thus promoting CRC cell proliferation. The pharmacological inhibition of TRPM8 or RNA interference experiments performed in established CRC cell lines, such as Caco-2 and SW620, showed that the involvement of TRPM8 is essential, greater than that of the other two known iPolyP receptors, P2Y1 and RAGE. The presence of iPolyP drives cancer cells towards the mitotic phase of the cell cycle by enhancing the expression of ccnb1, which encodes the Cyclin B protein. In vitro 2D and 3D data reflected the ex vivo results, obtained by the generation of CRC-derived organoids, which increased in size. CONCLUSIONS These results indicate that iPolyP may be considered a novel and unexpected early biomarker supporting colorectal cancer cell proliferation.
Collapse
Affiliation(s)
- Valentina Arrè
- Personalized Medicine Laboratory, National Institute of Gastroenterology “S. de Bellis”, IRCCS Research Hospital, Via Turi 27, Castellana Grotte, 70013 Bari, Italy; (F.B.); (R.S.); (F.D.); (M.P.S.)
| | - Francesco Balestra
- Personalized Medicine Laboratory, National Institute of Gastroenterology “S. de Bellis”, IRCCS Research Hospital, Via Turi 27, Castellana Grotte, 70013 Bari, Italy; (F.B.); (R.S.); (F.D.); (M.P.S.)
| | - Rosanna Scialpi
- Personalized Medicine Laboratory, National Institute of Gastroenterology “S. de Bellis”, IRCCS Research Hospital, Via Turi 27, Castellana Grotte, 70013 Bari, Italy; (F.B.); (R.S.); (F.D.); (M.P.S.)
| | - Francesco Dituri
- Personalized Medicine Laboratory, National Institute of Gastroenterology “S. de Bellis”, IRCCS Research Hospital, Via Turi 27, Castellana Grotte, 70013 Bari, Italy; (F.B.); (R.S.); (F.D.); (M.P.S.)
| | - Rossella Donghia
- Data Science, National Institute of Gastroenterology “S. de Bellis”, IRCCS Research Hospital, Via Turi 27, Castellana Grotte, 70013 Bari, Italy;
| | - Sergio Coletta
- Core Facility Biobank, National Institute of Gastroenterology “S. de Bellis”, IRCCS Research Hospital, Via Turi 27, Castellana Grotte, 70013 Bari, Italy; (S.C.); (D.S.); (A.B.)
| | - Dolores Stabile
- Core Facility Biobank, National Institute of Gastroenterology “S. de Bellis”, IRCCS Research Hospital, Via Turi 27, Castellana Grotte, 70013 Bari, Italy; (S.C.); (D.S.); (A.B.)
| | - Antonia Bianco
- Core Facility Biobank, National Institute of Gastroenterology “S. de Bellis”, IRCCS Research Hospital, Via Turi 27, Castellana Grotte, 70013 Bari, Italy; (S.C.); (D.S.); (A.B.)
| | - Leonardo Vincenti
- Unit of Surgery, Department of Surgery Sciences, National Institute of Gastroenterology “S. de Bellis”, IRCCS Research Hospital, Via Turi 27, Castellana Grotte, 70013 Bari, Italy; (L.V.); (S.F.)
| | - Salvatore Fedele
- Unit of Surgery, Department of Surgery Sciences, National Institute of Gastroenterology “S. de Bellis”, IRCCS Research Hospital, Via Turi 27, Castellana Grotte, 70013 Bari, Italy; (L.V.); (S.F.)
| | - Chen Shen
- Division of Infectious Diseases, Washington University School in Medicine in St. Louis, 660 S Euclid Ave., St. Louis, MO 63110, USA;
| | - Giuseppe Pettinato
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA;
| | - Maria Principia Scavo
- Personalized Medicine Laboratory, National Institute of Gastroenterology “S. de Bellis”, IRCCS Research Hospital, Via Turi 27, Castellana Grotte, 70013 Bari, Italy; (F.B.); (R.S.); (F.D.); (M.P.S.)
| | - Gianluigi Giannelli
- Scientific Direction, National Institute of Gastroenterology “S. de Bellis”, IRCCS Research Hospital, Via Turi 27, Castellana Grotte, 70013 Bari, Italy;
| | - Roberto Negro
- Personalized Medicine Laboratory, National Institute of Gastroenterology “S. de Bellis”, IRCCS Research Hospital, Via Turi 27, Castellana Grotte, 70013 Bari, Italy; (F.B.); (R.S.); (F.D.); (M.P.S.)
| |
Collapse
|
|
31
|
M. Imanbayev N, K. Koyshybaev A, M. Kereyeva N, A. Aitmagambetova M, B. Zharylgapov A. Colorectal Cancer and Its Microenvironment: A Brief Review. Med J Islam Repub Iran 2024; 38:108. [PMID: 39781313 PMCID: PMC11707720 DOI: 10.47176/mjiri.38.108] [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: 05/27/2024] [Indexed: 01/12/2025] Open
Abstract
Background The narrative review aims to explore CRC pathogenesis by deciphering genetic-environmental interactions, analyzing the tumor microenvironment's role, and assessing treatment responses. These objectives seek to enhance clinical decision-making and improve CRC patient care through a comprehensive understanding of the disease. Methods A narrative review from 2019 to 2024 on colorectal cancer (CRC) pathogenesis and treatment strategies was conducted. Systematic literature searches were performed on PubMed, using CRC-related keywords ("Colorectal Neoplasms"[Mesh]) AND "Tumor Microenvironment"[Mesh]. Screening yielded 233 eligible studies, with 14 highly relevant ones included. PRISMA guidelines were followed for transparency and reproducibility. Results This narrative review spanning 2019-2024 shows diverse study designs (5 clinical studies, 4 randomized controlled trials, 2 cohort studies, and 3 systematic literature reviews) with varied sample sizes (from 14 to 4000 participants). Genetic mutations like KRAS and BRAF are significant in colorectal cancer pathogenesis, with 8% exhibiting MMR proficiency. Immune cells and paracrine signaling are influential, and therapeutic responses vary, with limited efficacy reported in certain combinations. Conclusion This narrative review highlights CRC's multifactorial nature and complex tumor dynamics. Integrating genetic, environmental, and immune factors, personalized therapies are pivotal for efficacy. Continued research is crucial for optimizing treatments and improving patient outcomes, emphasizing the need for multifaceted, patient-tailored approaches in CRC management.
Collapse
Affiliation(s)
- Nauryzbay M. Imanbayev
- Department of Oncology, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
| | - Arip K. Koyshybaev
- Department of Oncology, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
| | - Nurgul M. Kereyeva
- Department of Oncology, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
| | | | - Azamat B. Zharylgapov
- Department of Oncology, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
| |
Collapse
|
|
32
|
Wasuwanich P, Karnsakul W. Gastrointestinal Cancers in Hospitalized Patients with Cystic Fibrosis: A Nationwide Study, 2010-2020. Diagnostics (Basel) 2024; 14:1999. [PMID: 39335678 PMCID: PMC11431327 DOI: 10.3390/diagnostics14181999] [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: 08/05/2024] [Revised: 09/04/2024] [Accepted: 09/09/2024] [Indexed: 09/30/2024] Open
Abstract
BACKGROUND As life expectancy in cystic fibrosis (CF) patients has increased, so has the incidence of cancers. We aimed to investigate and describe gastrointestinal cancers in CF hospitalized patients from 2010 to 2020. METHODS Utilizing the National Inpatient Sample, we extracted cases of CF-associated hospitalizations and gastrointestinal cancers as well as demographic and clinical data. We compared our CF cohort to age, sex, and race/ethnicity-matched controls. Trends were analyzed by Poisson regression. RESULTS We identified a total of 902 hospitalizations of CF with gastrointestinal cancer; among them, 539 (59.8%) were colorectal, 139 (15.4%) were liver, 105 (11.6%) were pancreatic, 54 (6.0%) were small bowel, 35 (3.9%) were gastric, and 30 (3.3%) were esophageal cancers. The median age of hospitalization for gastrointestinal cancers ranged from 39 years in liver cancer to 65 years in small bowel cancer. Mortality ranged from 9.5% in pancreatic to 0.0% in small bowel cancer. Colorectal cancer (IRR: 1.09; p = 0.005), pancreatic cancer (IRR: 1.17; p = 0.023), gastric cancer (IRR: 1.41; p = 0.003), and esophageal cancer (IRR: 1.50; p = 0.023) hospitalization rates have been increasing over time. Rates of colorectal (p = 0.037) cancer were significantly higher in our CF cohort compared to controls. CONCLUSIONS Colorectal cancers are the major gastrointestinal cancers in CF patients, and the incidence of these hospitalizations is increasing.
Collapse
Affiliation(s)
- Paul Wasuwanich
- Department of Internal Medicine, Naples Comprehensive Health, Naples, FL 34102, USA
- Department of Internal Medicine, University of Florida College of Medicine, Gainesville, FL 32610, USA
| | - Wikrom Karnsakul
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, 550 N. Broadway, 10th Floor Suite 1003, Baltimore, MD 21205, USA
| |
Collapse
|
|
33
|
Chatterjee S, Leach ST, Lui K, Mishra A. Symbiotic symphony: Understanding host-microbiota dialogues in a spatial context. Semin Cell Dev Biol 2024; 161-162:22-30. [PMID: 38564842 DOI: 10.1016/j.semcdb.2024.03.001] [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: 10/31/2023] [Revised: 02/23/2024] [Accepted: 03/20/2024] [Indexed: 04/04/2024]
Abstract
Modern precision sequencing techniques have established humans as a holobiont that live in symbiosis with the microbiome. Microbes play an active role throughout the life of a human ranging from metabolism and immunity to disease tolerance. Hence, it is of utmost significance to study the eukaryotic host in conjunction with the microbial antigens to obtain a complete picture of the host-microbiome crosstalk. Previous attempts at profiling host-microbiome interactions have been either superficial or been attempted to catalogue eukaryotic transcriptomic profile and microbial communities in isolation. Additionally, the nature of such immune-microbial interactions is not random but spatially organised. Hence, for a holistic clinical understanding of the interplay between hosts and microbiota, it's imperative to concurrently analyze both microbial and host genetic information, ensuring the preservation of their spatial integrity. Capturing these interactions as a snapshot in time at their site of action has the potential to transform our understanding of how microbes impact human health. In examining early-life microbial impacts, the limited presence of communities compels analysis within reduced biomass frameworks. However, with the advent of spatial transcriptomics we can address this challenge and expand our horizons of understanding these interactions in detail. In the long run, simultaneous spatial profiling of host-microbiome dialogues can have enormous clinical implications especially in gaining mechanistic insights into the disease prognosis of localised infections and inflammation. This review addresses the lacunae in host-microbiome research and highlights the importance of profiling them together to map their interactions while preserving their spatial context.
Collapse
Affiliation(s)
- Soumi Chatterjee
- Telethon Kids Institute, Perth Children Hospital, Perth, Western Australia 6009, Australia; Curtin Medical School, Curtin University, Perth, Western Australia 6102, Australia
| | - Steven T Leach
- Discipline Paediatrics, School of Clinical Medicine, University of New South Wales, Sydney 2052, Australia
| | - Kei Lui
- Department of Newborn Care, Royal Hospital for Women and Discipline of Paediatrics and Child Health, School of Clinical Medicine, Faculty of Medicine, University of New South Wales, Sydney 2052, Australia
| | - Archita Mishra
- Telethon Kids Institute, Perth Children Hospital, Perth, Western Australia 6009, Australia; Curtin Medical School, Curtin University, Perth, Western Australia 6102, Australia.
| |
Collapse
|
|
34
|
Guardamagna M, Meyer ML, Berciano-Guerrero MÁ, Mesas-Ruiz A, Cobo-Dols M, Perez-Ruiz E, Cantero Gonzalez A, Lavado-Valenzuela R, Barragán I, Oliver J, Garrido-Aranda A, Alvarez M, Rueda-Dominguez A, Queipo-Ortuño MI, Alba Conejo E, Benitez JC. Oncogene-addicted solid tumors and microbiome-lung cancer as a main character: a narrative review. Transl Lung Cancer Res 2024; 13:2050-2066. [PMID: 39263011 PMCID: PMC11384476 DOI: 10.21037/tlcr-24-216] [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: 03/06/2024] [Accepted: 07/03/2024] [Indexed: 09/13/2024]
Abstract
Background and Objective Lung cancer stands as the main cause of cancer-related deaths worldwide. With the advent of immunotherapy and the discovery of targetable oncogenic driver genes, although prognosis has changed in the last few years, survival rates remain dismal for most patients. This emphasizes the urgent need for new strategies that could enhance treatment in precision medicine. The role of the microbiota in carcinogenesis constitutes an evolving landscape of which little is known. It has been suggested these microorganisms may influence in responses, resistance, and adverse effects to cancer treatments, particularly to immune checkpoint blockers. However, evidence on the impact of microbiota composition in oncogene-addicted tumors is lacking. This review aims to provide an overview of the relationship between microbiota, daily habits, the immune system, and oncogene-addicted tumors, focusing on lung cancer. Methods A PubMed and Google Scholar search from 2013 to 2024 was conducted. Relevant articles were reviewed in order to guide our research and generate hypothesis of clinical applicability. Key Content and Findings Microbiota is recognized to participate in immune reprogramming, fostering inflammatory, immunosuppressive, or anti-tumor responses. Therefore, identifying the microbiota that impact response to treatment and modulating its composition by interventions such as dietary modifications, probiotics or antibiotics, could potentially yield better outcomes for cancer patients. Additionally, targeted therapies that modulate molecular signaling pathways may impact both immunity and microbiota. Understanding this intricate interplay could unveil new therapeutic strategies. Conclusions By comprehending how microbiota may influence efficacy of targeted therapies, even though current evidence is scarce, we may generate interesting hypotheses that could improve clinical practice.
Collapse
Affiliation(s)
- Mora Guardamagna
- Medical Oncology Department, Virgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
- Department of Medicine and Dermatology, Medical School University of Málaga, Campus Teatinos, Málaga, Spain
- Department of Cancer Medicine, Institute Gustave Roussy, Villejuif, France
| | - May-Lucie Meyer
- The Tisch Cancer Institute, Mount Sinai Hospital, New York, NY, USA
| | - Miguel Ángel Berciano-Guerrero
- Medical Oncology Department, Virgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
- Department of Medicine and Dermatology, Medical School University of Málaga, Campus Teatinos, Málaga, Spain
- Group of Translational Research in Cancer Immunotherapy, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
| | - Andres Mesas-Ruiz
- Medical Oncology Department, Virgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
| | - Manuel Cobo-Dols
- Group of Translational Research in Cancer Immunotherapy, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
- Medical Oncology Department, Regional University Hospital, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
| | - Elisabeth Perez-Ruiz
- Group of Translational Research in Cancer Immunotherapy, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
- Medical Oncology Department, Regional University Hospital, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
| | - Alexandra Cantero Gonzalez
- Group of Translational Research in Cancer Immunotherapy, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
- Medical Oncology Department, Regional University Hospital, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
| | - Rocío Lavado-Valenzuela
- Medical Oncology Department, Virgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
- Cancer Molecular Biology Laboratory, CIMES, Malaga, Spain
| | - Isabel Barragán
- Group of Translational Research in Cancer Immunotherapy, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
- Group of Pharmacoepigenetics, Department of Physiology and Pharmacology, Karolinska Institute, Solna, Sweden
| | - Javier Oliver
- Group of Translational Research in Cancer Immunotherapy, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
| | - Alicia Garrido-Aranda
- Medical Oncology Department, Virgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
- Cancer Molecular Biology Laboratory, CIMES, Malaga, Spain
| | - Martina Alvarez
- Medical Oncology Department, Virgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
- Cancer Molecular Biology Laboratory, CIMES, Malaga, Spain
| | - Antonio Rueda-Dominguez
- Medical Oncology Department, Virgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
- Department of Medicine and Dermatology, Medical School University of Málaga, Campus Teatinos, Málaga, Spain
- Group of Translational Research in Cancer Immunotherapy, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
| | - María Isabel Queipo-Ortuño
- Medical Oncology Department, Virgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
- Department of Surgical Specialties, Biochemical and Immunology, Faculty of Medicine, University of Málaga, Málaga, Spain
| | - Emilio Alba Conejo
- Medical Oncology Department, Virgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
- Department of Medicine and Dermatology, Medical School University of Málaga, Campus Teatinos, Málaga, Spain
- Group of Translational Research in Cancer Immunotherapy, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
| | - Jose Carlos Benitez
- Medical Oncology Department, Virgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
- Group of Translational Research in Cancer Immunotherapy, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
| |
Collapse
|
|
35
|
Zhang Y, Kang Q, He L, Chan KI, Gu H, Xue W, Zhong Z, Tan W. Exploring the immunometabolic potential of Danggui Buxue Decoction for the treatment of IBD-related colorectal cancer. Chin Med 2024; 19:117. [PMID: 39210410 PMCID: PMC11360867 DOI: 10.1186/s13020-024-00978-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 08/07/2024] [Indexed: 09/04/2024] Open
Abstract
Danggui Buxue (DGBX) decoction is a classical prescription composed of Astragali Radix (AR) and Angelicae Sinensis Radix (ASR), used to enrich blood, and nourish Qi in Chinese medicine, with the potential to recover energy and stimulate metabolism. Chronic inflammation is a risk factor in the development of inflammatory bowel disease (IBD)-related colorectal cancer (CRC). More importantly, AR and ASR have anti-inflammatory and anti-cancer activities, as well as prefiguring a potential effect on inflammation-cancer transformation. We, therefore, aimed to review the immunometabolism potential of DGBX decoction and its components in this malignant transformation, to provide a helpful complement to manage the risk of IBD-CRC. The present study investigates the multifaceted roles of DGBX decoction and its entire components AR and ASR, including anti-inflammation effects, anti-cancer properties, immune regulation, and metabolic regulation. This assessment is informed by a synthesis of scholarly literature, with more than two hundred articles retrieved from PubMed, Web of Science, and Scopus databases within the past two decades. The search strategy employed utilized keywords such as "Danggui Buxue", "Astragali Radix", "Angelicae Sinensis Radix", "Inflammation", and "Metabolism", alongside the related synonyms, with a particular emphasis on high-quality research and studies yielding significant findings. The potential of DGBX decoction in modulating immunometabolism holds promise for the treatment of IBD-related CRC. It is particularly relevant given the heterogeneity of CRC and the growing trend towards personalized medicine, but the precise and detailed mechanism necessitate further in vivo validation and extensive clinical studies to substantiate the immunometabolic modulation and delineate the pathways involved.
Collapse
Affiliation(s)
- Yang Zhang
- School of Pharmacy, Lanzhou University, Lanzhou, 730000, China
| | - Qianming Kang
- School of Pharmacy, Lanzhou University, Lanzhou, 730000, China
| | - Luying He
- School of Pharmacy, Lanzhou University, Lanzhou, 730000, China
| | - Ka Iong Chan
- Macao Centre for Research and Development in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, 999078, SAR, China
| | - Hui Gu
- School of Pharmacy, Lanzhou University, Lanzhou, 730000, China
| | - Wenjing Xue
- School of Pharmacy, Lanzhou University, Lanzhou, 730000, China
| | - Zhangfeng Zhong
- Macao Centre for Research and Development in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, 999078, SAR, China.
| | - Wen Tan
- School of Pharmacy, Lanzhou University, Lanzhou, 730000, China.
| |
Collapse
|
|
36
|
Shakhpazyan NK, Mikhaleva LM, Bedzhanyan AL, Gioeva ZV, Mikhalev AI, Midiber KY, Pechnikova VV, Biryukov AE. Exploring the Role of the Gut Microbiota in Modulating Colorectal Cancer Immunity. Cells 2024; 13:1437. [PMID: 39273009 PMCID: PMC11394638 DOI: 10.3390/cells13171437] [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: 06/24/2024] [Revised: 07/26/2024] [Accepted: 08/23/2024] [Indexed: 09/15/2024] Open
Abstract
The gut microbiota plays an essential role in maintaining immune homeostasis and influencing the immune landscape within the tumor microenvironment. This review aims to elucidate the interactions between gut microbiota and tumor immune dynamics, with a focus on colorectal cancer (CRC). The review spans foundational concepts of immuno-microbial interplay, factors influencing microbiome composition, and evidence linking gut microbiota to cancer immunotherapy outcomes. Gut microbiota modulates anti-cancer immunity through several mechanisms, including enhancement of immune surveillance and modulation of inflammatory responses. Specific microbial species and their metabolic byproducts can significantly influence the efficacy of cancer immunotherapies. Furthermore, microbial diversity within the gut microbiota correlates with clinical outcomes in CRC, suggesting potential as a valuable biomarker for predicting response to immunotherapy. Conclusions: Understanding the relationship between gut microbiota and tumor immune responses offers potential for novel therapeutic strategies and biomarker development. The gut microbiota not only influences the natural history and treatment response of CRC but also serves as a critical modulator of immune homeostasis and anti-cancer activity. Further exploration into the microbiome's role could enhance the effectiveness of existing treatments and guide the development of new therapeutic modalities.
Collapse
Affiliation(s)
- Nikolay K. Shakhpazyan
- Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, 119435 Moscow, Russia; (L.M.M.); (Z.V.G.); (K.Y.M.); (V.V.P.); (A.E.B.)
| | - Liudmila M. Mikhaleva
- Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, 119435 Moscow, Russia; (L.M.M.); (Z.V.G.); (K.Y.M.); (V.V.P.); (A.E.B.)
| | - Arkady L. Bedzhanyan
- Department of Abdominal Surgery and Oncology II (Coloproctology and Uro-Gynecology), Petrovsky National Research Center of Surgery, 119435 Moscow, Russia;
| | - Zarina V. Gioeva
- Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, 119435 Moscow, Russia; (L.M.M.); (Z.V.G.); (K.Y.M.); (V.V.P.); (A.E.B.)
| | - Alexander I. Mikhalev
- Department of Hospital Surgery No. 2, Pirogov Russian National Research Medical University, 117997 Moscow, Russia;
| | - Konstantin Y. Midiber
- Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, 119435 Moscow, Russia; (L.M.M.); (Z.V.G.); (K.Y.M.); (V.V.P.); (A.E.B.)
- Institute of Medicine, Peoples’ Friendship University of Russia named after Patrice Lumumba, 6 Miklukho-Maklaya St., 117198 Moscow, Russia
| | - Valentina V. Pechnikova
- Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, 119435 Moscow, Russia; (L.M.M.); (Z.V.G.); (K.Y.M.); (V.V.P.); (A.E.B.)
| | - Andrey E. Biryukov
- Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, 119435 Moscow, Russia; (L.M.M.); (Z.V.G.); (K.Y.M.); (V.V.P.); (A.E.B.)
| |
Collapse
|
|
37
|
Cheraghpour M, Fatemi N, Shadnoush M, Talebi G, Tierling S, Bermúdez-Humarán LG. Immunomodulation aspects of gut microbiome-related interventional strategies in colorectal cancer. Med Oncol 2024; 41:231. [PMID: 39162936 DOI: 10.1007/s12032-024-02480-9] [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] [Accepted: 08/12/2024] [Indexed: 08/21/2024]
Abstract
Colorectal cancer (CRC), the third most common cancer worldwide, develops mainly due to the accumulation of genetic and epigenetic changes over many years. Substantial evidence suggests that gut microbiota plays a significant role in the initiation, progression, and control of CRC, depending on the balance between beneficial and pathogenic microorganisms. Nonetheless, gut microbiota composition by regulating the host immune response may either promote or inhibit CRC. Thus, modification of gut microbiota potentially impacts clinical outcomes of immunotherapy. Previous studies have indicated that therapeutic strategies such as probiotics, prebiotics, and postbiotics enhance the intestinal immune system and improve the efficacy of immunotherapeutic agents, potentially serving as a complementary strategy in cancer immunotherapy. This review discusses the role of the gut microbiota in the onset and development of CRC in relation to the immune response. Additionally, we focus on the effect of strategies manipulating gut microbiome on the immune response and efficacy of immunotherapy against CRC. We demonstrate that manipulation of gut microbiome can enhance immune response and outcomes of immunotherapy through downregulating Treg cells and other immunosuppressive cells while improving the function of T cells within the tumor; however, further research, especially clinical trials, are needed to evaluate its efficacy in cancer treatment.
Collapse
Affiliation(s)
- Makan Cheraghpour
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nayeralsadat Fatemi
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahdi Shadnoush
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Clinical Nutrition & Dietetics, Faculty of Nutrition Science and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ghazaleh Talebi
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sascha Tierling
- Department of Genetics/Epigenetics, Faculty NT, Life Sciences, Saarland University, Saarbrücken, Germany
| | - Luis G Bermúdez-Humarán
- INRAE, AgroParisTech, Micalis Institute, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
| |
Collapse
|
|
38
|
Abedi Elkhichi P, Aslanimehr M, Javadi A, Yadegar A. Immunomodulatory effects of live and UV-killed Bacillus subtilis natto on inflammatory response in human colorectal adenocarcinoma cell line in vitro. IRANIAN JOURNAL OF MICROBIOLOGY 2024; 16:434-442. [PMID: 39267934 PMCID: PMC11389770 DOI: 10.18502/ijm.v16i4.16301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 09/15/2024]
Abstract
Background and Objectives Colorectal cancer (CRC) is a heterogeneous disease of the colon or rectum arising from adenoma precursors and serrated polyps. Recently, probiotics have been proposed as an effective and potential therapeutic approach for CRC prevention and treatment. Probiotics have been shown to alleviate inflammation by restoring the integrity of the mucosal barrier and impeding cancer progression. Materials and Methods In this study, we aimed to investigate the immunomodulatory effects of live and UV-killed Bacillus subtilis natto on the inflammatory response in CRC. Caco-2 cells were exposed to various concentrations of live and UV- killed B. subtilis natto, and cell viability was assessed using MTT assay. Gene expression analysis of IL-10, TGF-β, TLR2 and TLR4 was performed using RT-qPCR. Results Our findings showed that both live and UV-killed B. subtilis natto caused significant reduction in inflammatory response by decreasing the gene expression of TLR2 and TLR4, and enhancing the gene expression of IL-10 and TGF-β in Caco-2 cells as compared to control group. Conclusion The results of this study suggest that live and UV-killed B. subtilis natto may hold potential as a therapeutic supplement for modulating inflammation in CRC.
Collapse
Affiliation(s)
- Parisa Abedi Elkhichi
- Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Masoumeh Aslanimehr
- Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Amir Javadi
- Department of Statistics, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
39
|
Chan DSM, Cariolou M, Markozannes G, Balducci K, Vieira R, Kiss S, Becerra-Tomás N, Aune D, Greenwood DC, González-Gil EM, Copson E, Renehan AG, Bours M, Demark-Wahnefried W, Hudson MM, May AM, Odedina FT, Skinner R, Steindorf K, Tjønneland A, Velikova G, Baskin ML, Chowdhury R, Hill L, Lewis SJ, Seidell J, Weijenberg MP, Krebs J, Cross AJ, Tsilidis KK. Post-diagnosis dietary factors, supplement use and colorectal cancer prognosis: A Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis. Int J Cancer 2024; 155:445-470. [PMID: 38692645 DOI: 10.1002/ijc.34906] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 12/15/2023] [Accepted: 01/17/2024] [Indexed: 05/03/2024]
Abstract
The role of diet in colorectal cancer prognosis is not well understood and specific lifestyle recommendations are lacking. We searched for randomised controlled trials (RCTs) and longitudinal observational studies on post-diagnosis dietary factors, supplement use and colorectal cancer survival outcomes in PubMed and Embase from inception until 28th February 2022. Random-effects dose-response meta-analyses were conducted when at least three studies had sufficient information. The evidence was interpreted and graded by the CUP Global independent Expert Committee on Cancer Survivorship and Expert Panel. Five RCTs and 35 observational studies were included (30,242 cases, over 8700 all-cause and 2100 colorectal cancer deaths, 3700 progression, recurrence, or disease-free events). Meta-analyses, including 3-10 observational studies each, were conducted for: whole grains, nuts/peanuts, red and processed meat, dairy products, sugary drinks, artificially sweetened beverages, coffee, alcohol, dietary glycaemic load/index, insulin load/index, marine omega-3 polyunsaturated fatty acids, supplemental calcium, circulating 25-hydroxyvitamin D (25[OH]D) and all-cause mortality; for alcohol, supplemental calcium, circulating 25(OH)D and colorectal cancer-specific mortality; and for circulating 25(OH)D and recurrence/disease-free survival. The overall evidence was graded as 'limited'. The inverse associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant-based foods), whole grains, total, caffeinated, or decaffeinated coffee and all-cause mortality and the positive associations between unhealthy dietary patterns, sugary drinks and all-cause mortality provided 'limited-suggestive' evidence. All other exposure-outcome associations provided 'limited-no conclusion' evidence. Additional, well-conducted cohort studies and carefully designed RCTs are needed to develop specific lifestyle recommendations for colorectal cancer survivors.
Collapse
Affiliation(s)
- Doris S M Chan
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Margarita Cariolou
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Georgios Markozannes
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece
| | - Katia Balducci
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Rita Vieira
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Sonia Kiss
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Nerea Becerra-Tomás
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Dagfinn Aune
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- Department of Nutrition, Oslo New University College, Oslo, Norway
- Department of Research, The Cancer Registry of Norway, Oslo, Norway
| | - Darren C Greenwood
- Leeds Institute for Data Analytics, Faculty of Medicine and Health, University of Leeds, Leeds, UK
| | - Esther M González-Gil
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Ellen Copson
- Cancer Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Andrew G Renehan
- The Christie NHS Foundation Trust, Manchester Cancer Research Centre, NIHR Manchester Biomedical Research Centre, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
| | - Martijn Bours
- Department of Epidemiology, GROW School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands
| | - Wendy Demark-Wahnefried
- O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Melissa M Hudson
- Department of Oncology, St Jude Children's Research Hospital, Memphis, Tennessee, USA
| | - Anne M May
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | | | - Roderick Skinner
- Department of Paediatric and Adolescent Haematology/Oncology, Great North Children's Hospital and Translational and Clinical Research Institute, and Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK
| | - Karen Steindorf
- Division of Physical Activity, Prevention and Cancer, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
| | - Anne Tjønneland
- Danish Cancer Society Research Center, Diet, Cancer and Health, Copenhagen, Denmark
- Department of Public Health, University of Copenhagen, Copenhagen, Denmark
| | - Galina Velikova
- School of Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, UK
| | | | - Rajiv Chowdhury
- Department of Global Health, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, Florida, USA
| | - Lynette Hill
- World Cancer Research Fund International, London, UK
| | - Sarah J Lewis
- Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Jaap Seidell
- Department of Health Sciences, Faculty of Science, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Matty P Weijenberg
- Department of Epidemiology, GROW School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands
| | - John Krebs
- Department of Biology, University of Oxford, Oxford, UK
| | - Amanda J Cross
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Konstantinos K Tsilidis
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece
| |
Collapse
|
|
40
|
Zhao L, Kan Y, Wang L, Pan J, Li Y, Zhu H, Yang Z, Xiao L, Fu X, Peng F, Ren H. Roles of long non‑coding RNA SNHG16 in human digestive system cancer (Review). Oncol Rep 2024; 52:106. [PMID: 38940337 PMCID: PMC11234248 DOI: 10.3892/or.2024.8765] [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: 05/23/2023] [Accepted: 04/26/2024] [Indexed: 06/29/2024] Open
Abstract
The incidence of tumors in the human digestive system is relatively high, including esophageal cancer, liver cancer, pancreatic cancer, gastric cancer and colorectal cancer. These malignancies arise from a complex interplay of environmental and genetic factors. Among them, long non‑coding RNAs (lncRNAs), which cannot be translated into proteins, serve an important role in the development, progression, migration and prognosis of tumors. Small nucleolar RNA host gene 16 (SNHG16) is a typical lncRNA, and its relationship with digestive system tumors has been widely explored. The prevailing hypothesis suggests that the principal molecular mechanism of SNHG16 in digestive system tumors involves it functioning as a competitive endogenous RNA that interacts with other proteins, regulates various genes and influences a downstream target molecule. The present review summarizes recent research on the relationship between SNHG16 and numerous types of digestive system cancer, encompassing its biological functions, underlying mechanisms and potential clinical implications. Furthermore, it outlines the association between SNHG16 expression and pertinent risk factors, such as smoking, infection and diet. The present review indicated the promise of SNHG16 as a potential biomarker and therapeutic target in human digestive system cancer.
Collapse
Affiliation(s)
- Lujie Zhao
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Yuling Kan
- Central Laboratory of Binzhou People's Hospital, Binzhou, Shandong 256600, P.R. China
| | - Lu Wang
- School of Clinical Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Jiquan Pan
- School of Clinical Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Yun Li
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Haiyan Zhu
- Department of Medical Oncology, Weifang People's Hospital, Weifang, Shandong 261000, P.R. China
- Department of Medical Oncology, The First Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Zhongfa Yang
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Lin Xiao
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Xinhua Fu
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Fujun Peng
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
- Weifang Key Laboratory of Collaborative Innovation of Intelligent Diagnosis and Treatment and Molecular Diseases, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Haipeng Ren
- Department of Medical Oncology, Weifang People's Hospital, Weifang, Shandong 261000, P.R. China
- Department of Medical Oncology, The First Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| |
Collapse
|
|
41
|
Lang Y, Zhong C, Guo L, Liu Z, Zuo D, Chen X, Ding L, Huang B, Li B, Yuan Y, Niu Y, Qiu J, Qian C. Monoacylglycerol acyltransferase-2 inhibits colorectal carcinogenesis in APC min+/- mice. iScience 2024; 27:110205. [PMID: 39055928 PMCID: PMC11269928 DOI: 10.1016/j.isci.2024.110205] [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: 09/24/2023] [Revised: 04/18/2024] [Accepted: 06/04/2024] [Indexed: 07/28/2024] Open
Abstract
Monoacylglycerol acyltransferase-2 (MOGAT2), encodes MOGAT enzyme in the re-synthesis of triacylglycerol and protects from metabolism disorders. While, its precise involvement in colorectal cancer (CRC) progression remains inadequately understood. Our study demonstrated that knockout of Mogat2 in Apcmin/+ mice expedited intestinal tumor growth and progression, indicating that Mogat2 plays a tumor-suppressing role in CRC. Mechanically, Mogat2 deletion resulted in a significant alter the gut microbiota, while Fecal Microbiota Transplantation (FMT) experiments demonstrated that the gut microbiota in Mogat2 deleted mice promoted tumor growth. Furthermore, we identified Mogat2 as a functional regulator suppressing CRC cell proliferation and tumor growth by inhibiting the NF-κB signaling pathway in vivo. Collectively, these results provide novel insights into the protective double roles of Mogat2, inhibiting of NF-κB pathway and keeping gut microbiota homeostasis in colorectal cancer, which may help the development of novel cancer treatments for CRC.
Collapse
Affiliation(s)
- Yanhong Lang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P.R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, P.R. China
| | - Chengrui Zhong
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P.R. China
| | - Lingling Guo
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P.R. China
| | - Zhijie Liu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P.R. China
| | - Dinglan Zuo
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P.R. China
| | - Xi Chen
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P.R. China
| | - Liuyan Ding
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P.R. China
| | - Bijun Huang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P.R. China
| | - Binkui Li
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P.R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, P.R. China
| | - Yunfei Yuan
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P.R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, P.R. China
| | - Yi Niu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P.R. China
| | - Jiliang Qiu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P.R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, P.R. China
| | - Chaonan Qian
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P.R. China
- Department of Radiation Oncology, Guangzhou Concord Cancer Center, 9 Ciji Road, Huangpu District, Guangzhou 510555, P.R. China
| |
Collapse
|
|
42
|
Yang Q, Qu R, Lu S, Zhang Y, Zhang Z, Fu W. Biological and Clinical Characteristics of Proximal Colon Cancer: Far from Its Anatomical Subsite. Int J Med Sci 2024; 21:1824-1839. [PMID: 39113889 PMCID: PMC11302569 DOI: 10.7150/ijms.97574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Accepted: 07/02/2024] [Indexed: 08/10/2024] Open
Abstract
Colorectal cancer is a heterogeneous disease which can be divided into proximal colon cancer, distal colon cancer and rectal cancer according to the anatomical location of the tumor. Each anatomical location of colorectal cancer exhibits distinct characteristics in terms of incidence, clinical manifestations, molecular phenotypes, treatment, and prognosis. Notably, proximal colon cancer differs significantly from cancers of other anatomical subsites. An increasing number of studies have highlighted the presence of unique tumor biological characteristics in proximal colon cancer. Gaining a deeper understanding of these characteristics will facilitate accurate diagnosis and treatment approaches.
Collapse
Affiliation(s)
- Qing Yang
- Department of General Surgery, Peking University Third Hospital, Beijing China
- Cancer Center, Peking University Third Hospital, Beijing China
| | - Ruize Qu
- Department of General Surgery, Peking University Third Hospital, Beijing China
- Cancer Center, Peking University Third Hospital, Beijing China
| | - Siyi Lu
- Department of General Surgery, Peking University Third Hospital, Beijing China
- Cancer Center, Peking University Third Hospital, Beijing China
| | - Yi Zhang
- Department of General Surgery, Peking University Third Hospital, Beijing China
- Cancer Center, Peking University Third Hospital, Beijing China
| | - Zhipeng Zhang
- Department of General Surgery, Peking University Third Hospital, Beijing China
- Cancer Center, Peking University Third Hospital, Beijing China
| | - Wei Fu
- Department of General Surgery, Peking University Third Hospital, Beijing China
- Cancer Center, Peking University Third Hospital, Beijing China
| |
Collapse
|
|
43
|
Biondi A, Vacante M, Catania R, Sangiorgio G. Extracellular Vesicles and Immune System Function: Exploring Novel Approaches to Colorectal Cancer Immunotherapy. Biomedicines 2024; 12:1473. [PMID: 39062046 PMCID: PMC11275211 DOI: 10.3390/biomedicines12071473] [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: 05/29/2024] [Revised: 06/26/2024] [Accepted: 07/02/2024] [Indexed: 07/28/2024] Open
Abstract
This review explores the emerging role of extracellular vesicles (EVs) in modulating immune system function and their application in novel cancer immunotherapy strategies, with a focus on colorectal cancer (CRC). EVs, as carriers of bioactive molecules, have shown potential in enhancing immune responses and overcoming the limitations of traditional therapies. We discuss the biogenesis, types, and functional roles of immune cell-derived EVs, their interactions with cancer cells, and their implications in antitumor immunity. Challenges such as tumor heterogeneity and immune evasion are addressed, alongside the promising therapeutic prospects of EV-based strategies. This comprehensive analysis underscores the transformative potential of EVs in cancer treatment paradigms.
Collapse
Affiliation(s)
- Antonio Biondi
- Department of General Surgery and Medical-Surgical Specialties, University of Catania, Via Santa Sofia 78, 95123 Catania, Italy; (A.B.); (R.C.)
| | - Marco Vacante
- Unit of Internal Medicine Critical Area—ARNAS Garibaldi, Piazza Santa Maria di Gesù, 5, 95124 Catania, Italy;
| | - Roberta Catania
- Department of General Surgery and Medical-Surgical Specialties, University of Catania, Via Santa Sofia 78, 95123 Catania, Italy; (A.B.); (R.C.)
| | - Giuseppe Sangiorgio
- Department of General Surgery and Medical-Surgical Specialties, University of Catania, Via Santa Sofia 78, 95123 Catania, Italy; (A.B.); (R.C.)
- Department of Biomedical and Biotechnological Sciences, University of Catania, Via Santa Sofia 97, 95123 Catania, Italy
| |
Collapse
|
|
44
|
Pereira F, Fernández-Barral A, Larriba MJ, Barbáchano A, González-Sancho JM. From molecular basis to clinical insights: a challenging future for the vitamin D endocrine system in colorectal cancer. FEBS J 2024; 291:2485-2518. [PMID: 37699548 DOI: 10.1111/febs.16955] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 08/03/2023] [Accepted: 09/11/2023] [Indexed: 09/14/2023]
Abstract
Colorectal cancer (CRC) is one of the most life-threatening neoplasias in terms of incidence and mortality worldwide. Vitamin D deficiency has been associated with an increased risk of CRC. 1α,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the most active vitamin D metabolite, is a pleiotropic hormone that, through its binding to a transcription factor of the nuclear receptor superfamily, is a major regulator of the human genome. 1,25(OH)2D3 acts on colon carcinoma and stromal cells and displays tumor protective actions. Here, we review the variety of molecular mechanisms underlying the effects of 1,25(OH)2D3 in CRC, which affect multiple processes that are dysregulated during tumor initiation and progression. Additionally, we discuss the epidemiological data that associate vitamin D deficiency and CRC, and the most relevant randomized controlled trials of vitamin D3 supplementation conducted in both healthy individuals and CRC patients.
Collapse
Affiliation(s)
- Fábio Pereira
- Instituto de Investigaciones Biomédicas Sols-Morreale, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Spain
- Servicio de Oncología Radioterápica, Complejo Hospitalario Universitario de Ourense, Spain
| | - Asunción Fernández-Barral
- Instituto de Investigaciones Biomédicas Sols-Morreale, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
- Instituto de Investigación Sanitaria del Hospital Universitario La Paz-IdiPAZ (Hospital Universitario La Paz-Universidad Autónoma de Madrid), Spain
| | - María Jesús Larriba
- Instituto de Investigaciones Biomédicas Sols-Morreale, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
- Instituto de Investigación Sanitaria del Hospital Universitario La Paz-IdiPAZ (Hospital Universitario La Paz-Universidad Autónoma de Madrid), Spain
| | - Antonio Barbáchano
- Instituto de Investigaciones Biomédicas Sols-Morreale, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
- Instituto de Investigación Sanitaria del Hospital Universitario La Paz-IdiPAZ (Hospital Universitario La Paz-Universidad Autónoma de Madrid), Spain
| | - José Manuel González-Sancho
- Instituto de Investigaciones Biomédicas Sols-Morreale, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
- Instituto de Investigación Sanitaria del Hospital Universitario La Paz-IdiPAZ (Hospital Universitario La Paz-Universidad Autónoma de Madrid), Spain
- Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Madrid, Spain
| |
Collapse
|
|
45
|
Chaudhary PP, Kaur M, Myles IA. Does "all disease begin in the gut"? The gut-organ cross talk in the microbiome. Appl Microbiol Biotechnol 2024; 108:339. [PMID: 38771520 PMCID: PMC11108886 DOI: 10.1007/s00253-024-13180-9] [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: 04/03/2024] [Revised: 05/06/2024] [Accepted: 05/10/2024] [Indexed: 05/22/2024]
Abstract
The human microbiome, a diverse ecosystem of microorganisms within the body, plays pivotal roles in health and disease. This review explores site-specific microbiomes, their role in maintaining health, and strategies for their upkeep, focusing on oral, lung, vaginal, skin, and gut microbiota, and their systemic connections. Understanding the intricate relationships between these microbial communities is crucial for unraveling mechanisms underlying human health. Recent research highlights bidirectional communication between the gut and distant microbiome sites, influencing immune function, metabolism, and disease susceptibility. Alterations in one microbiome can impact others, emphasizing their interconnectedness and collective influence on human physiology. The therapeutic potential of gut microbiota in modulating distant microbiomes offers promising avenues for interventions targeting various disorders. Through interdisciplinary collaboration and technological advancements, we can harness the power of the microbiome to revolutionize healthcare, emphasizing microbiome-centric approaches to promote holistic well-being while identifying areas for future research.
Collapse
Affiliation(s)
- Prem Prashant Chaudhary
- Laboratory of Clinical Immunology and Microbiology, Epithelial Therapeutics Unit, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, 20892, USA.
| | - Mahaldeep Kaur
- Laboratory of Clinical Immunology and Microbiology, Epithelial Therapeutics Unit, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, 20892, USA
| | - Ian A Myles
- Laboratory of Clinical Immunology and Microbiology, Epithelial Therapeutics Unit, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, 20892, USA
| |
Collapse
|
|
46
|
Wu QL, Fang XT, Wan XX, Ding QY, Zhang YJ, Ji L, Lou YL, Li X. Fusobacterium nucleatum-induced imbalance in microbiome-derived butyric acid levels promotes the occurrence and development of colorectal cancer. World J Gastroenterol 2024; 30:2018-2037. [PMID: 38681125 PMCID: PMC11045493 DOI: 10.3748/wjg.v30.i14.2018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 01/11/2024] [Accepted: 02/29/2024] [Indexed: 04/12/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) ranks among the most prevalent malignant tumors globally. Recent reports suggest that Fusobacterium nucleatum (F. nucleatum) contributes to the initiation, progression, and prognosis of CRC. Butyrate, a short-chain fatty acid derived from the bacterial fermentation of soluble dietary fiber, is known to inhibit various cancers. This study is designed to explore whether F. nucleatum influences the onset and progression of CRC by impacting the intestinal metabolite butyric acid. AIM To investigate the mechanism by which F. nucleatum affects CRC occurrence and development. METHODS Alterations in the gut microbiota of BALB/c mice were observed following the oral administration of F. nucleatum. Additionally, DLD-1 and HCT116 cell lines were exposed to sodium butyrate (NaB) and F. nucleatum in vitro to examine the effects on proliferative proteins and mitochondrial function. RESULTS Our research indicates that the prevalence of F. nucleatum in fecal samples from CRC patients is significantly greater than in healthy counterparts, while the prevalence of butyrate-producing bacteria is notably lower. In mice colonized with F. nucleatum, the population of butyrate-producing bacteria decreased, resulting in altered levels of butyric acid, a key intestinal metabolite of butyrate. Exposure to NaB can impair mitochondrial morphology and diminish mitochondrial membrane potential in DLD-1 and HCT116 CRC cells. Consequently, this leads to modulated production of adenosine triphosphate and reactive oxygen species, thereby inhibiting cancer cell proliferation. Additionally, NaB triggers the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, blocks the cell cycle in HCT116 and DLD-1 cells, and curtails the proliferation of CRC cells. The combined presence of F. nucleatum and NaB attenuated the effects of the latter. By employing small interfering RNA to suppress AMPK, it was demonstrated that AMPK is essential for NaB's inhibition of CRC cell proliferation. CONCLUSION F. nucleatum can promote cancer progression through its inhibitory effect on butyric acid, via the AMPK signaling pathway.
Collapse
Affiliation(s)
- Qi-Long Wu
- School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou 325035, Zhejiang Province, China
| | - Xiao-Ting Fang
- Department of Health Inspection and Quarantine, School of Laboratory Medicine and Life Sciences, Wenzhou 325035, Zhejiang Province, China
| | - Xin-Xin Wan
- School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Zhejiang Provincial Key Laboratory of Medical Genetics, Ministry of Education, Wenzhou 325035, Zhejiang Province, China
| | - Qing-Yong Ding
- School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Zhejiang Provincial Key Laboratory of Medical Genetics, Ministry of Education, Wenzhou 325035, Zhejiang Province, China
| | - Yan-Jun Zhang
- School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Zhejiang Provincial Key Laboratory of Medical Genetics, Ministry of Education, Wenzhou 325035, Zhejiang Province, China
| | - Ling Ji
- Department of General Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Yong-Liang Lou
- School of Laboratory Medicine and Life Sciences, Institute of One Health, Wenzhou Medical University, Zhejiang Provincial Key Laboratory of Medical Genetics, Ministry of Education, Wenzhou 325035, Zhejiang Province, China
| | - Xiang Li
- Department of Health Inspection and Quarantine, School of Laboratory Medicine and Life Sciences, Institute of One Health, Wenzhou Medical University, Zhejiang Provincial Key Laboratory of Medical Genetics, Ministry of Education, Wenzhou 325035, Zhejiang Province, China
| |
Collapse
|
|
47
|
Alves S, Santos-Pereira C, Oliveira CSF, Preto A, Chaves SR, Côrte-Real M. Enhancement of Acetate-Induced Apoptosis of Colorectal Cancer Cells by Cathepsin D Inhibition Depends on Oligomycin A-Sensitive Respiration. Biomolecules 2024; 14:473. [PMID: 38672489 PMCID: PMC11048611 DOI: 10.3390/biom14040473] [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: 03/18/2024] [Revised: 04/08/2024] [Accepted: 04/09/2024] [Indexed: 04/28/2024] Open
Abstract
Colorectal cancer (CRC) is a leading cause of death worldwide. Conventional therapies are available with varying effectiveness. Acetate, a short-chain fatty acid produced by human intestinal bacteria, triggers mitochondria-mediated apoptosis preferentially in CRC but not in normal colonocytes, which has spurred an interest in its use for CRC prevention/therapy. We previously uncovered that acetate-induced mitochondrial-mediated apoptosis in CRC cells is significantly enhanced by the inhibition of the lysosomal protease cathepsin D (CatD), which indicates both mitochondria and the lysosome are involved in the regulation of acetate-induced apoptosis. Herein, we sought to determine whether mitochondrial function affects CatD apoptotic function. We found that enhancement of acetate-induced apoptosis by CatD inhibition depends on oligomycin A-sensitive respiration. Mechanistically, the potentiating effect is associated with an increase in cellular and mitochondrial superoxide anion accumulation and mitochondrial mass. Our results provide novel clues into the regulation of CatD function and the effect of tumor heterogeneity in the outcome of combined treatment using acetate and CatD inhibitors.
Collapse
Affiliation(s)
| | | | | | | | - Susana R. Chaves
- CBMA—Centre of Molecular and Environmental Biology, Department of Biology, University of Minho, 4710-057 Braga, Portugal; (S.A.); (C.S.-P.); (C.S.F.O.); (A.P.)
| | - Manuela Côrte-Real
- CBMA—Centre of Molecular and Environmental Biology, Department of Biology, University of Minho, 4710-057 Braga, Portugal; (S.A.); (C.S.-P.); (C.S.F.O.); (A.P.)
| |
Collapse
|
|
48
|
Singhabahu R, Kodagoda Gamage SM, Gopalan V. Pathological significance of heme oxygenase-1 as a potential tumor promoter in heme-induced colorectal carcinogenesis. CANCER PATHOGENESIS AND THERAPY 2024; 2:65-73. [PMID: 38601482 PMCID: PMC11002664 DOI: 10.1016/j.cpt.2023.04.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 04/01/2023] [Accepted: 04/06/2023] [Indexed: 04/12/2024]
Abstract
The significance of the heme-metabolizing enzyme heme oxygenase-1 (HMOX1) in the pathogenesis of colorectal cancer (CRC) has not been fully explored. HMOX1 cytoprotection is imperative to limit oxidative stress. However, its roles in preventing carcinogenesis in response to high levels of heme are not thoroughly understood. This study reviews various mechanisms associated with the paradoxical role of HMOX1, which is advantageous for tumor growth, refractoriness, and survival of cancer cells amid oxidative stress in heme-induced CRC. The alternate role of HMOX1 promotes cell proliferation and metastasis through immune modulation and angiogenesis. Inhibiting HMOX1 has been found to reverse tumor promotion. Thus, HMOX1 acts as a conditional tumor promoter in CRC pathogenesis.
Collapse
Affiliation(s)
- Rachitha Singhabahu
- Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Queensland 4222, Australia
| | - Sujani M. Kodagoda Gamage
- Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Queensland 4222, Australia
- Faculty of Health Sciences and Medicine, Bond University, Robina 4226, Australia
| | - Vinod Gopalan
- Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Queensland 4222, Australia
| |
Collapse
|
|
49
|
Johnson-Martínez JP, Diener C, Levine AE, Wilmanski T, Suskind DL, Ralevski A, Hadlock J, Magis AT, Hood L, Rappaport N, Gibbons SM. Generally-healthy individuals with aberrant bowel movement frequencies show enrichment for microbially-derived blood metabolites associated with reduced kidney function. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2023.03.04.531100. [PMID: 36945445 PMCID: PMC10028848 DOI: 10.1101/2023.03.04.531100] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/11/2023]
Abstract
Bowel movement frequency (BMF) has been linked to changes in the composition of the human gut microbiome and to many chronic conditions, like metabolic disorders, neurodegenerative diseases, chronic kidney disease (CKD), and other intestinal pathologies like irritable bowel syndrome and inflammatory bowel disease. Lower BMF (constipation) can lead to compromised intestinal barrier integrity and a switch from saccharolytic to proteolytic fermentation within the microbiota, giving rise to microbially-derived toxins that may make their way into circulation and cause damage to organ systems. However, the connections between BMF, gut microbial metabolism, and the early-stage development and progression of chronic disease remain underexplored. Here, we examined the phenotypic impact of BMF variation in a cohort of generally-healthy, community dwelling adults with detailed clinical, lifestyle, and multi-omic data. We showed significant differences in microbially-derived blood plasma metabolites, gut bacterial genera, clinical chemistries, and lifestyle factors across BMF groups that have been linked to inflammation, cardiometabolic health, liver function, and CKD severity and progression. We found that the higher plasma levels of 3-indoxyl sulfate (3-IS), a microbially-derived metabolite associated with constipation, was in turn negatively associated with estimated glomerular filtration rate (eGFR), a measure of kidney function. Causal mediation analysis revealed that the effect of BMF on eGFR was significantly mediated by 3-IS. Finally, we identify self-reported diet, lifestyle, and psychological factors associated with BMF variation, which indicate several common-sense strategies for mitigating constipation and diarrhea. Overall, we suggest that aberrant BMF is an underappreciated risk factor in the development of chronic diseases, even in otherwise healthy populations.
Collapse
Affiliation(s)
- Johannes P. Johnson-Martínez
- Institute for Systems Biology, Seattle, WA 98109, USA
- Department of Bioengineering, University of Washington, Seattle, WA 98195, USA
| | | | - Anne E. Levine
- Institute for Systems Biology, Seattle, WA 98109, USA
- Seattle Children’s Hospital, Seattle, WA 98105, USA
| | | | | | | | | | | | - Leroy Hood
- Institute for Systems Biology, Seattle, WA 98109, USA
- Department of Bioengineering, University of Washington, Seattle, WA 98195, USA
- Phenome Health, Seattle, WA 98109
- Department of Immunology, University of Washington, Seattle, WA 98195, USA
- Paul G. Allen School of Computer Science & Engineering, University of Washington, Seattle, WA 98195, USA
| | - Noa Rappaport
- Institute for Systems Biology, Seattle, WA 98109, USA
| | - Sean M. Gibbons
- Institute for Systems Biology, Seattle, WA 98109, USA
- Department of Bioengineering, University of Washington, Seattle, WA 98195, USA
- Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
- eScience Institute, University of Washington, Seattle, WA 98195, USA
| |
Collapse
|
|
50
|
Wu Z, Huang Y, Zhang R, Zheng C, You F, Wang M, Xiao C, Li X. Sex differences in colorectal cancer: with a focus on sex hormone-gut microbiome axis. Cell Commun Signal 2024; 22:167. [PMID: 38454453 PMCID: PMC10921775 DOI: 10.1186/s12964-024-01549-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Accepted: 03/01/2024] [Indexed: 03/09/2024] Open
Abstract
Sexual dimorphism has been observed in the incidence and prognosis of colorectal cancer (CRC), with men generally exhibiting a slightly higher incidence than women. Research suggests that this difference may be attributed to variations in sex steroid hormone levels and the gut microbiome. The gut microbiome in CRC shows variations in composition and function between the sexes, leading to the concept of 'microgenderome' and 'sex hormone-gut microbiome axis.' Conventional research indicates that estrogens, by promoting a more favorable gut microbiota, may reduce the risk of CRC. Conversely, androgens may have a direct pro-tumorigenic effect by increasing the proportion of opportunistic pathogens. The gut microbiota may also influence sex hormone levels by expressing specific enzymes or directly affecting gonadal function. However, this area remains controversial. This review aims to explore the differences in sex hormone in CRC incidence, the phenomenon of sexual dimorphism within the gut microbiome, and the intricate interplay of the sex hormone-gut microbiome axis in CRC. The objective is to gain a better understanding of these interactions and their potential clinical implications, as well as to introduce innovative approaches to CRC treatment.
Collapse
Affiliation(s)
- Zihong Wu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yuqing Huang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Renyi Zhang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Chuan Zheng
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Fengming You
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Institute of Oncology, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Min Wang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Chong Xiao
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
| | - Xueke Li
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
| |
Collapse
|