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Shah H, Patel P, Nath A, Shah U, Sarkar R. Role of human microbiota in facilitating the metastatic journey of cancer cells. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-03957-8. [PMID: 40072555 DOI: 10.1007/s00210-025-03957-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Accepted: 02/18/2025] [Indexed: 03/14/2025]
Abstract
Cancer continues to be the leading cause of mortality worldwide, with metastasis being the primary contributor to cancer-related deaths. Despite significant advancements in cancer therapies, metastasis remains a major challenge in effective cancer management. Metastasis, the process by which cancer cells spread from the primary tumor to distant organs, is a complex phenomenon influenced by multiple factors, including the human microbiota. The human body encompasses various microorganisms, comprising bacteria, viruses, fungi, and protozoa, collectively known as microbiota. In fact, the microbiota is more abundant than human cells, and its disruption, leading to an imbalance in host-microbiota interactions (dysbiosis), has been linked to various diseases, including cancer. Among all microbiota, bacteria are one of the key contributors to cancer progression. Bacteria and bacteria-derived components such as secondary metabolites, QSPs, and toxins play a pivotal role in the metastatic progression of cancers. This review explores the intricate relationship between the human microbiota and cancer progression, focusing on different bacterial species which have been implicated in tumorigenesis, immune evasion, and metastasis. The present review explores the role of the human microbiome, specifically of bacteria in promoting metastasis in different types of cancers, demonstrating its ability to impact both the spread of tumors and their underlying mechanisms. This review also highlights the therapeutic potential and challenges of microbiome-based interventions in combating metastatic cancers. By addressing these challenges and by integrating microbiome-targeted strategies into clinical cancer treatment could represent a transformative approach in the fight against metastasis.
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Affiliation(s)
- Himisa Shah
- B. D. Patel Institute of Paramedical Sciences, Charotar University of Science and Technology, CHARUSAT Campus, Changa, 388421, Gujarat, India
| | - Princy Patel
- B. D. Patel Institute of Paramedical Sciences, Charotar University of Science and Technology, CHARUSAT Campus, Changa, 388421, Gujarat, India
| | - Abhay Nath
- Devang Patel Institute of Advanced Technology and Research, Charotar University of Science and Technology, CHARUSAT Campus, Anand, 388421, Gujarat, India
| | - Umang Shah
- Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT Campus, Anand, 388421, Gujarat, India
| | - Ruma Sarkar
- B. D. Patel Institute of Paramedical Sciences, Charotar University of Science and Technology, CHARUSAT Campus, Changa, 388421, Gujarat, India.
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Zhang H, Tian Y, Xu C, Chen M, Xiang Z, Gu L, Xue H, Xu Q. Crosstalk between gut microbiotas and fatty acid metabolism in colorectal cancer. Cell Death Discov 2025; 11:78. [PMID: 40011436 DOI: 10.1038/s41420-025-02364-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 01/30/2025] [Accepted: 02/17/2025] [Indexed: 02/28/2025] Open
Abstract
Colorectal cancer (CRC) is the third most common malignancy globally and the second leading cause of cancer-related mortality. Its development is a multifactorial and multistage process influenced by a dynamic interplay between gut microbiota, environmental factors, and fatty acid metabolism. Dysbiosis of intestinal microbiota and abnormalities in microbiota-associated metabolites have been implicated in colorectal carcinogenesis, highlighting the pivotal role of microbial and metabolic interactions. Fatty acid metabolism serves as a critical nexus linking dietary patterns with gut microbial activity, significantly impacting intestinal health. In CRC patients, reduced levels of short-chain fatty acids (SCFAs) and SCFA-producing bacteria have been consistently observed. Supplementation with SCFA-producing probiotics has demonstrated tumor-suppressive effects, while therapeutic strategies aimed at modulating SCFA levels have shown potential in enhancing the efficacy of radiation therapy and immunotherapy in both preclinical and clinical settings. This review explores the intricate relationship between gut microbiota, fatty acid metabolism, and CRC, offering insights into the underlying mechanisms and their potential translational applications. Understanding this interplay could pave the way for novel diagnostic, therapeutic, and preventive strategies in the management of CRC.
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Affiliation(s)
- Hao Zhang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China
| | - Yuan Tian
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China
| | - Chunjie Xu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China
| | - Miaomiao Chen
- Department of Radiology, Huashan Hospital, National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200040, PR China
| | - Zeyu Xiang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China
| | - Lei Gu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
| | - Hanbing Xue
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
| | - Qing Xu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
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Ataollahi H, Hedayati M, Zia-Jahromi N, Daneshpour M, Siadat SD. Investigating the role of the intratumoral microbiome in thyroid cancer development and progression. Crit Rev Oncol Hematol 2024; 204:104545. [PMID: 39476992 DOI: 10.1016/j.critrevonc.2024.104545] [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: 07/11/2024] [Revised: 10/14/2024] [Accepted: 10/24/2024] [Indexed: 11/04/2024] Open
Abstract
The intratumoral microbiome (ITM) is in the spotlight due to its possible contribution to the initiation, progression, and invasion of a wide range of cancers. Its precise contribution to cancer tumorigenesis is still elusive, though. Thyroid cancer(TC), the ninth leading cause of cancer globally and the most prevalent endocrine malignancy with a rapidly rising incidence among all cancers, has attracted much attention nowadays. Still, the association between the tumor's microbiome and TC progression and development is an evolving area of investigation with significant consequences for disease understanding and intervention. Therefore, this review offers an appropriate perspective on this emerging concept in TC based on prior studies on the ITM among the most common tumors worldwide, concentrating on TC. Moreover, information on the origin of the ITM and practical methods can pave the way for researchers to opt for the most appropriate method for further investigations on the ITM more accurately.
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Affiliation(s)
- Hanieh Ataollahi
- Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
| | - Mehdi Hedayati
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No 23, Shahid Arabi St.Yemen St, Velenjak, PO Box:19395-4763, Tehran, Iran.
| | - Noosha Zia-Jahromi
- Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran.
| | - Maryam Daneshpour
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No 23, Shahid Arabi St.Yemen St, Velenjak, PO Box:19395-4763, Tehran, Iran
| | - Seyed Davar Siadat
- Microbiology Research Center(MRC), Pasteur Institute of Iran, Tehran, Iran; Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
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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.
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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
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Chauhan A, Pathak VM, Yadav M, Chauhan R, Babu N, Chowdhary M, Ranjan A, Mathkor DM, Haque S, Tuli HS, Ramniwas S, Yadav V. Role of ursolic acid in preventing gastrointestinal cancer: recent trends and future perspectives. Front Pharmacol 2024; 15:1405497. [PMID: 39114347 PMCID: PMC11303223 DOI: 10.3389/fphar.2024.1405497] [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: 03/23/2024] [Accepted: 06/03/2024] [Indexed: 08/10/2024] Open
Abstract
Gastrointestinal malignancies are one of the major worldwide health concerns. In the present review, we have assessed the plausible therapeutic implication of Ursolic Acid (UA) against gastrointestinal cancer. By modulating several signaling pathways critical in cancer development, UA could offer anti-inflammatory, anti-proliferative, and anti-metastatic properties. However, being of low oral bioavailability and poor permeability, its clinical value is restricted. To deliver and protect the drug, liposomes and polymer micelles are two UA nanoformulations that can effectively increase medicine stability. The use of UA for treating cancers is safe and appropriate with low toxicity characteristics and a predictable pharmacokinetic profile. Although the bioavailability of UA is limited, its nanoformulations could emerge as an alternative to enhance its efficacy in treating GI cancers. Further optimization and validation in the clinical trials are necessary. The combination of molecular profiling with nanoparticle-based drug delivery technologies holds the potential for bringing UA to maximum efficacy, looking for good prospects with GI cancer treatment.
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Affiliation(s)
- Abhishek Chauhan
- Amity Institute of Environmental Toxicology Safety and Management, Amity University, Noida, Uttar Pradesh, India
| | | | - Monika Yadav
- Cancer Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India
| | - Ritu Chauhan
- Department of Biotechnology, Graphic Era Deemed to be University, Dehradun, Uttarakhand, India
| | - Neelesh Babu
- Department of Microbiology, Baba Farid Institute of Technology, Dehradun, Uttarakhand, India
| | - Manish Chowdhary
- CSIR-Institute of Genomics and Integrative Biology, New Delhi, India
| | - Anuj Ranjan
- Academy of Biology and Biotechnology, Southern Federal University, Rostov-on-Don, Russia
| | - Darin Mansor Mathkor
- Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Saudi Arabia
| | - Shafiul Haque
- Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Saudi Arabia
- Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Beirut, Lebanon
| | - Hardeep Singh Tuli
- Department of Bio-Sciences and Technology, Maharishi Markandeshwar Engineering College, Maharishi Markandeshwar (Deemed to Be University), Ambala, India
| | - Seema Ramniwas
- University Centre for Research and Development, University Institute of Pharmaceutical Sciences, Chandigarh University, Mohali, India
| | - Vikas Yadav
- Department of Translational Medicine, Clinical Research Centre, Skåne University Hospital, Lund University, Malmö, Sweden
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Domblides C, Crampton S, Liu H, Bartleson JM, Nguyen A, Champagne C, Landy EE, Spiker L, Proffitt C, Bhattarai S, Grawe AP, Fuentealba Valenzuela M, Lartigue L, Mahouche I, Dupaul-Chicoine J, Nishimura K, Lefort F, Decraecker M, Velasco V, Netzer S, Pitard V, Roy C, Soubeyran I, Racine V, Blanco P, Déchanet-Merville J, Saleh M, Canna SW, Furman D, Faustin B. Human NLRC4 expression promotes cancer survival and associates with type I interferon signaling and immune infiltration. J Clin Invest 2024; 134:e166085. [PMID: 38652550 PMCID: PMC11142746 DOI: 10.1172/jci166085] [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: 10/10/2022] [Accepted: 04/09/2024] [Indexed: 04/25/2024] Open
Abstract
The immune system can control cancer progression. However, even though some innate immune sensors of cellular stress are expressed intrinsically in epithelial cells, their potential role in cancer aggressiveness and subsequent overall survival in humans is mainly unknown. Here, we show that nucleotide-binding oligomerization domain-like receptor (NLR) family CARD domain-containing 4 (NLRC4) is downregulated in epithelial tumor cells of patients with colorectal cancer (CRC) by using spatial tissue imaging. Strikingly, only the loss of tumor NLRC4, but not stromal NLRC4, was associated with poor immune infiltration (mainly DCs and CD4+ and CD8+ T cells) and accurately predicted progression to metastatic stage IV and decrease in overall survival. By combining multiomics approaches, we show that restoring NLRC4 expression in human CRC cells triggered a broad inflammasome-independent immune reprogramming consisting of type I interferon (IFN) signaling genes and the release of chemokines and myeloid growth factors involved in the tumor infiltration and activation of DCs and T cells. Consistently, such reprogramming in cancer cells was sufficient to directly induce maturation of human DCs toward a Th1 antitumor immune response through IL-12 production in vitro. In multiple human carcinomas (colorectal, lung, and skin), we confirmed that NLRC4 expression in patient tumors was strongly associated with type I IFN genes, immune infiltrates, and high microsatellite instability. Thus, we shed light on the epithelial innate immune sensor NLRC4 as a therapeutic target to promote an efficient antitumor immune response against the aggressiveness of various carcinomas.
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Affiliation(s)
- Charlotte Domblides
- University of Bordeaux, Bordeaux, France
- ImmunoConcEpt, CNRS UMR 5164, INSERM ERL 1303, Bordeaux University, Bordeaux, France
- Department of Medical Oncology, University Hospital of Bordeaux, Bordeaux, France
| | - Steven Crampton
- Discovery Immunology, Johnson & Johnson Innovative Medicine, San Diego, California, USA
| | - Hong Liu
- GI and Immune-Oncology DDUs, Takeda Pharmaceuticals, San Diego, California, and Cambridge, Massachusetts, USA
| | | | - Annie Nguyen
- Discovery Immunology, Johnson & Johnson Innovative Medicine, San Diego, California, USA
| | | | - Emily E. Landy
- Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Lindsey Spiker
- Department of Genetics, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania, USA
| | - Christopher Proffitt
- GI and Immune-Oncology DDUs, Takeda Pharmaceuticals, San Diego, California, and Cambridge, Massachusetts, USA
| | - Sunil Bhattarai
- Discovery Immunology, Johnson & Johnson Innovative Medicine, San Diego, California, USA
| | - Anissa P. Grawe
- Buck Institute for Research on Aging, Novato, California, USA
| | | | | | | | | | - Kazuho Nishimura
- GI and Immune-Oncology DDUs, Takeda Pharmaceuticals, San Diego, California, and Cambridge, Massachusetts, USA
| | - Félix Lefort
- ImmunoConcEpt, CNRS UMR 5164, INSERM ERL 1303, Bordeaux University, Bordeaux, France
- Department of Medical Oncology, University Hospital of Bordeaux, Bordeaux, France
| | - Marie Decraecker
- ImmunoConcEpt, CNRS UMR 5164, INSERM ERL 1303, Bordeaux University, Bordeaux, France
| | - Valérie Velasco
- Comprehensive Cancer Center, Department of Biopathology, Institut Bergonié, Bordeaux, France
| | - Sonia Netzer
- University of Bordeaux, Bordeaux, France
- ImmunoConcEpt, CNRS UMR 5164, INSERM ERL 1303, Bordeaux University, Bordeaux, France
| | - Vincent Pitard
- University of Bordeaux, Bordeaux, France
- ImmunoConcEpt, CNRS UMR 5164, INSERM ERL 1303, Bordeaux University, Bordeaux, France
| | - Christian Roy
- GI and Immune-Oncology DDUs, Takeda Pharmaceuticals, San Diego, California, and Cambridge, Massachusetts, USA
| | - Isabelle Soubeyran
- Comprehensive Cancer Center, Department of Biopathology, Institut Bergonié, Bordeaux, France
| | - Victor Racine
- QuantaCell, Hôpital Saint Eloi, IRMB, Montpellier, France
| | - Patrick Blanco
- University of Bordeaux, Bordeaux, France
- ImmunoConcEpt, CNRS UMR 5164, INSERM ERL 1303, Bordeaux University, Bordeaux, France
| | - Julie Déchanet-Merville
- University of Bordeaux, Bordeaux, France
- ImmunoConcEpt, CNRS UMR 5164, INSERM ERL 1303, Bordeaux University, Bordeaux, France
| | - Maya Saleh
- INRS Santé Biotechnologie, Laval, Québec, Canada
| | - Scott W. Canna
- Pediatric Rheumatology, The Children’s Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - David Furman
- Buck Institute for Research on Aging, Novato, California, USA
- Stanford 1000 Immunomes Project, Stanford School of Medicine, Stanford, California, USA
| | - Benjamin Faustin
- University of Bordeaux, Bordeaux, France
- ImmunoConcEpt, CNRS UMR 5164, INSERM ERL 1303, Bordeaux University, Bordeaux, France
- Discovery Immunology, Johnson & Johnson Innovative Medicine, San Diego, California, USA
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Fan S, Zhou L, Zhang W, Wang D, Tang D. Role of imbalanced gut microbiota in promoting CRC metastasis: from theory to clinical application. Cell Commun Signal 2024; 22:232. [PMID: 38637851 PMCID: PMC11025274 DOI: 10.1186/s12964-024-01615-9] [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] [Received: 02/12/2024] [Accepted: 04/12/2024] [Indexed: 04/20/2024] Open
Abstract
Metastasis poses a major challenge in colorectal cancer (CRC) treatment and remains a primary cause of mortality among patients with CRC. Recent investigations have elucidated the involvement of disrupted gut microbiota homeostasis in various facets of CRC metastasis, exerting a pivotal influence in shaping the metastatic microenvironment, triggering epithelial-mesenchymal transition (EMT), and so on. Moreover, therapeutic interventions targeting the gut microbiota demonstrate promise in enhancing the efficacy of conventional treatments for metastatic CRC (mCRC), presenting novel avenues for mCRC clinical management. Grounded in the "seed and soil" hypothesis, this review consolidates insights into the mechanisms by which imbalanced gut microbiota promotes mCRC and highlights recent strides in leveraging gut microbiota modulation for the clinical prevention and treatment of mCRC. Emphasis is placed on the considerable potential of manipulating gut microbiota within clinical settings for managing mCRC.
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Affiliation(s)
- Shiying Fan
- Clinical Medical College, Yangzhou University, 225000, Yangzhou, P. R. China
| | - Lujia Zhou
- Clinical Medical College, Yangzhou University, 225000, Yangzhou, P. R. China
| | - Wenjie Zhang
- School of Medicine, Chongqing University, 400030, Chongqing, P. R. China
| | - Daorong Wang
- Department of General Surgery, Institute of General Surgery, Clinical Medical College, Northern Jiangsu People's Hospital, Yangzhou University, 225000, Yangzhou, P. R. China
| | - Dong Tang
- Department of General Surgery, Institute of General Surgery, Clinical Medical College, Northern Jiangsu People's Hospital, Yangzhou University, 225000, Yangzhou, P. R. China.
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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.
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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
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Akinduti PA, Izevbigie OO, Akinduti OA, Enwose EO, Amoo EO. Fecal Carriage of Colibactin-Encoding Escherichia coli Associated With Colorectal Cancer Among a Student Populace. Open Forum Infect Dis 2024; 11:ofae106. [PMID: 38560611 PMCID: PMC10981395 DOI: 10.1093/ofid/ofae106] [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: 08/10/2023] [Accepted: 02/22/2024] [Indexed: 04/04/2024] Open
Abstract
Fecal carriage of the colibactin (clb) gene in Escherichia coli is described as a source that could promote carcinogenesis, progressing to colorectal cancer. The present study investigated the demographic, dietary, and antibiotic consumption variables as correlates for fecal carriage of clb+/E coli among the student populace. In a randomized cross-sectional survey, E coli (N = 136) from the fecal samples of eligible students were characterized and evaluated for antibiotic resistance, β-lactamase (blm), biofilm, virulence factor production, and strain tryptophan reverse mutagenic activity. The encoded clb+/E coli were analyzed for correlates with principal component analysis. Of all the E coli strains, a low rate of 2 clb+/E coli (1.5%) and higher rates of biofilm (13.2%) and blm producers (11.8%) were recorded among the mutant strains as compared with the nonmutant types. All the clb+/E coli showed complete resistance to amoxicillin, Augmentin (amoxicillin and clavulanate), gentamicin, and trimethoprim/sulfamethoxazole. The fecal clb-encoded E coli (1.5%) were not associated with demographic status, fiber-based food (odds ratio [OR], 1.03; 95% CI, 56.74-138.7; P = .213), alcohol (OR, 1.27; 95% CI, 61.74-147.1; P = .221), antibiotic consumptions (OR, 1.11; 95% CI, 61.29-145.3; P = .222), and handwashing (OR, 1.17; 95% CI, 60.19-145.5; P = .216). The hierarchical cluster of blm+/E coli revealed high-level resistance with a multiantibiotic resistance index ≥0.2 (P < .05). Only 12% of all strains were tryptophan mutant/blm+, and 1.5% of clb+/ECblm+ were observed in fecal samples with a 452-base pair size. Trimethoprim/sulfamethoxazole and biofilm production positively regressed with clb expression (P > .05). Principal component analysis score plot indicated an association of clb+/ECblm+ with dietary pattern, alcohol, blm, and hemolysin production. The combined activity of blm and biofilm production in the gut microbiota could promote clb+/E coli colonization, facilitating genotoxin production and possible colorectal cancer induction.
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Affiliation(s)
- Paul A Akinduti
- Microbiology Unit, Department of Biological Sciences, Covenant University, Ota, Nigeria
| | - Ovbiosa O Izevbigie
- Microbiology Unit, Department of Biological Sciences, Covenant University, Ota, Nigeria
| | | | - Ezekiel O Enwose
- Department of Medical Laboratory Sciences, Neuropsychiatric Hospital, Aro Abeokuta, Nigeria
| | - Emmanuel O Amoo
- Demography and Social Statistics, Covenant University, Ota, Nigeria
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10
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Maleki EH, Bahrami AR, Matin MM. Cancer cell cycle heterogeneity as a critical determinant of therapeutic resistance. Genes Dis 2024; 11:189-204. [PMID: 37588236 PMCID: PMC10425754 DOI: 10.1016/j.gendis.2022.11.025] [Citation(s) in RCA: 37] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 10/20/2022] [Accepted: 11/16/2022] [Indexed: 01/15/2023] Open
Abstract
Intra-tumor heterogeneity is now arguably one of the most-studied topics in tumor biology, as it represents a major obstacle to effective cancer treatment. Since tumor cells are highly diverse at genetic, epigenetic, and phenotypic levels, intra-tumor heterogeneity can be assumed as an important contributing factor to the nullification of chemotherapeutic effects, and recurrence of the tumor. Based on the role of heterogeneous subpopulations of cancer cells with varying cell-cycle dynamics and behavior during cancer progression and treatment; herein, we aim to establish a comprehensive definition for adaptation of neoplastic cells against therapy. We discuss two parallel and yet distinct subpopulations of tumor cells that play pivotal roles in reducing the effects of chemotherapy: "resistant" and "tolerant" populations. Furthermore, this review also highlights the impact of the quiescent phase of the cell cycle as a survival mechanism for cancer cells. Beyond understanding the mechanisms underlying the quiescence, it provides an insightful perspective on cancer stem cells (CSCs) and their dual and intertwined functions based on their cell cycle state in response to treatment. Moreover, CSCs, epithelial-mesenchymal transformed cells, circulating tumor cells (CTCs), and disseminated tumor cells (DTCs), which are mostly in a quiescent state of the cell cycle are proved to have multiple biological links and can be implicated in our viewpoint of cell cycle heterogeneity in tumors. Overall, increasing our knowledge of cell cycle heterogeneity is a key to identifying new therapeutic solutions, and this emerging concept may provide us with new opportunities to prevent the dreadful cancer recurrence.
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Affiliation(s)
- Ebrahim H. Maleki
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, 9177948974 Mashhad, Iran
- Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, 31-007 Krakow, Poland
- Doctoral School of Exact and Natural Sciences, Jagiellonian University, 30-348 Krakow, Poland
| | - Ahmad Reza Bahrami
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, 9177948974 Mashhad, Iran
- Industrial Biotechnology Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, 9177948974 Mashhad, Iran
| | - Maryam M. Matin
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, 9177948974 Mashhad, Iran
- Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, 9177948974 Mashhad, Iran
- Stem Cell and Regenerative Medicine Research Group, Iranian Academic Center for Education, Culture and Research (ACECR), Khorasan Razavi Branch, 917751376 Mashhad, Iran
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11
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Park SJ, Greer PL, Lee N. From odor to oncology: non-canonical odorant receptors in cancer. Oncogene 2024; 43:304-318. [PMID: 38087050 DOI: 10.1038/s41388-023-02908-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 11/16/2023] [Accepted: 11/23/2023] [Indexed: 01/31/2024]
Abstract
Odorant receptors, traditionally associated with olfaction as chemoreceptors, have been increasingly recognized for their presence and diverse functions in various non-nasal tissues throughout the body. Beyond their roles in sensory perception, emerging evidence suggests a compelling interplay between odorant receptors and cancer progression as well. Alongside the canonical GPCR odorant receptors, dysregulation of non-canonical odorant receptors such as trace amine-associated receptors (TAARs), formyl peptide receptors (FPRs), and membrane-spanning 4A family (MS4As) has been observed in various cancer types, suggesting their contributions to cancer progression. The roles of these non-canonical chemoreceptors in cancer are complex, with some receptors promoting tumorigenesis and others acting as tumor-suppressing factors upon activation, depending on the cancer type. These findings shed light on the potential of non-canonical odorant receptors as therapeutic targets and prognostic markers in cancer, inviting further exploration to unravel their precise mechanisms of action and implications in cancer biology. In this review, we provide a comprehensive overview of the intricate relationships between these chemoreceptors and various types of cancer, potentially paving the way for innovative odor-based therapeutics. Ultimately, this review discusses the potential development of novel therapeutic strategies targeting these non-canonical chemoreceptors.
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Affiliation(s)
- Sung Jin Park
- Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Paul L Greer
- Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Namgyu Lee
- Department of Biomedical Science and Engineering, Dankook University, Cheonan, 31116, Republic of Korea.
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12
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Yousefi N, Salimi A, Mohammadnezhad G, Taheri S, Peiravian F. A Cost-effectiveness Analysis of Adding Cetuximab to the First-line Treatment of Metastatic Colorectal Carcinoma in Iran; Considering Genetic Screening for Precision Medicine. J Gastrointest Cancer 2023; 54:1212-1219. [PMID: 36622516 DOI: 10.1007/s12029-022-00904-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/18/2022] [Indexed: 01/10/2023]
Abstract
PURPOSE This study aimed to evaluate the cost-effectiveness of cetuximab in different genetic populations of metastatic colorectal carcinoma patients, including KRAS and RAS wild types and mutants, when added to FOLFIRI treatment regimens for evidence-based disease management in Iran. METHOD A Markov decision model was designed in TreeAge software with the three states of stable, progress, and death. Clinical outcomes were extracted from published clinical studies, and costs were extracted from the Iranian local data. The primary outcome was an incremental cost-effectiveness ratio (ICER) in the simulated population. RESULTS The cost-utility model from the perspective of the health system indicated that the average direct medical costs of a patient that has not been genetically screened are $56,985.27 and $20,767.74 in FOLFIRI + cetuximab and FOLFIRI regimens, respectively. However, costs per patient in the KRAS wild-type population were $21,845.52 in FOLFIRI and $78,321.22 in FOLFIRI + cetuximab. In RAS wild-type patients, FOLFIRI and FOLFIRI + cetuximab costs per patient were $23,111.62 and $84,976.39, respectively. Incremental QALYs for the above scenarios were 0.069, 0.193, and 0.285, respectively. Therefore, the ICER of add-on cetuximab in Iran compared to the treatment alternatives in the scenarios with and without KRAS screening was $520,771.55/QALY, $292,768.16/QALY, and $217,460.51/QALY. CONCLUSION Although genetic screening in precision medicine reduces costs per outcome, according to the willingness-to-pay threshold of $4349.50 in the Iranian health system, add-on cetuximab to the FOLFIRI regimen is not a cost-effective strategy even with genetic screening and a 20% price reduction.
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Affiliation(s)
- Nazila Yousefi
- Department of Pharmacoeconomics and Pharma Management, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Alireza Salimi
- School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Saeed Taheri
- Department of Pharmacoeconomics and Pharma Management, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farzad Peiravian
- Department of Pharmacoeconomics and Pharma Management, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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13
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Ottaiano A, Circelli L, Santorsola M, Caraglia M. Multifaceted Insights into Innovative Approaches to Treating Colorectal Cancer Metastasis: From Emerging Biological Factors to Radiomics. Cancers (Basel) 2023; 15:4644. [PMID: 37760613 PMCID: PMC10526760 DOI: 10.3390/cancers15184644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 09/19/2023] [Accepted: 09/19/2023] [Indexed: 09/29/2023] Open
Abstract
We extend our appreciation to the authors who have made substantial contributions to the Special Issue focusing on "Colorectal Cancer Metastasis" [...].
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Affiliation(s)
- Alessandro Ottaiano
- Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, Via M. Semmola, 80131 Naples, Italy;
| | - Luisa Circelli
- AMES, Centro Polidiagnostico Strumentale srl, Via Padre Carmine Fico 24, 80013 Casalnuovo Di Napoli, Italy;
| | - Mariachiara Santorsola
- Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, Via M. Semmola, 80131 Naples, Italy;
| | - Michele Caraglia
- Department of Precision Medicine, University of Campania “L. Vanvitelli”, Via L. De Crecchio 7, 80138 Naples, Italy;
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14
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Masood L, Müller A, Ali NZ, Mummadisetty A, Yahya A, Burugu SS, Sajid R, Lakkimsetti M, Sagireddy S, Abdin ZU, Nazir Z. A Narrative Literature Review on Sepsis: A Primary Manifestation of Colorectal Neoplasm. Cureus 2023; 15:e44803. [PMID: 37809261 PMCID: PMC10560076 DOI: 10.7759/cureus.44803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Accepted: 09/06/2023] [Indexed: 10/10/2023] Open
Abstract
Sepsis and colorectal cancer (CRC) exhibit a complex relationship that warrants further exploration. This review delves into the interplay of factors between sepsis and CRC, uncovering shared pathophysiological traits and potential bacterial associations. Understanding these connections could pave the way for earlier diagnosis, improved management, and enhanced outcomes in CRC patients. The role of immune system dysfunction, hypoalbuminemia, and specific microbial imbalances, such as Streptococcus bovis and Clostridium septicum, are discussed. Recognizing sepsis in CRC patients is crucial for timely intervention, and tailored approaches encompassing antibiotic therapy, source control measures, and cancer treatment are essential for comprehensive care. Monitoring biomarkers and ratios can provide valuable insights into complications and overall health outcomes. A multidisciplinary approach involving various specialists is necessary to address the global burden of CRC and its association with sepsis while exploring novel interventions, such as fecal microbiota transplantation and personalized care. We conducted a thorough search using reputable databases such as PubMed, Scopus, and Google Scholar to investigate the connection between sepsis and CRC. We refined our search terms, utilized sidebar filters, and examined references in selected articles. This meticulous process helped us create a comprehensive literature review and gain valuable insights into this relationship.
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Affiliation(s)
- Lalain Masood
- Department of Internal Medicine, Bahria University Health Sciences Campus, Karachi, PAK
| | - Agustina Müller
- Department of General Medicine, Austral University Hospital, Pilar, ARG
| | - Nayab Z Ali
- Department of Internal Medicine, Sialkot Medical College, Sialkot, PAK
| | - Anvitha Mummadisetty
- Department of Internal Medicine, Modern Government Maternity Hospital, Hyderabad, IND
| | - Anam Yahya
- Department of Pharmacology, Dr. D. Y. Patil Medical College, Navi Mumbai, IND
| | | | - Rabia Sajid
- Department of Internal Medicine, Mayo Hospital, Lahore, PAK
| | - Mohit Lakkimsetti
- Department of Internal Medicine, Mamata Medical College, Khammam, IND
| | - Sowmya Sagireddy
- Department of Internal Medicine, Coney Island Hospital, New York, USA
| | - Zain U Abdin
- Department of Internal Medicine, District Head Quarter Hospital, Faisalabad, PAK
| | - Zahra Nazir
- Department of Internal Medicine, Combined Military Hospital, Quetta, PAK
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15
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Mazzio E, Barnes A, Badisa R, Council S, Soliman KFA. Plants against cancer: the immune-boosting herbal microbiome: not of the plant, but in the plant. Basic concepts, introduction, and future resource for vaccine adjuvant discovery. Front Oncol 2023; 13:1180084. [PMID: 37588095 PMCID: PMC10426289 DOI: 10.3389/fonc.2023.1180084] [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: 03/05/2023] [Accepted: 05/30/2023] [Indexed: 08/18/2023] Open
Abstract
The presence of microorganism communities (MOCs) comprised of bacteria, fungi, archaea, algae, protozoa, viruses, and the like, are ubiquitous in all living tissue, including plant and animal. MOCs play a significant role in establishing innate and acquired immunity, thereby influencing susceptibility and resistance to disease. This understanding has fostered substantial advancements in several fields such as agriculture, food science/safety, and the development of vaccines/adjuvants, which rely on administering inactivated-attenuated MOC pathogens. Historical evidence dating back to the 1800s, including reports by Drs Busch, Coley, and Fehleisen, suggested that acute febrile infection in response to "specific microbes" could trigger spontaneous tumor remission in humans. This discovery led to the purposeful administration of the same attenuated strains, known as "Coley's toxin," marking the onset of the first microbial (pathogen) associated molecular pattern (MAMPs or PAMPs)-based tumor immunotherapy, used clinically for over four decades. Today, these same MAMPS are consumed orally by billions of consumers around the globe, through "specific" mediums (immune boosting "herbal supplements") as carriers of highly concentrated MOCs accrued in roots, barks, hulls, sea algae, and seeds. The American Herbal Products Association (AHPA) mandates microbial reduction in botanical product processing but does not necessitate the removal of dead MAMP laden microbial debris, which we ingest. Moreover, while existing research has focused on the immune-modulating role of plant phytochemicals, the actual immune-boosting properties might instead reside solely in the plant's MOC MAMP laden biomass. This assertion is logical, considering that antigenic immune-provoking epitopes, not phytochemicals, are known to stimulate immune response. This review explores a neglected area of research regarding the immune-boosting effects of the herbal microbiome - a presence which is indirectly corroborated by various peripheral fields of study and poses a fundamental question: Given that food safety focuses on the elimination of harmful pathogens and crop science acknowledges the existence of plant microbiomes, what precisely are the immune effects of ingesting MAMPs of diverse structural composition and concentration, and where are these distributed in our botanicals? We will discuss the topic of concentrated edible MAMPs as acid and thermally stable motifs found in specific herbs and how these would activate cognate pattern recognition receptors (PPRs) in the upper gut-associated lymphoid tissue (GALT), including Peyer's patches and the lamina propria, to boost antibody titers, CD8+ and CD4+ T cells, NK activity, hematopoiesis, and facilitating M2 to M1 macrophage phenotype transition in a similar manner as vaccines. This new knowledge could pave the way for developing bioreactor-grown/heat-inactivated MOC therapies to boost human immunity against infections and improve tumor surveillance.
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Affiliation(s)
- Elizabeth Mazzio
- Divison of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health, Florida A & M University, Tallahassee, FL, United States
| | - Andrew Barnes
- Divison of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health, Florida A & M University, Tallahassee, FL, United States
| | - Ramesh Badisa
- Divison of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health, Florida A & M University, Tallahassee, FL, United States
| | - Stevie Council
- John Gnabre Science Research Institute, Baltimore, MD, United States
| | - Karam F. A. Soliman
- Divison of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health, Florida A & M University, Tallahassee, FL, United States
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16
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Panyathep A, Punturee K, Chewonarin T. Inhibitory Effects of Chlorogenic Acid Containing Green Coffee Bean Extract on Lipopolysaccharide-Induced Inflammatory Responses and Progression of Colon Cancer Cell Line. Foods 2023; 12:2648. [PMID: 37509740 PMCID: PMC10378980 DOI: 10.3390/foods12142648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/05/2023] [Accepted: 07/07/2023] [Indexed: 07/30/2023] Open
Abstract
An inflammatory response, related to colorectal cancer (CRC) progression, is a major subsequent result of bacterial infection following CRC surgery and should be of serious concern. Lipopolysaccharide (LPS), from the bacterial membrane, is a vital mediator of this event through binding with a Toll-like receptor 4 (TLR4) and activating through NF-κB in CRC. To identify a novel inhibitor of LPS-induced colon cancer cells (SW480), green coffee bean extract (GBE) was investigated. Ethyl acetate insoluble fraction (EIF) was mainly collected from GBE and classified as chlorogenic acid (CGA)-rich fractions. EIF and CGA inhibited TLR4 expression in LPS-induced SW480 cells. However, EIF was more dominant than CGA, via inhibition of expression and secretion of several associated mediators in inflammatory responses and CRC metastasis through NF-κB inactivation, which resulted in the abrogation of CRC migration and invasion. Thus, CGA-rich fraction from GBE can be further developed as an alternative treatment, coupled with CRC surgical treatment, to increase therapeutic efficiency and survival rate.
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Affiliation(s)
- Atita Panyathep
- School of Medicine, Mae Fah Luang University, Chiang Rai 57100, Thailand
| | - Khanittha Punturee
- Cancer Research Unit of Associated Medical Sciences (AMS-CRU), Faculties of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Teera Chewonarin
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
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17
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Glajzner P, Szewczyk EM, Szemraj M. Phenotypic and Genotypic Characterization of Antimicrobial Resistance in Streptococci Isolated from Human and Animal Clinical Specimens. Curr Microbiol 2023; 80:228. [PMID: 37256427 DOI: 10.1007/s00284-023-03337-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 05/19/2023] [Indexed: 06/01/2023]
Abstract
Recently, the phenomenon of infection of humans as hosts by animal pathogens has been increasing. Streptococcus is an example of a genus in which bacteria overcome the species barrier. Therefore, monitoring infections caused by new species of human pathogens is critical to their spread. Seventy-five isolates belonging to streptococcal species that have recently been reported as a cause of human infections with varying frequency, were tested. The aim of the study was to determine the drug resistance profiles of the tested strains, the occurrence of resistance genes and genes encoding the most important streptococcal virulence factors. All tested isolates retained sensitivity to β-lactam antibiotics. Resistance to tetracyclines occurred in 56% of the tested strains. We have detected the MLSB type resistance (cross-resistance to macrolide, lincosamide, and streptogramin B) in 20% of the tested strains. 99% of the strains had tetracycline resistance genes. The erm class genes encoding MLSB resistance were present in 47% of strains. Among the strains with MLSB resistance, 92% had the streptokinase gene, 58% the streptolysin O gene and 33% the streptolysin S gene. The most extensive resistance concerned isolates that accumulated the most traits and genes, both resistance genes and virulence genes, increasing their pathogenic potential. Among the tested strains, the gene encoding streptokinase was the most common. The results of the prove that bacteria of the species S. uberis, S. dysgalactiae and S. gallolyticus are characterized by a high pathogenic potential and can pose a significant threat in case of infection of the human body.
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Affiliation(s)
- Paulina Glajzner
- Department of Pharmaceutical Microbiology and Microbiological Diagnostics, Medical University of Lodz, Ul. Muszyńskiego 1, 90-001, Łódź, Poland
| | - Eligia M Szewczyk
- Department of Pharmaceutical Microbiology and Microbiological Diagnostics, Medical University of Lodz, Ul. Muszyńskiego 1, 90-001, Łódź, Poland
| | - Magdalena Szemraj
- Department of Pharmaceutical Microbiology and Microbiological Diagnostics, Medical University of Lodz, Ul. Muszyńskiego 1, 90-001, Łódź, Poland.
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18
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Novoa Díaz MB, Carriere P, Gentili C. How the interplay among the tumor microenvironment and the gut microbiota influences the stemness of colorectal cancer cells. World J Stem Cells 2023; 15:281-301. [PMID: 37342226 PMCID: PMC10277969 DOI: 10.4252/wjsc.v15.i5.281] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 03/06/2023] [Accepted: 04/17/2023] [Indexed: 05/26/2023] Open
Abstract
Colorectal cancer (CRC) remains the third most prevalent cancer disease and involves a multi-step process in which intestinal cells acquire malignant characteristics. It is well established that the appearance of distal metastasis in CRC patients is the cause of a poor prognosis and treatment failure. Nevertheless, in the last decades, CRC aggressiveness and progression have been attributed to a specific cell population called CRC stem cells (CCSC) with features like tumor initiation capacity, self-renewal capacity, and acquired multidrug resistance. Emerging data highlight the concept of this cell subtype as a plastic entity that has a dynamic status and can be originated from different types of cells through genetic and epigenetic changes. These alterations are modulated by complex and dynamic crosstalk with environmental factors by paracrine signaling. It is known that in the tumor niche, different cell types, structures, and biomolecules coexist and interact with cancer cells favoring cancer growth and development. Together, these components constitute the tumor microenvironment (TME). Most recently, researchers have also deepened the influence of the complex variety of microorganisms that inhabit the intestinal mucosa, collectively known as gut microbiota, on CRC. Both TME and microorganisms participate in inflammatory processes that can drive the initiation and evolution of CRC. Since in the last decade, crucial advances have been made concerning to the synergistic interaction among the TME and gut microorganisms that condition the identity of CCSC, the data exposed in this review could provide valuable insights into the biology of CRC and the development of new targeted therapies.
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Affiliation(s)
- María Belén Novoa Díaz
- Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, Bahía Blanca 8000, Buenos Aires, Argentina
- Instituto de Ciencias Biológicas y Biomédicas del Sur, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)- Universidad Nacional del Sur (UNS), Bahía Blanca 8000, Buenos Aires, Argentina
| | - Pedro Carriere
- Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, Bahía Blanca 8000, Buenos Aires, Argentina
- Instituto de Ciencias Biológicas y Biomédicas del Sur, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)- Universidad Nacional del Sur (UNS), Bahía Blanca 8000, Buenos Aires, Argentina
| | - Claudia Gentili
- Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, Bahía Blanca 8000, Buenos Aires, Argentina
- Instituto de Ciencias Biológicas y Biomédicas del Sur, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)- Universidad Nacional del Sur (UNS), Bahía Blanca 8000, Buenos Aires, Argentina
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Motamedi H, Ari MM, Shahlaei M, Moradi S, Farhadikia P, Alvandi A, Abiri R. Designing multi-epitope vaccine against important colorectal cancer (CRC) associated pathogens based on immunoinformatics approach. BMC Bioinformatics 2023; 24:65. [PMID: 36829112 PMCID: PMC9951438 DOI: 10.1186/s12859-023-05197-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 02/20/2023] [Indexed: 02/26/2023] Open
Abstract
BACKGROUND It seems that several members of intestinal gut microbiota like Streptococcus bovis, Bacteroides fragilis, Helicobacter pylori, Fusobacterium nucleatum, Enterococcus faecalis, Escherichia coli, Peptostreptococcus anaerobius may be considered as the causative agents of Colorectal Cancer (CRC). The present study used bioinformatics and immunoinformatics approaches to design a potential epitope-based multi-epitope vaccine to prevent CRC with optimal population coverage. METHODS In this study, ten amino acid sequences of CRC-related pathogens were retrieved from the NCBI database. Three ABCpred, BCPREDS and LBtope online servers were considered for B cells prediction and the IEDB server for T cells (CD4+ and CD8+) prediction. Then, validation, allergenicity, toxicity and physicochemical analysis of all sequences were performed using web servers. A total of three linkers, AAY, GPGPG, and KK were used to bind CTL, HTL and BCL epitopes, respectively. In addition, the final construct was subjected to disulfide engineering, molecular docking, immune simulation and codon adaptation to design an effective vaccine production strategy. RESULTS A total of 19 sequences of different lengths for linear B-cell epitopes, 19 and 18 sequences were considered as epitopes of CD4+ T and CD8+ cells, respectively. The predicted epitopes were joined by appropriate linkers because they play an important role in producing an extended conformation and protein folding. The final multi-epitope construct and Toll-like receptor 4 (TLR4) were evaluated by molecular docking, which revealed stable and strong binding interactions. Immunity simulation of the vaccine showed significantly high levels of immunoglobulins, helper T cells, cytotoxic T cells and INF-γ. CONCLUSION Finally, the results showed that the designed multi-epitope vaccine could serve as an excellent prophylactic candidate against CRC-associated pathogens, but in vitro and animal studies are needed to justify our findings for its use as a possible preventive measure.
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Affiliation(s)
- Hamid Motamedi
- grid.412112.50000 0001 2012 5829Department of Microbiology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran ,grid.412112.50000 0001 2012 5829Student Research Committee, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Marzie Mahdizade Ari
- grid.411746.10000 0004 4911 7066Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran ,grid.411746.10000 0004 4911 7066Microbial Biotechnology Research Centre, Iran University of Medical Sciences, Tehran, Iran
| | - Mohsen Shahlaei
- grid.412112.50000 0001 2012 5829Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Sajad Moradi
- grid.412112.50000 0001 2012 5829Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Parisa Farhadikia
- grid.412112.50000 0001 2012 5829Department of Microbiology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Amirhoushang Alvandi
- Department of Microbiology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. .,Medical Technology Research Center, Health Technology Institute,, Kermanshah University of Medical Sciences, Kermanshah, Iran.
| | - Ramin Abiri
- Department of Microbiology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. .,Fertility and Infertility Research Center, Health Technology Institute,, Kermanshah University of Medical Sciences, Kermanshah, Iran.
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20
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Hou X, Zheng Z, Wei J, Zhao L. Effects of gut microbiota on immune responses and immunotherapy in colorectal cancer. Front Immunol 2022; 13:1030745. [PMID: 36426359 PMCID: PMC9681148 DOI: 10.3389/fimmu.2022.1030745] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 10/24/2022] [Indexed: 08/13/2023] Open
Abstract
Accumulating evidence suggests that gut microbial dysbiosis is implicated in colorectal cancer (CRC) initiation and progression through interaction with host immune system. Given the intimate relationship between the gut microbiota and the antitumor immune responses, the microbiota has proven to be effective targets in modulating immunotherapy responses of preclinical CRC models. However, the proposed putative mechanisms of how these bacteria affect immune responses and immunotherapy efficacy remains obscure. In this review, we summarize recent findings of clinical gut microbial dysbiosis in CRC patients, the reciprocal interactions between gut microbiota and the innate and/or the adaptive immune system, as well as the effect of gut microbiota on immunotherapy response in CRC. Increased understanding of the gut microbiota-immune system interactions will benefit the rational application of microbiota to the clinical promising biomarker or therapeutic strategy as a cancer immunotherapy adjuvant.
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Affiliation(s)
| | | | | | - Ling Zhao
- Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Bacterial Involvement in Progression and Metastasis of Adenocarcinoma of the Stomach. Cancers (Basel) 2022; 14:cancers14194886. [PMID: 36230809 PMCID: PMC9562638 DOI: 10.3390/cancers14194886] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 09/26/2022] [Accepted: 10/03/2022] [Indexed: 12/03/2022] Open
Abstract
Simple Summary Infectious bacteria influence primary gastric carcinogenesis, organotropism, and metastatic progression by altering the microenvironment at the primary and secondary tumors. Key species include Helicobacter pylori (H. pylori) and Mycoplasma hyorhinis (M. hyorhinis). Inflammation caused by H. pylori virulence factors, such as CagA, VacA, and oipA, disrupt epithelial integrity, which allows the primary tumor to progress through the metastatic process. Evidence supports the activation of aquaporin-5 by CagA-positive H. pylori infection, promoting epithelial–mesenchymal transition via the extracellular signal-regulated kinase/mitogen-activated protein kinase (MEK/ERK) pathway, thus laying the foundation for metastatic disease. M. hyorhinis has also been implicated in gastric neoplasia via β-catenin stabilization and subsequent activation of the WNT-signaling pathway, promoting gastric cancer cell motility and inciting cancer progression. Abstract Gastric cancer metastasis is a process in which the tumor microenvironment may carry significant influence. Helicobacter pylori (H. pylori) infection is well-established as a contributor to gastric carcinoma. However, the role that these bacteria and others may play in gastric carcinoma metastasis is a current focus of study. A review of the literature was conducted to elucidate the process by which gastric adenocarcinoma metastasizes, including its ability to utilize both the lymphatic system and the venous system to disseminate. Studies that investigate the tumor microenvironment at both the primary and secondary sites were assessed in detail. H. pylori and Mycoplasma hyorhinis (M. hyorhinis) were found to be important drivers of the pathogenesis of gastric adenocarcinoma by modifying various steps in cell metastasis, including epithelial–mesenchymal transition, cell migration, and cell invasion. H. pylori is also a known driver of MALT lymphoma, which is often reversible simply with the eradication of infection. M. hyorhinis has been implicated in gastric neoplasia via β-catenin stabilization and subsequent activation of the WNT-signaling pathway, promoting gastric cancer cell motility and inciting cancer progression. Fusobacterium nucleatum (F. nucleatum) and its association with worse prognosis in diffuse-type gastric adenocarcinoma are also reviewed. Recognition of the roles that bacteria play within the metastatic cascade is vital in gastrointestinal adenocarcinoma treatment and potential reoccurrence. Further investigation is needed to establish potential treatment for metastatic gastric carcinoma by targeting the tumor microenvironment.
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22
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Sadrekarimi H, Gardanova ZR, Bakhshesh M, Ebrahimzadeh F, Yaseri AF, Thangavelu L, Hasanpoor Z, Zadeh FA, Kahrizi MS. Emerging role of human microbiome in cancer development and response to therapy: special focus on intestinal microflora. Lab Invest 2022; 20:301. [PMID: 35794566 PMCID: PMC9258144 DOI: 10.1186/s12967-022-03492-7] [Citation(s) in RCA: 68] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Accepted: 06/20/2022] [Indexed: 12/12/2022]
Abstract
In recent years, there has been a greater emphasis on the impact of microbial populations inhabiting the gastrointestinal tract on human health and disease. According to the involvement of microbiota in modulating physiological processes (such as immune system development, vitamins synthesis, pathogen displacement, and nutrient uptake), any alteration in its composition and diversity (i.e., dysbiosis) has been linked to a variety of pathologies, including cancer. In this bidirectional relationship, colonization with various bacterial species is correlated with a reduced or elevated risk of certain cancers. Notably, the gut microflora could potentially play a direct or indirect role in tumor initiation and progression by inducing chronic inflammation and producing toxins and metabolites. Therefore, identifying the bacterial species involved and their mechanism of action could be beneficial in preventing the onset of tumors or controlling their advancement. Likewise, the microbial community affects anti-cancer approaches’ therapeutic potential and adverse effects (such as immunotherapy and chemotherapy). Hence, their efficiency should be evaluated in the context of the microbiome, underlining the importance of personalized medicine. In this review, we summarized the evidence revealing the microbiota's involvement in cancer and its mechanism. We also delineated how microbiota could predict colon carcinoma development or response to current treatments to improve clinical outcomes.
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