1
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Ma X, Ning S, Sun T, Liu M, Liu J. Expression and clinical significance of NLRC5 in hepatocellular carcinoma. Cancer Biol Ther 2024; 25:2390205. [PMID: 39132868 PMCID: PMC11321415 DOI: 10.1080/15384047.2024.2390205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 08/01/2024] [Accepted: 08/05/2024] [Indexed: 08/13/2024] Open
Abstract
NLRC5, the largest member of the nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family, has been reported to participate in the regulation of immune function and is associated with chronic inflammatory diseases. However, the biological function of NLRC5 in hepatocellular carcinoma (HCC) has not been fully demonstrated. The aim of this study is to evaluate NLRC5 expression in the tumor tissues of HCC patients undergoing surgical treatment, assess its prognostic value, and explore its relationship with critical immune-related molecules within the tumor microenvironment. A total of 100 patients with hepatitis B virus-associated HCC receiving surgical treatment were enrolled in the study. Immunohistochemical results were obtained by scoring the intensity of cellular staining and the percentage of positive cells in the tissue sections. The association between NLRC5 expression levels and the main clinicopathological factors was analyzed by Chi-square test method. The prognostic values were analyzed by COX regression model and the Kaplan-Meier survival curve. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive performance of NLRC5 in postoperative patients with HCC. IHC showed that high expression of NLRC5 was observed in 67% of HCC tissue samples. Chi-square test showed that NLRC5 was a risk factor associated with tumor number, satellite nodule, and envelope invasion. Kaplan-Meier survival curves and COX survival analysis showed that high expression of NLRC5 was significantly associated with decreased overall survival (OS) in HCC patients (HR = 1.79, 95% CI 1.03-3.12, p = .041). However, univariate logistic regression analysis revealed that NLRC5 showed positive relationship with GZMB and CD8α suggesting its role in immune escape of HCC. ROC curve analysis showed that the combination of tumor number, envelope invasion, and NLRC5 expression (area under the curve = 0.824, sensitivity = 77.30%, specificity = 82.4%) can more accurately evaluate the prognosis of HCC patients compared to the combination of only tumor number and envelope invasion (area under the curve = 0.690, sensitivity = 43.9%, specificity = 94.1%).NLRC5 plays a crucial role in progression of HCC and can be considered as a potential prognostic and predictive biomarker. Targeting NLRC5 may provide an attractive therapeutic approach for HCC.
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Affiliation(s)
- Xiangyu Ma
- Department of Interventional Surgical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Shangkun Ning
- Department of Interventional Surgical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Tong Sun
- Department of Interventional Surgical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Mei Liu
- Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jibing Liu
- Department of Interventional Surgical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
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2
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Dorobisz K, Dorobisz T, Pazdro-Zastawny K. Analysis of Risk Factors with Assessment of the Impact of the Microbiome on the Risk of Squamous Cell Carcinoma of the Larynx. J Clin Med 2024; 13:6101. [PMID: 39458051 PMCID: PMC11508926 DOI: 10.3390/jcm13206101] [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: 07/28/2024] [Revised: 09/26/2024] [Accepted: 10/10/2024] [Indexed: 10/28/2024] Open
Abstract
Introduction: Head and neck squamous cell carcinoma (HNSCC) ranks sixth among cancers in the world, and the 5-year survival rate ranges from 25% to 60%. The risk factors for HNSCC are primarily smoking, alcohol consumption and human papillomavirus (HPV). Data indicate that 15-20% of cancers are caused by infectious agents, 20-30% by smoking and 30-35% by unhealthy lifestyles, diet, lack of physical activity and obesity. Dysbiosis is a microbiome imbalance, which promotes oncogenesis by intensifying inflammatory processes and affecting the host's metabolism. Profiling the microbiome in various types of cancer is currently the subject of research and analysis. However, there is still little information on the correlation of the microbiome with HNSCC and its impact on oncogenesis, the course of the disease and its treatment. Objective: The aim of the study was to prospectively assess risk factors with assessment of the impact of the microbiome on the risk of squamous cell carcinoma of the larynx. The study included a group of 44 patients diagnosed with squamous cell carcinoma of the larynx and 30 patients from the control group. Results: In the control group, bacteria of the normal microbiome dominated-the genus Streptococcus, Gemella, Neisseria and Kingella. In the group of patients with laryngeal cancer, Prevotella, Clostridiales and Stomatobaculum were found significantly more often. Porphyromonas, Fusobacterium, Lactobacillus, Actinobacteria, Actinomyces and Shaalia odontolytica were also found at a higher percentage in the study group. Analyzing the phylum, Firmicutes dominated in the control group; there were statistically significantly more of them than in patients from the study group. Bacteroides and Bacillota were found significantly more often in patients with laryngeal cancer. Conclusions: The importance of the microbiome in oncology has been confirmed in many studies. Independent risk factors for laryngeal cancer were primarily a lower number of Firmicutes in the microbiome, but also an increased leukocyte level above 6.52 × 103/mm and a decreased total protein level below 6.9 g/dL. Prevotella, Clostridiales, Stomatobaculum, Porphyromonas, Fusobacterium, Lactobacillus, Actinobacteria, Actinomyces and Shaalia were considered to be the bacteria contributing to the development of laryngeal cancer. Streptococcus, Gemella, Neisserie and Kingella were considered to be protective bacteria. Moreover, the study confirmed the significant impact of smoking, alcohol consumption and poor oral hygiene on the development of laryngeal cancer. The microbiome, its identification and manipulation may constitute a breakthrough discovery for improving the diagnosis and oncological therapy of laryngeal cancer, and also of the entire group of HNSCC. Profiling the microbiome may allow for personalized therapy related to its modification. Assessing the microbiome of patients diagnosed with cancer may provide an opportunity to predict treatment response and effectiveness.
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Affiliation(s)
- Karolina Dorobisz
- Department of Otolaryngology, Head and Neck Surgery, Wrocław Medical University, Borowska 213, 50-556 Wrocław, Poland
| | - Tadeusz Dorobisz
- Department of Vascular and General Surgery, Wrocław Medical University, Borowska 213, 50-556 Wrocław, Poland
| | - Katarzyna Pazdro-Zastawny
- Department of Otolaryngology, Head and Neck Surgery, Wrocław Medical University, Borowska 213, 50-556 Wrocław, Poland
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3
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Zhou Y, Meyle J, Groeger S. Periodontal pathogens and cancer development. Periodontol 2000 2024; 96:112-149. [PMID: 38965193 PMCID: PMC11579836 DOI: 10.1111/prd.12590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 05/03/2024] [Accepted: 06/11/2024] [Indexed: 07/06/2024]
Abstract
Increasing evidence suggests a significant association between periodontal disease and the occurrence of various cancers. The carcinogenic potential of several periodontal pathogens has been substantiated in vitro and in vivo. This review provides a comprehensive overview of the diverse mechanisms employed by different periodontal pathogens in the development of cancer. These mechanisms induce chronic inflammation, inhibit the host's immune system, activate cell invasion and proliferation, possess anti-apoptotic activity, and produce carcinogenic substances. Elucidating these mechanisms might provide new insights for developing novel approaches for tumor prevention, therapeutic purposes, and survival improvement.
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Affiliation(s)
- Yuxi Zhou
- Department of PeriodontologyJustus‐Liebig‐University of GiessenGiessenGermany
| | - Joerg Meyle
- Department of PeriodontologyJustus‐Liebig‐University of GiessenGiessenGermany
| | - Sabine Groeger
- Department of PeriodontologyJustus‐Liebig‐University of GiessenGiessenGermany
- Department of OrthodonticsJustus‐Liebig‐University of GiessenGiessenGermany
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4
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Aruwa CE, Sabiu S. Interplay of poultry-microbiome interactions - influencing factors and microbes in poultry infections and metabolic disorders. Br Poult Sci 2024; 65:523-537. [PMID: 38920059 DOI: 10.1080/00071668.2024.2356666] [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: 01/31/2024] [Accepted: 03/06/2024] [Indexed: 06/27/2024]
Abstract
1. The poultry microbiome and its stability at every point in time, either free range or reared under different farming systems, is affected by several environmental and innate factors. The interaction of the poultry birds with their microbiome, as well as several inherent and extraneous factors contribute to the microbiome dynamics. A poor understanding of this could worsen poultry heath and result in disease/metabolic disorders.2. Many diseased states associated with poultry have been linked to dysbiosis state, where the microbiome experiences some perturbation. Dysbiosis itself is too often downplayed; however, it is considered a disease which could lead to more serious conditions in poultry. The management of interconnected factors by conventional and emerging technologies (sequencing, nanotechnology, robotics, 3D mini-guts) could prove to be indispensable in ensuring poultry health and welfare.3. Findings showed that high-throughput technological advancements enhanced scientific insights into emerging trends surrounding the poultry gut microbiome and ecosystem, the dysbiotic condition, and the dynamic roles of intrinsic and exogenous factors in determining poultry health. Yet, a combination of conventional, -omics based and other techniques further enhance characterisation of key poultry microbiome actors, their mechanisms of action, and roles in maintaining gut homoeostasis and health, in a bid to avert metabolic disorders and infections.4. In conclusion, there is an important interplay of innate, environmental, abiotic and biotic factors impacting on poultry gut microbiome homoeostasis, dysbiosis, and overall health. Associated infections and metabolic disorders can result from the interconnected nature of these factors. Emerging concepts (interkingdom or network signalling and neurotransmitter), and future technologies (mini-gut models, cobots) need to include these interactions to ensure accurate control and outcomes.
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Affiliation(s)
- C E Aruwa
- Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, Durban, South Africa
| | - S Sabiu
- Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, Durban, South Africa
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5
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Réthi-Nagy Z, Juhász S. Microbiome's Universe: Impact on health, disease and cancer treatment. J Biotechnol 2024; 392:161-179. [PMID: 39009231 DOI: 10.1016/j.jbiotec.2024.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 05/27/2024] [Accepted: 07/07/2024] [Indexed: 07/17/2024]
Abstract
The human microbiome is a diverse ecosystem of microorganisms that reside in the body and influence various aspects of health and well-being. Recent advances in sequencing technology have brought to light microbial communities in organs and tissues that were previously considered sterile. The gut microbiota plays an important role in host physiology, including metabolic functions and immune modulation. Disruptions in the balance of the microbiome, known as dysbiosis, have been linked to diseases such as cancer, inflammatory bowel disease and metabolic disorders. In addition, the administration of antibiotics can lead to dysbiosis by disrupting the structure and function of the gut microbial community. Targeting strategies are the key to rebalancing the microbiome and fighting disease, including cancer, through interventions such as probiotics, fecal microbiota transplantation (FMT), and bacteria-based therapies. Future research must focus on understanding the complex interactions between diet, the microbiome and cancer in order to optimize personalized interventions. Multidisciplinary collaborations are essential if we are going to translate microbiome research into clinical practice. This will revolutionize approaches to cancer prevention and treatment.
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Affiliation(s)
- Zsuzsánna Réthi-Nagy
- Hungarian Centre of Excellence for Molecular Medicine, Cancer Microbiome Core Group, Budapesti út 9, Szeged H-6728, Hungary
| | - Szilvia Juhász
- Hungarian Centre of Excellence for Molecular Medicine, Cancer Microbiome Core Group, Budapesti út 9, Szeged H-6728, Hungary.
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6
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Yu R, Wang S, Han L. Relevance of harmful intratumoral microbiota in cancer progression and its clinical application. Biomed Pharmacother 2024; 178:117238. [PMID: 39106707 DOI: 10.1016/j.biopha.2024.117238] [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: 06/06/2024] [Revised: 07/22/2024] [Accepted: 07/30/2024] [Indexed: 08/09/2024] Open
Abstract
Microorganisms are closely related to human health, and changes in the microbiome can lead to the occurrence of diseases. With advances in sequencing technology and research, it has been discovered that intratumoral microbiota exists in various cancer tissues and differs in various cancers. Microorganism can colonize tumor tissues through intestine of damaged mucosal barrier, proximity to normal tissues and bloodstream circulation. Increasing evidence suggests that intratumoral microbiota promotes tumor progression by increasing genomic instability, affecting host immune systems, promoting tumor migration, and regulating tumor signaling pathways. This review article summarizes the latest progress in intratumoral microbiome research, including the development history of intratumoral microbiota, their composition and sources within tumors, their distribution in various cancer tissues, as well as their role in cancer development. Furthermore, the application of intratumoral microbiota in clinical settings is emphasized and we innovatively summarize the clinical trials involving microbial applications for cancer diagnosis and treatment across different countries.
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Affiliation(s)
- Runze Yu
- Tianjin Neurological Institute, Key Laboratory of Post-Neuro injury, Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Sheng Wang
- School of Life Sciences, Tianjin University, Tianjin 300072, China.
| | - Lei Han
- Tianjin Neurological Institute, Key Laboratory of Post-Neuro injury, Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin Medical University General Hospital, Tianjin 300052, China.
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7
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Pan Y, Lv H, Feng X, Zhou S, Hu H, Chen S, Cheng Y, Fan F, Gong S, Chen P, Chu Q. Epigallocatechin gallate (EGCG) alleviates the inflammatory response and recovers oral microbiota in acetic acid-induced oral inflammation mice. Food Funct 2023; 14:10069-10082. [PMID: 37867423 DOI: 10.1039/d3fo03107a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2023]
Abstract
The oral microbiota, the second largest microbiome in the human body, plays an integral role in maintaining both the local oral and systemic health of the host. Oral microecological imbalances have been identified as a potential risk factor for numerous oral and systemic diseases. As a representative component of tea, epigallocatechin gallate (EGCG) has demonstrated inhibitory effects on most pathogens in single-microbial models. In this study, the regulatory effect of EGCG on more complex oral microbial systems was further explored through a mouse model of acetic acid-induced oral inflammation. Acetic acid induces histological damage in the cheek pouch, tongue, and throat, such as broken mucosa, submucosal edema, and muscular disorders. These detrimental effects were ameliorated significantly following EGCG treatment. Additionally, EGCG reduced the levels of the inflammatory cytokines interleukin-6 and tumor necrosis factor-α to alleviate the inflammation of the tongue, cheek pouch, and throat. According to the 16S rDNA gene sequencing data, EGCG treatment contributed to increased diversity of the oral microbiota and the reversal of oral microecological disorder. This study demonstrates the regulatory effect of EGCG on dysregulated oral microbiota, providing a potential option for the prevention and treatment of oral-microbiota-associated diseases.
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Affiliation(s)
- Yani Pan
- Tea Research Institute, Zhejiang University, Hangzhou 310058, China.
| | - Helin Lv
- Tea Research Institute, Zhejiang University, Hangzhou 310058, China.
| | - Xinyu Feng
- Tea Research Institute, Zhejiang University, Hangzhou 310058, China.
| | - Su Zhou
- Tea Research Institute, Zhejiang University, Hangzhou 310058, China.
| | - Hao Hu
- College of Food and Health, Zhejiang A & F University, Hangzhou 311300, China
| | - Shuxi Chen
- Tea Research Institute, Zhejiang University, Hangzhou 310058, China.
| | - Yan Cheng
- Hangzhou Real Taste Tea Culture Development Co., Ltd., Hangzhou 311100, China
| | - Fangyuan Fan
- Tea Research Institute, Zhejiang University, Hangzhou 310058, China.
| | - Shuying Gong
- Tea Research Institute, Zhejiang University, Hangzhou 310058, China.
| | - Ping Chen
- Tea Research Institute, Zhejiang University, Hangzhou 310058, China.
| | - Qiang Chu
- Tea Research Institute, Zhejiang University, Hangzhou 310058, China.
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8
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Czarnecka-Chrebelska KH, Kordiak J, Brzeziańska-Lasota E, Pastuszak-Lewandoska D. Respiratory Tract Oncobiome in Lung Carcinogenesis: Where Are We Now? Cancers (Basel) 2023; 15:4935. [PMID: 37894302 PMCID: PMC10605430 DOI: 10.3390/cancers15204935] [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: 09/08/2023] [Revised: 10/02/2023] [Accepted: 10/09/2023] [Indexed: 10/29/2023] Open
Abstract
The importance of microbiota in developing and treating diseases, including lung cancer (LC), is becoming increasingly recognized. Studies have shown differences in microorganism populations in the upper and lower respiratory tracts of patients with lung cancer compared to healthy individuals, indicating a link between dysbiosis and lung cancer. However, it is not only important to identify "which bacteria are present" but also to understand "how" they affect lung carcinogenesis. The interactions between the host and lung microbiota are complex, and our knowledge of this relationship is limited. This review presents research findings on the bacterial lung microbiota and discusses the mechanisms by which lung-dwelling microorganisms may directly or indirectly contribute to the development of lung cancer. These mechanisms include influences on the host immune system regulation and the local immune microenvironment, the regulation of oncogenic signaling pathways in epithelial cells (causing cell cycle disorders, mutagenesis, and DNA damage), and lastly, the MAMPs-mediated path involving the effects of bacteriocins, TLRs signaling induction, and TNF release. A better understanding of lung microbiota's role in lung tumor pathology could lead to identifying new diagnostic and therapeutic biomarkers and developing personalized therapeutic management for lung cancer patients.
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Affiliation(s)
| | - Jacek Kordiak
- Department of Thoracic, General and Oncological Surgery, Medical University of Lodz, 90-151 Lodz, Poland
| | - Ewa Brzeziańska-Lasota
- Department of Biomedicine and Genetics, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland
| | - Dorota Pastuszak-Lewandoska
- Department of Microbiology and Laboratory Medical Immunology, Medical University of Lodz, Pomorska 251, 90-151 Lodz, Poland;
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9
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Bahuguna A, Dubey SK. Relevance of tumor microbiome in cancer incidence, prognosis, and its clinical implications in therapeutics. Biochim Biophys Acta Rev Cancer 2023; 1878:188956. [PMID: 37473857 DOI: 10.1016/j.bbcan.2023.188956] [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: 05/09/2023] [Revised: 07/07/2023] [Accepted: 07/13/2023] [Indexed: 07/22/2023]
Abstract
The microbiota is garnering progressively greater consideration as an essential facet of the tumor microenvironment that regulates tumor proliferation and affects cancer prognosis. Microbial populations that inhabit different body locations are involved in the carcinogenesis and tumor progression of their corresponding malignancies. It has been learned that the microbial populations primarily thriving within tumors are tumor-type specific. Mechanistic studies have revealed that the tumor-associated microbiota contributes to playing a pivotal role in the establishment of the tumor microenvironment, regulation of local immunity, modulation of tumor cell biology, and directly influences the therapeutic efficacy of drug treatment for tumors. This review article incorporates the pertinent studies on recent advancements in tumor microbiome studies, the interplay between the intratumor microbiota and cancer, and, discusses their role and mechanism of action in the emergence and treatment of cancer, and their relationship to clinical characteristics.
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Affiliation(s)
- Ananya Bahuguna
- Department of Biochemistry, College of Basic Sciences and Humanities, Govind Ballabh Pant University of Agriculture and Technology, Pantnagar 263145, Uttarakhand, India
| | - Shiv Kumar Dubey
- Department of Biochemistry, College of Basic Sciences and Humanities, Govind Ballabh Pant University of Agriculture and Technology, Pantnagar 263145, Uttarakhand, India.
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10
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Carlson E, Savardekar H, Hu X, Lapurga G, Johnson C, Sun SH, Carson WE, Peterson BR. Fluorescent Detection of Peroxynitrite Produced by Myeloid-Derived Suppressor Cells in Cancer and Inhibition by Dasatinib. ACS Pharmacol Transl Sci 2023; 6:738-747. [PMID: 37200815 PMCID: PMC10186365 DOI: 10.1021/acsptsci.3c00014] [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: 01/20/2023] [Indexed: 05/20/2023]
Abstract
Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that expand dramatically in many cancer patients. This expansion contributes to immunosuppression in cancer and reduces the efficacy of immune-based cancer therapies. One mechanism of immunosuppression mediated by MDSCs involves production of the reactive nitrogen species peroxynitrite (PNT), where this strong oxidant inactivates immune effector cells through destructive nitration of tyrosine residues in immune signal transduction pathways. As an alternative to analysis of nitrotyrosines indirectly generated by PNT, we used an endoplasmic reticulum (ER)-targeted fluorescent sensor termed PS3 that allows direct detection of PNT produced by MDSCs. When the MDSC-like cell line MSC2 and primary MDSCs from mice and humans were treated with PS3 and antibody-opsonized TentaGel microspheres, phagocytosis of these beads led to production of PNT and generation of a highly fluorescent product. Using this method, we show that splenocytes from a EMT6 mouse model of cancer, but not normal control mice, produce high levels of PNT due to elevated numbers of granulocytic (PMN) MDSCs. Similarly, peripheral blood mononuclear cells (PBMCs) isolated from blood of human melanoma patients produced substantially higher levels of PNT than healthy human volunteers, coincident with higher peripheral MDSC levels. The kinase inhibitor dasatinib was found to potently block the production of PNT both by inhibiting phagocytosis in vitro and by reducing the number of granulocytic MDSCs in mice in vivo, providing a chemical tool to modulate the production of this reactive nitrogen species (RNS) in the tumor microenvironment.
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Affiliation(s)
- Erick
J. Carlson
- Division
of Medicinal Chemistry and Pharmacognosy, The Ohio State University, Columbus, Ohio 43210, United States
| | - Himanshu Savardekar
- Division
of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, Ohio 43210, United States
| | - Xiaojun Hu
- Division
of Medicinal Chemistry and Pharmacognosy, The Ohio State University, Columbus, Ohio 43210, United States
| | - Gabriella Lapurga
- Division
of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, Ohio 43210, United States
| | - Courtney Johnson
- Division
of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, Ohio 43210, United States
| | - Steven H. Sun
- Division
of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, Ohio 43210, United States
| | - William E. Carson
- Division
of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, Ohio 43210, United States
| | - Blake R. Peterson
- Division
of Medicinal Chemistry and Pharmacognosy, The Ohio State University, Columbus, Ohio 43210, United States
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11
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Li X, Yan X, Wang Y, Kaur B, Han H, Yu J. The Notch signaling pathway: a potential target for cancer immunotherapy. J Hematol Oncol 2023; 16:45. [PMID: 37131214 PMCID: PMC10155406 DOI: 10.1186/s13045-023-01439-z] [Citation(s) in RCA: 46] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Accepted: 04/13/2023] [Indexed: 05/04/2023] Open
Abstract
Dysregulation of the Notch signaling pathway, which is highly conserved across species, can drive aberrant epigenetic modification, transcription, and translation. Defective gene regulation caused by dysregulated Notch signaling often affects networks controlling oncogenesis and tumor progression. Meanwhile, Notch signaling can modulate immune cells involved in anti- or pro-tumor responses and tumor immunogenicity. A comprehensive understanding of these processes can help with designing new drugs that target Notch signaling, thereby enhancing the effects of cancer immunotherapy. Here, we provide an up-to-date and comprehensive overview of how Notch signaling intrinsically regulates immune cells and how alterations in Notch signaling in tumor cells or stromal cells extrinsically regulate immune responses in the tumor microenvironment (TME). We also discuss the potential role of Notch signaling in tumor immunity mediated by gut microbiota. Finally, we propose strategies for targeting Notch signaling in cancer immunotherapy. These include oncolytic virotherapy combined with inhibition of Notch signaling, nanoparticles (NPs) loaded with Notch signaling regulators to specifically target tumor-associated macrophages (TAMs) to repolarize their functions and remodel the TME, combining specific and efficient inhibitors or activators of Notch signaling with immune checkpoint blockers (ICBs) for synergistic anti-tumor therapy, and implementing a customized and effective synNotch circuit system to enhance safety of chimeric antigen receptor (CAR) immune cells. Collectively, this review aims to summarize how Notch signaling intrinsically and extrinsically shapes immune responses to improve immunotherapy.
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Affiliation(s)
- Xinxin Li
- Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi'an, 710072, Shaanxi, People's Republic of China
| | - Xianchun Yan
- State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, People's Republic of China
| | - Yufeng Wang
- Cancer Institute, The First Hospital of Jilin University, Changchun, 130021, People's Republic of China
| | - Balveen Kaur
- Department of Neurosurgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, 77225, USA
| | - Hua Han
- State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, People's Republic of China.
| | - Jianhua Yu
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, 1500 East Duarte, Los Angeles, CA, 91010, USA.
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12
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Chen C, Wang Z, Ding Y, Qin Y. Tumor microenvironment-mediated immune evasion in hepatocellular carcinoma. Front Immunol 2023; 14:1133308. [PMID: 36845131 PMCID: PMC9950271 DOI: 10.3389/fimmu.2023.1133308] [Citation(s) in RCA: 81] [Impact Index Per Article: 40.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 02/02/2023] [Indexed: 02/12/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is the third leading cause of tumor-related mortality worldwide. In recent years, the emergency of immune checkpoint inhibitor (ICI) has revolutionized the management of HCC. Especially, the combination of atezolizumab (anti-PD1) and bevacizumab (anti-VEGF) has been approved by the FDA as the first-line treatment for advanced HCC. Despite great breakthrough in systemic therapy, HCC continues to portend a poor prognosis owing to drug resistance and frequent recurrence. The tumor microenvironment (TME) of HCC is a complex and structured mixture characterized by abnormal angiogenesis, chronic inflammation, and dysregulated extracellular matrix (ECM) remodeling, collectively contributing to the immunosuppressive milieu that in turn prompts HCC proliferation, invasion, and metastasis. The tumor microenvironment coexists and interacts with various immune cells to maintain the development of HCC. It is widely accepted that a dysfunctional tumor-immune ecosystem can lead to the failure of immune surveillance. The immunosuppressive TME is an external cause for immune evasion in HCC consisting of 1) immunosuppressive cells; 2) co-inhibitory signals; 3) soluble cytokines and signaling cascades; 4) metabolically hostile tumor microenvironment; 5) the gut microbiota that affects the immune microenvironment. Importantly, the effectiveness of immunotherapy largely depends on the tumor immune microenvironment (TIME). Also, the gut microbiota and metabolism profoundly affect the immune microenvironment. Understanding how TME affects HCC development and progression will contribute to better preventing HCC-specific immune evasion and overcoming resistance to already developed therapies. In this review, we mainly introduce immune evasion of HCC underlying the role of immune microenvironment, describe the dynamic interaction of immune microenvironment with dysfunctional metabolism and the gut microbiome, and propose therapeutic strategies to manipulate the TME in favor of more effective immunotherapy.
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Affiliation(s)
| | | | | | - Yanru Qin
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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13
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Deducing the Interplay Between Gut Flora and Respiratory Diseases: A New Therapeutic Strategy? Indian J Microbiol 2022; 63:1-17. [PMID: 36575670 PMCID: PMC9778463 DOI: 10.1007/s12088-022-01051-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 12/02/2022] [Indexed: 12/24/2022] Open
Abstract
The gastrointestinal system, also referred to as the gut, is a universe that colonizes trillions of microbes. In addition to its digestive functions, the gut represents a biosystem that determines all the health vectors. It is now recognized as one of the body's defense systems, and good gut health regulates the body's immune responses. Disturbance of this barrier can trigger many diseases, including respiratory tract infections, as there is a close correlation between the gut microbiome and the chances of triggering illness. This review investigates the various factors affecting the gut microbiome, the diseases that can result from the dysregulation of the same, and their molecular mechanisms. The most basic solution to tackle this problem is to maintain the gut microbiome at the desired level. Timely diagnosis and interventions are needed for the proper management of the ensuing conditions. It is important to address the effects of factors on the gut microbiome and thereby regulate this level. The study also found that dysregulation in the system can lead to various diseases such as asthma, COPD, lung cancer following their respective pathways. In short, this paper reinforces the importance of the gut microbiome, the need to maintain its average level, and the need for proper interventions to treat the consequences. The manuscript posit that medications, diet as well and good physiological conditions of the human body can alter the microbiome and can ward off respiratory infections.
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He Y, Huang J, Li Q, Xia W, Zhang C, Liu Z, Xiao J, Yi Z, Deng H, Xiao Z, Hu J, Li H, Zu X, Quan C, Chen J. Gut Microbiota and Tumor Immune Escape: A New Perspective for Improving Tumor Immunotherapy. Cancers (Basel) 2022; 14:5317. [PMID: 36358736 PMCID: PMC9656981 DOI: 10.3390/cancers14215317] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 10/17/2022] [Accepted: 10/25/2022] [Indexed: 10/15/2023] Open
Abstract
The gut microbiota is a large symbiotic community of anaerobic and facultative aerobic bacteria inhabiting the human intestinal tract, and its activities significantly affect human health. Increasing evidence has suggested that the gut microbiome plays an important role in tumor-related immune regulation. In the tumor microenvironment (TME), the gut microbiome and its metabolites affect the differentiation and function of immune cells regulating the immune evasion of tumors. The gut microbiome can indirectly influence individual responses to various classical tumor immunotherapies, including immune checkpoint inhibitor therapy and adoptive immunotherapy. Microbial regulation through antibiotics, prebiotics, and fecal microbiota transplantation (FMT) optimize the composition of the gut microbiome, improving the efficacy of immunotherapy and bringing a new perspective and hope for tumor treatment.
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Affiliation(s)
- Yunbo He
- Department of Urology, Xiangya Hospital, Central South University, Changsha 410013, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410013, China
| | - Jinliang Huang
- Department of Urology, Xiangya Hospital, Central South University, Changsha 410013, China
| | - Qiaorong Li
- Department of Ultrasound, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410000, China
| | - Weiping Xia
- Department of Intensive Care Medicine, Xiangya Hospital, Central South University, Changsha 410013, China
| | - Chunyu Zhang
- Department of Urology, Xiangya Hospital, Central South University, Changsha 410013, China
| | - Zhi Liu
- Department of Urology, Xiangya Hospital, Central South University, Changsha 410013, China
| | - Jiatong Xiao
- Department of Urology, Xiangya Hospital, Central South University, Changsha 410013, China
| | - Zhenglin Yi
- Department of Urology, Xiangya Hospital, Central South University, Changsha 410013, China
| | - Hao Deng
- Department of Urology, Xiangya Hospital, Central South University, Changsha 410013, China
| | - Zicheng Xiao
- Department of Urology, Xiangya Hospital, Central South University, Changsha 410013, China
| | - Jiao Hu
- Department of Urology, Xiangya Hospital, Central South University, Changsha 410013, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410013, China
| | - Huihuang Li
- Department of Urology, Xiangya Hospital, Central South University, Changsha 410013, China
| | - Xiongbing Zu
- Department of Urology, Xiangya Hospital, Central South University, Changsha 410013, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410013, China
| | - Chao Quan
- Department of Urology, Xiangya Hospital, Central South University, Changsha 410013, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410013, China
| | - Jinbo Chen
- Department of Urology, Xiangya Hospital, Central South University, Changsha 410013, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410013, China
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15
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Kapsetaki SE, Marquez Alcaraz G, Maley CC, Whisner CM, Aktipis A. Diet, Microbes, and Cancer Across the Tree of Life: a Systematic Review. Curr Nutr Rep 2022; 11:508-525. [PMID: 35704266 PMCID: PMC9197725 DOI: 10.1007/s13668-022-00420-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/21/2022] [Indexed: 11/09/2022]
Abstract
PURPOSE OF REVIEW Cancers are a leading cause of death in humans and for many other species. Diet has often been associated with cancers, and the microbiome is an essential mediator between diet and cancers. Here, we review the work on cancer and the microbiome across species to search for broad patterns of susceptibility associated with different microbial species. RECENT FINDINGS Some microbes, such as Helicobacter bacteria, papillomaviruses, and the carnivore-associated Fusobacteria, consistently induce tumorigenesis in humans and other species. Other microbes, such as the milk-associated Lactobacillus, consistently inhibit tumorigenesis in humans and other species. We systematically reviewed over a thousand published articles and identified links between diet, microbes, and cancers in several species of mammals, birds, and flies. Future work should examine a larger variety of host species to discover new model organisms for human preclinical trials, to better understand the observed variance in cancer prevalence across species, and to discover which microbes and diets are associated with cancers across species. Ultimately, this could help identify microbial and dietary interventions to diagnose, prevent, and treat cancers in humans as well as other animals.
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Affiliation(s)
- Stefania E Kapsetaki
- Arizona Cancer Evolution Center, Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ, USA.
- Biodesign Center for Biocomputing, Security and Society, Arizona State University, Tempe, USA.
| | - Gissel Marquez Alcaraz
- Arizona Cancer Evolution Center, Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ, USA
- Biodesign Center for Biocomputing, Security and Society, Arizona State University, Tempe, USA
| | - Carlo C Maley
- Arizona Cancer Evolution Center, Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ, USA
- Biodesign Center for Biocomputing, Security and Society, Arizona State University, Tempe, USA
| | - Corrie M Whisner
- College of Health Solutions, Arizona State University, Phoenix, AZ, USA
- Biodesign Center for Health Through Microbiomes, Arizona State University, Tempe, AZ, USA
| | - Athena Aktipis
- Arizona Cancer Evolution Center, Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ, USA
- Department of Psychology, Arizona State University, Tempe, AZ, USA
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16
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Liu J, Zhang Y. Intratumor microbiome in cancer progression: current developments, challenges and future trends. Biomark Res 2022; 10:37. [PMID: 35642013 PMCID: PMC9153132 DOI: 10.1186/s40364-022-00381-5] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Accepted: 05/01/2022] [Indexed: 11/29/2022] Open
Abstract
Cancer is a complicated disease attributed to multifactorial changes, which causes difficulties with treatment strategies. Various factors have been regarded as the main contributors, and infectious etiological factors have recently attracted interest. Several microbiomes contribute to carcinogenesis, cancer progression, and modulating cancer treatment by inducing cancerous epithelial cells and chronic inflammation. Most of our knowledge on the role of microbiota in tumor oncogenesis and clinical efficiency is associated with the intestinal microbiome. However, compelling evidence has also confirmed the contribution of the intratumor microbiome in cancer. Indeed, the findings of clinical tumor samples, animal models, and studies in vitro have revealed that many intratumor microbiomes promote tumorigenesis and immune evasion. In addition, the intratumor microbiome participates in regulating the immune response and even affects the outcomes of cancer treatment. This review summarizes the interplay between the intratumor microbiota and cancer, focusing on the contribution and mechanism of intratumor microbiota in cancer initiation, progression, and potential applications to cancer therapy.
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Affiliation(s)
- Jinyan Liu
- Biotherapy Center and Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Yi Zhang
- Biotherapy Center and Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. .,State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou, Henan, China.
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17
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Doocey CM, Finn K, Murphy C, Guinane CM. The impact of the human microbiome in tumorigenesis, cancer progression, and biotherapeutic development. BMC Microbiol 2022; 22:53. [PMID: 35151278 PMCID: PMC8840051 DOI: 10.1186/s12866-022-02465-6] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 02/03/2022] [Indexed: 02/08/2023] Open
Abstract
Abstract
Background
Cancer impacts millions of lives globally each year, with approximately 10 million cancer-related deaths recorded worldwide in 2020. Mounting research has recognised the human microbiome as a key area of interest in the pathophysiology of various human diseases including cancer tumorigenesis, progression and in disease outcome. It is suggested that approximately 20% of human cancers may be linked to microbes. Certain residents of the human microbiome have been identified as potentially playing a role, including: Helicobacter pylori, Fusobacterium nucleatum, Escherichia coli, Bacteroides fragilis and Porphyromonas gingivalis.
Main body
In this review, we explore the current evidence that indicate a link between the human microbiome and cancer. Microbiome compositional changes have been well documented in cancer patients. Furthermore, pathogenic microbes harbouring specific virulence factors have been implicated in driving the carcinogenic activity of various malignancies including colorectal, gastric and pancreatic cancer. The associated genetic mechanisms with possible roles in cancer will be outlined. It will be indicated which microbes have a potential direct link with cancer cell proliferation, tumorigenesis and disease progression. Recent studies have also linked certain microbial cytotoxins and probiotic strains to cancer cell death, suggesting their potential to target the tumour microenvironment given that cancer cells are integral to its composition. Studies pertaining to such cytotoxic activity have suggested the benefit of microbial therapies in oncological treatment regimes. It is also apparent that bacterial pathogenic protein products encoded for by certain loci may have potential as oncogenic therapeutic targets given their possible role in tumorigenesis.
Conclusion
Research investigating the impact of the human microbiome in cancer has recently gathered pace. Vast amounts of evidence indicate the human microbiome as a potential player in tumorigenesis and progression. Promise in the development of cancer biomarkers and in targeted oncological therapies has also been demonstrated, although more studies are needed. Despite extensive in vitro and in vivo research, clinical studies involving large cohorts of human patients are lacking. The current literature suggests that further intensive research is necessary to validate both the role of the human microbiome in cancer, and the use of microbiome modification in cancer therapy.
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18
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Wang C, Shi J, Xu J, Fu Q, Ding Y, Yang J, Liu B, Gao Q, Qin J, Liang C. NLRC3 High Expression Represents a Novel Predictor for Positive Overall Survival Correlated With CCL5 and CXCL9 in HCC Patients. Front Oncol 2022; 12:815326. [PMID: 35145917 PMCID: PMC8821914 DOI: 10.3389/fonc.2022.815326] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Accepted: 01/03/2022] [Indexed: 12/19/2022] Open
Abstract
NLRC3 (NLR family caspase recruitment domain containing 3) has been reported as a factor of inhibiting inflammatory responses. It’s role in HCC (hepatocellular carcinoma) is still unknown. In this study we firstly used the GEO (Gene Expression Omnibus) database and mIHC (multiple immunohistochemical analysis) with TMAs (tumor tissue microarrays) of HCC patients to evaluate NLRC3 levels. The tumor-bearing mouse models were also established with NLRC3 over-expressing and knock-down Hepal-6 cells to assess its effect. The data showed high NLRC3 expression was related with favorable overall survival (P=0.0386) and disease-free survival (P=0.0458). In addition, NLRC3 expression showed a positive correlation between CD8+ T cells infiltration. In vivo, NLRC3-overexpressing Hepal-6 tumors showed increased CD8+ T cell infiltration. NLRC3-knockdown Hepa1-6 tumors displayed decreased CD8+ T cell infiltration. At the same time, we also found the positive correlations between NLRC3 and CCL5 (C-C motif chemokine ligand 5, P<0.0001, R2 = 0.2372) as well as CXCL9 (C-X-C motif chemokine ligand 9, P<0.0001, R2 = 0.2338) expressions. So NLRC3 high expression represents a novel predictor for positive survival outcomes in HCC patients, and NLRC3 is involved in CD8+ T cell infiltration, which is correlated with increased CCL5 and CXCL9 in TME (tumor microenvironment). This study implies that boosting NLRC3 is a promising treatment to enhance survival in HCC patients.
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Affiliation(s)
- Chengpan Wang
- Lab of Tumor Immunology, Department of Human Anatomy, Histology and Embryology, Basic Medical School of Fudan University, Shanghai, China
| | - Jieyi Shi
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Jietian Xu
- Lab of Tumor Immunology, Department of Human Anatomy, Histology and Embryology, Basic Medical School of Fudan University, Shanghai, China
| | - Qiaoyu Fu
- Lab of Tumor Immunology, Department of Human Anatomy, Histology and Embryology, Basic Medical School of Fudan University, Shanghai, China
| | - Youpeng Ding
- Lab of Tumor Immunology, Department of Human Anatomy, Histology and Embryology, Basic Medical School of Fudan University, Shanghai, China
| | - Jessie Yang
- Lab of Tumor Immunology, Department of Human Anatomy, Histology and Embryology, Basic Medical School of Fudan University, Shanghai, China
| | - Binbin Liu
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Qiang Gao
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Jie Qin
- Lab of Tumor Immunology, Department of Human Anatomy, Histology and Embryology, Basic Medical School of Fudan University, Shanghai, China
| | - Chunmin Liang
- Lab of Tumor Immunology, Department of Human Anatomy, Histology and Embryology, Basic Medical School of Fudan University, Shanghai, China
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19
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Marzhoseyni Z, Shojaie L, Tabatabaei SA, Movahedpour A, Safari M, Esmaeili D, Mahjoubin-Tehran M, Jalili A, Morshedi K, Khan H, Okhravi R, Hamblin MR, Mirzaei H. Streptococcal bacterial components in cancer therapy. Cancer Gene Ther 2022; 29:141-155. [PMID: 33753868 DOI: 10.1038/s41417-021-00308-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 01/25/2021] [Accepted: 02/05/2021] [Indexed: 02/01/2023]
Abstract
The incidence rate of cancer is steadily increasing all around the world, and there is an urgent need to develop novel and more effective treatment strategies. Recently, bacterial therapy has been investigated as a new approach to target cancer, and is becoming a serious option. Streptococcus strains are among the most common and well-studied virulent bacteria that cause a variety of human infections. Everyone has experienced a sore throat during their lifetime, or has been asymptomatically colonized by streptococci. The ability of Streptococcus bacteria to fight cancer was discovered more than 100 years ago, and over the years has undergone clinical trials, but the mechanism is not yet completely understood. Recently, several animal models and human clinical trials have been reported. Streptococcal strains can have an intrinsic anti-tumor activity, or can activate the host immune system to fight the tumor. Bacteria can selectively accumulate and proliferate in the hypoxic regions of solid tumors. Moreover, the bacteria can be genetically engineered to secrete toxins or enzymes that can specifically attack the tumors.
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Affiliation(s)
- Zeynab Marzhoseyni
- Department of Microbiology and Immunology, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Layla Shojaie
- Research Center for Liver Diseases, Keck School of Medicine, Department of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Seyed Alireza Tabatabaei
- Department of Internal Medicine, School of Medicine, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Ahmad Movahedpour
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahmood Safari
- Department of Microbiology and Immunology, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Davoud Esmaeili
- Department of Microbiology and Applied Microbiology Research Center, Systems Biology and Poisonings Institute and Department of Microbiology, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Maryam Mahjoubin-Tehran
- Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amin Jalili
- Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Korosh Morshedi
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University Mardan, Mardan, 23200, Pakistan
| | - Ranaa Okhravi
- Department of Medical Sciences, Shahrood Branch, Islamic Azad University, Shahrood, Iran.
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, 2028, South Africa.
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
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20
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Zhou ZW, Long HZ, Cheng Y, Luo HY, Wen DD, Gao LC. From Microbiome to Inflammation: The Key Drivers of Cervical Cancer. Front Microbiol 2021; 12:767931. [PMID: 34867901 PMCID: PMC8634716 DOI: 10.3389/fmicb.2021.767931] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 10/21/2021] [Indexed: 12/12/2022] Open
Abstract
Cervical cancer is the third leading cause of cancer-related death worldwide. Microbes and hosts form a mutually beneficial symbiosis relationship, and various parts of the host body are microbial habitats. Microbes can trigger inflammation in certain parts of the host body, contributing to cervical cancer development. This article reviews the relationship between cervicovaginal microbes, inflammation and cervical cancer, and discusses the effect of some key cervical microbes on cervical cancer. Finally, probiotic therapy and immunotherapy are summarized.
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Affiliation(s)
- Zi-Wei Zhou
- Department of Pharmacy, Cancer Institute, Phase I Clinical Trial Centre, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Hengyang, China
- Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang, China
| | - Hui-Zhi Long
- Department of Pharmacy, Cancer Institute, Phase I Clinical Trial Centre, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Hengyang, China
- Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang, China
| | - Yan Cheng
- Department of Pharmacy, Cancer Institute, Phase I Clinical Trial Centre, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Hengyang, China
- Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang, China
| | - Hong-Yu Luo
- Department of Pharmacy, Cancer Institute, Phase I Clinical Trial Centre, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Hengyang, China
- Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang, China
| | - Dan-Dan Wen
- Department of Pharmacy, Cancer Institute, Phase I Clinical Trial Centre, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Li-Chen Gao
- Department of Pharmacy, Cancer Institute, Phase I Clinical Trial Centre, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Hengyang, China
- Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang, China
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21
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Tsai MM, Lin HC, Yu MC, Lin WJ, Chu MY, Tsai CC, Cheng CY. Anticancer Effects of Helminthostachys zeylanica Ethyl acetate Extracts on Human Gastric Cancer Cells through Downregulation of the TNF-α-activated COX-2-cPLA2-PGE 2 Pathway. J Cancer 2021; 12:7052-7068. [PMID: 34729107 PMCID: PMC8558661 DOI: 10.7150/jca.64638] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 09/24/2021] [Indexed: 12/13/2022] Open
Abstract
Background: Gastric cancer (GC) is the second most prevalent cancer worldwide and the eighth most common cause of tumor-related death in Taiwan. Helminthostachys zeylanica, a flavonoid compound, has anti-inflammatory, immunomodulatory, and anticancer effects. We examined whether an extract of H. zeylanica (E1 and E2) has potential as a treatment for GC. Methods: We investigated the effects (pro-apoptosis, pro-autophagy, and antiproliferation ability) of H. zeylanica-E2 on cell viability in healthy gastric epithelial (GES-1) and GC cells (AGS and BGC823). H. zeylanica-E2 was toxic to GC cells but had little or no toxicity to normal cells. Results: In this study, H. zeylanica-E2 induced apoptosis through caspase 3/7, Bcl-2, Bax, cyclooxygenase-2 (COX-2), and cleaved poly (ADP-ribose) polymerase pathways in GC cells. In addition, it increased autophagy by stimulating autophagy-related protein (ATG)5, ATG7, LC3-I/LC3-II, and inhibiting COX-2 activity in GC cells. We also found that H. zeylanica-E2 exhibited antiproliferation ability through cell cycle arrest in G0/G1 and G2/M and suppressed the migration of GC cells. The anticancer effects of H. zeylanica-E2 in GC cells might be mediated partly through inhibition of tumor necrosis factor-α (TNF-α)-activated proinflammatory cytosolic phospholipase A2 (cPLA2)-COX-2-prostaglandin E2 (PGE2) pathway. Conclusions: Our results suggest that H. zeylanica-E2 has potential as a novel adjunctive agent for the treatment of GC.
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Affiliation(s)
- Ming-Ming Tsai
- Department of Nursing, Division of Basic Medical Sciences, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan and Department of General Surgery, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan
| | - Horng-Chyuan Lin
- Department of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ming-Chin Yu
- Department of Surgery, New Taipei Municipal TuCheng Hospital, Chang Gung Memorial Hospital at Linkou, and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Wan-Jung Lin
- Graduate Institute of Health Industry Technology, Research Center for Chinese Herbal Medicine and Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan
| | - Mei-Yi Chu
- Graduate Institute of Health Industry Technology, Research Center for Chinese Herbal Medicine and Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan
| | - Ching-Ching Tsai
- Department of Nursing, College of Nursing, Chang Gung University of Science and Technology, and Department of Cardiology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Ching-Yi Cheng
- Graduate Institute of Health Industry Technology, Research Center for Chinese Herbal Medicine and Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.,Department of Pulmonary Infection and Immunology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
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22
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Mamgain G, Patra P, Naithani M, Nath UK. The Role of Microbiota in the Development of Cancer Tumour Cells and Lymphoma of B and T Cells. Cureus 2021; 13:e19047. [PMID: 34853760 PMCID: PMC8608681 DOI: 10.7759/cureus.19047] [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] [Accepted: 10/25/2021] [Indexed: 11/26/2022] Open
Abstract
Human body harbours enormous numbers of microbial organisms, including bacteria, viruses, and fungi which have a momentous role in well-being and illness in humans. Immune system shelters us from pathogenic bacteria, microorganisms found in human tissues have many benefits related to the functional movement of the host by regulating important procedures such as immunity, signalling, and breakdown. Lymphocytes assume a significant part in the reaction to bacterial colonization, primarily by prompting a safe reaction to obstruction or initiation. Most immunologically occupant cells have a place with the mucosal invulnerable framework and are continually motioned by dendritic cells or other Antigen introducing cells that gather intestinal samples. Thus, Microbiome is a key contributor to developing lymphoma and specific alterations to microbiome composition could attenuate the risk. There is an indication that microbial morphology can affect and control humanoids. The difference in the composition of these microorganisms is associated with tumour development. With the increased knowledge of the connection among the human microbiome and carcinogenesis, the use of these findings to prevent, predict or diagnose of lymphomas has attracted a great attention. In this article, we explored current knowledge of various microbial ecosystems, their connection with carcinogens and the potential for useful microorganisms to control and prevent B and T cell lymphoma.
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Affiliation(s)
- Garima Mamgain
- Medical Oncology and Haematology, All India Institute of Medical Sciences, Rishikesh, IND
| | - Priyanka Patra
- Biochemistry, All India Institute of Medical Sciences, Rishikesh, IND
| | - Manisha Naithani
- Biochemistry & Advanced Center of Continuous Professional Development, All India Institute of Medical Sciences, Rishikesh, IND
| | - Uttam Kumar Nath
- Medical Oncology and Haematology, All India Institute of Medical Sciences, Rishikesh, IND
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23
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Wang D, Cheng J, Zhang J, Zhou F, He X, Shi Y, Tao Y. The Role of Respiratory Microbiota in Lung Cancer. Int J Biol Sci 2021; 17:3646-3658. [PMID: 34512172 PMCID: PMC8416743 DOI: 10.7150/ijbs.51376] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Accepted: 02/09/2021] [Indexed: 12/20/2022] Open
Abstract
Recently, the impact of microorganisms on tumor growth and metastasis has attracted great attention. The pathogenesis and progression of lung cancer are related to an increase in respiratory bacterial load as well as changes in the bacterial community because the microbiota affects tumors in many ways, including canceration, metastasis, angiogenesis, and treatment. The microbiota may increase tumor susceptibility by altering metabolism and immune responses, promoting inflammation, and increasing toxic effects. The microbiota can regulate tumor metastasis by altering multiple cell signaling pathways and participate in tumor angiogenesis through vascular endothelial growth factors (VEGF), endothelial cells (ECs), inflammatory factors and inflammatory cells. Tumor angiogenesis not only maintains tumor growth at the primary site but also promotes tumor metastasis and invasion. Therefore, angiogenesis is an important mediator of the interaction between microorganisms and tumors. The microbiota also plays a part in antitumor therapy. Alteration of the microbiota caused by antibiotics can regulate tumor growth and metastasis. Moreover, the microbiota also influences the efficacy and toxicity of tumor immunotherapy and chemotherapy. Finally, the effects of air pollution, a risk factor for lung cancer, on microorganisms and the possible role of respiratory microorganisms in the effects of air pollution on lung cancer are discussed.
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Affiliation(s)
- Dan Wang
- Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Department of Pathology, Xiangya Hospital, Central South University, Hunan, 410078 China.,NHC Key Laboratory of Carcinogenesis (Central South University), Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, Hunan, 410078 China
| | - Jingyi Cheng
- Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Department of Pathology, Xiangya Hospital, Central South University, Hunan, 410078 China.,NHC Key Laboratory of Carcinogenesis (Central South University), Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, Hunan, 410078 China
| | - Jia Zhang
- Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Department of Pathology, Xiangya Hospital, Central South University, Hunan, 410078 China.,NHC Key Laboratory of Carcinogenesis (Central South University), Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, Hunan, 410078 China
| | - Fangyu Zhou
- Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Department of Pathology, Xiangya Hospital, Central South University, Hunan, 410078 China.,NHC Key Laboratory of Carcinogenesis (Central South University), Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, Hunan, 410078 China
| | - Xiao He
- Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Department of Pathology, Xiangya Hospital, Central South University, Hunan, 410078 China.,NHC Key Laboratory of Carcinogenesis (Central South University), Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, Hunan, 410078 China
| | - Ying Shi
- Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Department of Pathology, Xiangya Hospital, Central South University, Hunan, 410078 China.,NHC Key Laboratory of Carcinogenesis (Central South University), Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, Hunan, 410078 China
| | - Yongguang Tao
- Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Department of Pathology, Xiangya Hospital, Central South University, Hunan, 410078 China.,NHC Key Laboratory of Carcinogenesis (Central South University), Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, Hunan, 410078 China.,Hunan Key Laboratory of Tumor Models and Individualized Medicine, Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, Changsha, 410011 China
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24
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Sun L, Li L, Wang Y, Li M, Xu S, Zhang C. A collagen-based bi-layered composite dressing for accelerated wound healing. J Tissue Viability 2021; 31:180-189. [PMID: 34538555 DOI: 10.1016/j.jtv.2021.09.003] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Revised: 08/10/2021] [Accepted: 09/07/2021] [Indexed: 10/20/2022]
Abstract
AIM OF THE STUDY The aim of the study was to fabricate collagen-based composite dressings, evaluate the efficiency for wound healing and reveal the mechanism of promoting wound healing. MATERIALS AND METHODS An innovative bi-layered composite wound dressing was developed using two marine biomacromolecules (collagen and chitosan). Full-thickness skin defect model was performed to evaluate the wound healing activity in vivo. The levels of inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin (IL-1, IL-6, IL-8) and growth factors like transforming growth factor beta (TGF-β), vascular epidermal growth factor (VEGF) and basic fibroblast growth factor (bFGF) were quantified by ELISA assays. The total amount of collagen was quantified by hydroxyproline content. The proliferation and viability of fibroblast cells cultured on collagen sponges were determined by CCK-8 assay. RESULTS The results of wound closure and histopathological analysis indicated that non-crosslinked collagen-based bi-layered composite dressing stimulated wound healing, accelerated re-epithelialization and accomplished wound healing within a time span of 28 days. The results of levels of inflammatory cytokines and growth factors showed that collagen-based composite dressings could reduce the inflammatory response and upregulate growth factors levels to accelerate the wound healing. The results of hydroxyproline content and CCK-8 assay indicated that collagen-based composite dressings could also promote collagen synthesis and fibroblasts viability and proliferation. CONCLUSION The non-crosslinked collagen-based bi-layered composite dressing could be applied for an efficient and ideal wound dressing. Therefore, the findings provided the essential theoretical basis for the potential of collagen-based composite dressing applied in wound healing fields.
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Affiliation(s)
- Leilei Sun
- College of Life Science, Yantai University, No.30, Qing Quan Road, Yantai, Shandong Province, 264005, PR China
| | - Laihao Li
- Key Laboratory of Aquatic Product Processing, Ministry of Agriculture and Rural Affairs, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, Guangdong Province, 510300, PR China.
| | - Yueqi Wang
- Key Laboratory of Aquatic Product Processing, Ministry of Agriculture and Rural Affairs, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, Guangdong Province, 510300, PR China.
| | - Mingbo Li
- College of Life Science, Yantai University, No.30, Qing Quan Road, Yantai, Shandong Province, 264005, PR China
| | - Shumin Xu
- College of Life Science, Yantai University, No.30, Qing Quan Road, Yantai, Shandong Province, 264005, PR China
| | - Chengpeng Zhang
- College of Life Science, Yantai University, No.30, Qing Quan Road, Yantai, Shandong Province, 264005, PR China
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25
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Links between Infections, Lung Cancer, and the Immune System. Int J Mol Sci 2021; 22:ijms22179394. [PMID: 34502312 PMCID: PMC8431665 DOI: 10.3390/ijms22179394] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 08/25/2021] [Accepted: 08/25/2021] [Indexed: 12/25/2022] Open
Abstract
Lung cancer is the leading disease of cancer-related deaths worldwide. Since the beginning of the 20th century, various infectious agents associated with lung cancer have been identified. The mechanisms that include systemic inflammatory pathways as effect of microbial persistence in the lung can secondarily promote the development of lung carcinogenesis. Chronic inflammation associated with lung-cancer infections is known to precede tumor development, and it has a strong effect on the response(s) to therapy. In fact, both viral and bacterial infections can activate inflammatory cells and inflammatory signaling pathways. In this review, an overview of critical findings of recent studies investigating associations between each of viral and bacterial pathogens and lung carcinoma is provided, with particular emphasis on how infectious organisms can interfere with oncogenic processes and all the way through immunity. Moreover, a discussion of the direct crosstalk between lung tumor development and inflammatory processes is also presented.
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26
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The Role of DNA Damage Response in Dysbiosis-Induced Colorectal Cancer. Cells 2021; 10:cells10081934. [PMID: 34440703 PMCID: PMC8391204 DOI: 10.3390/cells10081934] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 07/23/2021] [Accepted: 07/23/2021] [Indexed: 12/16/2022] Open
Abstract
The high incidence of colorectal cancer (CRC) in developed countries indicates a predominant role of the environment as a causative factor. Natural gut microbiota provides multiple benefits to humans. Dysbiosis is characterized by an unbalanced microbiota and causes intestinal damage and inflammation. The latter is a common denominator in many cancers including CRC. Indeed, in an inflammation scenario, cellular growth is promoted and immune cells release Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS), which cause DNA damage. Apart from that, many metabolites from the diet are converted into DNA damaging agents by microbiota and some bacteria deliver DNA damaging toxins in dysbiosis conditions as well. The interactions between diet, microbiota, inflammation, and CRC are not the result of a straightforward relationship, but rather a network of multifactorial interactions that deserve deep consideration, as their consequences are not yet fully elucidated. In this paper, we will review the influence of dysbiosis in the induction of DNA damage and CRC.
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27
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Yan X, Hu S, Yang Y, Xu D, Liu W, Li G, Cai W, Bu Z. Proteomics Investigation of the Time Course Responses of RAW264.7 Macrophages to Infections With the Wild-Type and Twin-Arginine Translocation Mutant Strains of Brucella melitensis. Front Cell Infect Microbiol 2021; 11:679571. [PMID: 34195100 PMCID: PMC8238042 DOI: 10.3389/fcimb.2021.679571] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 05/18/2021] [Indexed: 11/13/2022] Open
Abstract
Brucella, a notorious intracellular pathogen, causes chronic infections in many mammals, including humans. The twin-arginine translocation (Tat) pathway transports folded proteins across the cytoplasmic membrane; protein substrates translocated by Brucella include ABC transporters, oxidoreductases, and cell envelope biosynthesis proteins. Previously, we showed that a Tat mutant of Brucella melitensis M28 exhibits reduced survival within murine macrophages. In this study, we compared the host responses elicited by wild-type M28 and its Tat-mutant strains ex vivo. We utilized label-free quantitative proteomics to assess proteomic changes in RAW264.7 macrophages after infection with M28 and its Tat mutants. A total of 6085 macrophage proteins were identified with high confidence, and 79, 50, and 99 proteins were differentially produced upon infection with the Tat mutant at 4, 24, and 48 hpi, respectively, relative to the wild-type infection. Gene ontology and KEGG enrichment analysis indicated that immune response-related proteins were enriched among the upregulated proteins. Compared to the wild-type M28 infection, the most upregulated proteins upon Tat-mutant infection included the cytosolic nucleic acid signaling pathway-related proteins IFIH1, DHX58, IFI202, IFI204, and ISG15 and the NF-κB signaling pathway-related proteins PTGS2, CD40, and TRAF1, suggesting that the host increases the production of these proteins in response to Tat mutant infection. Upregulation of some proteins was further verified by a parallel reaction monitoring (PRM) assay. ELISA and qRT-PCR assays indicated that Tat mutant infection significantly induced proinflammatory cytokine (TNF-α and IL-6) and nitric oxide (NO) production. Finally, we showed that the Tat mutant displays higher sensitivity to nitrosative stress than the wild type and that treatment with the NO synthase inhibitor L-NMMA significantly increases the intracellular survival of the Tat mutant, indicating that NO production contributes to restricting Tat mutant survival within macrophages. Collectively, this work improves our understanding of host immune responses to Tat mutants and provides insights into the mechanisms underlying the attenuated virulence of Tat mutants.
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Affiliation(s)
- Xin Yan
- Key Laboratory of Veterinary Public Health of Ministry of Agriculture, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
| | - Sen Hu
- Key Laboratory of Veterinary Public Health of Ministry of Agriculture, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
| | - Yan Yang
- Key Laboratory of Veterinary Public Health of Ministry of Agriculture, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
| | - Da Xu
- Key Laboratory of Veterinary Public Health of Ministry of Agriculture, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
| | - Wenxing Liu
- Key Laboratory of Veterinary Public Health of Ministry of Agriculture, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
| | - Ganwu Li
- Key Laboratory of Veterinary Public Health of Ministry of Agriculture, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.,Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
| | - Wentong Cai
- Key Laboratory of Veterinary Public Health of Ministry of Agriculture, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.,Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou, China
| | - Zhigao Bu
- Key Laboratory of Veterinary Public Health of Ministry of Agriculture, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.,Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou, China
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28
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Abstract
The immune tumor microenvironment (TME) of colorectal cancer (CRC) is a crucial contributor to disease biology, making it an important target for therapeutic intervention. The diversity of immune cell populations within various subsets of CRC has led to the discovery that immune characterization of the TME has both prognostic and predictive value for patients. The convergence of improved molecular and cellular characterization of CRC along with the widespread use of immunotherapy in solid tumors has led to a revolution in the approach to clinical care. Monoclonal antibodies (mAbs) which target key immune checkpoints, such as programmed death-1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4), have demonstrated remarkable clinical activity in microsatellite instability-high (MSI-H) CRCs and are now used in routine practice. The observation that MSI-H cancers are highly infiltrated with immune cells and carry a high neoantigen load led to the successful targeting of these cancers with immunotherapy. More recently, the Food and Drug Administration (FDA) approved a PD-1 inhibitor for microsatellite stable (MSS) cancers with high tumor mutation burden. However, the anti-tumor activity of immunotherapy is rare in the majority of CRC. While immune cell characterization does provide prognostic value in these patients, these observations have not yet led to therapeutic interventions. By delineating factors that predict efficacy, resistance, and therapeutic targets, ongoing research will inform the development of effective combination strategies for the vast majority of MSS CRC and immunotherapy-resistant MSI-H cancers.
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Affiliation(s)
- Parul Agarwal
- Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, United States
| | - Dung T Le
- Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, United States.
| | - Patrick M Boland
- Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, United States
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29
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Gade IS, Richard TS, Chadeneau C, Seite P, Vannier B, Atchade ADT, Seke Etet PF, Talla E, Nwabo Kamdje AH, Muller JM. Anticancer Activity of Combretum fragrans F. Hoffm on Glioblastoma and Prostate Cancer Cell Lines. Asian Pac J Cancer Prev 2021; 22:1087-1093. [PMID: 33906300 PMCID: PMC8325120 DOI: 10.31557/apjcp.2021.22.4.1087] [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: 11/12/2020] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Cancer incidence has been growing in an alarming rate worldwide and new therapeutics are needed, particularly for intractable and chemoresistant cases. We evaluated the cytotoxic effects of Combretum fragrans F. Hoffm (Combretaceae) on glioblastoma (U87MG and C6) and prostate (PC-3) cancer cell lines. METHODS The cytotoxic effect of the methanolic extract of the stem bark of Combretum fragrans was assessed using XTT (2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide) test. Expressions of Akt and ERK1/2 were determined using Western blot technique, while Caspase-3/7 kits were used to evaluate caspase-3/7 activity. RESULTS C. fragrans extract inhibited the proliferation of U87 (IC50 = 20.13 µg/mL), C6 (IC50 = 12.17 µg/mL), and PC-3 (IC50 = 11.50 µg/mL) cells. Treatment with the extract resulted in lower levels (p < 0.001) of phospho-ERK1/2 and phospho-Akt in U87 cells, and instead, higher levels of phospho-ERK1/2 (p < 0.001) in C6 and PC-3 cells. An increase in caspase-3/7 activity was observed, mainly after 24 hours of treatment, indicating the activation of apoptotic processes. CONCLUSION Altogether, these results suggest that C. fragrans have potent anticancer properties. This plant should be further investigated for developing new anticancer drugs.
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Affiliation(s)
- Isaac Silvère Gade
- Department of Organic Chemistry, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon. ,UFR Sciences Fondamentales et Appliquées, Team “Récepteurs, Régulations, Cellules Tumorales” (2RCT)-EA 3842 CAPTuR, Pôle Biologie Santé-Bât. B36/B37, University of Poitiers, 1 rue Georges Bonnet-TSA, France. ,Department of Chemistry, Faculty of Science, University of Ngaoundere, Ngaoundéré, Cameroon.
| | - Tagne Simo Richard
- Department of Biomedical Sciences, Faculty of Science, University of Ngaoundere, Ngaoundéré, Cameroon. ,For Correspondence:
| | - Corinne Chadeneau
- Department of Chemistry, Faculty of Science, University of Ngaoundere, Ngaoundéré, Cameroon.
| | - Paule Seite
- UFR Sciences Fondamentales et Appliquées, Team “Récepteurs, Régulations, Cellules Tumorales” (2RCT)-EA 3842 CAPTuR, Pôle Biologie Santé-Bât. B36/B37, University of Poitiers, 1 rue Georges Bonnet-TSA, France.
| | - Brigitte Vannier
- UFR Sciences Fondamentales et Appliquées, Team “Récepteurs, Régulations, Cellules Tumorales” (2RCT)-EA 3842 CAPTuR, Pôle Biologie Santé-Bât. B36/B37, University of Poitiers, 1 rue Georges Bonnet-TSA, France.
| | - Alex De Theodore Atchade
- Department of Organic Chemistry, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon.
| | - Paul F. Seke Etet
- Department of Physiological Sciences and Biochemistry, FMBS, University of Ngaoundere, Garoua, Cameroon.
| | - Emmanuel Talla
- Department of Chemistry, Faculty of Science, University of Ngaoundere, Ngaoundéré, Cameroon.
| | - Armel H. Nwabo Kamdje
- Department of Biomedical Sciences, Faculty of Science, University of Ngaoundere, Ngaoundéré, Cameroon.
| | - Jean-Marc Muller
- UFR Sciences Fondamentales et Appliquées, Team “Récepteurs, Régulations, Cellules Tumorales” (2RCT)-EA 3842 CAPTuR, Pôle Biologie Santé-Bât. B36/B37, University of Poitiers, 1 rue Georges Bonnet-TSA, France.
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30
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Jiang L, Li B, Zhang Y, Ma S, Liu C, Liang F, Wei Z, Huang T, Wang R. Influence of Pelvic Intensity-Modulated Radiation Therapy With Concurrent Cisplatin-Based Chemotherapy of Cervical Cancer on the Vaginal Microbiome. Front Oncol 2021; 11:615439. [PMID: 33708628 PMCID: PMC7940522 DOI: 10.3389/fonc.2021.615439] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Accepted: 01/06/2021] [Indexed: 01/18/2023] Open
Abstract
Pelvic intensity-modulated radiation therapy (IMRT) combined with concurrent chemotherapy is an effective treatment for cervical cancer; however, radiation resistance impairs its clinical benefit. The vaginal microbiome plays an important but poorly understood role in cancer radiochemotherapy. In this study, we investigated the effects of treatment on the overall composition and alteration of the vaginal microbiome in patients receiving pelvic IMRT with concurrent cisplatin-based chemotherapy. We collected samples from twenty patients with cervical cancer and six healthy controls and performed 16S rRNA sequencing. Vaginal microbial composition analysis revealed significant differences between the two groups, but no significant differences between radiation treatment time points. However, the relative abundances of Gammaproteobacteria, Gemmatimonadetes, Gemmatimonadales, Pseudomonadales, Gemmatimonadaceae, Rikenellaceae, Acinetobacter, Desulfovibrio, Prevotella 9, Rikenellaceae RC9 gut group, Turicibacter, and the metagenome increased with time. The results encourage further study into the effects of the vaginal microbiome on cervical cancer treatment strategies, especially radiochemotherapy. Better understanding of these effects could inform new therapeutic approaches to enhance the efficacy of radiochemotherapy.
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Affiliation(s)
| | | | | | | | | | | | | | - Tingting Huang
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Rensheng Wang
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
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31
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Zhang W, Zhang K, Zhang P, Zheng J, Min C, Li X. Research Progress of Pancreas-Related Microorganisms and Pancreatic Cancer. Front Oncol 2021; 10:604531. [PMID: 33520714 PMCID: PMC7841623 DOI: 10.3389/fonc.2020.604531] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 11/30/2020] [Indexed: 12/16/2022] Open
Abstract
Pancreatic cancer is one of the most common digestive system cancers. Early diagnosis is difficult owing to the lack of specific symptoms and reliable biomarkers. The cause of pancreatic cancer remains ambiguous. Smoking, drinking, new-onset diabetes, and chronic pancreatitis have been proven to be associated with the occurrence of pancreatic cancer. In recent years, a large number of studies have clarified that a variety of microorganisms colonized in pancreatic cancer tissues are also closely related to the occurrence and development of pancreatic cancer, and the specific mechanisms include inflammatory induction, immune regulation, metabolism, and microenvironment changes caused by microorganism. The mechanism of action of the pancreatic colonized microbiome in the tumor microenvironment, as well as immunotherapy approaches require further study in order to find more evidence to explain the complex relationship between the pancreatic colonized microbiome and PDAC. Relevant studies targeting the microbiome may provide insight into the mechanisms of PDAC development and progression, improving treatment effectiveness and overall patient prognosis. In this article, we focus on the research relating to the microorganisms colonized in pancreatic cancer tissues, including viruses, bacteria, and fungi. We also highlight the microbial diversity in the occurrence, invasion, metastasis, treatment, and prognosis of pancreatic cancer in order to elucidate its significance in the early diagnosis and new therapeutic treatment of pancreatic cancer, which urgently need to be improved in clinical practice. The elimination or increase in diversity of the pancreatic microbiome is beneficial for prolonging the survival of PDAC patients, improving the response to chemotherapy drugs, and reducing tumor burden. The colonization of microorganisms in the pancreas may become a new hotspot in the diagnosis and treatment of pancreatic cancer.
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Affiliation(s)
| | | | | | | | | | - Xiaoyu Li
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
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32
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Irfan M, Delgado RZR, Frias-Lopez J. The Oral Microbiome and Cancer. Front Immunol 2020; 11:591088. [PMID: 33193429 PMCID: PMC7645040 DOI: 10.3389/fimmu.2020.591088] [Citation(s) in RCA: 160] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Accepted: 09/29/2020] [Indexed: 12/24/2022] Open
Abstract
There is mounting evidence that members of the human microbiome are highly associated with a wide variety of cancer types. Among oral cancers, oral squamous cell carcinoma (OSCC) is the most prevalent and most commonly studied, and it is the most common malignancy of the head and neck worldwide. However, there is a void regarding the role that the oral microbiome may play in OSCC. Previous studies have not consistently found a characteristic oral microbiome composition associated with OSCC. Although a direct causality has not been proven, individual members of the oral microbiome are capable of promoting various tumorigenic functions related to cancer development. Two prominent oral pathogens, Porphyromonas gingivalis, and Fusobacterium nucleatum can promote tumor progression in mice. P. gingivalis infection has been associated with oro-digestive cancer, increased oral cancer invasion, and proliferation of oral cancer stem cells. The microbiome can influence the evolution of the disease by directly interacting with the human body and significantly altering the response and toxicity to various forms of cancer therapy. Recent studies have shown an association of certain phylogenetic groups with the immunotherapy treatment outcomes of certain tumors. On the other side of the coin, recently it has been a resurgence in interest on the potential use of bacteria to cure cancer. These kinds of treatments were used in the late nineteenth and early twentieth centuries as the first line of defense against cancer in some hospitals but later displaced by other types of treatments such as radiotherapy. Currently, organisms such as Salmonella typhimurium and Clostridium spp. have been used for targeted strategies as potential vectors to treat cancer. In this review, we briefly summarize our current knowledge of the role of the oral microbiome, focusing on its bacterial fraction, in cancer in general and in OSCC more precisely, and a brief description of the potential use of bacteria to target tumors.
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Affiliation(s)
- Muhammad Irfan
- Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, United States
| | | | - Jorge Frias-Lopez
- Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, United States
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33
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Pietrangeli P, Capuozzo E, Mateescu MA, Marcocci L. Copper‑containing amine oxidase purified from Lathyrus sativus as a modulator of human neutrophil functions. Int J Mol Med 2020; 45:1583-1590. [PMID: 32323757 DOI: 10.3892/ijmm.2020.4535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Accepted: 01/27/2020] [Indexed: 11/06/2022] Open
Abstract
Over the last few decades, copper‑containing amine oxidase (Cu‑AO) from vegetal sources, and belonging to the class of diamine oxidase, has been documented to exhibit beneficial effects in both in vivo and ex vivo animal models of inflammatory or allergic conditions, including asthma‑like reaction and myocardial or intestinal ischemia‑reperfusion injuries. The aim of the present study was to assess the potential of vegetal Cu‑AO as an anti‑inflammatory and an antiallergic agent and to clarify its antioxidant properties. In cell‑free systems, the reactive oxygen species and reactive nitrogen species scavenging properties of Cu‑AO that is purified from Lathyrus sativus were investigated. Its effect on the formyl‑methionyl‑leucyl‑phenylalanine peptide (fMLP)‑activated cellular functions of human neutrophils were subsequently analyzed. The obtained results demonstrated that Cu‑AO is not a scavenger of superoxide or nitric oxide, and does not decompose hydrogen peroxide. However, it inhibits the fMLP‑dependent superoxide generation, elastase release and cell migration, and interferes with the process of calcium flux, supporting the idea that plant Cu‑AO can interact with human neutrophils to modulate their inflammatory function. Therefore, the importance of these properties on the possible use of vegetal Cu‑AO to control inflammatory conditions, particularly intestinal inflammation, is discussed in the current study.
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Affiliation(s)
- Paola Pietrangeli
- Department of Biochemical Sciences 'A. Rossi Fanelli', Sapienza University of Rome, I‑00185 Rome, Italy
| | - Elisabetta Capuozzo
- Department of Biochemical Sciences 'A. Rossi Fanelli', Sapienza University of Rome, I‑00185 Rome, Italy
| | - Mircea Alexandru Mateescu
- Department of Chemistry, Research Chair on Enteric Dysfunctions 'Allerdys' and CERMO‑FC Centre, University of Quebec at Montreal (UQAM), Montreal, (QC) H3C 3P8, Canada
| | - Lucia Marcocci
- Department of Biochemical Sciences 'A. Rossi Fanelli', Sapienza University of Rome, I‑00185 Rome, Italy
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34
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Dash S, Aydin Y, Widmer KE, Nayak L. Hepatocellular Carcinoma Mechanisms Associated with Chronic HCV Infection and the Impact of Direct-Acting Antiviral Treatment. J Hepatocell Carcinoma 2020; 7:45-76. [PMID: 32346535 PMCID: PMC7167284 DOI: 10.2147/jhc.s221187] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Accepted: 03/06/2020] [Indexed: 12/12/2022] Open
Abstract
Hepatitis C virus (HCV) infection is the major risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). The mechanisms of HCC initiation, growth, and metastasis appear to be highly complex due to the decade-long interactions between the virus, immune system, and overlapping bystander effects of host metabolic liver disease. The lack of a readily accessible animal model system for HCV is a significant obstacle to understand the mechanisms of viral carcinogenesis. Traditionally, the primary prevention strategy of HCC has been to eliminate infection by antiviral therapy. The success of virus elimination by antiviral treatment is determined by the SVR when the HCV is no longer detectable in serum. Interferon-alpha (IFN-α) and its analogs, pegylated IFN-α (PEG-IFN-α) alone with ribavirin (RBV), have been the primary antiviral treatment of HCV for many years with a low cure rate. The cloning and sequencing of HCV have allowed the development of cell culture models, which accelerated antiviral drug discovery. It resulted in the selection of highly effective direct-acting antiviral (DAA)-based combination therapy that now offers incredible success in curing HCV infection in more than 95% of all patients, including those with cirrhosis. However, several emerging recent publications claim that patients who have liver cirrhosis at the time of DAAs treatment face the risk of HCC occurrence and recurrence after viral cure. This remains a substantial challenge while addressing the long-term benefit of antiviral medicine. The host-related mechanisms that drive the risk of HCC in the absence of the virus are unknown. This review describes the multifaceted mechanisms that create a tumorigenic environment during chronic HCV infection. In addition to the potential oncogenic programming that drives HCC after viral clearance by DAAs, the current status of a biomarker development for early prediction of cirrhosis regression and HCC detection post viral treatment is discussed. Since DAAs treatment does not provide full protection against reinfection or viral transmission to other individuals, the recent studies for a vaccine development are also reviewed.
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Affiliation(s)
- Srikanta Dash
- Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, LA70112, USA
- Southeast Louisiana Veterans Health Care System, New Orleans, LA70119, USA
- Department of Medicine, Division of Gastroenterology, Tulane University Health Sciences Center, New Orleans, LA70112, USA
| | - Yucel Aydin
- Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, LA70112, USA
| | - Kyle E Widmer
- Southeast Louisiana Veterans Health Care System, New Orleans, LA70119, USA
| | - Leela Nayak
- Southeast Louisiana Veterans Health Care System, New Orleans, LA70119, USA
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Abstract
There is mounting evidence that members of the human microbiome are highly associated with a wide variety of cancer types. Among oral cancers, oral squamous cell carcinoma (OSCC) is the most prevalent and most commonly studied, and it is the most common malignancy of the head and neck worldwide. However, there is a void regarding the role that the oral microbiome may play in OSCC. Previous studies have not consistently found a characteristic oral microbiome composition associated with OSCC. Although a direct causality has not been proven, individual members of the oral microbiome are capable of promoting various tumorigenic functions related to cancer development. Two prominent oral pathogens, Porphyromonas gingivalis, and Fusobacterium nucleatum can promote tumor progression in mice. P. gingivalis infection has been associated with oro-digestive cancer, increased oral cancer invasion, and proliferation of oral cancer stem cells. The microbiome can influence the evolution of the disease by directly interacting with the human body and significantly altering the response and toxicity to various forms of cancer therapy. Recent studies have shown an association of certain phylogenetic groups with the immunotherapy treatment outcomes of certain tumors. On the other side of the coin, recently it has been a resurgence in interest on the potential use of bacteria to cure cancer. These kinds of treatments were used in the late nineteenth and early twentieth centuries as the first line of defense against cancer in some hospitals but later displaced by other types of treatments such as radiotherapy. Currently, organisms such as Salmonella typhimurium and Clostridium spp. have been used for targeted strategies as potential vectors to treat cancer. In this review, we briefly summarize our current knowledge of the role of the oral microbiome, focusing on its bacterial fraction, in cancer in general and in OSCC more precisely, and a brief description of the potential use of bacteria to target tumors.
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Affiliation(s)
- Muhammad Irfan
- Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, United States
| | | | - Jorge Frias-Lopez
- Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, United States
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Peng M, Lee SH, Rahaman SO, Biswas D. Dietary probiotic and metabolites improve intestinal homeostasis and prevent colorectal cancer. Food Funct 2020; 11:10724-10735. [DOI: 10.1039/d0fo02652b] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Metabolites from Lactobacillus casei display substantial antioxidant and anti-inflammatory activities, inhibit colorectal cancer cell proliferation and growth, and modulate gut microfloral composition, specifically reducing sulfidogenic bacteria.
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Affiliation(s)
- Mengfei Peng
- Department of Animal and Avian Sciences
- University of Maryland
- College Park
- USA
- Biological Sciences Program
| | - Seong-Ho Lee
- Department of Nutrition and Food Science
- University of Maryland
- College Park
- USA
| | - Shaik O. Rahaman
- Department of Nutrition and Food Science
- University of Maryland
- College Park
- USA
| | - Debabrata Biswas
- Department of Animal and Avian Sciences
- University of Maryland
- College Park
- USA
- Biological Sciences Program
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37
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Frias-Lopez J, Duran-Pinedo AE. The Function of the Oral Microbiome in Health and Disease. EMERGING THERAPIES IN PERIODONTICS 2020:141-173. [DOI: 10.1007/978-3-030-42990-4_10] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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38
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de la Fuente S, Citores MJ, Lucena JL, Muñoz P, Cuervas-Mons V. TLR9-1486C/T polymorphism is associated with hepatocellular carcinoma recurrence after liver transplantation. Biomark Med 2019; 13:995-1004. [PMID: 31317790 DOI: 10.2217/bmm-2019-0030] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Aim: To determine whether TLR9 polymorphisms are associated with tumor recurrence after liver transplantation for hepatocellular carcinoma (HCC). Patients & methods: All patients who underwent liver transplantation, and had viable HCC in the explanted liver were included. TLR9-1237C/T and -1486C/T polymorphisms were analyzed by real-time PCR and melting curves analysis. Results: 20 of 159 patients (12.6%) developed post-transplant HCC recurrence. Tumors exceeding Milan criteria, moderately-to-poorly differentiated tumors and microvascular invasion on explants, and pretransplant α-fetoprotein level (all p < 0.01) were associated with an increased risk, while TLR9-1486TT genotype was associated with a decreased risk of HCC recurrence (p = 0.03). Conclusion: TLR9-1486C/T might help to preoperatively identify patients at low risk of post-transplant HCC recurrence.
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Affiliation(s)
- Sara de la Fuente
- Liver Transplantation Unit, Hospital Universitario Puerta de Hierro-Majadahonda, Manuel de Falla 1, 28022 Majadahonda, Madrid, Spain
- Department of Internal Medicine, Hospital Universitario Puerta de Hierro-Majadahonda, Manuel de Falla 1, 28022 Majadahonda, Madrid, Spain
| | - María-Jesús Citores
- Department of Internal Medicine, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Joaquin Rodrigo 2, 28022 Majadahonda, Madrid, Spain
| | - José-Luis Lucena
- Liver Transplantation Unit, Hospital Universitario Puerta de Hierro-Majadahonda, Manuel de Falla 1, 28022 Majadahonda, Madrid, Spain
- Department of Surgery, Hospital Universitario Puerta de Hierrdo-Majadahonda, Manuel de Falla 1, 28022 Majadahonda, Madrid, Spain
| | - Pablo Muñoz
- Department of Internal Medicine, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Joaquin Rodrigo 2, 28022 Majadahonda, Madrid, Spain
| | - Valentín Cuervas-Mons
- Liver Transplantation Unit, Hospital Universitario Puerta de Hierro-Majadahonda, Manuel de Falla 1, 28022 Majadahonda, Madrid, Spain
- Department of Internal Medicine, Hospital Universitario Puerta de Hierro-Majadahonda, Manuel de Falla 1, 28022 Majadahonda, Madrid, Spain
- Department of Medicine, Universidad Autónoma de Madrid, Arzobispo Morcillo, s/n, 28029 Madrid, Spain
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Ai D, Pan H, Li X, Gao Y, Liu G, Xia LC. Identifying Gut Microbiota Associated With Colorectal Cancer Using a Zero-Inflated Lognormal Model. Front Microbiol 2019; 10:826. [PMID: 31068913 PMCID: PMC6491826 DOI: 10.3389/fmicb.2019.00826] [Citation(s) in RCA: 103] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Accepted: 04/01/2019] [Indexed: 12/26/2022] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide. Its incidence is still increasing, and the mortality rate is high. New therapeutic and prognostic strategies are urgently needed. It became increasingly recognized that the gut microbiota composition differs significantly between healthy people and CRC patients. Thus, identifying the difference between gut microbiota of the healthy people and CRC patients is fundamental to understand these microbes' functional roles in the development of CRC. We studied the microbial community structure of a CRC metagenomic dataset of 156 patients and healthy controls, and analyzed the diversity, differentially abundant bacteria, and co-occurrence networks. We applied a modified zero-inflated lognormal (ZIL) model for estimating the relative abundance. We found that the abundance of genera: Anaerostipes, Bilophila, Catenibacterium, Coprococcus, Desulfovibrio, Flavonifractor, Porphyromonas, Pseudoflavonifractor, and Weissella was significantly different between the healthy and CRC groups. We also found that bacteria such as Streptococcus, Parvimonas, Collinsella, and Citrobacter were uniquely co-occurring within the CRC patients. In addition, we found that the microbial diversity of healthy controls is significantly higher than that of the CRC patients, which indicated a significant negative correlation between gut microbiota diversity and the stage of CRC. Collectively, our results strengthened the view that individual microbes as well as the overall structure of gut microbiota were co-evolving with CRC.
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Affiliation(s)
- Dongmei Ai
- Basic Experimental of Natural Science, University of Science and Technology Beijing, Beijing, China
- School of Mathematics and Physics, University of Science and Technology Beijing, Beijing, China
| | - Hongfei Pan
- School of Mathematics and Physics, University of Science and Technology Beijing, Beijing, China
| | - Xiaoxin Li
- School of Mathematics and Physics, University of Science and Technology Beijing, Beijing, China
| | - Yingxin Gao
- School of Mathematics and Physics, University of Science and Technology Beijing, Beijing, China
| | - Gang Liu
- School of Mathematics and Physics, University of Science and Technology Beijing, Beijing, China
| | - Li C Xia
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States
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40
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Yu R, Zuo F, Ma H, Chen S. Exopolysaccharide-Producing Bifidobacterium adolescentis Strains with Similar Adhesion Property Induce Differential Regulation of Inflammatory Immune Response in Treg/Th17 Axis of DSS-Colitis Mice. Nutrients 2019; 11:nu11040782. [PMID: 30987344 PMCID: PMC6520857 DOI: 10.3390/nu11040782] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2019] [Revised: 03/28/2019] [Accepted: 04/01/2019] [Indexed: 12/14/2022] Open
Abstract
Intestinal bifidobacteria benefit human health by promoting and modulating the gut flora, and boosting therapeutic efficiency for chronic metabolic diseases and cancer. Recently, Bifidobacterium adolescentis strains with high adhesion to intestinal epithelial cells were associated with induction of T-helper 17 (Th17) cells in humans and rodents. Here, two B. adolescentis strains with similar adhesive ability but different aggregation properties were investigated for specific immunoregulatory effects, including the underlying cellular pathway, on macrophage and T-regulatory (Treg)/Th17 axis activation in vitro and in the colon of dextran sodium sulfate (DSS)-colitis mice in vivo. In-vitro, the auto-aggregative B. adolescentis strain IF1-11 induced significantly higher IL-6 and lower IL-10 secretion from immune cells, and it induced abundant Th17 cells. The non-aggregating strain IF1-03 induced significantly higher IL-10, less IL-6 and a high proportion of Treg/Th17 cells compared to total T cells. In vivo, orally administered IF1-03 protected DSS-colitis mice via activation of dendritic cells or macrophages and skewing of Treg/Th17 cells, consistent with Treg cell induction in vitro. IF1-03 exopolysaccharides showed a functional recognition pattern similar to IF1-03 for IL-10 cytokine secretion and Treg cell-differentiation induction, both dependent on the toll-like receptor 2–ERK/p38 MAPK-signaling cascade for macrophage activation. We suggest that B. adolescentis exopolysaccharide-associated enterocyte adhesion/aggregation phenotypes determine strain-specific adaptive immune responses in the gut via the macrophage-regulated Treg/Th17 axis.
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Affiliation(s)
- Rui Yu
- Key Laboratory of Functional Dairy Science, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
| | - Fanglei Zuo
- Key Laboratory of Functional Dairy Science, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
| | - Huiqin Ma
- College of Horticulture, China Agricultural University, Beijing 100193, China.
| | - Shangwu Chen
- Key Laboratory of Functional Dairy Science, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
- The Research & Innovation Centre of Food Nutrition and Human Health (Beijing), China Agricultural University, Beijing 100083, China.
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41
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20-Hydroxy-3-Oxolupan-28-Oic Acid Attenuates Inflammatory Responses by Regulating PI3K⁻Akt and MAPKs Signaling Pathways in LPS-Stimulated RAW264.7 Macrophages. Molecules 2019; 24:molecules24030386. [PMID: 30678231 PMCID: PMC6385096 DOI: 10.3390/molecules24030386] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Revised: 01/18/2019] [Accepted: 01/21/2019] [Indexed: 12/16/2022] Open
Abstract
20-Hydroxy-3-oxolupan-28-oic acid (HOA), a lupane-type triterpene, was obtained from the leaves of Mahonia bealei, which is described in the Chinese Pharmacopeia as a remedy for inflammation and related diseases. The anti-inflammatory mechanisms of HOA, however, have not yet been fully elucidated. Therefore, the objective of this study was to characterize the molecular mechanisms of HOA in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. HOA suppressed the release of nitric oxide (NO), pro-inflammatory cytokine tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 macrophages without affecting cell viability. Quantitative real-time reverse-transcription polymerase chain reaction (RT-qPCR) analysis indicated that HOA also suppressed the gene expression of inducible NO synthase (iNOS), TNF-α, and IL-6. Further analyses demonstrated that HOA inhibited the phosphorylation of upstream signaling molecules, including p85, PDK1, Akt, IκBα, ERK, and JNK, as well as the nuclear translocation of nuclear factor κB (NF-κB) p65. Interestingly, HOA had no effect on the LPS-induced nuclear translocation of activator protein 1 (AP-1). Taken together, these results suggest that HOA inhibits the production of cytokine by downregulating iNOS, TNF-α, and IL-6 gene expression via the downregulation of phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinases (MAPKs), and the inhibition of NF-κB activation. Our findings indicate that HOA could potentially be used as an anti-inflammatory agent for medical use.
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42
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Maddi A, Sabharwal A, Violante T, Manuballa S, Genco R, Patnaik S, Yendamuri S. The microbiome and lung cancer. J Thorac Dis 2019; 11:280-291. [PMID: 30863606 DOI: 10.21037/jtd.2018.12.88] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
It has become increasingly clear that we live in a symbiotic relationship with microbes within us. We are just beginning to unravel the nature and strength of this relationship and its impact on both physiology and by extension, pathology. While microorganisms have long been known to have carcinogenic potential, their role may have been underestimated. The knowledge of the role of the microbiome in carcinogenesis is rapidly evolving. This evolution has reached a tipping point with current omics technologies used for cataloguing the microbiome. The lung is an organ constantly exposed to the environment. It is now clear that the lung has a distinct microbiome and that this may influence the development of lung cancer. In addition, evidence suggests that this microbiome originates from the oral microbiome. This review summarizes current knowledge about the role of microbiome, especially the oral and lung microbiome in human lung cancer. The goal of the manuscript is to provide a summary of this rapidly evolving field while providing a context of the general role of the microbiome in carcinogenesis. In addition, a primer of the current technology used in evaluating the microbiome is provided to familiarize the practicing clinician with the experimental methods used to generate the information that will likely impact the field of lung cancer.
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Affiliation(s)
- Abhiram Maddi
- Department of Periodontics & Endodontics, School of Dental Medicine, State University of New York, Buffalo, NY, USA
| | - Amarpreet Sabharwal
- Department of Periodontics & Endodontics, School of Dental Medicine, State University of New York, Buffalo, NY, USA
| | - Timothy Violante
- Department of Periodontics & Endodontics, School of Dental Medicine, State University of New York, Buffalo, NY, USA
| | - Sunita Manuballa
- Department of Oral Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
| | - Robert Genco
- Department of Periodontics & Endodontics, School of Dental Medicine, State University of New York, Buffalo, NY, USA
| | - Santosh Patnaik
- Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
| | - Sai Yendamuri
- Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
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43
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Lu Y, Xu X, Jiang T, Jin L, Zhao XD, Cheng JH, Jin XJ, Ma J, Piao HN, Piao LX. Sertraline ameliorates inflammation in CUMS mice and inhibits TNF-α-induced inflammation in microglia cells. Int Immunopharmacol 2018; 67:119-128. [PMID: 30544065 DOI: 10.1016/j.intimp.2018.12.011] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2018] [Revised: 11/16/2018] [Accepted: 12/03/2018] [Indexed: 01/16/2023]
Abstract
Evidence indicates that inflammation plays a crucial role in depression. Therefore, new antidepressants might be identified by screening drugs for their anti-inflammatory actions. Sertraline hydrochloride (SERT), a widely used antidepressant, has anti-inflammatory effects in clinical studies, but the mechanism involved is unclear. In this study, we used cell and molecular biology to determine the possible anti-inflammatory mechanism of SERT in vivo and in vitro. Experimental data from the in vivo study showed that mice exposed to chronic unpredictable mild stress (CUMS) had significantly higher levels of major inflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β] and inducible nitric oxide synthase [iNOS]) in peripheral and central tissues compared with the control group. Treatment of CUMS mice with SERT significantly reduced the levels of these inflammatory cytokines and inhibited the phosphorylation of nuclear factor-κB (NF-κB) and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκB-α). Moreover, SERT reduced serum levels of transaminase in CUMS mice. Our in vitro study revealed that SERT suppressed TNF-α-induced NF-κB activation in a dose-dependent manner. SERT also inhibited the TNF-α-induced nuclear translocation of NF-κB by inhibiting IκB-α phosphorylation. Furthermore, SERT inhibited TNF-α-induced inflammatory cytokines in BV2 microglia cells. SERT directly bound to TNF-α and TNF-α receptor 1 (TNFR1) to potently block TNF-α/TNFR1-triggered signaling. These results indicate that SERT might treat depression by inhibiting the activation of microglia via the NF-κB signaling pathway. This study provides a basis for the research and development of antidepressants that act to reduce inflammation and the expression of inflammatory mediators.
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Affiliation(s)
- Ying Lu
- Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, Jilin, China
| | - Xiang Xu
- Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, Jilin, China
| | - Tong Jiang
- Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, Jilin, China
| | - Lan Jin
- Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, Jilin, China
| | - Xu-Dong Zhao
- Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, Jilin, China
| | - Jia-Hui Cheng
- Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, Jilin, China
| | - Xue-Jun Jin
- Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, Jilin, China
| | - Juan Ma
- Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, Jilin, China
| | - Hu-Nan Piao
- Department of Neurology, Affliated Hospital of Yanbian University, Yanji 133000, Jilin, China.
| | - Lian-Xun Piao
- Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, Jilin, China.
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44
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Hua Y, Yan K, Wan C. Clever Cooperation: Interactions Between EspF and Host Proteins. Front Microbiol 2018; 9:2831. [PMID: 30524410 PMCID: PMC6262023 DOI: 10.3389/fmicb.2018.02831] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Accepted: 11/05/2018] [Indexed: 12/12/2022] Open
Abstract
EspF is a central effector protein of enterohemorrhagic Escherichia coli (EHEC), enteropathogenic E. coli (EPEC), and Citrobacter rodentium (CR) that is secreted through the type III secretion system to host cells. The interaction between EspF and host proteins plays an important role in bacterial pathogenesis. EspF protein binds to host SNX9 and N-WASP proteins to promote the colonization of pathogenic bacteria in intestinal epithelial cells; combines with cytokeratin 18, actin, 14-3-3ζ, Arp2/3, profilin, and ZO-1 proteins to intervene in the redistribution of intermediate filaments, the rearrangement of actin, and the disruption of tight junctions; acts together with Abcf2 to boost host cell intrinsic apoptosis; and collaborates with Anxa6 protein to inhibit phagocytosis. The interaction between EspF and host proteins is key to the pathogenic mechanism of EHEC and EPEC. Here, we review how EspF protein functions through interactions with these 10 host proteins and contributes to the pathogenicity of EHEC/EPEC.
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Affiliation(s)
- Ying Hua
- Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou, China.,Key Laboratory of Tropical Disease Research of Guangdong Province, Guangzhou, China
| | - Kaina Yan
- Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou, China.,Key Laboratory of Tropical Disease Research of Guangdong Province, Guangzhou, China
| | - Chengsong Wan
- Department of Microbiology, School of Public Health, Southern Medical University, Guangzhou, China.,Key Laboratory of Tropical Disease Research of Guangdong Province, Guangzhou, China
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45
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Yost S, Stashenko P, Choi Y, Kukuruzinska M, Genco CA, Salama A, Weinberg EO, Kramer CD, Frias-Lopez J. Increased virulence of the oral microbiome in oral squamous cell carcinoma revealed by metatranscriptome analyses. Int J Oral Sci 2018; 10:32. [PMID: 30420594 PMCID: PMC6232154 DOI: 10.1038/s41368-018-0037-7] [Citation(s) in RCA: 93] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Revised: 08/22/2018] [Accepted: 08/28/2018] [Indexed: 02/06/2023] Open
Abstract
Oral squamous cell carcinoma (OSCC) is the most prevalent and most commonly studied oral cancer. However, there is a void regarding the role that the oral microbiome may play in OSCC. Although the relationship between microbial community composition and OSCC has been thoroughly investigated, microbial profiles of the human microbiome in cancer are understudied. Here we performed a small pilot study of community-wide metatranscriptome analysis to profile mRNA expression in the entire oral microbiome in OSCC to reveal molecular functions associated with this disease. Fusobacteria showed a statistically significantly higher number of transcripts at tumour sites and tumour-adjacent sites of cancer patients compared to the healthy controls analysed. Regardless of the community composition, specific metabolic signatures were consistently found in disease. Activities such as iron ion transport, tryptophanase activity, peptidase activities and superoxide dismutase were over-represented in tumour and tumour-adjacent samples when compared to the healthy controls. The expression of putative virulence factors in the oral communities associated with OSCC showed that activities related to capsule biosynthesis, flagellum synthesis and assembly, chemotaxis, iron transport, haemolysins and adhesins were upregulated at tumour sites. Moreover, activities associated with protection against reactive nitrogen intermediates, chemotaxis, flagellar and capsule biosynthesis were also upregulated in non-tumour sites of cancer patients. Although they are preliminary, our results further suggest that Fusobacteria may be the leading phylogenetic group responsible for the increase in expression of virulence factors in the oral microbiome of OSCC patients.
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Affiliation(s)
- Susan Yost
- Forsyth Institute, 245 First Street, Cambridge, MA, 02142, USA
| | - Philip Stashenko
- Boston University Henry M. Goldman School of Dental Medicine, 100 East Newton Street, Boston, MA, 02118, USA
| | - Yoonhee Choi
- Forsyth Institute, 245 First Street, Cambridge, MA, 02142, USA
| | - Maria Kukuruzinska
- Boston University Henry M. Goldman School of Dental Medicine, 100 East Newton Street, Boston, MA, 02118, USA
| | - Caroline A Genco
- Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA, 02111, USA
| | - Andrew Salama
- Boston University Henry M. Goldman School of Dental Medicine, 100 East Newton Street, Boston, MA, 02118, USA
| | - Ellen O Weinberg
- Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA, 02111, USA
| | - Carolyn D Kramer
- Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA, 02111, USA
| | - Jorge Frias-Lopez
- Department of Oral Biology, College of Dentistry, University of Florida, 1395 Center Drive, Gainesville, FL, 32610-0424, USA.
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46
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Hajialyani M, Tewari D, Sobarzo-Sánchez E, Nabavi SM, Farzaei MH, Abdollahi M. Natural product-based nanomedicines for wound healing purposes: therapeutic targets and drug delivery systems. Int J Nanomedicine 2018; 13:5023-5043. [PMID: 30214204 PMCID: PMC6128268 DOI: 10.2147/ijn.s174072] [Citation(s) in RCA: 114] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Wound healing process is an intricate sequence of well-orchestrated biochemical and cellular phenomena to restore the integrity of the skin and subcutaneous tissue. Several plant extracts and their phytoconstituents are known as a promising alternative for wound healing agents due to the presence of diverse active components, ease of access, and their limited side effects. The development of nanotechnological methods can help to improve the efficacy of different therapeutics as well as herbal-based products. Here, we present a review of the efficacy of the plant based-nanomaterials in the management of wounds and discuss the involved therapeutic targets. For this purpose, a profound search has been conducted on in vitro, in vivo, and/or clinical evidences evaluating the efficacy and pharmacological mechanisms of natural product-based nanostructures on different types of wounds. Different pharmacological targets are involved in the wound healing effects of herbal-based nanostructures, including suppressing the production of inflammatory cytokines and inflammatory transduction cascades, reducing oxidative factors and enhancing antioxidative enzymes, and promoting neovascularization and angiogenic pathways through increasing the expression of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor. Moreover, nanostructure of plant extracts and their phytochemicals can enhance their bioavailability, control their release in the form of sustained delivery systems to the wound site, and enhance the permeability of these therapeutics to the underlying skin layers, which are all necessary for the healing process. Overall, various plant extracts and their natural compounds, used in nanoformulations, have demonstrated high activity in the management of wounds and thus can be assumed as future pharmaceutical drugs.
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Affiliation(s)
- Marziyeh Hajialyani
- Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran,
| | - Devesh Tewari
- Department of Pharmaceutical Sciences, Faculty of Technology, Kumaun University, Nainital, India
| | - Eduardo Sobarzo-Sánchez
- Laboratory of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, Spain.,Instituto de Investigación e Innovación en Salud, Facultad de Ciencias de la Salud, Universidad Central de Chile, Chile
| | - Seyed Mohammad Nabavi
- Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Mohammad Hosein Farzaei
- Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran,
| | - Mohammad Abdollahi
- Toxicologyand Diseases Group, The Institute of Pharmaceutical Sciences (TIPS) and Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran,
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47
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Wassenaar TM. E. coli and colorectal cancer: a complex relationship that deserves a critical mindset. Crit Rev Microbiol 2018; 44:619-632. [DOI: 10.1080/1040841x.2018.1481013] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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48
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Trivedi-Parmar V, Jorgensen WL. Advances and Insights for Small Molecule Inhibition of Macrophage Migration Inhibitory Factor. J Med Chem 2018; 61:8104-8119. [PMID: 29812929 DOI: 10.1021/acs.jmedchem.8b00589] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Macrophage migration inhibitory factor (MIF) is an upstream regulator of the immune response whose dysregulation is tied to a broad spectrum of inflammatory and proliferative disorders. As its complex signaling pathways and pleiotropic nature have been elucidated, it has become an attractive target for drug discovery. Remarkably, MIF is both a cytokine and an enzyme that functions as a keto-enol tautomerase. Strategies including in silico modeling, virtual screening, high-throughput screening, and screening of anti-inflammatory natural products have led to a large and diverse catalogue of MIF inhibitors as well as some understanding of the structure-activity relationships for compounds binding MIF's tautomerase active site. With possible clinical trials of some MIF inhibitors on the horizon, it is an opportune time to review the literature to seek trends, address inconsistencies, and identify promising new avenues of research.
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Affiliation(s)
- Vinay Trivedi-Parmar
- Department of Chemistry , Yale University , New Haven , Connecticut 06520-8107 , United States
| | - William L Jorgensen
- Department of Chemistry , Yale University , New Haven , Connecticut 06520-8107 , United States
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Abstract
The concept that progression of cancer is regulated by interactions of cancer cells with their microenvironment was postulated by Stephen Paget over a century ago. Contemporary tumour microenvironment (TME) research focuses on the identification of tumour-interacting microenvironmental constituents, such as resident or infiltrating non-tumour cells, soluble factors and extracellular matrix components, and the large variety of mechanisms by which these constituents regulate and shape the malignant phenotype of tumour cells. In this Timeline article, we review the developmental phases of the TME paradigm since its initial description. While illuminating controversies, we discuss the importance of interactions between various microenvironmental components and tumour cells and provide an overview and assessment of therapeutic opportunities and modalities by which the TME can be targeted.
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Affiliation(s)
- Shelly Maman
- Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
| | - Isaac P Witz
- Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
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50
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He A, Shao J, Zhang Y, Lu H, Wu Z, Xu Y. CD200Fc reduces LPS-induced IL-1β activation in human cervical cancer cells by modulating TLR4-NF-κB and NLRP3 inflammasome pathway. Oncotarget 2018; 8:33214-33224. [PMID: 28402258 PMCID: PMC5464862 DOI: 10.18632/oncotarget.16596] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Accepted: 03/16/2017] [Indexed: 12/21/2022] Open
Abstract
Chronic inflammation plays an important role in tumorigenesis of cervical cancer. CD200Fc, a CD200R1 agonist, has been found to have anti-inflammatory effects in autoimmune diseases and neuro-degeneration. However, the anti-inflammatory effect of CD200Fc on cervical cancer has not yet to be completely understood. This study investigated the anti-inflammatory effects and mechanisms of CD200Fc in LPS-induced human SiHa cells and Caski cells. SiHa cells and Caski cells were stimulated with 40 μg/ml LPS under different concentrations of CD200Fc for 90 min or 12 hours. The mRNA and protein levels of pro-IL-1β, cleaved-IL-1β and NLRP3, as well as the protein level of cleaved caspase-1, were significantly increased in LPS-induced SiHa cells and Caski cells. LPS stimulation did not change ASC and pro-caspase-1 expression. CD200Fc down-regulated protein expression of cleaved caspase-1 and mRNA and protein expression of pro-IL-1β, cleaved-IL-1β and NLRP3. In addition, the protein levels of TLR4, p-P65 and p-IκB, as well as the translocation of P65 to nucleus, were significantly increased in LPS-induced SiHa cells and Caski cells. LPS stimulation did not change t-P65 and t-IκB on protein levels, which were components of TLR-NF-κB pathway. CD200Fc down-regulated protein expression of TLR4, p-P65 and p-IκB and inhibited the translocation of P65 to nucleus in LPS-induced SiHa cells and Caski cells. These results indicated that CD200Fc appeared to suppress the inflammatory activity of TLR4-NF-κB and NLRP3 inflammasome pathway in LPS-induced SiHa cells and Caski cells. It provided novel mechanistic insights into the potential therapeutic uses of CD200Fc for cervical cancer.
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Affiliation(s)
- Aiqin He
- Department of Gynecology Oncology, Nantong Tumor Hospital, Tumor Hospital Affiliated to Nantong University, Nantong, China
| | - Jia Shao
- Department of Gynecology Oncology, Nantong Tumor Hospital, Tumor Hospital Affiliated to Nantong University, Nantong, China
| | - Yu Zhang
- Department of Gynecology Oncology, Nantong Tumor Hospital, Tumor Hospital Affiliated to Nantong University, Nantong, China
| | - Hong Lu
- Department of Gynecology Oncology, Nantong Tumor Hospital, Tumor Hospital Affiliated to Nantong University, Nantong, China
| | - Zhijun Wu
- Department of Gynecology Oncology, Nantong Tumor Hospital, Tumor Hospital Affiliated to Nantong University, Nantong, China
| | - Yunzhao Xu
- Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Nantong, China
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