1
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Thet D, Areepium N, Siritientong T. Effects of Probiotics on Chemotherapy-induced Diarrhea. Nutr Cancer 2023; 75:1811-1821. [PMID: 37908158 DOI: 10.1080/01635581.2023.2267779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 09/04/2023] [Accepted: 09/06/2023] [Indexed: 11/02/2023]
Abstract
Chemotherapy-induced diarrhea (CID) is a common adverse event in cancer patients, which, unless treated, may lead to drug discontinuation and treatment failure. Some probiotics such as Lactobacillus, Bifidobacterium, and Saccharomyces species have been gaining clinical attention in alleviating chemotherapy-induced adverse events including diarrhea. This comprehensive review provides an overview and discusses preventive approaches of probiotics with respect to CID in several types of cancers. The potential mechanisms of probiotics may comprise regulation of intestinal microbiota, modulation of immune functions, or reduction of proinflammatory cytokines. The efficacy and safety precautions of probiotics in immunocompromised cancer patients are discussed. The non-pharmacological strategy using probiotics could reduce the use of anti-diarrheal or antibiotic agents. Some individuals experienced shorter length of hospital stay, better gastrointestinal function, and reduced incidence of chemotherapy dose reduction after probiotic administration. Nonetheless, some studies failed to report the benefits of probiotics in certain patients. This review also highlights preventive protocols and therapeutic implications by considering the potential influencing factors, particularly types of probiotic strains, dosages of probiotics, duration of their administration, patients' tolerability, and variations in probiotic effects over the cancer stages.
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Affiliation(s)
- Daylia Thet
- Department of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
| | - Nutthada Areepium
- Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
| | - Tippawan Siritientong
- Department of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
- Metabolomics for Life Sciences Research Unit, Chulalongkorn University, Bangkok, Thailand
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2
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Hjazi A, Nasir F, Noor R, Alsalamy A, Zabibah RS, Romero-Parra RM, Ullah MI, Mustafa YF, Qasim MT, Akram SV. The pathological role of C-X-C chemokine receptor type 4 (CXCR4) in colorectal cancer (CRC) progression; special focus on molecular mechanisms and possible therapeutics. Pathol Res Pract 2023; 248:154616. [PMID: 37379710 DOI: 10.1016/j.prp.2023.154616] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 06/07/2023] [Accepted: 06/10/2023] [Indexed: 06/30/2023]
Abstract
Colorectal cancer (CRC) is comprised of transformed cells and non-malignant cells including cancer-associated fibroblasts (CAF), endothelial vasculature cells, and tumor-infiltrating cells. These nonmalignant cells, as well as soluble factors (e.g., cytokines), and the extracellular matrix (ECM), form the tumor microenvironment (TME). In general, the cancer cells and their surrounding TME can crosstalk by direct cell-to-cell contact and via soluble factors, such as cytokines (e.g., chemokines). TME not only promotes cancer progression through growth-promoting cytokines but also provides resistance to chemotherapy. Understanding the mechanisms of tumor growth and progression and the roles of chemokines in CRC will likely suggest new therapeutic targets. In this line, a plethora of reports has evidenced the critical role of chemokine receptor type 4 (CXCR4)/C-X-C motif chemokine ligand 12 (CXCL12 or SDF-1) axis in CRC pathogenesis. In the current review, we take a glimpse into the role of the CXCR4/CXCL12 axis in CRC growth, metastasis, angiogenesis, drug resistance, and immune escape. Also, a summary of recent reports concerning targeting CXCR4/CXCL12 axis for CRC management and therapy has been delivered.
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Affiliation(s)
- Ahmed Hjazi
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | | | - Rabia Noor
- Amna Inayat Medical College, Lahore, Pakistan
| | - Ali Alsalamy
- College of Medical Technique, Imam Ja'afar Al-Sadiq University, Al-Muthanna 66002, Iraq
| | - Rahman S Zabibah
- Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, Iraq
| | | | - Muhammad Ikram Ullah
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 75471, Aljouf, Saudi Arabia
| | - Yasser Fakri Mustafa
- Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul 41001, Iraq
| | - Maytham T Qasim
- Department of Anesthesia, College of Health and Medical Technololgy, Al-Ayen University, Thi-Qar, Iraq
| | - Shaik Vaseem Akram
- Uttaranchal Institute of Technology, Division of Research & Innovation, Uttaranchal University, Dehradun 248007, India
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3
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Artemev A, Naik S, Pougno A, Honnavar P, Shanbhag NM. The Association of Microbiome Dysbiosis With Colorectal Cancer. Cureus 2022; 14:e22156. [PMID: 35174040 PMCID: PMC8840808 DOI: 10.7759/cureus.22156] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/12/2022] [Indexed: 02/06/2023] Open
Abstract
Many studies have been conducted to identify the causative organisms in colorectal cancer (CRC) and compare the microbiota of healthy individuals and those with CRC. The pathways by which the microbiota promotes CRC development are not yet fully understood. The hypothesized mechanisms include damage to the DNA, production of carcinogenic metabolites, and promotion of chronic inflammation. In a state of dysbiosis, the gut loses protective bacteria and is enriched with pathogenic and cancer-promoting bacteria, which promotes functions associated with cancer such as angiogenesis, loss of apoptosis, and cell proliferation. We have established a strong link between microbiota dysbiosis and certain species of bacteria and even viruses involved in tumorigenesis. In this review, we look at some of the major identified species and how they are related to CRC. Future research should include and even focus on mycobiome and virome on CRC development. Due to the diversity of the gut microbiome, there is a high possibility that the gain and loss of bacteria and their metabolic functions lead to CRC.
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Affiliation(s)
- Artem Artemev
- Medicine, Xavier University School of Medicine, Oranjestad, ABW
| | - Sheetal Naik
- Physiology, American University of Antigua, St. Johns, ATG
| | | | - Prasanna Honnavar
- Microbiology and Immunology, American University of Antigua, St. Johns, ATG
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4
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Zhang Q, Li X, Li J, Hu Y, Liu J, Wang F, Zhang W, Chang F. Mechanism of Anti-Inflammatory and Antibacterial Effects of QingXiaoWuWei Decoction Based on Network Pharmacology, Molecular Docking and In Vitro Experiments. Front Pharmacol 2021; 12:678685. [PMID: 34335250 PMCID: PMC8320847 DOI: 10.3389/fphar.2021.678685] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 06/21/2021] [Indexed: 12/11/2022] Open
Abstract
Background and Aim: QingXiaoWuWei Decoction (QXWWD) is a traditional Chinese medicine that is commonly used in clinical settings to treat inflammatory and bacterial diseases. However, there is still a lot to learn about its molecular mechanism. A network pharmacology approach was applied to investigate the pharmacological mechanisms of QXWWD in inflammation treatment. Methods: The basic mechanisms involved in the anti-inflammatory and antibacterial potentials of QXWWD were identified using network pharmacology and molecular docking. The principal components of QXWWD were identified by the HPLC-Q-Exactive-MS method. The antibacterial bioactivity of QXWWD was further investigated using the Kirby-Bauer disc diffusion method and the determination of the minimum inhibitory concentration. The anti-inflammatory activity of QXWWD was evaluated using mice ear swelling test, RAW264.7 cell culture, and pro-inflammatory cytokines measurement. Skin irritation and HE staining were employed to evaluate the safety of QXWWD topical use and to depict the drug’s potential therapeutic function. The hub genes and signaling pathways associated with inflammatory and bacterial diseases were validated by western blot in addition to biochemical and pathological markers. Results: Our findings revealed that the ethanolic extract of QXWWD had a strong inhibitory effect against Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pneumoniae. Meanwhile, QXWWD was potentially effective in suppressing ear swelling, elevated white blood cell counts, and the TNF-α, IL-1, and IL-6 levels. According to skin irritation, QXWWD was found to be safe when tested for topical application. The results of HE staining showed that the possible therapeutic role of QXWWD was related to the change in skin microstructure. Also, the network pharmacology, molecular docking as well as Q-Exactive-MS and HPLC analysis suggested that the synergistic effect of quercetin, luteolin and other ingredients could serve as main contributor of QXWWD for its anti-inflammatory and antibacterial activities. Moreover, the JUN, MAPK1, RELA, NFKBIA, MYC, and AKT1 were the potential identified key targets, and MAPK/PI3K/Akt was among the possibly involved signaling pathways in the anti-inflammatory and antibacterial activities of QXWWD. Conclusions: From a therapeutic standpoint, QXWWD may be a promising antibacterial and anti-inflammatory agent for the treatment of bacterial, acute, and chronic dermatitis.
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Affiliation(s)
- Qian Zhang
- The Center for New Drug Safety Evaluation and Research, Inner Mongolia Medical University, Hohhot, China.,The Center for New Drug Screening Engineering and Research of Inner Mongolia Autonomous Region, Inner Mongolia Medical University, Hohhot, China.,College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Xue Li
- College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Jun Li
- The Center for New Drug Safety Evaluation and Research, Inner Mongolia Medical University, Hohhot, China.,The Center for New Drug Screening Engineering and Research of Inner Mongolia Autonomous Region, Inner Mongolia Medical University, Hohhot, China.,College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Yuxia Hu
- The Center for New Drug Safety Evaluation and Research, Inner Mongolia Medical University, Hohhot, China.,The Center for New Drug Screening Engineering and Research of Inner Mongolia Autonomous Region, Inner Mongolia Medical University, Hohhot, China.,College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Jing Liu
- The Center for New Drug Safety Evaluation and Research, Inner Mongolia Medical University, Hohhot, China.,The Center for New Drug Screening Engineering and Research of Inner Mongolia Autonomous Region, Inner Mongolia Medical University, Hohhot, China.,College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Fang Wang
- The Center for New Drug Safety Evaluation and Research, Inner Mongolia Medical University, Hohhot, China.,The Center for New Drug Screening Engineering and Research of Inner Mongolia Autonomous Region, Inner Mongolia Medical University, Hohhot, China.,College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Wei Zhang
- The Center for New Drug Safety Evaluation and Research, Inner Mongolia Medical University, Hohhot, China.,The Center for New Drug Screening Engineering and Research of Inner Mongolia Autonomous Region, Inner Mongolia Medical University, Hohhot, China.,College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Fuhou Chang
- The Center for New Drug Safety Evaluation and Research, Inner Mongolia Medical University, Hohhot, China.,The Center for New Drug Screening Engineering and Research of Inner Mongolia Autonomous Region, Inner Mongolia Medical University, Hohhot, China.,College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
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5
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Zhou X, Ding S, Hu R. The Related Study on the Pathogenesis of Gastrointestinal Diseases in Gastrointestinal Flora and the Risk of Gastric Ulcer Carcinogenesis. J BIOMATER TISS ENG 2021. [DOI: 10.1166/jbt.2021.2755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Gastrointestinal diseases are common diseases of many kinds. The pathogenesis of gastrointestinal disease has not been fully understood. In this study with gastric mucosa specimen, among the three groups of chronic gastritis, gastric ulcer, and duodenal ulcer, there were differences
of Helicobacter pylori (H. pylori), Lactobacillus, Prevotella, Clostridium, B. fragilis, and Enterobacteriaceae. There was no significant difference in Lactobacillus among chronic gastritis, gastric ulcers, and duodenal ulcers with fecal specimens, but there was a significant
difference between these three groups and the gastric cancer group. Correlation analysis showed that six kinds of flora had a negative correlation with H. pylori, procalcitonin (PCT), tumor necrosis factor α (TNF-α), cluster of differentiation 4 (CD4+),
cluster of differentiation 8 (CD8+), immunoglobulin G (IgG), and immunoglobulin M (IgM) were different in different gastrointestinal diseases, and PCT, TNF-α and CD8+ were positively correlated with H. pylori and negatively correlated with CD4+,
IgM and IgG. Logistic regression analysis showed that age, recurrent gastric ulcer times, atrophic gastritis, and H. pylori were independent risk factors of gastric ulcer canceration. Therefore, we believe that gastrointestinal flora, especially H. pylori, plays a vital role
in the pathogenesis of gastrointestinal diseases, and H. pylori is an essential risk factor for gastric ulcer carcinogenesis.
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Affiliation(s)
- Xiaomin Zhou
- Department of Gastroenterology & Hepatology, Shanghai Jinshan District Tinglin Hospital, Shanghai 201505, PR China
| | - Songze Ding
- Department of Gastroenterology & Hepatology, Henan Provincial People’s Hospital, People’s Hospital ofZhengzhou University, Zhengzhou 450003, Henan, PR China
| | - Ruobing Hu
- Department of Gastroenterology & Hepatology, Henan Provincial People’s Hospital, People’s Hospital ofZhengzhou University, Zhengzhou 450003, Henan, PR China
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6
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Cígerová V, Adamkov M, Drahošová S, Grendár M. Immunohistochemical expression and significance of SATB2 protein in colorectal cancer. Ann Diagn Pathol 2021; 52:151731. [PMID: 33894556 DOI: 10.1016/j.anndiagpath.2021.151731] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 02/02/2021] [Accepted: 03/10/2021] [Indexed: 10/21/2022]
Abstract
In this study we evaluated the expression of SATB2 protein in colorectal cancer (CRC) and its association with microsatellite instability (MSI) status, inflammation and hypoxia. Immunohistochemical SATB2 expression was observed in 111 CRC samples. We assessed the correlation between SATB2 expression and clinico-morphological parameters, MSI, COX-2 and HIF-1α expression. SATB2 was noticed in 92.8% CRC. We observed nuclear staining with predominantly strong immunoreaction intensity (67.6%) and percentage of SATB-2 positive cells in more than 50% of cells (87.4%). The statistically significant associations were recorded between high SATB2 expression and low grade, negative lymph nodes and negative vascular invasion. Statistical analysis confirmed a significant correlation between SATB2 expression and microsatellite stability, tendency to correlate with COX-2 and no significant correlation with HIF-1α. SATB2 is overexpressed in CRC and its high expression is a marker of good prognosis. Moreover, SATB2 expression is significantly associated with microsatellite stability, there is tendency to correlate with pro-inflammatory COX-2 and there is no association with hypoxia.
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Affiliation(s)
- Veronika Cígerová
- Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of Histology and Embryology, Malá Hora 4, 036 01 Martin, Slovakia.
| | - Marian Adamkov
- Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of Histology and Embryology, Malá Hora 4, 036 01 Martin, Slovakia
| | - Slávka Drahošová
- Hermes LabSystems, s.r.o., Púchovská 12, 83106 Bratislava, Slovakia
| | - Marián Grendár
- Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Biomedical Center Martin, Department of Bioinformatics, Malá Hora 4C/4D, 036 01 Martin, Slovakia
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7
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Uyar A, Doğan A, Yaman T, Keleş ÖF, Yener Z, Çelik İ, Alkan EE. The Protective Role of Urtica dioica Seed Extract Against Azoxymethane-Induced Colon Carcinogenesis in Rats. Nutr Cancer 2021; 74:306-319. [PMID: 33560145 DOI: 10.1080/01635581.2021.1881568] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
The aim of this study was to investigate the protective role of Urtica dioica seed (UDS) extract against azoxymethane (AOM)-induced colon carcinogenesis in rats. Thirty-two male Wistar albino rats were divided into four groups: Control, AOM, AOM + UDS, and UDS. The AOM and AOM + UDS groups were induced by AOM (15 mg/kg body weight) subcutaneously once a week for 10 weeks. AOM + UDS and UDS groups additionally received fed with pellets included 30 ml/kg UDS extract. At the end of the trial, blood and colon tissue samples were taken from the rats following necropsy. The gross and histopathological findings revealed that the administration of UDS extract significantly decreased lesions including aberrant cript foci, adenoma, and adenocarcinoma formation both numerically and dimensionally. Immunohistochemically, slight CEA and COX-2, strong Caspase-3 immune-expressions were detected in the group AOM + UDS compared to AOM group. Biochemical examinations indicated that a markedly increase in the malondialdehyde and fluctuated antioxidant defense system constituents levels such as reduced glutathione, glutathione s-transferase, glutathione peroxidase, superoxide dismutase were restored in AOM + UDS group. These results reveal that the UDS may act as a chemopreventive dietary agent, inducing apoptosis, resulting in a significant reduction of colon carcinogenesis.
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Affiliation(s)
- Ahmet Uyar
- Faculty of Veterinary Medicine, Department of Pathology, Hatay Mustafa Kemal University, Hatay, Turkey
| | - Abdulahad Doğan
- Faculty of Pharmacy, Department of Biochemistry, Van Yuzuncu Yil University, Van, Turkey
| | - Turan Yaman
- Faculty of Veterinary Medicine, Department of Pathology, Van Yuzuncu Yil University, Van, Turkey
| | - Ömer Faruk Keleş
- Faculty of Veterinary Medicine, Department of Pathology, Van Yuzuncu Yil University, Van, Turkey
| | - Zabit Yener
- Faculty of Veterinary Medicine, Department of Pathology, Van Yuzuncu Yil University, Van, Turkey
| | - İsmail Çelik
- Faculty of Science, Department of Molecular Biology and Genetics, Van Yuzuncu Yil University, Van, Turkey
| | - Elif Ebru Alkan
- Faculty of Science, Department of Molecular Biology and Genetics, Van Yuzuncu Yil University, Van, Turkey
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8
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Babakhanov AT, Dzhumabekov AT, Zhao AV, Kuandykov YK, Tanabayeva SB, Fakhradiyev IR, Nazarenko Y, Saliev TM. Impact of Appendectomy on Gut Microbiota. Surg Infect (Larchmt) 2021; 22:651-661. [PMID: 33523761 DOI: 10.1089/sur.2020.422] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background: Considered vestigial from the classic point of view, the vermiform appendix has long been the subject of intensive studies. The recent understanding of appendix function in the context of unique architecture and bacterial complexity and density allows considering it as a safehouse for intestinal biodiversity. Methods: This review analyzes and assesses the current state of scientific knowledge regarding the role of the vermiform appendix in normal gut microbiota maintenance as a crucial factor of host homeostasis. It also highlights the difference in microbial composition between the large bowel and the appendix, as well as the association between the surgical excision, appendectomy, and dysbiosis-induced diseases. In addition, the review discusses the results of epidemiologic studies on appendectomy as a risk factor for the initiation of gastrointestinal carcinogenesis. It also highlights the association between appendectomy and a series of chronic inflammatory and neurologic disorders, including inflammatory bowel disease.
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Affiliation(s)
| | | | - Alexey V Zhao
- Institute of Surgery named after A.V. Vishnevsky, Moscow, Russia
| | - Yerlan K Kuandykov
- Khoja Akhmet Yassawi International Kazakh-Turkish University, Shymkent Medical Institute Postgraduate Studies Faculty, Shymkent, Kazakhstan
| | | | | | - Yana Nazarenko
- S.D. Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
| | - Timur M Saliev
- S.D. Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
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9
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Tommonaro G, El-Hagrassi AM, Fayad W, Iodice C, Shaker KH, EL-Hady FKA. Fatty Acid Profile and In Vitro Anticancer Activity of Two Marine Sponge- Associated Bacteria. CURRENT BIOACTIVE COMPOUNDS 2020; 16:1273-1280. [DOI: 10.2174/1573407216666200214095114] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Revised: 01/17/2020] [Accepted: 01/22/2020] [Indexed: 09/02/2023]
Abstract
Background:
Colorectal cancer represents one of the prominent causes of mortality worldwide
in men and women. The objective of this study was to search for new potential anticancer compounds,
both in prevention and treatment of colorectal cancer. The anticancer potential of marine bacterial
extracts against Human colorectal carcinoma cell line (HCT116) was evaluated as well as the partial
identification of bioactive metabolites.
Methods:
All bacterial extracts were tested for their cytotoxicity against HCT116 cell line by means of
MTT assay. The highly cytotoxic dichloromethane extracts of marine sponge-associated bacteria Vibrio
sp. and Bacillus sp. were analyzed by GC-MS.
Results:
Two fractions, Vib3 and Bac3, exhibited a very interesting cytotoxicity against human colorectal
carcinoma (HCT116) cell line, with a percentage of cytotoxicity of 96.04 % and 29.48 %, respectively.
Discussion:
The GC-MS analysis revealed the presence of two major fatty acids, palmitic and oleic
acids, in Vib3 fraction and fatty acid esters and phenolic compounds in Bac3 fraction.
Conclusion:
Based on previous literature, it may be hypothesized that the anticancer activity of
bacterial extracts could be, at least partially, to the fatty acids fraction.
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Affiliation(s)
- Giuseppina Tommonaro
- National Research Council of Italy (CNR), Institute of Biomolecular Chemistry, Via Campi Flegrei, 34 - 80078, Pozzuoli, Italy
| | - Ali M. El-Hagrassi
- Phytochemistry and Plant Systematics Department, National Research Centre, Giza, Egypt
| | - Walid Fayad
- Drug Bioassay- Cell Culture Laboratory, Pharmacognosy Department, National Research Centre, Giza, Egypt
| | - Carmine Iodice
- National Research Council of Italy (CNR), Institute of Biomolecular Chemistry, Via Campi Flegrei, 34 - 80078, Pozzuoli, Italy
| | - Kamel H. Shaker
- Chemistry of Natural Compounds Department, National Research Centre, Giza, Egypt
| | - Faten K. Abd EL-Hady
- Chemistry of Natural and Microbial Products Department, National Research Centre, Giza, Egypt
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10
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Boehm ET, Thon C, Kupcinskas J, Steponaitiene R, Skieceviciene J, Canbay A, Malfertheiner P, Link A. Fusobacterium nucleatum is associated with worse prognosis in Lauren's diffuse type gastric cancer patients. Sci Rep 2020; 10:16240. [PMID: 33004953 PMCID: PMC7530997 DOI: 10.1038/s41598-020-73448-8] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2020] [Accepted: 09/17/2020] [Indexed: 02/06/2023] Open
Abstract
Fusobacterium nucleatum (F. nucleatum) is frequently detected in primary colorectal cancer (CRC) and matching metastasis, and has been linked to a worse prognosis. We investigated the presence of F. nucleatum in gastric cancer (GC) and gastric preneoplastic conditions of the stomach, and its potential prognostic value in GC patients. Fusobacterium spp. and F. nucleatum were quantified in various specimens from gastrointestinal tract including paired CRC and GC tissues using probe-based qPCR. Fusobacterium spp. and F. nucleatum were more frequently found in tumorous tissue of CRC and GC compared to non-tumorous tissues. The frequency and bacterial load were higher in CRC compared to GC patients. F. nucleatum positivity showed no association to chronic gastritis or preneoplastic conditions such as intestinal metaplasia. F. nucleatum-positivity was associated with significantly worse overall survival in patients with Lauren's diffuse type, but not with intestinal type GC. There was no association with gender, Helicobacter pylori-status, tumor stage or tumor localization. However, F. nucleatum was positively associated with patient's age and a trend for a lower global long interspersed element-1 DNA methylation. In conclusion, our work provides novel evidence for clinical relevance of F. nucleatum in GC by showing an association between F. nucleatum positivity with worse prognosis of patients with Laurens's diffuse type gastric cancer. Further studies are necessary to explore related mechanistic insights and potential therapeutic benefit of targeted antibiotic treatment in GC patients.
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Affiliation(s)
- Ellen Teresa Boehm
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-Von-Guericke University Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany
| | - Cosima Thon
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-Von-Guericke University Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany
| | - Juozas Kupcinskas
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
- Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Ruta Steponaitiene
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Jurgita Skieceviciene
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Ali Canbay
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-Von-Guericke University Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany
| | - Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-Von-Guericke University Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany
| | - Alexander Link
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-Von-Guericke University Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.
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11
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Jiao J, Li P, Gu Y, Du X, Wang S, Wang J. A fluorescence quenching-recovery sensor based on RCA for the specific analysis of Fusobacterium nucleatum. nucleatum. Anal Biochem 2020; 604:113808. [DOI: 10.1016/j.ab.2020.113808] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Revised: 05/09/2020] [Accepted: 05/28/2020] [Indexed: 02/07/2023]
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12
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Okubo R, Kinoshita T, Katsumata N, Uezono Y, Xiao J, Matsuoka YJ. Impact of chemotherapy on the association between fear of cancer recurrence and the gut microbiota in breast cancer survivors. Brain Behav Immun 2020; 85:186-191. [PMID: 30818031 DOI: 10.1016/j.bbi.2019.02.025] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2018] [Revised: 01/29/2019] [Accepted: 02/22/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Dysfunctional processing of fear memory may be involved in the pathophysiology of fear of cancer recurrence (FCR), which is cited as the major unmet psychological need of cancer survivors. Emerging evidence has shown that the microbiota-gut-brain (MGB) axis affects depressive and anxiety disorders, and chemotherapy-associated psychological distress. We therefore hypothesized that the gut microbiota is associated with FCR in cancer survivors. METHODS This cross-sectional study enrolled women diagnosed with invasive breast cancer who were not currently undergoing chemotherapy. Fecal samples were obtained to assess the gut microbiota. FCR grade was assessed using the Concerns About Recurrence Scale (CARS). RESULTS Mean age of the participants (n = 126) was 58 years; 47% had stage I disease. Multiple regression analysis with adjustment for possible confounders showed that the relative abundance of the Bacteroides genus (beta = 0.180, p = 0.03) was significantly and directly associated with FCR. In the 57 participants with a history of chemotherapy, higher FCR was associated with lower microbial diversity (p = 0.04), lower relative abundance of Firmicutes (p = 0.03) and higher relative abundance of Bacteroidetes (p = 0.04) at the phylum level, and higher relative abundance of Bacteroides (p < 0.01) and lower relative abundance of Lachnospiraceae.g (p = 0.03) and Ruminococcus (p = 0.02) at the genus level. CONCLUSION Our findings provide the first evidence of an association between the gut microbiota and FCR and suggest that chemotherapy-induced changes in gut microbiota can influence FCR. Further studies should examine the effects of the gut microbiota on FCR using a prospective design.
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Affiliation(s)
- Ryo Okubo
- Division of Health Care Research, Center for Public Health Sciences, National Cancer Center Japan, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
| | - Takayuki Kinoshita
- Department of Breast Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
| | - Noriko Katsumata
- Next Generation Science Institute, Morinaga Milk Industry Co., Ltd., 5-1-83 Higashihara, Zama, Kanagawa 252-8583, Japan
| | - Yasuhito Uezono
- Division of Cancer Pathophysiology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
| | - Jinzhong Xiao
- Next Generation Science Institute, Morinaga Milk Industry Co., Ltd., 5-1-83 Higashihara, Zama, Kanagawa 252-8583, Japan
| | - Yutaka J Matsuoka
- Division of Health Care Research, Center for Public Health Sciences, National Cancer Center Japan, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
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13
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Cochrane K, Robinson AV, Holt RA, Allen-Vercoe E. A survey of Fusobacterium nucleatum genes modulated by host cell infection. Microb Genom 2020; 6:e000300. [PMID: 31661053 PMCID: PMC7067209 DOI: 10.1099/mgen.0.000300] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 09/10/2019] [Indexed: 12/23/2022] Open
Abstract
Here, we report comprehensive transcriptomic profiles from Fusobacterium nucleatum under conditions that mimic the first stages of bacterial infection in a highly differentiated adenocarcinoma epithelial cell line. Our transcriptomic in vitro adenocarcinoma approach allows us to measure the expression dynamics and regulation of bacterial virulence and response factors in real time, and is a novel strategy for clarifying the role of F. nucleatum infection in colorectal cancer (CRC) progression. Our data show that: (i) infection alters metabolic and functional pathways in F. nucleatum, allowing the bacterium to adapt to the host-imposed milieu; (ii) infection also stimulates the expression of genes required to help induce and promote a hypoxic and inflammatory microenvironment in the host; and (iii) F. nucleatum invasion occurs by a haematogenous route of infection. Our study identifies novel gene targets from F. nucleatum that are activated during invasion and which may aid in determining how this species invades and promotes disease within the human gastrointestinal tract. These invasion-specific genes may be useful as biomarkers for CRC progression in a host and could also assist in the development of new diagnostic tools and treatments (such as vaccines or small molecule drug targets), which will be able to combat infection and inflammation in the host while circumventing the potential problem of F. nucleatum tolerization.
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Affiliation(s)
- Kyla Cochrane
- Genome Sciences Center, BC Cancer Agency, Vancouver, British Columbia, V5Z 1L3, Canada
- Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, N1G 2W1, Canada
| | - Avery V. Robinson
- Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, N1G 2W1, Canada
| | - Robert A. Holt
- Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada
- Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada
- Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia, Canada
| | - Emma Allen-Vercoe
- Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, N1G 2W1, Canada
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14
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Pan HW, Du LT, Li W, Yang YM, Zhang Y, Wang CX. Biodiversity and richness shifts of mucosa-associated gut microbiota with progression of colorectal cancer. Res Microbiol 2020; 171:107-114. [PMID: 31982498 DOI: 10.1016/j.resmic.2020.01.001] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Revised: 01/14/2020] [Accepted: 01/14/2020] [Indexed: 12/19/2022]
Abstract
The host-associated gut microbiota is considered critical for the occurrence and progression of colorectal cancer (CRC); however, systematic evaluations of the changes in the biodiversity and richness of mucosa-associated gut microbiota with the development of CRC have been limited. Twenty-three paired samples from colorectal tumor sites and the surrounding non-tumor tissues were collected from stage I to IV CRC patients. The microbial compositions of the samples were analyzed by Illumina MiSeq sequencing of the V4 region of the 16S rRNA gene. Gut bacterial alterations at the tumor sites and surrounding healthy tissue sites collected from the different stages of CRC patients were analyzed. No significant differences were observed in the overall microbial richness and biodiversity between the CRC tissue and surrounding non-CRC tissue samples, however, composition and community segregation of the gut microbiota with the progression of CRC were observed. A general increasing trend of Bacteroidetes, Firmicutes, and Fusobacteria and decreasing trend of Proteobacteria were observed at the phylum level with the development of CRC. Further analysis revealed that thirty-four taxa differed significantly with the progression of CRC. Conclusively, our findings provide a comprehensive view of the human mucosa-associated gut microbiota, in association with the different stages of CRC.
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Affiliation(s)
- Hong-Wei Pan
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, 250012, Shandong Province, China
| | - Lu-Tao Du
- Department of Clinical Laboratory, Second Hospital of Shandong University, Jinan, 250033, Shandong Province, China
| | - Wei Li
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, 250012, Shandong Province, China
| | - Yong-Mei Yang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, 250012, Shandong Province, China
| | - Yi Zhang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, 250012, Shandong Province, China
| | - Chuan-Xin Wang
- Department of Clinical Laboratory, Second Hospital of Shandong University, Jinan, 250033, Shandong Province, China.
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15
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Tupá V, Drahošová S, Grendár M, Adamkov M. Expression and association of carbonic anhydrase IX and cyclooxygenase-2 in colorectal cancer. Pathol Res Pract 2019; 215:705-711. [DOI: 10.1016/j.prp.2019.01.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Revised: 12/14/2018] [Accepted: 01/05/2019] [Indexed: 12/24/2022]
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16
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Xiao X, Long W, Huang T, Xia T, Ye R, Liu Y, Long H. Differences Between the Intestinal Lumen Microbiota of Aberrant Crypt Foci (ACF)-Bearing and Non-bearing Rats. Dig Dis Sci 2018; 63:2923-2929. [PMID: 30014223 DOI: 10.1007/s10620-018-5180-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Accepted: 06/22/2018] [Indexed: 01/19/2023]
Abstract
BACKGROUND Multiple factors including host-microbiota interaction could contribute to the conversion of healthy mucosa to sporadic precancerous lesions. An imbalance of the gut microbiota may be a cause or consequence of this process. AIM The goal was to investigate and analyze the composition of gut microbiota during the genesis of precancerous lesions of colorectal cancer. METHODS To analyze the composition of gut microbiota in the genesis of precancerous lesions, a rat model of 1, 2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) was established. The feces of these rats and healthy rats were collected for 16S rRNA sequencing. RESULTS The diversity and density of the rat intestinal microbiota were significantly different between ACF-bearing and non-bearing group. ACF were induced in rats treated with DMH and showed increased expression of the inflammatory cytokines IL-6, IL-8, and TNF-α. Firmicutes was the most predominant phylum in both ACF-bearing and non-bearing group, followed by Bacteroidetes. Interestingly, although the density of Bacteroidetes decreased from the fifth week to the 17th week in both groups, it was significantly reduced in ACF-bearing group at the 13th week (P < 0.01). At the genus level, no significant difference was observed in the most predominant genus, Lactobacillus. Instead, Bacteroides and Prevotella were significantly less abundant (P < 0.01), while Akkermansia was significantly more abundant (P < 0.05) in ACF-bearing group at the 13th week. CONCLUSION Imbalance of the intestinal microbiota existed between ACF-bearing and non-bearing rats, which could be used as biomarker to predict the genesis of precancerous lesions in the gut.
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Affiliation(s)
- Xiuli Xiao
- Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Wenbo Long
- Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Tingyu Huang
- Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
- Department of Pathology, The First People's Hospital of Neijiang, Neijiang, 641000, Sichuan, China
| | - Tian Xia
- Department of Pathology, The First People's Hospital of Neijiang, Neijiang, 641000, Sichuan, China
| | - Rupei Ye
- Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Yong Liu
- Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
| | - Hanan Long
- Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China.
- Department of Science and Technology, Southwest Medical University, Luzhou, 646000, Sichuan, China.
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17
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Noguti J, Chan AA, Bandera B, Brislawn CJ, Protic M, Sim MS, Jansson JK, Bilchik AJ, Lee DJ. Both the intratumoral immune and microbial microenvironment are linked to recurrence in human colon cancer: results from a prospective, multicenter nodal ultrastaging trial. Oncotarget 2018; 9:23564-23576. [PMID: 29805756 PMCID: PMC5955112 DOI: 10.18632/oncotarget.25276] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Accepted: 04/08/2018] [Indexed: 12/15/2022] Open
Abstract
Colon cancer (CC) is the third most common cancer diagnosed in the United States and the incidence has been rising among young adults. We and others have shown a relationship between the immune infiltrate and prognosis, with improved disease-free survival (DFS) being associated with a higher expression of CD8+ T cells. We hypothesized that a microbial signature might be associated with intratumoral immune cells as well as DFS. We found that the relative abundance of one Operational Taxonomic Unit (OTU), OTU_104, was significantly associated with recurrence even after applying false discovery correction (HR 1.21, CI 1.08 to 1.36). The final multivariable model showed that DFS was influenced by three parameters: N-stage, CD8+ labeling, as well as this OTU_104 belonging to the order Clostridiales. Not only were CD8+ labeling and OTU_104 significant contributors in the final DFS model, but they were also inversely correlated to each other (p=0.022). Interestingly, CD8+ was also significantly associated with the microbiota composition in the tumor: CD8+ T cells was inversely correlated with alpha diversity (p=0.027) and significantly associated with the beta diversity. This study is the first to demonstrate an association among the intratumoral microbiome, CD8+ T cells, and recurrence in CC. An increased relative abundance of a specific OTU_104 was inversely associated with CD8+ T cells and directly associated with CC recurrence. The link between this microbe, CD8+ T cells, and DFS has not been previously shown.
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Affiliation(s)
- Juliana Noguti
- Dirks/Dougherty Laboratory for Cancer Research, Department of Translational Immunology, John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.,Los Angeles Biomedical Research Institute, Harbor - UCLA Medical Center, Torrance, CA, USA
| | - Alfred A Chan
- Dirks/Dougherty Laboratory for Cancer Research, Department of Translational Immunology, John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.,Los Angeles Biomedical Research Institute, Harbor - UCLA Medical Center, Torrance, CA, USA
| | - Bradley Bandera
- Department of Surgical Oncology. The John Wayne Cancer Institute at Providence St. John's Health Center, Santa Monica, CA, USA
| | - Colin J Brislawn
- Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington, USA
| | - Mladjan Protic
- University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia.,Oncology Institute of Vojvodina, Sremska Kamenica, Serbia
| | - Myung S Sim
- UCLA Department of Medicine, Statistics Core, Los Angeles, CA, USA
| | - Janet K Jansson
- Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington, USA
| | - Anton J Bilchik
- Department of Surgical Oncology. The John Wayne Cancer Institute at Providence St. John's Health Center, Santa Monica, CA, USA
| | - Delphine J Lee
- Dirks/Dougherty Laboratory for Cancer Research, Department of Translational Immunology, John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.,Los Angeles Biomedical Research Institute, Harbor - UCLA Medical Center, Torrance, CA, USA.,Division of Dermatology, Department of Medicine, Harbor - UCLA Medical Center, Torrance, CA, USA.,David Geffen School of Medicine, University of California - Los Angeles, Los Angeles, CA, USA
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18
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Gut microbiome of Moroccan colorectal cancer patients. Med Microbiol Immunol 2018; 207:211-225. [PMID: 29687353 PMCID: PMC6096775 DOI: 10.1007/s00430-018-0542-5] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Accepted: 03/24/2018] [Indexed: 12/18/2022]
Abstract
Although colorectal cancer is the third leading cause of death in Morocco, there are no studies of the microbiome changes associated with the disease in the Moroccan population. The aim of our study was to compare the stool microbiome of Moroccan cancer patients with healthy individuals. We analyzed the microbiome composition of samples from 11 CRC patients and 12 healthy individuals by 16S rRNA amplicon sequencing. Principal coordinate analysis of samples revealed defined cancer versus healthy clusters. Our findings showed that cancer samples had higher proportions of Firmicutes (T = 50.5%; N = 28.4%; p = 0.04), specifically of Clostridia (T = 48.3%; N = 19.0%; p = 0.002), and Fusobacteria (T = 0.1%; N = 0.0%; p = 0.02), especially of Fusobacteriia (T = 0.1%; N = 0.0%; p = 0.02), while Bacteroidetes were enriched in healthy samples (T = 35.1%; N = 62.8%; p = 0.06), particularly the class Bacteroidia (T = 35.1%; N = 62.6%; p = 0.06). Porphyromonas, Clostridium, Ruminococcus, Selenomonas, and Fusobacterium were significantly overrepresented in diseased patients, similarly to other studies. Predicted functional information showed that bacterial motility proteins, flagellar assembly, and fatty acid biosynthesis metabolism were significantly overrepresented in cancer patients, while amino acid metabolism and glycan biosynthesis were overrepresented in controls. This suggests that involvement of these functional metagenomes is similar and relevant in the carcinogenesis process, independent of the origin of the samples. Results from this study allowed identification of bacterial taxa relevant to the Moroccan population and encourages larger studies to facilitate population-directed therapeutic approaches.
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19
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García-Heredia JM, Carnero A. Dr. Jekyll and Mr. Hyde: MAP17's up-regulation, a crosspoint in cancer and inflammatory diseases. Mol Cancer 2018; 17:80. [PMID: 29650022 PMCID: PMC5896160 DOI: 10.1186/s12943-018-0828-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Accepted: 03/28/2018] [Indexed: 12/14/2022] Open
Affiliation(s)
- José M García-Heredia
- Instituto de Biomedicina de Sevilla, IBIS/Hospital Universitario Virgen del Rocío/ Universidad de Sevilla/Consejo Superior de Investigaciones Científicas, Avda. Manuel Siurot s/n, 41013, Sevilla, Spain.,Department of Vegetal Biochemistry and Molecular Biology, University of Seville, Seville, Spain.,CIBER de Cáncer, Instituto de Salud Carlos III, Pabellón 11, Madrid, Spain
| | - Amancio Carnero
- Instituto de Biomedicina de Sevilla, IBIS/Hospital Universitario Virgen del Rocío/ Universidad de Sevilla/Consejo Superior de Investigaciones Científicas, Avda. Manuel Siurot s/n, 41013, Sevilla, Spain. .,CIBER de Cáncer, Instituto de Salud Carlos III, Pabellón 11, Madrid, Spain.
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20
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Okubo R, Chen C, Sekiguchi M, Hamazaki K, Matsuoka YJ. Mechanisms underlying the effects of n-3 polyunsaturated fatty acids on fear memory processing and their hypothetical effects on fear of cancer recurrence in cancer survivors. Prostaglandins Leukot Essent Fatty Acids 2018; 131:14-23. [PMID: 29628046 DOI: 10.1016/j.plefa.2018.03.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Revised: 03/14/2018] [Accepted: 03/21/2018] [Indexed: 12/26/2022]
Abstract
The relationship of n-3 polyunsaturated fatty acids (PUFAs) and gut microbiota with brain function has been extensively reported. Here, we review how n-3 polyunsaturated fatty acids affect fear memory processing. n-3 PUFAs may improve dysfunctional fear memory processing via immunomodulation/anti-inflammation, increased BDNF, upregulated adult neurogenesis, modulated signal transduction, and microbiota-gut-brain axis normalization. We emphasize how n-3 PUFAs affect this axis and also focus on the hypothetical effects of PUFAs in fear of cancer recurrence (FCR), the primary psychological unmet need of cancer survivors. Its pathophysiology may be similar to that of post-traumatic stress disorder (PTSD), which involves dysfunctional fear memory processing. Due to fewer adverse effects than psychotropic drugs, nutritional interventions involving n-3 PUFAs should be acceptable for physically vulnerable cancer survivors. We are currently studying the relationship of FCR with n-3 PUFAs and gut microbiota in cancer survivors to provide them with a nutritional intervention that protects against FCR.
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Affiliation(s)
- R Okubo
- Division of Health Care Research, Center for Public Health Science, National Cancer Center Japan, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
| | - C Chen
- RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
| | - M Sekiguchi
- Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira City, Tokyo 187-8551, Japan
| | - K Hamazaki
- Department of Public Health, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama City, Toyama 930-0194, Japan
| | - Y J Matsuoka
- Division of Health Care Research, Center for Public Health Science, National Cancer Center Japan, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
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21
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Doulberis M, Kotronis G, Thomann R, Polyzos SA, Boziki M, Gialamprinou D, Deretzi G, Katsinelos P, Kountouras J. Review: Impact of Helicobacter pylori on Alzheimer's disease: What do we know so far? Helicobacter 2018; 23. [PMID: 29181894 DOI: 10.1111/hel.12454] [Citation(s) in RCA: 93] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Helicobacter pylori has changed radically gastroenterologic world, offering a new concept in patients' management. Over time, more medical data gave rise to diverse distant, extragastric manifestations and interactions of the "new" discovered bacterium. Special interest appeared within the field of neurodegenerative diseases and particularly Alzheimer's disease, as the latter and Helicobacter pylori infection are associated with a large public health burden and Alzheimer's disease ranks as the leading cause of disability. However, the relationship between Helicobacter pylori infection and Alzheimer's disease remains uncertain. METHODS We performed a narrative review regarding a possible connection between Helicobacter pylori and Alzheimer's disease. All accessible relevant (pre)clinical studies written in English were included. Both affected pathologies were briefly analyzed, and relevant studies are discussed, trying to focus on the possible pathogenetic role of this bacterium in Alzheimer's disease. RESULTS Data stemming from both epidemiologic studies and animal experiments seem to be rather encouraging, tending to confirm the hypothesis that Helicobacter pylori infection might influence the course of Alzheimer's disease pleiotropically. Possible main mechanisms may include the bacterium's access to the brain via the oral-nasal-olfactory pathway or by circulating monocytes (infected with Helicobacter pylori due to defective autophagy) through disrupted blood-brain barrier, thereby possibly triggering neurodegeneration. CONCLUSIONS Current data suggest that Helicobacter pylori infection might influence the pathophysiology of Alzheimer's disease. However, further large-scale randomized controlled trials are mandatory to clarify a possible favorable effect of Helicobacter pylori eradication on Alzheimer's disease pathophysiology, before the recommendation of short-term and cost-effective therapeutic regimens against Helicobacter pylori-related Alzheimer's disease.
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Affiliation(s)
- Michael Doulberis
- Department of Internal Medicine, Bürgerspital Hospital, Solothurn, Switzerland
| | - Georgios Kotronis
- Department of Internal Medicine, Agios Pavlos General Hospital, Thessaloniki, Macedonia, Greece
| | - Robert Thomann
- Department of Internal Medicine, Bürgerspital Hospital, Solothurn, Switzerland
| | - Stergios A Polyzos
- Department of Internal Medicine, Ippokration Hospital, Second Medical Clinic, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Marina Boziki
- Department of Internal Medicine, Ippokration Hospital, Second Medical Clinic, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Dimitra Gialamprinou
- Department of Pediatrics, Papageorgiou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Georgia Deretzi
- Department of Neurology, Papageorgiou General Hospital, Multiple Sclerosis Unit, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Panagiotis Katsinelos
- Department of Internal Medicine, Ippokration Hospital, Second Medical Clinic, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Jannis Kountouras
- Department of Internal Medicine, Ippokration Hospital, Second Medical Clinic, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
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22
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Bullman S, Pedamallu CS, Sicinska E, Clancy TE, Zhang X, Cai D, Neuberg D, Huang K, Guevara F, Nelson T, Chipashvili O, Hagan T, Walker M, Ramachandran A, Diosdado B, Serna G, Mulet N, Landolfi S, Ramon Y Cajal S, Fasani R, Aguirre AJ, Ng K, Élez E, Ogino S, Tabernero J, Fuchs CS, Hahn WC, Nuciforo P, Meyerson M. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science 2017; 358:1443-1448. [PMID: 29170280 DOI: 10.1126/science.aal5240] [Citation(s) in RCA: 1029] [Impact Index Per Article: 128.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Revised: 08/17/2017] [Accepted: 11/13/2017] [Indexed: 12/12/2022]
Abstract
Colorectal cancers comprise a complex mixture of malignant cells, nontransformed cells, and microorganisms. Fusobacterium nucleatum is among the most prevalent bacterial species in colorectal cancer tissues. Here we show that colonization of human colorectal cancers with Fusobacterium and its associated microbiome-including Bacteroides, Selenomonas, and Prevotella species-is maintained in distal metastases, demonstrating microbiome stability between paired primary and metastatic tumors. In situ hybridization analysis revealed that Fusobacterium is predominantly associated with cancer cells in the metastatic lesions. Mouse xenografts of human primary colorectal adenocarcinomas were found to retain viable Fusobacterium and its associated microbiome through successive passages. Treatment of mice bearing a colon cancer xenograft with the antibiotic metronidazole reduced Fusobacterium load, cancer cell proliferation, and overall tumor growth. These observations argue for further investigation of antimicrobial interventions as a potential treatment for patients with Fusobacterium-associated colorectal cancer.
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Affiliation(s)
- Susan Bullman
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.,Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Chandra S Pedamallu
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.,Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Ewa Sicinska
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
| | - Thomas E Clancy
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Xiaoyang Zhang
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.,Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Diana Cai
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.,Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Donna Neuberg
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
| | - Katherine Huang
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Fatima Guevara
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
| | - Timothy Nelson
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
| | - Otari Chipashvili
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
| | - Timothy Hagan
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
| | - Mark Walker
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Aruna Ramachandran
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.,Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Begoña Diosdado
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.,Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Garazi Serna
- Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, CIBERONC, Universitat Autònoma de Barcelona, Spain
| | - Nuria Mulet
- Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, CIBERONC, Universitat Autònoma de Barcelona, Spain
| | - Stefania Landolfi
- Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, CIBERONC, Universitat Autònoma de Barcelona, Spain
| | - Santiago Ramon Y Cajal
- Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, CIBERONC, Universitat Autònoma de Barcelona, Spain
| | - Roberta Fasani
- Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, CIBERONC, Universitat Autònoma de Barcelona, Spain
| | - Andrew J Aguirre
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.,Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.,Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Kimmie Ng
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
| | - Elena Élez
- Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, CIBERONC, Universitat Autònoma de Barcelona, Spain
| | - Shuji Ogino
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.,Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.,Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
| | - Josep Tabernero
- Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, CIBERONC, Universitat Autònoma de Barcelona, Spain
| | - Charles S Fuchs
- Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA
| | - William C Hahn
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.,Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.,Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Paolo Nuciforo
- Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, CIBERONC, Universitat Autònoma de Barcelona, Spain
| | - Matthew Meyerson
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.,Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.,Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
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Brandão D, Ribeiro L. Dietary fatty acids modulation of human colon cancer cells: mechanisms and future perspectives. Int J Food Sci Nutr 2017; 69:437-450. [PMID: 28984495 DOI: 10.1080/09637486.2017.1382456] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Colorectal cancer (CRC) is one of the most common malignancies worldwide and its pathogenesis is proven to be related with dietary patterns, namely dietary fatty acid (FA) intake. We reviewed the evidences regarding the effect of different dietary FAs on human CRC cell lines proliferation and apoptosis. Altogether, the results obtained from in vitro studies show that monounsaturated FAs lack evidence regarding both proliferation and apoptosis, whereas there is a consensus about the anti-proliferative and pro-apoptotic effects, involving different intracellular targets, of n-3 polyunsaturated FAs, while n-6 series show a similar effect or no effects. The response to these dietary components depends on the cell type as well as the amount and duration of exposure. These results highlight the importance of identifying molecular targets for dietary components aiming to interfere with one of the main risk factors related with CRC incidence and prevalence.
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Affiliation(s)
- D Brandão
- a Department of Biomedicine, Unit of Biochemistry , Faculty of Medicine of the University of Porto , Porto , Portugal.,b Department of Public Health and Forensic Sciences, and Medical Education , Faculty of Medicine of the University of Porto , Porto , Portugal
| | - L Ribeiro
- a Department of Biomedicine, Unit of Biochemistry , Faculty of Medicine of the University of Porto , Porto , Portugal.,b Department of Public Health and Forensic Sciences, and Medical Education , Faculty of Medicine of the University of Porto , Porto , Portugal.,c I3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto , Porto , Portugal
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Toribio A, Marrodán T, Fernández-Natal I, Martínez-Blanco H, Rodríguez-Aparicio L, Ferrero MÁ. Study of conjunctival flora in anophthalmic patients: influence on the comfort of the socket. Graefes Arch Clin Exp Ophthalmol 2017; 255:1669-1679. [PMID: 28601909 DOI: 10.1007/s00417-017-3708-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Revised: 05/08/2017] [Accepted: 05/30/2017] [Indexed: 12/01/2022] Open
Abstract
PURPOSE To investigate the relationship between conjunctival flora and comfort of the socket in anophthalmic patients. METHODS A cross-sectional clinical study including 60 patients with unilateral anophthalmia who wear a prosthetic eye. From each patient three microbiological samples were taken from the lower conjunctival sac (healthy eye, pre-prosthesis, and retro-prosthesis space of socket). The 180 samples obtained were cultured. Samples from a randomized subgroup of 29 patients were measured by spectrophotometry at 540 nm after 48 h of growth, to determine their microbial density (MD). The grade of comfort of the socket (GCS) of each patient was established by a questionnaire. Epidemiological and clinical data of the anophthalmic socket and artificial eye care of each patient were also collected. RESULTS MD decreased in healthy eyes (0.213 ± 0.201, P = 0.004) compared with the pre-prosthesis (0.402 ± 0.323) and retro-prosthesis (0.438 ± 0.268) samples. Pre-prosthesis MD correlated with retro-prosthesis MD (R = 0.401, P = 0.031) and healthy eye MD (R = 0.482, P = 0.008), and it was also related to poor GCS (P = 0.017). Aerobic Gram-negative bacteria in retro-prosthesis samples of patients with poor GCS was higher than in patients with good or fair GCS (P = 0.008). In the same samples, coagulase-negative staphylococci proportion (excluding S. epidermidis) increased in patients with good GCS (P = 0.030). CONCLUSIONS Socket microflora is related to GCS. Increased pathogenic flora, especially Gram-negative bacteria, and high MD are related to discomfort, while coagulase-negative staphylococci (other than S. epidermidis) are associated with comfort.
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Affiliation(s)
- Alvaro Toribio
- Department of Ophthalmology, University Hospital of León, Altos de Nava s/n, 24071, Leon, Spain.
| | - Teresa Marrodán
- Department of Clinical Microbiology, University Hospital of León, León, Spain
| | | | | | | | - Miguel Á Ferrero
- Department of Molecular Biology, University of León, León, Spain
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Lee JY, Lee MK, Kim NK, Chu SH, Lee DC, Lee HS, Lee JW, Jeon JY. Serum chemerin levels are independently associated with quality of life in colorectal cancer survivors: A pilot study. PLoS One 2017; 12:e0176929. [PMID: 28475614 PMCID: PMC5419570 DOI: 10.1371/journal.pone.0176929] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2016] [Accepted: 04/19/2017] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Colorectal cancer (CRC) survivors are known to experience various symptoms that significantly affect their quality of life (QOL); therefore, it is important to identify clinical markers related with CRC survivor QOL. Here we investigated the relationship between serum chemerin levels, a newly identified proinflammatory adipokine, and QOL in CRC survivors. METHODS A data of total of 110 CRC survivors were analysed in the study. Serum chemerin levels were measured with an enzyme immunoassay analyser. Functional Assessment of Cancer Therapy (FACT) scores were used as an indicator of QOL in CRC survivors. RESULTS Weak but not negligible relationships were observed between serum chemerin levels and FACT-General (G) (r = -0.22, p<0.02), FACT-Colorectal cancer (C) (r = -0.23, p<0.02) and FACT-Fatigue (F) scores (r = -0.27, p<0.01) after adjusting for confounding factors. Both stepwise and enter method multiple linear regression analyses confirmed that serum chemerin levels were independently associated with FACT-G (stepwise: β = -0.15, p<0.01; enter: β = -0.12, p = 0.02), FACT-C (stepwise: β = -0.19, p<0.01; enter; β = -0.14, p = 0.02) and FACT-F scores (stepwise: β = -0.23, p<0.01; enter: β = -0.20, p<0.01). CONCLUSIONS Our results demonstrate a weak inverse relationship between serum chemerin and CRC survivor QOL. Although it is impossible to determine causality, our findings suggest that serum chemerin levels may have a significant association with CRC survivor QOL. Further prospective studies are required to confirm the clinical significance of our pilot study.
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Affiliation(s)
- Jee-Yon Lee
- Department of Family Medicine, Yonsei University, College of Medicine, Seoul, Republic of Korea
- Department of Family Medicine, CHA University College of Medicine, CHA Bundang Medical Center, Chaum Life Center, Seoul, Republic of Korea
| | - Mi-Kyung Lee
- Department of Sport and Leisure Studies, Sports Medicine Laboratory, Yonsei University, Seoul, Republic of Korea
| | - Nam-Kyu Kim
- Department of General Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sang-Hui Chu
- Department of Clinical Nursing Science, Yonsei University, College of Nursing, Nursing Policy Research Institute, Bio-behavioural Research Centre, Seoul, Republic of Korea
| | - Duk-Chul Lee
- Department of Family Medicine, Yonsei University, College of Medicine, Seoul, Republic of Korea
| | - Hye-Sun Lee
- Department of Biostatistics, Yonsei University, College of Medicine, Seoul, Republic of Korea
| | - Ji-Won Lee
- Department of Family Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
- * E-mail: (JWL); (JYJ)
| | - Justin Y. Jeon
- Department of Family Medicine, CHA University College of Medicine, CHA Bundang Medical Center, Chaum Life Center, Seoul, Republic of Korea
- * E-mail: (JWL); (JYJ)
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Thomas AM, Jesus EC, Lopes A, Aguiar S, Begnami MD, Rocha RM, Carpinetti PA, Camargo AA, Hoffmann C, Freitas HC, Silva IT, Nunes DN, Setubal JC, Dias-Neto E. Tissue-Associated Bacterial Alterations in Rectal Carcinoma Patients Revealed by 16S rRNA Community Profiling. Front Cell Infect Microbiol 2016; 6:179. [PMID: 28018861 PMCID: PMC5145865 DOI: 10.3389/fcimb.2016.00179] [Citation(s) in RCA: 90] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Accepted: 11/24/2016] [Indexed: 12/12/2022] Open
Abstract
Sporadic and inflammatory forms of colorectal cancer (CRC) account for more than 80% of cases. Recent publications have shown mechanistic evidence for the involvement of gut bacteria in the development of both CRC-forms. Whereas, colon and rectal cancer have been routinely studied together as CRC, increasing evidence show these to be distinct diseases. Also, the common use of fecal samples to study microbial communities may reflect disease state but possibly not the tumor microenvironment. We performed this study to evaluate differences in bacterial communities found in tissue samples of 18 rectal-cancer subjects when compared to 18 non-cancer controls. Samples were collected during exploratory colonoscopy (non-cancer group) or during surgery for tumor excision (rectal-cancer group). High throughput 16S rRNA amplicon sequencing of the V4-V5 region was conducted on the Ion PGM platform, reads were filtered using Qiime and clustered using UPARSE. We observed significant increases in species richness and diversity in rectal cancer samples, evidenced by the total number of OTUs and the Shannon and Simpson indexes. Enterotyping analysis divided our cohort into two groups, with the majority of rectal cancer samples clustering into one enterotype, characterized by a greater abundance of Bacteroides and Dorea. At the phylum level, rectal-cancer samples had increased abundance of candidate phylum OD1 (also known as Parcubacteria) whilst non-cancer samples had increased abundance of Planctomycetes. At the genera level, rectal-cancer samples had higher abundances of Bacteroides, Phascolarctobacterium, Parabacteroides, Desulfovibrio, and Odoribacter whereas non-cancer samples had higher abundances of Pseudomonas, Escherichia, Acinetobacter, Lactobacillus, and Bacillus. Two Bacteroides fragilis OTUs were more abundant among rectal-cancer patients seen through 16S rRNA amplicon sequencing, whose presence was confirmed by immunohistochemistry and enrichment verified by digital droplet PCR. Our findings point to increased bacterial richness and diversity in rectal cancer, along with several differences in microbial community composition. Our work is the first to present evidence for a possible role of bacteria such as B. fragilis and the phylum Parcubacteria in rectal cancer, emphasizing the need to study tissue-associated bacteria and specific regions of the gastrointestinal tract in order to better understand the possible links between the microbiota and rectal cancer.
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Affiliation(s)
- Andrew M Thomas
- Medical Genomics Laboratory, CIPE/A.C. Camargo Cancer CenterSão Paulo, Brazil; Departamento de Bioquímica, Instituto de Química, Universidade de São PauloSão Paulo, Brazil; Curso de Pós-Graduação em Bioinformática, Universidade de São PauloSão Paulo, Brazil
| | - Eliane C Jesus
- Medical Genomics Laboratory, CIPE/A.C. Camargo Cancer CenterSão Paulo, Brazil; Department of Pelvic Surgery, A.C. Camargo Cancer CenterSão Paulo, Brazil
| | - Ademar Lopes
- Department of Pelvic Surgery, A.C. Camargo Cancer Center São Paulo, Brazil
| | - Samuel Aguiar
- Department of Pelvic Surgery, A.C. Camargo Cancer Center São Paulo, Brazil
| | - Maria D Begnami
- Department of Pathology, A.C. Camargo Cancer Center São Paulo, Brazil
| | - Rafael M Rocha
- Laboratory of Molecular Gynecology, Department of Gynecology, Medicine College, Federal University of São Paulo São Paulo, Brazil
| | | | | | - Christian Hoffmann
- Departamento de Alimentos e Nutrição Experimental, Faculdade de Ciências Farmacêuticas, Food Research Center (FoRC), Universidade de São Paulo São Paulo, Brazil
| | - Helano C Freitas
- Medical Genomics Laboratory, CIPE/A.C. Camargo Cancer CenterSão Paulo, Brazil; Department of Clinical Oncology, A.C. Camargo Cancer CenterSão Paulo, Brazil
| | - Israel T Silva
- Laboratory of Computational Biology and Bioinformatics, A.C. Camargo Cancer Center São Paulo, Brazil
| | - Diana N Nunes
- Medical Genomics Laboratory, CIPE/A.C. Camargo Cancer Center São Paulo, Brazil
| | - João C Setubal
- Departamento de Bioquímica, Instituto de Química, Universidade de São PauloSão Paulo, Brazil; Biocomplexity Institute, Virginia TechBlacksburg, VA, USA
| | - Emmanuel Dias-Neto
- Medical Genomics Laboratory, CIPE/A.C. Camargo Cancer CenterSão Paulo, Brazil; Laboratory of Neurosciences (LIM-27) Alzira Denise Hertzog Silva, Institute of Psychiatry, Faculdade de Medicina, Universidade de São PauloSão Paulo, Brazil
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Patel T, Bhattacharya P, Das S. Gut microbiota: an Indicator to Gastrointestinal Tract Diseases. J Gastrointest Cancer 2016; 47:232-8. [DOI: 10.1007/s12029-016-9820-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Goc J, Hepworth MR, Sonnenberg GF. Group 3 innate lymphoid cells: regulating host-commensal bacteria interactions in inflammation and cancer. Int Immunol 2016; 28:43-52. [PMID: 26451009 PMCID: PMC5891988 DOI: 10.1093/intimm/dxv056] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2015] [Accepted: 09/28/2015] [Indexed: 12/15/2022] Open
Abstract
A delicate balance exists between the mammalian immune system and normally beneficial commensal bacteria that colonize the gastrointestinal tract, which is necessary to maintain tissue homeostasis. Dysregulation of these interactions between the host and commensal bacteria is causally associated with chronic inflammation and the development of cancer. In contrast, recent reports have highlighted that commensal bacteria also play an essential role in promoting anti-tumor immune responses in several contexts, highlighting a paradox whereby interactions between the host and commensal bacteria can influence both pro- and anti-tumor immunity. Given the critical roles for group 3 innate lymphoid cells (ILC3s) in regulating inflammation, tissue repair and host-microbe interactions in the intestine, here we discuss new evidence that ILC3s may profoundly influence the development, progression and control of tumors. In this review, we provide an overview of recent advances in understanding the impact of commensal bacteria on tumorigenesis, discuss recent findings identifying ILC3s as critical regulators of host-microbe interactions and highlight the emerging role of this immune cell population in cancer and their potential implication as a therapeutic target.
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Affiliation(s)
- Jeremy Goc
- Joan and Sanford I. Weill Department of Medicine, Division of Gastroenterology and Hepatology, Department of Microbiology and Immunology and The Jill Robert's Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, Cornell University, 413 East 69th Street, Belfer Research Building 512, Box 190, New York, NY 10021, USA
| | - Matthew R Hepworth
- Joan and Sanford I. Weill Department of Medicine, Division of Gastroenterology and Hepatology, Department of Microbiology and Immunology and The Jill Robert's Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, Cornell University, 413 East 69th Street, Belfer Research Building 512, Box 190, New York, NY 10021, USA
| | - Gregory F Sonnenberg
- Joan and Sanford I. Weill Department of Medicine, Division of Gastroenterology and Hepatology, Department of Microbiology and Immunology and The Jill Robert's Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, Cornell University, 413 East 69th Street, Belfer Research Building 512, Box 190, New York, NY 10021, USA
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Abstract
Esophageal cancer is one of the deadliest cancers, with a dismal prognosis. It is increasingly recognized that esophageal cancer is a heterogeneous disease. It can be subdivided into two distinct groups: squamous cell carcinoma and adenocarcinoma, based on histological appearance. In the Western world, the incidence of squamous cell carcinoma was considerably higher than esophageal adenocarcinoma (EA) until the 1990s when, due to a dramatic increase, the incidence of EA surpassed that of squamous cell carcinoma. EA typically follows a well-established stepwise evolution from chronic inflammation due to reflux esophagitis (RE) that progresses to metaplasia (Barrett's esophagus [BE]) to dysplasia, which often culminates in EA. The pathophysiology of EA is complex and involves diverse factors, including gastroesophageal reflux, gastric acid secretion, dysfunction of the antireflux barrier, gastric emptying disturbances, and abnormalities in esophageal defense mechanisms. The current understanding of the etiology of EA is mainly derived from epidemiological studies of risk factors such as cigarette smoking, obesity, gastroesophageal reflux disorders (GERD), and low fruit and vegetable consumption. Numerous studies have been done, but the factors that drive the dynamic increase in the incidence of EA remain elusive. The advent of widespread antibiotic use occurred in the 1950s, preceding the surge of EA. Based on this temporal sequence, it has been hypothesized that antibiotics alter the microbiome to which the esophagus is exposed in patients who have GERD and that chronic exposure to this abnormal microbiome (ie, changes in species diversity or abundance) accounts for the increase in EA. If changes in the proposed factors alter the stepwise progression (RE-BE-dysplasia-EA), they may represent potential targets for chemoprevention. New discoveries will help improve our understanding of the biology and pathogenesis of these cancers, and aid in finding novel therapeutic targets.
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Affiliation(s)
- Antonio Galvao Neto
- Department of Pathology, New York University School of Medicine, New York, NY, USA
| | - April Whitaker
- Department of Pathology, New York University School of Medicine, New York, NY, USA
| | - Zhiheng Pei
- Department of Veterans Affairs New York Harbor Healthcare System, New York, NY, USA; Departments of Medicine and Pathology, New York University School of Medicine, New York, NY, USA.
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Testerman TL. Fulfilling the Promise of Microbiomics to Revolutionize Medicine. JOURNAL OF MICROBIOLOGY & EXPERIMENTATION 2015; 2:00050. [PMID: 27030825 PMCID: PMC4809425 DOI: 10.15406/jmen.2015.02.00050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Affiliation(s)
- Traci L Testerman
- Corresponding author: Traci L Testerman, University of South Carolina School of Medicine, Columbia, SC 29209, USA,
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Rouhollahi E, Moghadamtousi SZ, Al-Henhena N, Kunasegaran T, Hasanpourghadi M, Looi CY, Abd Malek SN, Awang K, Abdulla MA, Mohamed Z. The chemopreventive potential of Curcuma purpurascens rhizome in reducing azoxymethane-induced aberrant crypt foci in rats. DRUG DESIGN DEVELOPMENT AND THERAPY 2015; 9:3911-22. [PMID: 26251570 PMCID: PMC4524378 DOI: 10.2147/dddt.s84560] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Curcuma purpurascens BI. rhizome, a member of the Zingiberaceae family, is a popular spice in Indonesia that is traditionally used in assorted remedies. Dichloromethane extract of C. purpurascens BI. rhizome (DECPR) has previously been shown to have an apoptosis-inducing effect on colon cancer cells. In the present study, we examined the potential of DECPR to prevent colon cancer development in rats treated with azoxymethane (AOM) (15 mg/kg) by determining the percentage inhibition in incidence of aberrant crypt foci (ACF). Starting from the day immediately after AOM treatment, three groups of rats were orally administered once a day for 2 months either 10% Tween 20 (5 mL/kg, cancer control), DECPR (250 mg/kg, low dose), or DECPR (500 mg/kg, high dose). Meanwhile, the control group was intraperitoneally injected with 5-fluorouracil (35 mg/kg) for 5 consecutive days. After euthanizing the rats, the number of ACF was enumerated in colon tissues. Bax, Bcl-2, and proliferating cell nuclear antigen (PCNA) protein expressions were examined using immunohistochemical and Western blot analyses. Antioxidant enzymatic activity was measured in colon tissue homogenates and associated with malondialdehyde level. The percentage inhibition of ACF was 56.04% and 68.68% in the low- and high-dose DECPR-treated groups, respectively. The ACF inhibition in the treatment control group was 74.17%. Results revealed that DECPR exposure at both doses significantly decreased AOM-induced ACF formation, which was accompanied by reduced expression of PCNA. Upregulation of Bax and downregulation of Bcl-2 suggested the involvement of apoptosis in the chemopreventive effect of DECPR. In addition, the oxidative stress resulting from AOM treatment was significantly attenuated after administration of DECPR, which was shown by the elevated antioxidant enzymatic activity and reduced malondialdehyde level. Taken together, the present data clearly indicate that DECPR significantly inhibits ACF formation in AOM-treated rats and may offer protection against colon cancer development.
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Affiliation(s)
- Elham Rouhollahi
- Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | | | - Nawal Al-Henhena
- Department of Biomedical Science, University of Malaya, Kuala Lumpur, Malaysia
| | - Thubasni Kunasegaran
- Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Mohadeseh Hasanpourghadi
- Cell Biology and Drug Discovery Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Chung Yeng Looi
- Cell Biology and Drug Discovery Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Sri Nurestri Abd Malek
- Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia
| | - Khalijah Awang
- Department of Chemistry, University of Malaya, Kuala Lumpur, Malaysia
| | | | - Zahurin Mohamed
- Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
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Fichtner-Feigl S, Kesselring R, Strober W. Chronic inflammation and the development of malignancy in the GI tract. Trends Immunol 2015. [PMID: 26194796 DOI: 10.1016/j.it.2015.06.007] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The role of immunologic factors in the development of gastrointestinal (GI) neoplasia, made evident from the high degree of association of chronic intestinal or gastric inflammation with the development of cancer, has attracted much attention because it promises new ways of treating disease. Here we develop the idea that immunologic factors influence the appearance of GI cancer on two levels: (i) a basic and initiating level during which the epithelial cell is induced to undergo pre-cancerous molecular changes that render it prone to further cancer progression; and (ii) a secondary level that builds on this vulnerability and drives the cell into frank malignancy. This secondary level is uniquely dependent on a single epithelial cell signaling pathway centered on STAT3, and it is this pathway upon which stimulation of mucosal cytokine production and microbiota effects converge.
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Affiliation(s)
- Stefan Fichtner-Feigl
- Department of Surgery, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany; Regensburg Center for Interventional Immunology, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany
| | - Rebecca Kesselring
- Department of Surgery, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany
| | - Warren Strober
- Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious, National Institutes of Health, Bethesda, MD 20892, USA.
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Xu R, Wang Q, Li L. A genome-wide systems analysis reveals strong link between colorectal cancer and trimethylamine N-oxide (TMAO), a gut microbial metabolite of dietary meat and fat. BMC Genomics 2015; 16 Suppl 7:S4. [PMID: 26100814 PMCID: PMC4474417 DOI: 10.1186/1471-2164-16-s7-s4] [Citation(s) in RCA: 131] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Background Dietary intakes of red meat and fat are established risk factors for both colorectal cancer (CRC) and cardiovascular disease (CVDs). Recent studies have shown a mechanistic link between TMAO, an intestinal microbial metabolite of red meat and fat, and risk of CVDs. Data linking TMAO directly to CRC is, however, lacking. Here, we present an unbiased data-driven network-based systems approach to uncover a potential genetic relationship between TMAO and CRC. Materials and methods We constructed two different epigenetic interaction networks (EINs) using chemical-gene, disease-gene and protein-protein interaction data from multiple large-scale data resources. We developed a network-based ranking algorithm to ascertain TMAO-related diseases from EINs. We systematically analyzed disease categories among TMAO-related diseases at different ranking cutoffs. We then determined which genetic pathways were associated with both TMAO and CRC. Results We show that CVDs and their major risk factors were ranked highly among TMAO-related diseases, confirming the newly discovered mechanistic link between CVDs and TMAO, and thus validating our algorithms. CRC was ranked highly among TMAO-related disease retrieved from both EINs (top 0.02%, #1 out of 4,372 diseases retrieved based on Mendelian genetics and top 10.9% among 882 diseases based on genome-wide association genetics), providing strong supporting evidence for our hypothesis that TMAO is genetically related to CRC. We have also identified putative genetic pathways that may link TMAO to CRC, which warrants further investigation. Through systematic disease enrichment analysis, we also demonstrated that TMAO is related to metabolic syndromes and cancers in general. Conclusions Our genome-wide analysis demonstrates that systems approaches to studying the epigenetic interactions among diet, microbiome metabolisms, and disease genetics hold promise for understanding disease pathogenesis. Our results show that TMAO is genetically associated with CRC. This study suggests that TMAO may be an important intermediate marker linking dietary meat and fat and gut microbiota metabolism to risk of CRC, underscoring opportunities for the development of new gut microbiome-dependent diagnostic tests and therapeutics for CRC.
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Paritsky M, Pastukh N, Brodsky D, Isakovich N, Peretz A. Association of Streptococcus bovis presence in colonic content with advanced colonic lesion. World J Gastroenterol 2015; 21:5663-5667. [PMID: 25987793 PMCID: PMC4427692 DOI: 10.3748/wjg.v21.i18.5663] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2014] [Revised: 12/22/2014] [Accepted: 02/05/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To prospectively examine the association between presence of Streptococcus bovis (S. bovis) in colonic suction fluid and the endoscopic findings on colonoscopy.
METHODS: From May 2012 to March 2013, 203 consecutive patients who underwent colonoscopy for any reason were enrolled in the study. Exclusion criteria included: antibiotic use in the previous month, age younger than 18 years, and inadequate preparation for colonoscopy. The colonoscopy was performed for the total length of the colon or to the occluding tumor. The endoscopic findings were registered. Samples were obtained proximal to the colonoscopic part of the suction tube from each patient and sent to the clinical microbiology laboratory for isolation and identification of S. bovis. Samples were incubated in enrichment media with addition of antibiotic disks for inhibition of growth of Gram-negative rods. The samples were seeded on differential growth media; suspected positive colonies were isolated and identified with Gram staining, catalase, and pyrrolidonyl arylamidase tests, and further identified using a VITEK2 system. Statistical analyses were performed using the Student’s t and χ2 tests.
RESULTS: Of the 203 patients recruited, 49 (24%) patients were found to be S. bovis carriers; of them, the endoscopic findings included: 17 (34.7%) cases with malignant tumors, 11 (22.4%) with large polyps, 5 (10.2%) with medium-sized polyps, 6 (12.2%) with small polyps, 4 (8.1%) with colitis, and 6 (12.2%) normal colonoscopies. Of 154 patients found negative for S. bovis, the endoscopic findings included: none with malignant tumors, 9 (5.8%) cases with large polyps, 11 (7.1%) with medium-sized polyps, 26 (16.9%) with small polyps, 7 (4.5%) with colitis, and 101 (65.6%) normal colonoscopies. S. bovis (Gram-positive coccus) is considered part of the normal intestinal flora. There is an association between S. bovis bacteremia and colonic neoplasia. It is not well understood whether the bacterium has a pathogenetic role in the development of neoplasia or constitutes an epiphenomenon of colorectal neoplasms. There was a clear relationship between positivity for S. bovis in colonic suction fluid and findings of malignant tumors and large polyps in the colon.
CONCLUSION: There is an association between S. bovis bacteremia and malignant colonic lesions; this should prompt for development of a reliable screening method for advanced colonic lesions.
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Application of the ApcMin/+ mouse model for studying inflammation-associated intestinal tumor. Biomed Pharmacother 2015; 71:216-21. [DOI: 10.1016/j.biopha.2015.02.023] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2015] [Accepted: 02/15/2015] [Indexed: 12/16/2022] Open
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Keku TO, Dulal S, Deveaux A, Jovov B, Han X. The gastrointestinal microbiota and colorectal cancer. Am J Physiol Gastrointest Liver Physiol 2015; 308:G351-63. [PMID: 25540232 PMCID: PMC4346754 DOI: 10.1152/ajpgi.00360.2012] [Citation(s) in RCA: 156] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The human gut is home to a complex and diverse microbiota that contributes to the overall homeostasis of the host. Increasingly, the intestinal microbiota is recognized as an important player in human illness such as colorectal cancer (CRC), inflammatory bowel diseases, and obesity. CRC in itself is one of the major causes of cancer mortality in the Western world. The mechanisms by which bacteria contribute to CRC are complex and not fully understood, but increasing evidence suggests a link between the intestinal microbiota and CRC as well as diet and inflammation, which are believed to play a role in carcinogenesis. It is thought that the gut microbiota interact with dietary factors to promote chronic inflammation and CRC through direct influence on host cell physiology, cellular homeostasis, energy regulation, and/or metabolism of xenobiotics. This review provides an overview on the role of commensal gut microbiota in the development of human CRC and explores its association with diet and inflammation.
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Affiliation(s)
- Temitope O. Keku
- 1Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina; ,2Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina, Chapel Hill, North Carolina; and
| | - Santosh Dulal
- 1Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina; ,2Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina, Chapel Hill, North Carolina; and
| | - April Deveaux
- 1Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina; ,2Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina, Chapel Hill, North Carolina; and
| | - Biljana Jovov
- 1Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina; ,2Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina, Chapel Hill, North Carolina; and
| | - Xuesong Han
- 3Surveillance and Health Services Research, American Cancer Society, Atlanta, Georgia
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Wada S, Matsushita Y, Tazawa H, Aoi W, Naito Y, Higashi A, Ohshima H, Yoshikawa T. Loss of p53 in stromal fibroblasts enhances tumor cell proliferation through nitric-oxide-mediated cyclooxygenase 2 activation. Free Radic Res 2015; 49:269-78. [PMID: 25511472 DOI: 10.3109/10715762.2014.997230] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Overexpression of cyclooxygenase 2 (COX-2) by stromal fibroblasts plays a critical role in the early stage of carcinogenesis. COX-2 expression is thought to be positively or negatively regulated by inflammatory chemical mediators or tumor suppressors. In this study, the contributions of inducible nitric oxide synthase (iNOS) and p53 to COX-2 expression were examined using mouse embryonic fibroblasts (MEFs) from wild-type, p53-deficient, iNOS-deficient, and p53/iNOS-deficient mice. These MEFs were treated with 1 μg/mL of lipopolysaccharide and 100 IU/mL of interferon gamma for up to 72 h. iNOS and COX-2 expression were analyzed by Western blotting. iNOS was induced earlier (16 h) in p53-deficient MEFs than in wild-type MEFs (48 h). Elevated expression of COX-2 was sustained for a longer duration in the p53-deficient MEFs. In contrast, COX-2 expression was reduced earlier in the iNOS-deficient MEFs. Addition of an exogenous NO donor (0.8 mM of S-nitroso-l-glutathione) to the iNOS-deficient MEFs augmented COX-2 expression. Co-culture with stimulated p53-deficient MEFs promoted cell proliferation of mouse rectal polyploid carcinoma CMT93 cells, but treatment with a COX-2-specific inhibitor counteracted this effect. These results suggest that loss of function of the p53 gene in stromal fibroblasts enhances COX-2 expression by enhancing iNOS expression and the resultant production of NO, contributing to the promotion of tumor growth.
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Affiliation(s)
- S Wada
- Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University , Shimogamo , Japan
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Ma S, Shen L, Chen M, Lin X, Wang Q, Du R, Feng Y. The study of metabonomics combined with diversity of intestinal flora in LDP intervention in kidney-yin deficiency hyperthyroid rats. RSC Adv 2015. [DOI: 10.1039/c5ra10134d] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
This study was to clarify the drug mechanism in the preparation of high-content plant polysaccharides.
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Affiliation(s)
- Shiyu Ma
- School of Traditional Chinese Medicine
- Shanghai University of Traditional Chinese Medicine
- Shanghai 201203
- China
| | - Lan Shen
- School of Traditional Chinese Medicine
- Shanghai University of Traditional Chinese Medicine
- Shanghai 201203
- China
- Engineering Research Center of Modern Preparation Technology of Traditional Chinese Medicine of Ministry of Education
| | - Meiwan Chen
- State Key Laboratory of Quality Research in Chinese Medicine
- Institute of Chinese Medical Sciences
- University of Macau
- Macao 999078
- China
| | - Xiao Lin
- School of Traditional Chinese Medicine
- Shanghai University of Traditional Chinese Medicine
- Shanghai 201203
- China
- Engineering Research Center of Modern Preparation Technology of Traditional Chinese Medicine of Ministry of Education
| | - Qiang Wang
- School of Traditional Chinese Medicine
- Shanghai University of Traditional Chinese Medicine
- Shanghai 201203
- China
| | - Ruofei Du
- School of Traditional Chinese Medicine
- Shanghai University of Traditional Chinese Medicine
- Shanghai 201203
- China
| | - Yi Feng
- Engineering Research Center of Modern Preparation Technology of Traditional Chinese Medicine of Ministry of Education
- Shanghai University of Traditional Chinese Medicine
- Shanghai 201203
- China
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Varela-Calviño R, Cordero OJ. Immunology and Immunotherapy of Colorectal Cancer. CANCER IMMUNOLOGY 2015:217-236. [DOI: 10.1007/978-3-662-46410-6_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Liu X, Chang X, Wu H, Xiao J, Gao Y, Zhang Y. Role of intestinal inflammation in predisposition of Edwardsiella tarda infection in zebrafish (Danio rerio). FISH & SHELLFISH IMMUNOLOGY 2014; 41:271-278. [PMID: 25224880 DOI: 10.1016/j.fsi.2014.09.009] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/14/2014] [Revised: 08/19/2014] [Accepted: 09/05/2014] [Indexed: 06/03/2023]
Abstract
Edwardsiella tarda, an enteric opportunistic pathogen, is associated with acute to chronic edwardsiellosis in cultured fish, resulting in heavy losses in aquaculture. To date, the pathogenesis of E. tarda has been extensively studied and a great deal of vaccine candidates have been attempted. However, the research on the predisposition of E. tarda infection is poorly reported. In this study, the effects of intestinal inflammation on E. tarda infection were investigated using a zebrafish model that influenced by perturbation of intestinal microbiota. Featured symptoms of edwardsiellosis were observed in intestinal inflammatory zebrafish compared with healthy fish. Higher bacterial numbers were detected in both mucosal tissues (intestine, skin and gills) and lymphoid tissues (liver, spleen and kidney) of inflammatory zebrafish while the bacterial loads in healthy zebrafish appeared to be relatively lower by 10-100 folds. Moreover, significant up-regulation of IL-1β, TNF-α and iNOS was noticed in multiple tissues of zebrafish with intestinal inflammation between 6 and 72 h post infection. However, only moderate elevation was observed in the gills and liver of healthy fish. Furthermore, the expression of genes involved in neutrophil recruitment (mpx, IL-8 and LECT2) and antimicrobial response (β-defensin and hepcidin) showed notable up-regulation in the intestine of inflammatory zebrafish. These results demonstrate that fish with intestinal inflammation is more susceptible to E. tarda and the antimicrobial response during E. tarda infection might inhibit the growth of intestinal microbiota. Our results suggest that maintaining good management to avoid intestinal inflammation is a feasible prevention measure against edwardsiellosis.
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Affiliation(s)
- Xiaohong Liu
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China
| | - Xinyue Chang
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China
| | - Haizhen Wu
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
| | - Jingfan Xiao
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China
| | - Yuan Gao
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China
| | - Yuanxing Zhang
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China; Shanghai Collaborative Innovation Center for Biomanufacturing Technology, 130 Meilong Road, Shanghai, 200237, China
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Lee JY, Chu SH, Jeon JY, Lee MK, Park JH, Lee DC, Lee JW, Kim NK. Effects of 12 weeks of probiotic supplementation on quality of life in colorectal cancer survivors: a double-blind, randomized, placebo-controlled trial. Dig Liver Dis 2014; 46:1126-32. [PMID: 25442120 DOI: 10.1016/j.dld.2014.09.004] [Citation(s) in RCA: 90] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2014] [Revised: 09/14/2014] [Accepted: 09/14/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Probiotics may help resolve bowel symptoms and improve quality of life. We investigated the effects of 12 weeks of probiotics administration in colorectal cancer patients. METHODS We conducted a double-blind, randomized, placebo-controlled trial. The participants took probiotics (Lacidofil) or placebo twice a day for 12 weeks. The cancer-related quality of life (FACT), patient's health-9 (PHQ-9), and bowel symptom questionnaires were completed by each participant. RESULTS We obtained data for 32 participants in the placebo group and 28 participants in the probiotics group. The mean ages of total participants were 56.18 ± .86 years and 58.3% were male. Administration of probiotics significantly decreased the proportion of patients suffering from irritable bowel symptoms (0 week vs. 12 week; 67.9% vs. 45.7%, p=0.03), improved colorectal cancer-related FACT (baseline vs. 12 weeks: 19.79 ± 4.66 vs. 21.18 ± 3.67, p=0.04) and fatigue-related FACT (baseline vs. 12 weeks: 43.00 (36.50-45.50) vs. 44.50 (38.50-49.00), p=0.02) and PHQ-9 scores (0 weeks vs. 12 weeks; 3.00 (0-8.00) vs. 1.00 (0-3.00), p=0.01). We found significant differences in changes of the proportion of patients with bowel symptoms (p<0.05), functional well-being scores (p=0.04) and cancer-related FACT scores (p=0.04) between the two groups. CONCLUSION Probiotics improved bowel symptoms and quality of life in colorectal cancer survivors.
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Affiliation(s)
- Jee-Yon Lee
- Department of Family Medicine, Yonsei University, College of Medicine, Republic of Korea
| | - Sang-Hui Chu
- Department of Clinical Nursing Science, Yonsei University, College of Nursing, Nursing Policy Research Institute, Biobehavioural Research Center, Republic of Korea
| | - Justin Y Jeon
- Department of Sport and Leisure Studies, Sports Medicine Laboratory, Yonsei University, Republic of Korea
| | - Mi-Kyung Lee
- Department of Sport and Leisure Studies, Sports Medicine Laboratory, Yonsei University, Republic of Korea
| | - Ji-Hye Park
- Department of Sport and Leisure Studies, Sports Medicine Laboratory, Yonsei University, Republic of Korea
| | - Duk-Chul Lee
- Department of Family Medicine, Yonsei University, College of Medicine, Republic of Korea
| | - Ji-Won Lee
- Department of Family Medicine, Yonsei University, College of Medicine, Republic of Korea.
| | - Nam-Kyu Kim
- Department of General Surgery, Yonsei University College of Medicine, Republic of Korea.
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Ahn J, Sinha R, Pei Z, Dominianni C, Wu J, Shi J, Goedert JJ, Hayes RB, Yang L. Human gut microbiome and risk for colorectal cancer. J Natl Cancer Inst 2013; 105:1907-11. [PMID: 24316595 DOI: 10.1093/jnci/djt300] [Citation(s) in RCA: 707] [Impact Index Per Article: 58.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
We tested the hypothesis that an altered community of gut microbes is associated with risk of colorectal cancer (CRC) in a study of 47 CRC case subjects and 94 control subjects. 16S rRNA genes in fecal bacterial DNA were amplified by universal primers, sequenced by 454 FLX technology, and aligned for taxonomic classification to microbial genomes using the QIIME pipeline. Taxonomic differences were confirmed with quantitative polymerase chain reaction and adjusted for false discovery rate. All statistical tests were two-sided. From 794217 16S rRNA gene sequences, we found that CRC case subjects had decreased overall microbial community diversity (P = .02). In taxonomy-based analyses, lower relative abundance of Clostridia (68.6% vs 77.8%) and increased carriage of Fusobacterium (multivariable odds ratio [OR] = 4.11; 95% confidence interval [CI] = 1.62 to 10.47) and Porphyromonas (OR = 5.17; 95% CI = 1.75 to 15.25) were found in case subjects compared with control subjects. Because of the potentially modifiable nature of the gut bacteria, our findings may have implications for CRC prevention.
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Affiliation(s)
- Jiyoung Ahn
- Affiliations of authors: Division of Epidemiology, Department of Population Health (JA, CD, JW, RBH), Department of Pathology (ZP), and Department of Medicine (ZP, LY), New York University School of Medicine, New York, NY; New York University Cancer Institute, New York, NY (JA, ZP, CD, JW, RBH); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD (RS, JS, JJG); Department of Pathology and Laboratory Medicine, New York Veterans Affairs Medical Center, New York, NY (ZP)
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Effects of antibiotics on bacterial species composition and metabolic activities in chemostats containing defined populations of human gut microorganisms. Antimicrob Agents Chemother 2013; 57:2016-25. [PMID: 23403424 DOI: 10.1128/aac.00079-13] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
The composition and metabolic activities of the human colonic microbiota are modulated by a number of external factors, including diet and antibiotic therapy. Changes in the structure and metabolism of the gut microbiota may have long-term consequences for host health. The large intestine harbors a complex microbial ecosystem comprising several hundreds of different bacterial species, which complicates investigations on intestinal physiology and ecology. To facilitate such studies, a highly simplified microbiota consisting of 14 anaerobic and facultatively anaerobic organisms (Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bifidobacterium longum, Bifidobacterium infantis, Bifidobacterium pseudolongum, Bifidobacterium adolescentis, Clostridium butyricum, C. perfringens, C. bifermentans, C. innocuum, Escherichia coli, Enterococcus faecalis, Enterococcus faecium, Lactobacillus acidophilus) was used in this investigation. Ampicillin [9.2 μg (ml culture)(-1)] was added to two chemostats operated at different dilution rates (D; 0.10 h(-1) and 0.21 h(-1)), and metronidazole [76.9 μg (ml culture)(-1)] was added to a third vessel (D = 0.21 h(-1)). Perturbations in bacterial physiology and metabolism were sampled over a 48-h period. Lactobacillus acidophilus and C. bifermentans populations did not establish in the fermentors under the imposed growth conditions. Ampicillin resulted in substantial reductions in bacteroides and C. perfringens populations at both dilution rates. Metronidazole strongly affected bacteroides communities but had no effect on bifidobacterial communities. The bacteriostatic effect of ampicillin on bifidobacterial species was growth rate dependent. Several metabolic activities were affected by antibiotic addition, including fermentation product formation and enzyme synthesis. The growth of antibiotic-resistant bifidobacteria in the large bowel may enable them to occupy ecological niches left vacant after antibiotic administration, preventing colonization by pathogenic species.
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44
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Maronpot RR, Davis J, Moser G, Giri DK, Hayashi SM. Evaluation of 90-day oral rat toxicity studies on the food additive, gum ghatti. Food Chem Toxicol 2013; 51:215-24. [DOI: 10.1016/j.fct.2012.09.037] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2012] [Revised: 09/28/2012] [Accepted: 09/29/2012] [Indexed: 10/27/2022]
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Grivennikov SI. Inflammation and colorectal cancer: colitis-associated neoplasia. Semin Immunopathol 2012; 35:229-44. [PMID: 23161445 DOI: 10.1007/s00281-012-0352-6] [Citation(s) in RCA: 419] [Impact Index Per Article: 32.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2012] [Accepted: 09/27/2012] [Indexed: 12/12/2022]
Abstract
Connection between inflammation and cancer is a rapidly developing field. Epidemiological data suggests that inflammation along with distinct arms of host immune system plays a very important role in the development and progression of many different cancers. Inflammatory bowel disease (IBD) is an important risk factor for the development of colon cancer, namely, colitis-associated cancer (CAC). The molecular mechanisms by which inflammation promotes cancer development are still being uncovered and may differ between CAC and other forms of colorectal cancer. Recent work has shed light on the role of distinct immune cells, cytokines, and other immune mediators in virtually all of the steps of colonic tumorigenesis, including tumor initiation and promotion as well as progression and metastasis. The close proximity of colonic tumors to the myriad of intestinal microbes, as well as instrumental role of microbiota in IBD, introduces microbes as new players capable of triggering inflammation and possibly promoting tumorigenesis. Various mechanisms of CAC tumorigenesis as well as new possible hints for the future approaches for prevention and therapy are discussed in this review.
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Affiliation(s)
- Sergei I Grivennikov
- Cancer Prevention and Control Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA.
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Grivennikov SI, Wang K, Mucida D, Stewart CA, Schnabl B, Jauch D, Taniguchi K, Yu GY, Osterreicher CH, Hung KE, Datz C, Feng Y, Fearon ER, Oukka M, Tessarollo L, Coppola V, Yarovinsky F, Cheroutre H, Eckmann L, Trinchieri G, Karin M. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 2012; 491:254-8. [PMID: 23034650 PMCID: PMC3601659 DOI: 10.1038/nature11465] [Citation(s) in RCA: 1030] [Impact Index Per Article: 79.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2012] [Accepted: 07/31/2012] [Indexed: 12/12/2022]
Abstract
Approximately 2% of colorectal cancer is linked to pre-existing inflammation known as colitis-associated cancer, but most develops in patients without underlying inflammatory bowel disease. Colorectal cancer often follows a genetic pathway whereby loss of the adenomatous polyposis coli (APC) tumour suppressor and activation of β-catenin are followed by mutations in K-Ras, PIK3CA and TP53, as the tumour emerges and progresses. Curiously, however, 'inflammatory signature' genes characteristic of colitis-associated cancer are also upregulated in colorectal cancer. Further, like most solid tumours, colorectal cancer exhibits immune/inflammatory infiltrates, referred to as 'tumour-elicited inflammation'. Although infiltrating CD4(+) T(H)1 cells and CD8(+) cytotoxic T cells constitute a positive prognostic sign in colorectal cancer, myeloid cells and T-helper interleukin (IL)-17-producing (T(H)17) cells promote tumorigenesis, and a 'T(H)17 expression signature' in stage I/II colorectal cancer is associated with a drastic decrease in disease-free survival. Despite its pathogenic importance, the mechanisms responsible for the appearance of tumour-elicited inflammation are poorly understood. Many epithelial cancers develop proximally to microbial communities, which are physically separated from immune cells by an epithelial barrier. We investigated mechanisms responsible for tumour-elicited inflammation in a mouse model of colorectal tumorigenesis, which, like human colorectal cancer, exhibits upregulation of IL-23 and IL-17. Here we show that IL-23 signalling promotes tumour growth and progression, and development of a tumoural IL-17 response. IL-23 is mainly produced by tumour-associated myeloid cells that are likely to be activated by microbial products, which penetrate the tumours but not adjacent tissue. Both early and late colorectal neoplasms exhibit defective expression of several barrier proteins. We propose that barrier deterioration induced by colorectal-cancer-initiating genetic lesions results in adenoma invasion by microbial products that trigger tumour-elicited inflammation, which in turn drives tumour growth.
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Affiliation(s)
- Sergei I Grivennikov
- Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, California 92093-0723, USA
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The presence of Helicobacter pylori in colorectal polyps detected by immunohistochemical methods in children. Pediatr Infect Dis J 2012; 31:364-7. [PMID: 22189526 DOI: 10.1097/inf.0b013e3182467538] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
AIM Polyps are a common cause of hematochezia in children, but the pathogenesis of polyps is unclear. The aim of this study was to investigate the relationship between Helicobacter pylori (HP) infection and colorectal polyps in children. METHODS Thirty-five patients who had undergone polypectomy after the detection of polyps served as the case group. Twenty-seven patients with gastrointestinal symptoms and normal colonoscopy served as the control group. Hematoxylin and eosin (HE) stains obtained from paraffin blocks were evaluated and classified according to histopathologic type and degree of dysplasia. The other sections were used to detect HP organisms for immunohistochemistry (IHC). The seroprevalence of HP antibodies in children with colorectal polyps was detected by protein chip technology. HP infection was diagnosed if the serum urease antibody was positive. RESULTS The HP-positive rate in children with colorectal polyps was 57.1% (20/35), which was higher than the rate of 22.2% (6/27) for colonic mucosa in the control group (P < 0.01). The differences in the presence and absence of HP infection between patients with juvenile polyps and juvenile polyposis syndrome were not statistically significant. Age, gender, and the number, size, and locations of the colonic polyps were not significantly different between the patients with HP-positive and HP-negative polyps. The HP-antibody-positive rate was 65.0% (13/20) in the patients with HP-infection-positive colorectal polyps, which was higher than the rate of 26.7% (4/15) for the patients with HP-infection-negative colorectal polyps (P < 0.05). CONCLUSION Our findings suggest a positive association between HP infection and colorectal polyps in children in this study, indicating that HP infection is a risk factor for colorectal polyps in children.
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Abstract
Recent scientific advances have contributed much to the dissection of the complex molecular and cellular pathways involved in the connection between cancer and inflammation. The evidence for this connection in humans is based on the association between infection or chronic sterile inflammation and cancer. The decreased incidence of tumors in individuals who have used nonsteroidal anti-inflammatory drugs is supportive of a role for inflammation in cancer susceptibility. The increased incidence of tumors in overweight patients points to a role for adipose tissue inflammation and energy metabolism in cancer. Energy metabolism, obesity, and genetic instability are regulated in part by the relationship of the organism with commensal bacteria that affect inflammation with both local and systemic effects. Different aspects of inflammation appear to regulate all phases of malignant disease, including susceptibility, initiation, progression, dissemination, morbidity, and mortality.
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Affiliation(s)
- Giorgio Trinchieri
- Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702-1201, USA.
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Wright WF. Clostridium septicum myonecrosis presenting as an acute painful foot. Am J Emerg Med 2012; 30:253.e3-5. [DOI: 10.1016/j.ajem.2010.10.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2010] [Accepted: 10/08/2010] [Indexed: 11/28/2022] Open
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50
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Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res 2011. [PMID: 22009990 DOI: 10.1101/gr.126573] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
The tumor microenvironment of colorectal carcinoma is a complex community of genomically altered cancer cells, nonneoplastic cells, and a diverse collection of microorganisms. Each of these components may contribute to carcinogenesis; however, the role of the microbiota is the least well understood. We have characterized the composition of the microbiota in colorectal carcinoma using whole genome sequences from nine tumor/normal pairs. Fusobacterium sequences were enriched in carcinomas, confirmed by quantitative PCR and 16S rDNA sequence analysis of 95 carcinoma/normal DNA pairs, while the Bacteroidetes and Firmicutes phyla were depleted in tumors. Fusobacteria were also visualized within colorectal tumors using FISH. These findings reveal alterations in the colorectal cancer microbiota; however, the precise role of Fusobacteria in colorectal carcinoma pathogenesis requires further investigation.
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