scholarly journals Analysis ofFusobacteriumpersistence and antibiotic response in colorectal cancer

Science ◽  
2017 ◽  
Vol 358 (6369) ◽  
pp. 1443-1448 ◽  
Author(s):  
Susan Bullman ◽  
Chandra S. Pedamallu ◽  
Ewa Sicinska ◽  
Thomas E. Clancy ◽  
Xiaoyang Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Bacterial Species ◽  
Complex Mixture ◽  
Fusobacterium Nucleatum ◽  
Colorectal Cancers ◽  
Metastatic Lesions ◽  
Antimicrobial Interventions ◽  
Antibiotic Response ◽  
Cancer Tissues

Colorectal cancers comprise a complex mixture of malignant cells, nontransformed cells, and microorganisms.Fusobacterium nucleatumis among the most prevalent bacterial species in colorectal cancer tissues. Here we show that colonization of human colorectal cancers withFusobacteriumand its associated microbiome—includingBacteroides,Selenomonas, andPrevotellaspecies—is maintained in distal metastases, demonstrating microbiome stability between paired primary and metastatic tumors. In situ hybridization analysis revealed thatFusobacteriumis predominantly associated with cancer cells in the metastatic lesions. Mouse xenografts of human primary colorectal adenocarcinomas were found to retain viableFusobacteriumand its associated microbiome through successive passages. Treatment of mice bearing a colon cancer xenograft with the antibiotic metronidazole reducedFusobacteriumload, cancer cell proliferation, and overall tumor growth. These observations argue for further investigation of antimicrobial interventions as a potential treatment for patients withFusobacterium-associated colorectal cancer.

scholarly journals Bacterial colonization of enamel in situ investigated using fluorescence in situ hybridization

2009 ◽  
Vol 58 (10) ◽  
pp. 1359-1366 ◽  
Author(s):  
Ali Al-Ahmad ◽  
Marie Follo ◽  
Ann-Carina Selzer ◽  
Elmar Hellwig ◽  
Matthias Hannig ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Laser Scanning ◽  
Bacterial Colonization ◽  
Bacterial Species ◽  
Fusobacterium Nucleatum ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Actinomyces Naeslundii ◽  
Oral Biofilms

Oral biofilms are one of the greatest challenges in dental research. The present study aimed to investigate initial bacterial colonization of enamel surfaces in situ using fluorescence in situ hybridization (FISH) over a 12 h period. For this purpose, bovine enamel slabs were fixed on buccal sites of individual splints worn by six subjects for 2, 6 and 12 h to allow biofilm formation. Specimens were processed for FISH and evaluated with confocal laser-scanning microscopy, using probes for eubacteria, Streptococcus species, Veillonella species, Fusobacterium nucleatum and Actinomyces naeslundii. The number of adherent bacteria increased with time and all tested bacterial species were detected in the biofilm formed in situ. The general percentage composition of the eubacteria did not change over the investigated period, but the number of streptococci, the most frequently detected species, increased significantly with time (2 h: 17.7±13.8 %; 6 h: 20.0±16.6 %; 12 h: 24.7±16.1 %). However, ≤1 % of the surface was covered with bacteria after 12 h of biofilm formation in situ. In conclusion, FISH is an appropriate method for quantifying initial biofilm formation in situ, and the proportion of streptococci increases during the first 12 h of bacterial adherence.

Relationship of pro-angiogenic factor Cyr61to colorectal cancer development and prognosis.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 446-446 ◽  
Author(s):  
M. Baek ◽  
S. Bae ◽  
D. Jeong
Keyword(s):  
Colorectal Cancer ◽  
Western Blot ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Clinicopathological Parameters ◽  
Colorectal Cancers ◽  
Colorectal Carcinomas ◽  
Over Expression ◽  
Normal Tissues ◽  
Cancer Tissues

446 Background: Angiogenic factorCysteine-rich 61 (Cyr61) is a member of the CCN protein family that has been implicated in diverse biological processes such as cell adhesion, proliferation, angiogenesis, and tumorigenesis. An altered expression of Cyr61 is found to be associated with several human cancers. However, the correlation of expression of Cyr61 protein and clinical features of colorectal cancer remains unknown. Methods: Cyr61 expression in colorectal cancer and normal tissues was evaluated by Western blot analysis. Immunohistochemical staining was carried out using tissue microassay (TMA) to examine the expression status of Cyr61. Correlations of Cyr61 over-expression with various clinicopathologic factors were also determined. Statistical analysis was performed to explore the links between expression of the Cyr61 and clinicopathological parameters. Results: On Western blot analysis Cyr61 up-regulation was observed in colorectal cancer tissues (17/21, 80.9%). In 234 colorectal cancers, tumor tissue microarray revealed significantly up-regulated Cyr61 protein expression in colorectal cancer tissues versus normal tissues adjacent to tumor. Cyr61 expression was high in 136 of 234 cases of colorectal carcinomas (58.1%). Cyr61 over-expression was significantly associated with TNM stage (p=0.012) and regional lymph node involvement (p=0.018). Kaplan-Meier survival analysis showed that over-expression of Cyr61 was related to poor survival of colorectal cancer patients (p=0.031). But significant associations were not found between CYR61 expression versus tumor grade, age and gender. Conclusions: Our results suggest that Cyr61 is highly expressed in colorectal carcinomas and Cyr61 may play a role in the progression of colorectal cancers. Also, Cyr61 might be a new molecular marker to predict the prognosis and serve as valuable targets for therapeutic intervention of patients with colorectal carcinoma. No significant financial relationships to disclose.

scholarly journals Characterization of the consensus mucosal microbiome of colorectal cancer

2021 ◽  
Author(s):  
Lan Zhao ◽  
Susan M Grimes ◽  
Stephanie U Greer ◽  
Matthew Kubit ◽  
HoJoon Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Cell ◽  
Bacterial Species ◽  
Fusobacterium Nucleatum ◽  
Cell Types ◽  
Data Sets ◽  
Data Resource ◽  
Bacterial Contaminants ◽  
Increased Risk ◽  
Tumor Biopsies

Recent evidence suggests that dysbiosis, an imbalance of microbiota, is associated with increased risk of colorectal cancer. Diverse microbial organisms are physically associated with the cells found in tumor biopsies. Characterizing this mucosa-associated microbiome through genome sequencing has advantages compared to culture-based profiling. However, there are notable challenges in accurately characterizing the features of tumor microbiomes with methods like transcriptome sequencing. Most sequence reads originate from the host. Moreover, there is a high likelihood of bacterial contaminants being introduced. Another major challenge is the microbiome diversity among different studies. Colorectal tumors demonstrate a significant extent of microbiome variation among individuals from different geographic and ethnic origins. To address these challenges, we identified a consensus microbiome for colorectal cancer through analyzing 924 tumors from eight independent RNA-Seq data sets. A standardized meta-transcriptomic analysis pipeline was established and applied to the complete CRC cohort. Common contaminants were filtered out. Our study involved taxonomic investigation of non-human sequences, linked microbial signatures to phenotypes and the association of microbiome with tumor microenvironment components. Microbiome profiles across different CRC cohorts were compared, and recurrently altered microbial shifts specific to CRC were determined. We identified cancer-specific set of 114 microbial species associated with tumors that were found among all investigated studies. Validating our approach, we found that Fusobacterium nucleatum was one of the most enriched bacterial species in CRC. Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria were among the four most abundant phyla for CRC microbiome. Signficant associations between the consensus species and specific immune cell types were noted. Our results are available as a web data resource for other researchers to explore (https://crc-microbiome.stanford.edu).

scholarly journals Alteration of microRNA-4474/4717 expression and CREB-binding protein in human colorectal cancer tissues infected with Fusobacterium nucleatum

PLoS ONE ◽  
2019 ◽  
Vol 14 (4) ◽  
pp. e0215088 ◽  
Author(s):  
Yu-yang Feng ◽  
Dong-zhu Zeng ◽  
Ya-nan Tong ◽  
Xiao-xue Lu ◽  
Guo-dong Dun ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Binding Protein ◽  
Fusobacterium Nucleatum ◽  
Creb Binding Protein ◽  
Human Colorectal Cancer ◽  
Cancer Tissues

scholarly journals Characterization of the consensus mucosal microbiome of colorectal cancer

NAR Cancer ◽  
2021 ◽  
Vol 3 (4) ◽  
Author(s):  
Lan Zhao ◽  
Susan M Grimes ◽  
Stephanie U Greer ◽  
Matthew Kubit ◽  
HoJoon Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Cell ◽  
Computational Study ◽  
Bacterial Species ◽  
Fusobacterium Nucleatum ◽  
Cell Types ◽  
Data Sets ◽  
Data Resource ◽  
Cancer Pathogenesis ◽  
Quality Control Metrics

Abstract Dysbioisis is an imbalance of an organ's microbiome and plays a role in colorectal cancer pathogenesis. Characterizing the bacteria in the microenvironment of a cancer through genome sequencing has advantages compared to culture-based profiling. However, there are notable technical and analytical challenges in characterizing universal features of tumor microbiomes. Colorectal tumors demonstrate microbiome variation among different studies and across individual patients. To address these issues, we conducted a computational study to determine a consensus microbiome for colorectal cancer, analyzing 924 tumors from eight independent RNA-Seq data sets. A standardized meta-transcriptomic analysis pipeline was established with quality control metrics. Microbiome profiles across different cohorts were compared and recurrently altered microbial shifts specific to colorectal cancer were determined. We identified cancer-specific set of 114 microbial species associated with tumors that were found among all investigated studies. Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria were among the four most abundant phyla for the colorectal cancer microbiome. Member species of Clostridia were depleted and Fusobacterium nucleatum was one of the most enriched bacterial species in tumors. Associations between the consensus species and specific immune cell types were noted. Our results are available as a web data resource for other researchers to explore (https://crc-microbiome.stanford.edu).

scholarly journals Invasion by Fusobacterium nucleatum Causes Upregulation of dll4 and klf4 Expression in Caco2 Cells

2020 ◽  
Author(s):  
Kyla Cochrane ◽  
Avery V. Robinson ◽  
Jacqueline Powers ◽  
Scott D. Brown ◽  
Robert A. Holt ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Transcriptional Profiling ◽  
Bacterial Species ◽  
Disease Patient ◽  
Fusobacterium Nucleatum ◽  
Non Invasive ◽  
Human Genes ◽  
Klf4 Expression ◽  
Host Genes

AbstractFusobacterium nucleatum is an emerging microbe of importance in the pathogenesis of colorectal cancer. Strains of this enigmatic bacterial species vary in their capacity to invade human epithelial cells, a virulence determinant which has important implications in disease. Here, we infected human colorectal epithelial (Caco-2) cells in vitro with a known, highly invasive strain of F. nucleatum isolated from a Crohn’s Disease patient, as well as a further invasive isolate of F. nucleatum derived from a colorectal cancer tumour. We used transcriptional profiling to determine the human genes upregulated during the invasion process compared to exposure to a non-invasive E.coli control strain. Infection with F. nucleatum strains resulted in the upregulation of several host genes, including two associated with tumorigenesis: dll4 and klf4.

scholarly journals Fusobacterium nucleatum in biopsied tissues from colorectal cancer patients and alcohol consumption in Korea

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Myungsook Kim ◽  
Seung-Tae Lee ◽  
Songyi Choi ◽  
Hyukmin Lee ◽  
Sun Sung Kwon ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Alcohol Consumption ◽  
16S Rrna ◽  
Bacterial Species ◽  
Fusobacterium Nucleatum ◽  
Integrated Analysis ◽  
Cancer Tissue ◽  
16S Rrna Analysis ◽  
Associated Bacteria ◽  
Epidemiological Characteristics

AbstractThe roles of individual bacteria and their relationship in the development of colorectal cancer (CRC) remain unclear. We aimed to determine the prevalence of CRC-associated bacteria using quantitative real-time PCR (qPCR) or 16S rRNA analysis and the statistical correlations of patient demographics and clinical characteristics comprising alcohol consumption with CRC-associated bacteria. We determined the prevalence of five CRC-associated bacterial species in 38 CRC patients (39 samples) and 21 normal individuals using qPCR, and the relative abundance of bacterial taxa in the gut microbiome was assessed using 16S rRNA analysis. Fusobacterium nucleatum was the only bacterium that was significantly (P < 0.0001) more prevalent in the cancer tissue (82.1%) than in the normal tissue (0%) by qPCR. 16S rRNA analysis showed a significant correlation between six operational taxonomic units (OTUs), namely, the genera Fusobacterium, Peptostreptococcus, Collinsella, Prevotella, Parvimonas, and Gemella, in patients with CRC. An integrated analysis using 16S rRNA data and epidemiological characteristics showed that alcohol consumption was significantly correlated with the abundance of Fusobacterium OTUs. The correlation of alcohol consumption with the abundance of Fusobacterium OTUs in cancer tissue discovered using 16S rRNA analysis suggests a possible link between alcohol metabolism and subsequent tumorigenesis caused by F. nucleatum.

scholarly journals Attachment and antibiotic response of early-stage biofilms studied using resonant hyperspectral imaging

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Yue Wang ◽  
Christopher P. Reardon ◽  
Nicholas Read ◽  
Stephen Thorpe ◽  
Adrian Evans ◽  
...  
Keyword(s):  
Hyperspectral Imaging ◽  
Cell Attachment ◽  
Early Stage ◽  
Bacterial Species ◽  
High Surface ◽  
Antimicrobial Treatment ◽  
Surface Sensitivity ◽  
Antibiotic Response ◽  
Non Destructive

AbstractMany bacterial species readily develop biofilms that act as a protective matrix against external challenge, e.g., from antimicrobial treatment. Therefore, biofilms are often responsible for persistent and recurring infections. Established methods for studying biofilms are either destructive or focus on the biofilm’s surface. A non-destructive method that is sensitive to the underside of the biofilm is highly desirable, as it allows studying the penetration of antibiotics through the film. Here, we demonstrate that the high surface sensitivity of resonant hyperspectral imaging provides this capability. The method allows us to monitor the early stages of Escherichia coli biofilm formation, cell attachment and microcolony formation, in-situ and in real-time. We study the response of the biofilm to a number of different antibiotics and verify our observations using confocal microscopy. Based on this ability to closely monitor the surface-bound cells, resonant hyperspectral imaging gives new insights into the antimicrobial resistance of biofilms.

scholarly journals Distinct gut microbiome patterns associate with consensus molecular subtypes of colorectal cancer

2017 ◽  
Author(s):  
Rachel V Purcell ◽  
Martina Visnovska ◽  
Patrick J Biggs ◽  
Sebastian Schmeier ◽  
Frank A Frizelle
Keyword(s):  
Colorectal Cancer ◽  
16S Rrna ◽  
Rna Sequencing ◽  
Molecular Mechanisms ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Bacterial Species ◽  
Fusobacterium Nucleatum ◽  
16S Rrna Analysis ◽  
Taxonomic Groups

AbstractColorectal cancer (CRC) is a heterogeneous disease and recent advances in subtype classification have successfully stratified the disease using molecular profiling. The contribution of bacterial species to CRC development is increasingly acknowledged, and here, we sought to analyse CRC microbiomes and relate them to tumour consensus molecular subtypes (CMS), in order to better understand the relationship between bacterial species and the molecular mechanisms associated with CRC subtypes. We classified 34 tumours into CRC subtypes using RNA-sequencing derived gene expression and determined relative abundances of bacterial taxonomic groups using 16S rRNA amplicon metabarcoding. 16S rRNA analysis showed enrichment of Fusobacteria and Bacteroidetes, and decreased levels of Firmicutes and Proteobacteria in CMS1. A more detailed analysis of bacterial taxa using non-human RNA-sequencing reads uncovered distinct bacterial communities associated with each molecular subtype. The most highly enriched species associated with CMS1 included Fusobacterium hwasookii and Porphyromonas gingivalis. CMS2 was enriched for Selenomas and Prevotella species, while CMS3 had few significant associations. Targeted quantitative PCR validated these findings and also showed an enrichment of Fusobacterium nucleatum, Parvimonas micra and Peptostreptococcus stomatis in CMS1. In this study, we have successfully associated individual bacterial species to CRC subtypes for the first time.

Comparison of Co-Presence of Epstein-Barr Virus and High-Risk Human Papillomaviruses in Colorectal Cancers in the Middle East Region

2020 ◽  
Author(s):  
Karim Nagi ◽  
Ishita Gupta ◽  
Hamda A Al-Thawadi ◽  
Ayesha Jabeen ◽  
Mohammed I. Malk ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Epstein Barr Virus ◽  
Human Papillomaviruses ◽  
Colorectal Cancers ◽  
Barr Virus ◽  
Human Carcinomas ◽  
Epstein Barr ◽  
Invasive Carcinomas ◽  
High Risk Hpv

Background: Several studies have shown the presence of onco viral DNA in colorectal tumor tissues. Viral infection by onco-viruses such as Human papillomaviruses (HPVs) and Epstein–Barr virus (EBV) are well-known to be involved in the onset and/or progression of numerous human carcinomas. Methods: We explored the co-presence of high-risk HPVs and EBV in a cohort of colorectal cancer samples from Lebanon (94) and Syria (102) by PCR, immunohistochemistry and tissue microarray. Results: The results of the study point out that 54% of colorectal cancer cases in Syria are positive for high-risk HPVs, while 30% of the cases in Lebanon are positive for these viruses; the most frequent high-risk HPV types in these populations are 16, 18, 31, 33 and 35. Analysis of LMP1 showed similar results in both populations; 36% of Syrian and 31% of Lebanese samples. Additionally, we report that EBV and high-risk HPVs are co-present in these samples. In Syrian samples, EBV and HPVs are co-present in 16% of the population, however, in the Lebanese samples, 20% of the cases are positive for both EBV and HPVs; their co-presence is associated with high/intermediate grade invasive carcinomas. Conclusion: These data suggest that EBV and high-risk HPVs are co-present in human colorectal cancers where they can cooperate in the progression of these cancers. Nevertheless, further studies are needed to elucidate the role of those oncoviruses in the development of human colorectal carcinomas.

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