scholarly journals Replication Study: Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
John Repass ◽  
Elizabeth Iorns ◽  
Alexandria Denis ◽  
Stephen R Williams ◽  
Nicole Perfito ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Cancer Biology ◽  
Normal Tissue ◽  
Matched Control ◽  
Fusobacterium Nucleatum ◽  
Original Study ◽  
Adjacent Normal Tissue ◽  
Control Tissue ◽  
Human Colorectal Carcinoma ◽  
The Difference

As part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Repass et al., 2016), that described how we intended to replicate an experiment from the paper ‘Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma’ (Castellarin et al., 2012). Here we report the results. When measuring Fusobacterium nucleatum DNA by qPCR in colorectal carcinoma (CRC), adjacent normal tissue, and separate matched control tissue, we did not detect a signal for F. nucleatum in most samples: 25% of CRCs, 15% of adjacent normal, and 0% of matched control tissue were positive based on quantitative PCR (qPCR) and confirmed by sequencing of the qPCR products. When only samples with detectable F. nucleatum in CRC and adjacent normal tissue were compared, the difference was not statistically significant, while the original study reported a statistically significant increase in F. nucleatum expression in CRC compared to adjacent normal tissue (Figure 2; Castellarin et al., 2012). Finally, we report a meta-analysis of the result, which suggests F. nucleatum expression is increased in CRC, but is confounded by the inability to detect F. nucleatum in most samples. The difference in F. nucleatum expression between CRC and adjacent normal tissues was thus smaller than the original study, and not detected in most samples.

scholarly journals Registered report: Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
John Repass ◽  
Nimet Maherali ◽  
Kate Owen ◽  
Keyword(s):  
Colorectal Carcinoma ◽  
Cancer Biology ◽  
Fusobacterium Nucleatum ◽  
Open Science ◽  
Gastrointestinal Cancers ◽  
Quantitative Real Time Pcr ◽  
Genome Research ◽  
Associated Bacteria ◽  
High Profile ◽  
Human Colorectal Carcinoma

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (<xref ref-type="bibr" rid="bib9">Errington et al., 2014</xref>). This Registered Report describes the proposed replication plan of key experiments from 'Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma' by Castellarin and colleagues published in Genome Research in 2012 (<xref ref-type="bibr" rid="bib5">Castellarin et al., 2012</xref>). The experiment to be replicated is reported in Figure 2. Here, Castellarin and colleagues performed a metagenomic analysis of colorectal carcinoma (CRC) to identify potential associations between inflammatory microorganisms and gastrointestinal cancers. They conducted quantitative real-time PCR on genomic DNA isolated from tumor and matched normal biopsies from a patient cohort and found that the overall abundance of Fusobacterium was 415 times greater in CRC versus adjacent normal tissue. These results confirmed earlier studies and provide evidence for a link between tissue-associated bacteria and tumorigenesis. The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange and the results of the replications will be published in eLife.

A Plasma Factor Which Stimulates Prostacyclin Formation Is Increased In Diabetes

1981 ◽  
Author(s):  
M Johnson ◽  
A H Reece ◽  
H E Harrison
Keyword(s):  
Matched Control ◽  
Freezing And Thawing ◽  
Control Tissue ◽  
Plasma Factor ◽  
The Difference ◽  
Plasma Factors ◽  
And Control ◽  
Free Plasma ◽  
Krebs Buffer ◽  
Stimulation Of

Vascular prostacyclin (PGI2) generation is decreased in diabetes in experimental animals and in man. In this study, we have investigated the possibility that levels of a plasma factor (s) modifying PGI2 production are abnormal in diabetes. Aortic rings from diabetic or age-matched control rats were washed in Krebs buffer to reduce endogenous PGI2 formation. Addition of rat or human cell-free plasma stimulated PGI2 release by the “exhausted” vascular rings, and this activity was still present after freezing and thawing. The stimulation of PGI2 synthesis by control tissue was significantly greater (p<0.001) with plasma from diabetic animals (0.25±0.04ng/mg) than from controls (0.05±0.02ng/mg). Similarly, plasma from diabetic volunteers showed increased (p<0.05) PGI2-stimulatory activity. Diabetic tissue was less responsive than control tissue to stimulation by diabetic plasma, and the difference between diabetic and control plasmas was not apparent. This suggests that the abnormal vascular PGI2 synthesis in diabetes may be due to a defect in the vessel wall and not to lack of stimulatory plasma factors.

scholarly journals Replication Study: Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Mee Rie Sheen ◽  
Jennifer L Fields ◽  
Brian Northan ◽  
Judith Lacoste ◽  
Lay-Hong Ang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Tumor Invasion ◽  
Cancer Biology ◽  
Original Study ◽  
Invasion And Metastasis ◽  
Caveolin 1 ◽  
Primary Mouse ◽  
Metastatic Burden ◽  
The Difference

As part of the Reproducibility Project: Cancer Biology we published a Registered Report (Fiering et al., 2015) that described how we intended to replicate selected experiments from the paper ‘Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis’ (Goetz et al., 2011). Here we report the results. Primary mouse embryonic fibroblasts (pMEFs) expressing caveolin 1 (Cav1WT) demonstrated increased extracellular matrix remodeling in vitro compared to Cav1 deficient (Cav1KO) pMEFs, similar to the original study (Goetz et al., 2011). In vivo, we found higher levels of intratumoral stroma remodeling, determined by fibronectin fiber orientation, in tumors from cancer cells co-injected with Cav1WT pMEFs compared to cancer cells only or cancer cells plus Cav1KO pMEFs, which were in the same direction as the original study (Supplemental Figure S7C; Goetz et al., 2011), but not statistically significant. Primary tumor growth was similar between conditions, like the original study (Supplemental Figure S7Ca; Goetz et al., 2011). We found metastatic burden was similar between Cav1WT and Cav1KO pMEFs, while the original study found increased metastases with Cav1WT (Figure 7C; Goetz et al., 2011); however, the duration of our in vivo experiments (45 days) were much shorter than in the study by Goetz et al. (2011) (75 days). This makes it difficult to interpret the difference between the studies as it is possible that the cells required more time to manifest the difference between treatments observed by Goetz et al. We also found a statistically significant negative correlation of intratumoral remodeling with metastatic burden, while the original study found a statistically significant positive correlation (Figure 7Cd; Goetz et al., 2011), but again there were differences between the studies in terms of the duration of the metastasis studies and the imaging approaches that could have impacted the outcomes. Finally, we report meta-analyses for each result.

scholarly journals Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma

2011 ◽  
Vol 22 (2) ◽  
pp. 299-306 ◽  
Author(s):  
M. Castellarin ◽  
R. L. Warren ◽  
J. D. Freeman ◽  
L. Dreolini ◽  
M. Krzywinski ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Fusobacterium Nucleatum ◽  
Human Colorectal Carcinoma

scholarly journals Author response: Replication Study: Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma

2017 ◽  
Author(s):  
John Repass ◽  
Elizabeth Iorns ◽  
Alexandria Denis ◽  
Stephen R Williams ◽  
Nicole Perfito ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Fusobacterium Nucleatum ◽  
Replication Study ◽  
Author Response ◽  
Human Colorectal Carcinoma

scholarly journals DNA methylation markers for diagnosis and prognosis of common cancers

2017 ◽  
Vol 114 (28) ◽  
pp. 7414-7419 ◽  
Author(s):  
Xiaoke Hao ◽  
Huiyan Luo ◽  
Michal Krawczyk ◽  
Wei Wei ◽  
Wenqiu Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Cancer Biology ◽  
Normal Tissue ◽  
Diagnostic Methods ◽  
Adjacent Normal Tissue ◽  
Tissue Samples ◽  
Diagnosis And Prognosis ◽  
Cancer Metastases ◽  
Colorectal Cancer Metastases

The ability to identify a specific cancer using minimally invasive biopsy holds great promise for improving the diagnosis, treatment selection, and prediction of prognosis in cancer. Using whole-genome methylation data from The Cancer Genome Atlas (TCGA) and machine learning methods, we evaluated the utility of DNA methylation for differentiating tumor tissue and normal tissue for four common cancers (breast, colon, liver, and lung). We identified cancer markers in a training cohort of 1,619 tumor samples and 173 matched adjacent normal tissue samples. We replicated our findings in a separate TCGA cohort of 791 tumor samples and 93 matched adjacent normal tissue samples, as well as an independent Chinese cohort of 394 tumor samples and 324 matched adjacent normal tissue samples. The DNA methylation analysis could predict cancer versus normal tissue with more than 95% accuracy in these three cohorts, demonstrating accuracy comparable to typical diagnostic methods. This analysis also correctly identified 29 of 30 colorectal cancer metastases to the liver and 32 of 34 colorectal cancer metastases to the lung. We also found that methylation patterns can predict prognosis and survival. We correlated differential methylation of CpG sites predictive of cancer with expression of associated genes known to be important in cancer biology, showing decreased expression with increased methylation, as expected. We verified gene expression profiles in a mouse model of hepatocellular carcinoma. Taken together, these findings demonstrate the utility of methylation biomarkers for the molecular characterization of cancer, with implications for diagnosis and prognosis.

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