scholarly journals Replication Study: Intestinal inflammation targets cancer-inducing activity of the microbiota

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Kathryn Eaton ◽  
Ali Pirani ◽  
Evan S Snitkin ◽  
Elizabeth Iorns ◽  
Rachel Tsui ◽  
...  
Keyword(s):  
Cancer Biology ◽  
Polyketide Synthase ◽  
Intestinal Inflammation ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Early Death ◽  
Interleukin 10 ◽  
Original Study ◽  
E Coli ◽  
Clear Description

As part of the Reproducibility Project: Cancer Biology we published a Registered Report (Eaton et al., 2015) that described how we intended to replicate selected experiments from the paper “Intestinal Inflammation Targets Cancer-Inducing Activity of the Microbiota” (Arthur et al., 2012). Here we report the results. We observed no impact on bacterial growth or colonization capacity when the polyketide synthase (pks) genotoxic island was deleted from E. coli NC101, similar to the original study (Supplementary Figure 7; Arthur et al., 2012). However, for the experiment that compared inflammation, invasion, and neoplasia in azoxymethane (AOM)-treated interleukin-10-deficient mice mono-associated with NC101 or NC101Δ pks the experimental timing of the replication attempt was longer than that of the original study. This difference was because in the original study the methodology was not clearly stated and likely led to the increased mortality and severity of inflammation observed in this replication attempt. Additionally, early death occurred during AOM treatment with higher mortality observed in NC101Δ pks mono-associated mice compared to NC101, which was in the same direction, but more severe than the original study (Suppleme1ntal Figure 10; Arthur et al., 2012). A meta-analysis suggests that mice mono-associated with NC101Δ pks have higher mortality compared to NC101. While these data were unable to address whether, under the conditions of the original study, NC101 and NC101Δ pks differ in inflammation, invasion, and neoplasia this replication attempt demonstrates that clear description of experimental methods is essential to ensure accurate reproduction of experimental studies.

scholarly journals Intestinal Inflammation Targets Cancer-Inducing Activity of the Microbiota

Science ◽  
2012 ◽  
Vol 338 (6103) ◽  
pp. 120-123 ◽  
Author(s):  
Janelle C. Arthur ◽  
Ernesto Perez-Chanona ◽  
Marcus Mühlbauer ◽  
Sarah Tomkovich ◽  
Joshua M. Uronis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Throughput Sequencing ◽  
Polyketide Synthase ◽  
Invasive Carcinoma ◽  
Intestinal Inflammation ◽  
Interleukin 10 ◽  
Microbial Composition ◽  
Tumor Multiplicity ◽  
E Coli ◽  
Inflammatory Bowel

Inflammation alters host physiology to promote cancer, as seen in colitis-associated colorectal cancer (CRC). Here, we identify the intestinal microbiota as a target of inflammation that affects the progression of CRC. High-throughput sequencing revealed that inflammation modifies gut microbial composition in colitis-susceptible interleukin-10–deficient (Il10−/−) mice. Monocolonization with the commensal Escherichia coli NC101 promoted invasive carcinoma in azoxymethane (AOM)–treated Il10−/− mice. Deletion of the polyketide synthase (pks) genotoxic island from E. coli NC101 decreased tumor multiplicity and invasion in AOM/Il10−/− mice, without altering intestinal inflammation. Mucosa-associated pks+E. coli were found in a significantly high percentage of inflammatory bowel disease and CRC patients. This suggests that in mice, colitis can promote tumorigenesis by altering microbial composition and inducing the expansion of microorganisms with genotoxic capabilities.

scholarly journals Replication Study: The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Stephen K Horrigan ◽  
Keyword(s):  
Solid Tumors ◽  
Therapeutic Target ◽  
Cancer Biology ◽  
Inflammatory Cell ◽  
Meta Analysis ◽  
Regulatory Protein ◽  
Original Study ◽  
Lymphocytic Infiltrate ◽  
Human Solid Tumors ◽  
Inhibition Of Tumor Growth

In 2015, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Chroscinski et al., 2015) that described how we intended to replicate selected experiments from the paper “The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors “(Willingham et al., 2012). Here we report the results of those experiments. We found that treatment of immune competent mice bearing orthotopic breast tumors with anti-mouse CD47 antibodies resulted in short-term anemia compared to controls, consistent with the previously described function of CD47 in normal phagocytosis of aging red blood cells and results reported in the original study (Table S4; Willingham et al., 2012). The weight of tumors after 30 days administration of anti-CD47 antibodies or IgG isotype control were not found to be statistically different, whereas the original study reported inhibition of tumor growth with anti-CD47 treatment (Figure 6A,B; Willingham et al., 2012). However, our efforts to replicate this experiment were confounded because spontaneous regression of tumors occurred in several of the mice. Additionally, the excised tumors were scored for inflammatory cell infiltrates. We found IgG and anti-CD47 treated tumors resulted in minimal to moderate lymphocytic infiltrate, while the original study observed sparse lymphocytic infiltrate in IgG-treated tumors and increased inflammatory cell infiltrates in anti-CD47 treated tumors (Figure 6C; Willingham et al., 2012). Furthermore, we observed neutrophilic infiltration was slightly increased in anti-CD47 treated tumors compared to IgG control. Finally, we report a meta-analysis of the result.

scholarly journals Registered report: Intestinal inflammation targets cancer-inducing activity of the microbiota

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Kate Eaton ◽  
Wanwan Yang ◽  
Keyword(s):  
Escherichia Coli ◽  
Cancer Biology ◽  
Intestinal Inflammation ◽  
Scientific Research ◽  
Open Science ◽  
Wild Type ◽  
E Coli ◽  
Neoplastic Lesions ◽  
Type Form ◽  
Wild Type Form

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of 50 papers in the field of cancer biology published between 2010 and 2012. This Registered report describes the proposed replication plan of key experiments from ‘Intestinal Inflammation Targets Cancer-Inducing Activity of the Microbiota’ by <xref ref-type="bibr" rid="bib2">Arthur et al. (2012)</xref>, published in Science in 2012. Arthur and colleagues identified a genotoxic island in Escherichia coli NC101 that appeared to be responsible for causing neoplastic lesions in inflammation-induced IL10−/− mice treated with azoxymethane. The experiments that will be replicated are those reported in Figure 4 (<xref ref-type="bibr" rid="bib2">Arthur et al., 2012)</xref>. Arthur and colleagues inoculated IL10−/− mice with a mutated strain of E. coli NC101 lacking the genotoxic island, and showed that those mice suffered from fewer neoplastic lesions than mice inoculated with the wild type form of E. coli NC101 (Figure 4). 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 by eLife.

scholarly journals Replication Study: BET bromodomain inhibition as a therapeutic strategy to target c-Myc

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Fraser Aird ◽  
Irawati Kandela ◽  
Christine Mantis ◽  
Keyword(s):  
Overall Survival ◽  
Cancer Biology ◽  
Therapeutic Strategy ◽  
Early Death ◽  
Vehicle Control ◽  
Tumor Burden ◽  
Original Study ◽  
Control Group ◽  
Minimal Impact ◽  
Significant Difference

In 2015, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Kandela et al., 2015) that described how we intended to replicate selected experiments from the paper "BET bromodomain inhibition as a therapeutic strategy to target c-Myc" (Delmore et al., 2011). Here we report the results of those experiments. We found that treatment of human multiple myeloma (MM) cells with the small-molecular inhibitor of BET bromodomains, (+)-JQ1, selectively downregulated MYC transcription, which is similar to what was reported in the original study (Figure 3B; Delmore et al., 2011). Efficacy of (+)-JQ1 was evaluated in an orthotopically xenografted model of MM. Overall survival was increased in (+)-JQ1 treated mice compared to vehicle control, similar to the original study (Figure 7E; Delmore et al., 2011). Tumor burden, as determined by bioluminescence, was decreased in (+)-JQ1 treated mice compared to vehicle control; however, while the effect was in the same direction as the original study (Figure 7C-D; Delmore et al., 2011), it was not statistically significant. The opportunity to detect a statistically significant difference was limited though, due to the higher rate of early death in the control group, and increased overall survival in (+)-JQ1 treated mice before the pre-specified tumor burden analysis endpoint. Additionally, we evaluated the (−)-JQ1 enantiomer that is structurally incapable of inhibiting BET bromodomains, which resulted in a minimal impact on MYC transcription, but did not result in a statistically significant difference in tumor burden or survival distributions compared to treatment with (+)-JQ1. Finally, we report meta-analyses for each result.

scholarly journals Effectiveness of Nutritional Education for Obese Older Adults With Frailty: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 401-401
Author(s):  
Yue-Heng Yin ◽  
Liu Yat Justina
Keyword(s):  
Systematic Review ◽  
Physical Function ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Well Being ◽  
Risk Of Bias ◽  
Cochrane Library ◽  
Nutritional Education ◽  
Hand Search ◽  
Education Interventions

Abstract Obesity has been shown to intensify the decline of physical function and lead to frailty. Nutrition is an important method in managing obesity and frailty, while seldom reviews have ever explored the effects of nutritional education interventions. We conducted a systematic review (PROSPERO: CRD42019142403) to explore the effectiveness of nutritional education interventions in managing body composition and physio-psychosocial parameters related to frailty. Randomized controlled trials and quasi-experimental studies were searched in CINAHL, Cochrane Library, EMBASE, MEDLINE, PsycINFO, PubMed and Scopus from 2001 to 2019. Hand search for the reference lists of included papers was conducted as well. We assessed the quality of included studies by Cochrane risk of bias tool. Meta-analyses and narrative synthesis were used to analyse the data. Two studies with low risk of bias were screened from 180 articles, which involved 177 older people with an average age of 69.69±4.08 years old. The results showed that nutritional education was significantly effective in reducing body weight and fat mass than exercises, and it was beneficial to enhancing physical function and psychosocial well-being. But the effects of nutritional education in increasing muscle strength were not better than exercises. The combined effects of nutritional education and exercises were superior than either exercises or nutritional education interventions solely in preventing the loss of lean mass and bone marrow density, and in improving physical function. Due to limited numbers of relevant studies, the strong evidence of effectiveness of nutritional education interventions on reversing frailty is still lacking.

scholarly journals Clinical safety of total glucosides of paeony adjuvant therapy for rheumatoid arthritis treatment: a systematic review and meta-analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bin Liu ◽  
Xiang Meng ◽  
Yanfang Ma ◽  
Huizhen Li ◽  
Yuqi Liu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Effect ◽  
Adjuvant Therapy ◽  
Statistical Difference ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Analysis Data ◽  
Eligibility Criteria ◽  
Clinical Safety ◽  
Total Glucosides Of Paeony

Abstract Background Total glucosides of paeony (TGP), an active compound extracted from the roots of Paeonia lactiflora Pallas, has been increasingly used as the adjunctive therapy for rheumatoid arthritis (RA) patients. Though TGP could mitigate the unanticipated adverse effects during the conventional treatment of RA, high-quality evidence-based meta-analysis data on this subject are still insufficient. The objective of this study is to evaluate the clinical safety of TGP adjuvant therapy in the RA treatment. Methods PubMed, EMBASE, Web of Science, China Network Knowledge Infrastructure (CNKI), SinoMed and WanFang Data were retrieved for randomized controlled trials (RCTs) and cohort study about TGP adjuvant therapy in patients with RA up to 28 January 2021. Literatures with eligibility criteria and information were screened and extracted by two researchers independently. The RevMan5.3 software was used for data analysis with effect estimates as risk ratio (RR) with 95% confidence interval (CI). Results A total of 39 studies involving 3680 RA participants were included. There were 8 comparisons: TGP plus methotrexate (MTX) therapy versus MTX therapy, TGP plus leflunomide (LEF) therapy versus LEF therapy, TGP plus MTX and LEF therapy versus MTX plus LEF therapy, TGP plus tripterygium glycosides (TG) therapy versus TG therapy, TGP plus meloxicam (MLX) therapy versus MLX therapy and TGP plus sulfasalazine (SSZ) therapy versus SSZ therapy, TGP plus iguratimod (IGU) therapy versus IGU therapy, TGP plus prednisone acetate tablets (PAT) therapy versus PAT therapy. The meta-analysis results showed that the occurrence of hepatic adverse effect (RR = 0.31, 95% CI = 0.23–0.41, P < 0.00001) and leukopenia (RR = 0.41, 95% CI = 0.26–0.66, P = 0.0002) in TGP adjuvant therapy was significant decreased compared with non-TGP therapy. However, only TGP plus LEF therapy (RR = 0.22, 95% CI = 0.08–0.60, P = 0.003) and TGP plus MTX and LEF therapy (RR = 0.31, 95% CI = 0.22–0.42, P < 0.00001) had statistical difference in the subgroups of hepatic adverse effect. In leukopenia, TGP plus MTX and LEF therapy (RR = 0.47, 95% CI = 0.25–0.87, P = 0.02) had statistical difference. Conclusions This meta-analysis indicated that TGP adjuvant therapy might alleviate the incidence of hepatic adverse effect and leukopenia for the RA treatment compared to non-TGP therapy. The clinical safety of TGP adjuvant therapy warrant further investigation in experimental studies.

A preliminary systematic review and meta-analysis on the effects of heart rate variability biofeedback on heart rate variability and respiration of athletes

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jeffrey Cayaban Pagaduan ◽  
Yung-Sheng Chen ◽  
James William Fell ◽  
Sam Shi Xuan Wu
Keyword(s):  
Systematic Review ◽  
Heart Rate ◽  
Heart Rate Variability ◽  
Web Of Science ◽  
Meta Analysis ◽  
Academic Research ◽  
Experimental Studies ◽  
Quantitative Review ◽  
Heart Rate Variability Biofeedback ◽  
Randomized Control

Abstract To date, there is no quantitative review examining the influence of heart rate variability biofeedback (HRV BFB) on the athlete population. Such an undertaking may provide valuable information on the autonomic and respiration responses of athletes when performing HRV BFB. Thus, purpose of this preliminary systematic review and meta-analysis on the effects of HRV BFB on HRV and respiration of athletes. Searches of Springerlink, SportDiscus, Web of Science, PROQUEST Academic Research Library, Google Scholar, and ScienceDirect were conducted for studies that met the following criteria: (1) experimental studies involving athletes that underwent randomized control trial; (2) availability of HRV BFB as a treatment compared with a control (CON)/placebo (PLA); (3) any pre and post HRV variable and/or breathing frequency as dependent variable/s; and, (4) peer-reviewed articles written in English. Four out of 660 studies involving 115 athletes (25 females and 90 males) ages 16–30 years old were assessed in this review. Preliminary findings suggest the promising ability of HRV BFB to improve respiratory mechanics in athlete population. More work is needed to determine the autonomic modulatory effect of HRV BFB in athletes.

Sign in / Sign up

Export Citation Format

Share Document