NF-κB regulates GDF-15 to suppress macrophage surveillance during early tumor development

Ratnam, Nivedita M.; Peterson, James W.; Talbert, Erin E.; Ladner, Katherine J.; Rajasekera, Priyani V.; Schmidt, Carl; Dillhoff, Mary; Swanson, Benjamin J.; Haverick, Ericka; Kladney, Raleigh D.; Williams, Terence M.; Leone, Gustavo; Wang, David J.; Guttridge, Denis C.

doi:10.1172/jci91561

Cited by 136 publications

(111 citation statements)

References 40 publications

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“…GDF15 was inversely correlated ( ρ = −0.33, FDR p ‐value = 0.0007) with M1‐type of macrophages (Fig. d ); interestingly GDF15 has been reported to inhibit macrophages surveillance during early tumor development . In Figure e , all the significant Pearson correlations (FDR corrected) between cytokine serum levels and the predicted immune infiltration using CIBERSORT are shown: the color of the dots indicates positive (blue) or negative correlations (red) and the size of the dots reflects the strength of the correlation.…”

Section: Resultsmentioning

confidence: 90%

“…4d); interestingly GDF15 has been reported to inhibit macrophages surveillance during early tumor development. 25 In Figure 4e, all the significant Pearson correlations (FDR corrected) between cytokine serum levels and the predicted immune infiltration using CIBERSORT are shown: the color of the dots indicates positive (blue) or negative correlations (red) and the size of the dots reflects the strength of the correlation. We further identified GDF15 serum levels correlated with antitumorigenic immune infiltration (Macrophages M1, T helper and activated T cells).…”

Section: Associating Circulating Molecule Levels To Tumor Phenotypementioning

confidence: 99%

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Serum levels of inflammation‐related markers and metabolites predict response to neoadjuvant chemotherapy with and without bevacizumab in breast cancers

Nome

Euceda

Jabeen

et al. 2019

Intl Journal of Cancer

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Angiogenesis is necessary for tumor growth and has been targeted in breast cancer; however, it is unclear which patients will respond and benefit from antiangiogenic therapy. We report noninvasive monitoring of patient response to neoadjuvant chemotherapy given alone or in combination with anti‐vascular endothelial growth factor (bevacizumab) in a randomized clinical trial. At four time points during neoadjuvant chemotherapy ± bevacizumab of receptor tyrosine‐protein kinase erbB‐2‐negative breast cancers, we measured metabolites and inflammation‐related markers in patient's serum. We report significant changes in the levels of several molecules induced by bevacizumab, the most prominent being an increase in pentraxin 3 (PTX3) and von Willebrand factor (VWF). Serum levels of AXL, VWF and pulmonary and activation‐regulated cytokine (PARC/CCL18) reflected response to chemotherapy alone or in combination with bevacizumab. We further analyzed serum cytokines in relation to tumor characteristics such as gene expression, tumor metabolites and tumor infiltrating leukocytes. We found that VWF and growth‐differentiation factor 15 tumor mRNA levels correlated with their respective serum protein levels suggesting that these cytokines may be produced by tumors and outflow to the bloodstream while influencing the tumor microenvironment locally. Finally, we used binomial logistic regression which allowed to predict patient's response using only 10 noninvasive biomarkers. Our study highlights the potential of monitoring circulating levels of cytokines and metabolites during breast cancer therapy.

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Section: Resultsmentioning

confidence: 90%

Section: Associating Circulating Molecule Levels To Tumor Phenotypementioning

confidence: 99%

Serum levels of inflammation‐related markers and metabolites predict response to neoadjuvant chemotherapy with and without bevacizumab in breast cancers

Nome

Euceda

Jabeen

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…This opens new targets in the field of analysing the pathways of cachexia. Ratnam et al . (Department of Cancer Biology and Genetics, The Ohio State University Wexner Medical Center, Columbus, OH, USA) gave an overview to the important functions of NF‐κB in myoblast to stimulate activin and inhibit muscle differentiation.…”

Section: Basic Sciencementioning

confidence: 99%

Recent developments in the field of cachexia, sarcopenia, and muscle wasting: highlights from the 11th Cachexia Conference

Ebner

Anker

Haehling

2019

J cachexia sarcopenia muscle

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This article highlights the updates from preclinical and clinical studies into the field of wasting disorders that were presented at the 11th Cachexia Conference held in Maastricht, the Netherlands, in December 2018. Herein, we summarize the biological and clinical significance of different markers and new diagnostic tools and cut‐offs for the detection of skeletal muscle wasting, including micro‐RNAs, siRNAs, epigenetic targets, the ubiquitin–proteasome system, mammalian target of rapamycin signalling, news in body composition analysis including the D3‐creatine dilution method, and electrocardiography that was modified to enable segmental impedance spectroscopy. Of particular interest were the beneficial effects of BIO101 on muscle cell differentiation, hypertrophy of myofibers associated with mammalian target of rapamycin pathways activation, and the effect of metal ion transporter ZIP14 loss that reduces cancer‐induced cachexia. The potential of anti‐ZIP14 antibodies and zinc chelation as anti‐cachexia therapy should be tested in patients with cancer cachexia. Big randomized studies were presented such as RePOWER (observational study of patients with primary mitochondrial myopathy), STRAMBO (influence of physical performance assessed as score and clinical testing), MMPOWER (treatment of elamipretide in subjects with primary mitochondrial myopathy), FORCE (examined differences in relative dose intensity and moderate and severe chemotherapy‐associated toxicities between a strength training intervention and a control group), and SPRINTT (effectiveness of exercise training in healthy aging). Effective treatments were urothelin A, rapamycin analogue treatment, epigenetic factor BRD 4 and epigenetic protein BET, and the gut pathobiont Klebsiella oxytoca . Clinical studies that investigated novel approaches, including urolithin A, the role of gut microbiota, metal ion transporter ZIP14, lysophosphatidylcholine and lysophosphatidylethanolamine, and BIO101, were described. It remains a fact, however, that effective treatments of cachexia and wasting disorders are urgently needed in order to improve patients' quality of life and their survival.

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“…Interestingly, Denis Guttridge et al . (Department of Cancer Biology and Genetics, The Ohio State University Wexner Medical Center, Columbus, OH, USA) presented data from multiplex array to screen a panel of biomarkers of cancer cachexia.…”

Section: Clinical Trials and Newly Treatment Targetsmentioning

confidence: 99%

Silver linings on the horizon: highlights from the 10th Cachexia Conference

Ebner

Haehling

2018

J cachexia sarcopenia muscle

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This article highlights the updates from preclinical and clinical studies into the field of wasting disorders that were presented at the 10th Cachexia Conference held in Rome, Italy, in December 2017. This year's conference saw some interesting results of larger‐scale studies and clinical trials and new therapeutic targets. Herein, we summarize the biological and clinical significance of different markers and new diagnostic tools and cut‐offs for the detection of skeletal muscle wasting, including micro RNAs, the ubiquitin‐proteasome system, mTOR signalling, news in body composition analysis including the D3‐creatine dilution method, and new biomarkers. Clinical studies investigated novel nutritional approaches, trials of elamipretide, enobosarm, and urolithin A. It remains a fact, however, that effective treatments of cachexia and wasting disorders are urgently needed in order to improve patients' quality of life and their survival.

show abstract

NF-κB regulates GDF-15 to suppress macrophage surveillance during early tumor development

Cited by 136 publications

References 40 publications

Serum levels of inflammation‐related markers and metabolites predict response to neoadjuvant chemotherapy with and without bevacizumab in breast cancers

Serum levels of inflammation‐related markers and metabolites predict response to neoadjuvant chemotherapy with and without bevacizumab in breast cancers

Recent developments in the field of cachexia, sarcopenia, and muscle wasting: highlights from the 11th Cachexia Conference

Silver linings on the horizon: highlights from the 10th Cachexia Conference

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