1H-NMR Based Serum Metabolomics Highlights Different Specific Biomarkers between Early and Advanced Hepatocellular Carcinoma Stages

Casadei-Gardini, Andrea; Coco, Laura Del; Marisi, Giorgia; Conti, Fabio; Rovesti, Giulia; Ulivi, Paola; Canale, Matteo; Frassineti, Giovanni Luca; Foschi, Francesco Giuseppe; Longo, Serena; Fanizzi, Francesco Paolo; Giudetti, Anna Maria

doi:10.3390/cancers12010241

Cited by 49 publications

(33 citation statements)

References 64 publications

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“…Unfortunately, in a substantial percentage of human patients, acquired sorafenib resistance remains a major clinical obstacle, leading to treatment failure. Several mechanisms are implicated in the reduction of tumor cell sensitivity to sorafenib, including metabolic rewiring [17][18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Sorafenib for the Treatment of Unresectable Hepatocellular Carcinoma: Preliminary Toxicity and Activity Data in Dogs

Marconato

Sabattini

Marisi

et al. 2020

Cancers

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Unresectable nodular and diffuse hepatocellular carcinoma (HCC) have a poor prognosis with limited treatment options. Systemic traditional chemotherapy has been only rarely reported, with unsatisfactory results. The aim of this prospective, non-randomized, non-blinded, single center clinical trial was to investigate safety profile, objective response rate, time to progression and overall survival of sorafenib in comparison with metronomic chemotherapy (MC) consisting of thalidomide, piroxicam and cyclophosphamide in dogs with advanced, unresectable HCC. Between December 2011 and June 2017, 13 dogs were enrolled: seven received sorafenib, and six were treated with MC. Median time to progression was 363 days (95% CI, 191–535) in dogs treated with sorafenib versus 27 days (95% CI, 0–68) in dogs treated with MC (p = 0.044). Median overall survival was 361 days (95% CI, 0–909) in dogs receiving sorafenib, while 32 days (95% CI, 0–235) in those receiving MC (p = 0.079). Sorafenib seems to be a good candidate for the treatment of dogs with advanced HCC, due to a benefit in disease control and an acceptable safety profile, offering a good basis on which new randomized prospective clinical trials should be undertaken to compare the efficacy and drawback of sorafenib versus MC or traditional chemotherapy.

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Section: Introductionmentioning

confidence: 99%

Sorafenib for the Treatment of Unresectable Hepatocellular Carcinoma: Preliminary Toxicity and Activity Data in Dogs

Marconato

Sabattini

Marisi

et al. 2020

Cancers

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“…Two parameters, R 2 and Q 2 , describe the goodness of the statistical models. The former ( R 2 ) explains the total variations in the data, whereas the latter ( Q 2 , calculated via 10-fold cross-validation, CV) is an estimate of the predictive ability of the models ( Del Coco et al, 2019 ; Casadei-Gardini et al, 2020 ). To better visualize data, a heat map was performed on metabolites and samples, using Euclidean for distance measure and Ward for clustering algorithm.…”

Section: Methodsmentioning

confidence: 99%

“…In the last few years, metabolite quantification by Mass Spectrometry approaches has been used to obtain a global unbiased view of small molecules in different biological samples thus contributing to the understanding of the molecular characteristics of many diseases and therapeutic outcomes in different pathologies ( Vergara et al, 2019 ; Casadei-Gardini et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Decanoic Acid and Not Octanoic Acid Stimulates Fatty Acid Synthesis in U87MG Glioblastoma Cells: A Metabolomics Study

et al. 2020

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Medium-chain fatty acids (MCFA) are dietary components with a chain length ranging from 6 to 12 carbon atoms. MCFA can cross the blood-brain barrier and in the brain can be oxidized through mitochondrial β-oxidation. As components of ketogenic diets, MCFA have demonstrated beneficial effects on different brain diseases, such as traumatic brain injury, Alzheimer's disease, drug-resistant epilepsy, diabetes, and cancer. Despite the interest in MCFA effects, not much information is available about MCFA metabolism in the brain. In this study, with a gas chromatographymass spectrometry (GC-MS)-based metabolomics approach, coupled with multivariate data analyses, we followed the metabolic changes of U87MG glioblastoma cells after the addition of octanoic (C8), or decanoic (C10) acids for 24 h. Our analysis highlighted significant differences in the metabolism of U87MG cells after the addition of C8 or C10 and identified several metabolites whose amount changed between the two groups of treated cells. Overall, metabolic pathway analyses suggested the citric acid cycle, Warburg effect, glutamine/glutamate metabolism, and ketone body metabolism as pathways influenced by C8 or C10 addition to U87MG cells. Our data demonstrated that, while C8 affected mitochondrial metabolism resulting in increased ketone body production, C10 mainly influenced cytosolic pathways by stimulating fatty acid synthesis. Moreover, glutamine might be the main substrate to support fatty acids synthesis in C10-treated cells. In conclusion, we identified a metabolic signature associated with C8 or C10 addition to U87MG cells that can be used to decipher metabolic responses of glioblastoma cells to MCFA treatment.

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“…Integral values for metabolite quantitative analysis were referred to as the internal standard (TSP and TMS for aqueous and lipid extracts, respectively). Results, represented as mean intensities and standard error mean of the selected NMR signals, were validated by the univariate t-test [61][62][63] . Levels of statistical significance were at least at p-values < 0.05 with a 95% confidence level.…”

Section: Multivariate Data Analysismentioning

confidence: 99%

1H-NMR metabolomics reveals a multitarget action of Crithmum maritimum ethyl acetate extract in inhibiting hepatocellular carcinoma cell growth

Gnocchi

Coco

Girelli

et al. 2021

Sci Rep

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Hepatocellular carcinoma (HCC) is nowadays the sixth cause of tumour-related deceases worldwide, estimated to become the third in Western countries by 2030. New drugs for HCC treatment still have many adverse effects. Several lines of evidence indicate that plant metabolites offer concrete opportunities for developing new therapeutic strategies for many diseases, including cancer. We previously reported that ethyl acetate extract of a spontaneous edible plant harvested in Apulia, Crithmum maritimum, significantly inhibited cell growth in HCC cells. By 1H-NMR spectroscopy, here we show that Crithmum maritimum ethyl acetate extract counteracts the Warburg effect, by reducing intracellular lactate, inhibits protein anabolism, by decreasing amino acid level, and affects membrane biosynthesis by lowering choline and phosphocholine. Also, we observed an effect on lipid homeostasis, with a reduction in triglycerides, cholesterol, monounsaturated fatty acids (MUFA), and diunsaturated fatty acids (DUFA), and an increase in polyunsaturated fatty acids (PUFA). Taken together, these data demonstrate that Crithmum maritimum-induced cytostasis is exerted through a multi-effect action, targeting key metabolic processes in HCC cells. Overall, our findings highlight the role of Crithmum maritimum as a promising tool for the prevention and the improvement of the therapeutic options for HCC and other types of tumours.

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1H-NMR Based Serum Metabolomics Highlights Different Specific Biomarkers between Early and Advanced Hepatocellular Carcinoma Stages

Cited by 49 publications

References 64 publications

Sorafenib for the Treatment of Unresectable Hepatocellular Carcinoma: Preliminary Toxicity and Activity Data in Dogs

Sorafenib for the Treatment of Unresectable Hepatocellular Carcinoma: Preliminary Toxicity and Activity Data in Dogs

Decanoic Acid and Not Octanoic Acid Stimulates Fatty Acid Synthesis in U87MG Glioblastoma Cells: A Metabolomics Study

1H-NMR metabolomics reveals a multitarget action of Crithmum maritimum ethyl acetate extract in inhibiting hepatocellular carcinoma cell growth

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