Metabolomic characterisation of progression and spontaneous regression of melanoma in the melanoma-bearing Libechov minipig model

Kertys, Martin; Grendár, Marian; Horák, Vratislav; Žideková, Nela; Skalníková, Helena Kupcová; Mokrý, Juraj; Halašová, Erika; Strnádel, Ján

doi:10.1097/cmr.0000000000000722

Cited by 3 publications

(3 citation statements)

References 58 publications

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“…Tumour associated myeloid cells have the ability to suppress the protective anti-tumour immune response by targeting arginine metabolism and reducing arginine levels by producing arginases [ 147 , 148 ]. In line with these findings result from our previous metabolomic study, where a highly significantly decreased level of arginine in plasma of MeLiM pigs with progression was the most striking difference compared to pigs with spontaneous regression [ 149 ]. Up-regulation of proline in melanoma cells compared to melanocytes was observed by de Ingeniis et al [ 150 ].…”

Section: Discussionsupporting

confidence: 87%

Dysbiosis of skin microbiome and gut microbiome in melanoma progression

et al. 2022

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Background The microbiome alterations are associated with cancer growth and may influence the immune system and response to therapy. Particularly, the gut microbiome has been recently shown to modulate response to melanoma immunotherapy. However, the role of the skin microbiome has not been well explored in the skin tumour microenvironment and the link between the gut microbiome and skin microbiome has not been investigated in melanoma progression. Therefore, the aim of the present study was to examine associations between dysbiosis in the skin and gut microbiome and the melanoma growth using MeLiM porcine model of melanoma progression and spontaneous regression. Results Parallel analysis of cutaneous microbiota and faecal microbiota of the same individuals was performed in 8 to 12 weeks old MeLiM piglets. The bacterial composition of samples was analysed by high throughput sequencing of the V4-V5 region of the 16S rRNA gene. A significant difference in microbiome diversity and richness between melanoma tissue and healthy skin and between the faecal microbiome of MeLiM piglets and control piglets were observed. Both Principal Coordinate Analysis and Non-metric multidimensional scaling revealed dissimilarities between different bacterial communities. Linear discriminant analysis effect size at the genus level determined different potential biomarkers in multiple bacterial communities. Lactobacillus, Clostridium sensu stricto 1 and Corynebacterium 1 were the most discriminately higher genera in the healthy skin microbiome, while Fusobacterium, Trueperella, Staphylococcus, Streptococcus and Bacteroides were discriminately abundant in melanoma tissue microbiome. Bacteroides, Fusobacterium and Escherichia-Shigella were associated with the faecal microbiota of MeLiM piglets. Potential functional pathways analysis based on the KEGG database indicated significant differences in the predicted profile metabolisms between the healthy skin microbiome and melanoma tissue microbiome. The faecal microbiome of MeLiM piglets was enriched by genes related to membrane transports pathways allowing for the increase of intestinal permeability and alteration of the intestinal mucosal barrier. Conclusion The associations between melanoma progression and dysbiosis in the skin microbiome as well as dysbiosis in the gut microbiome were identified. Results provide promising information for further studies on the local skin and gut microbiome involvement in melanoma progression and may support the development of new therapeutic approaches.

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Section: Discussionsupporting

confidence: 87%

Dysbiosis of skin microbiome and gut microbiome in melanoma progression

et al. 2022

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“…This chromatography system was coupled with a triple quadrupole mass spectrometer (XEVO TQ-S, Waters, Czechia). Metabolites were extracted and quantified following the manufacturer’s guidelines, as previously [ 27 , 57 , 58 ]. The values were subjected to a log2 transformation to achieve normally distributed data and to stabilize the variance, consistent with the previous description [ 38 ].…”

Section: Methodsmentioning

confidence: 99%

The First In Vivo Study Shows That Gyrophoric Acid Changes Behavior of Healthy Laboratory Rats

Simko,

Leskanicova,

Suvakova-Nunhart

et al. 2024

IJMS

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Gyrophoric acid (GA), a lichen secondary metabolite, has attracted more attention during the last years because of its potential biological effects. Until now, its effect in vivo has not yet been demonstrated. The aim of our study was to evaluate the basic physicochemical and pharmacokinetic properties of GA, which are directly associated with its biological activities. The stability of the GA in various pH was assessed by conducting repeated UV-VIS spectral measurements. Microsomal stability in rat liver microsomes was performed using Ultra-Performance LC/MS. Binding to human serum albumin (HSA) was assessed using synchronous fluorescence spectra, and molecular docking analysis was used to reveal the binding site of GA to HSA. In the in vivo experiment, 24 Sprague-Dawley rats (Velaz, Únetice, Czech Republic) were used. The animals were divided as follows. The first group (n = 6) included healthy males as control intact rats (♂INT), and the second group (n = 6) included healthy females as controls (♀INT). Groups three and four (♂GA/n = 6 and ♀GA/n = 6) consisted of animals with daily administered GA (10 mg/kg body weight) in an ethanol-water solution per os for a one-month period. We found that GA remained stable under various pH and temperature conditions. It bonded to human serum albumin with the binding constant 1.788 × 106 dm3mol−1 to reach the target tissue via this mechanism. In vivo, GA did not influence body mass gain, food, or fluid intake during the experiment. No liver toxicity was observed. However, GA increased the rearing frequency in behavioral tests (p < 0.01) and center crossings in the elevated plus-maze (p < 0.01 and p < 0.001, respectively). In addition, the time spent in the open arm was prolonged (p < 0.01 and p < 0.001, respectively). Notably, GA was able to pass through the blood–brain barrier, indicating its ability to permeate into the brain and to stimulate neurogenesis in the hilus and subgranular zone of the hippocampus. These observations highlight the potential role of GA in influencing brain function and neurogenesis.

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“…Chromatographic separation was achieved using the ultra-performance liquid chromatography system ACQUITY UPLC I-Class (Waters, Prague, Czech Republic) coupled with triple quadrupole mass spectrometer XEVO TQ-S (Waters, Prague, Czech Republic). Metabolites were extracted and measured following the manufacturer’s instructions as described previously in studies [ 20 , 21 ].…”

Section: Methodsmentioning

confidence: 99%

Biochemical Properties of Atranorin-Induced Behavioral and Systematic Changes of Laboratory Rats

Simko

Leškaničová

Suváková

et al. 2022

Life

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Atranorin (ATR) is a secondary metabolite of lichens. While previous studies investigated the effects of this substance predominantly in an in vitro environment, in our study we investigated the basic physicochemical properties, the binding affinity to human serum albumin (HSA), basic pharmacokinetics, and, mainly, on the systematic effects of ATR in vivo. Sporadic studies describe its effects during, predominantly, cancer. This project is original in terms of testing the efficacy of ATR on a healthy organism, where we can possibly attribute negative effects directly to ATR and not to the disease. For the experiment, 24 Sprague Dawley rats (Velaz, Únetice, Czech Republic) were used. The animals were divided into four groups. The first group (n = 6) included healthy males as control intact rats (♂INT) and the second group (n = 6) included healthy females as control intact rats (♀INT). Groups three and four (♂ATR/n = 6 and ♀ATR/n = 6) consisted of animals with daily administered ATR (10mg/kg body weight) in an ethanol–water solution per os for a one-month period. Our results demonstrate that ATR binds to HSA near the binding site TRP214 and acts on a systemic level. ATR caused mild anemia during the treatment. However, based on the levels of hepatic enzymes in the blood (ALT, ALP, or bilirubin levels), thiobarbituric acid reactive substances (TBARS), or liver histology, no impact on liver was recorded. Significantly increased creatinine and lactate dehydrogenase levels together with increased defecation activity during behavioral testing may indicate the anabolic effect of ATR in skeletal muscles. Interestingly, ATR changed some forms of behavior. ATR at a dose of 10 mg/kg body weight is non-toxic and, therefore, could be used in further research.

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Metabolomic characterisation of progression and spontaneous regression of melanoma in the melanoma-bearing Libechov minipig model

Cited by 3 publications

References 58 publications

Dysbiosis of skin microbiome and gut microbiome in melanoma progression

Dysbiosis of skin microbiome and gut microbiome in melanoma progression

The First In Vivo Study Shows That Gyrophoric Acid Changes Behavior of Healthy Laboratory Rats

Biochemical Properties of Atranorin-Induced Behavioral and Systematic Changes of Laboratory Rats

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