RÉSUMÉ
Oral mucositis (OM) caused by cancer therapy is the most common adverse reaction in the radiotherapy of head and neck tumors. In severe cases, it can lead to the interruption of treatment, which affects the control of the disease and the quality of life. Shuanghua Baihe Tablet (SBT) is a traditional Chinese medicine (TCM) formula, which is administerd to treat OM in China. It has been clinically effective for more than 30 years, but the underlying mechanism is not completely understood. With the development of multiple omics, it is possible to explore the mechanism of Chinese herbal compound prescriptions. Based on transcriptomics and metabolomics, we explored the underlying mechanism of SBT in the treatment of OM. An OM model of rats was established by 5-FU induction, and SBT was orally administered at dosages of 0.75 and 3 g·kg-1·d-1. In order to search for SBT targets and related metabolites, the dysregulated genes and metabolites were detected by transcriptomics and metabolomics. Immune related indicators such as interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) were detected by ELISA. Treg cell disorders was analyzed by flow cytometry. Our results showed that SBT significantly alleviated the symptoms of OM rats and the inflammatory infiltration of ulcer tissues. After SBT administration, inflammatory related metabolic pathways including linoleic acid metabolism, valine, leucine and isoleucine biosynthesis were significantly altered. Furthermore, the production of proinflammatory factors like IL-17 and TNF-α, were also dramatically reduced after SBT administration. Besides, the infiltration degree of Treg cells in the spleen of OM modeling rats was significantly improved by SBT administration, thus maintaining the immune balance of the body. The current study demonstrates that SBT regulates inoleic acid metabolism, glycerophospholipid metabolism and amino acid metabolism, and inhibits IL-17/TNF signal transduction to restore Treg and Th17 cell homeostasis in OM rats, thereby alleviating chemotherapy-induced OM.
Sujet(s)
Médicaments issus de plantes chinoises , Stomatite , Animaux , Métabolome , Qualité de vie , Rats , Comprimés , TranscriptomeRÉSUMÉ
Cancer is the leading cause of disease-related death worldwide due to its late diagnosis and poor outcomes. Precision medicine plays an important role in the treatment of tumors. As found for many types of tumors, mental stress plays a vital role in the promotion and progression of tumors. In this paper, we briefly introduce the manifestation and effects of mental symptoms in tumor patients. We next specifically discuss the multiple roles of precision medicine in the tumor therapy. Finally, we also highlight the precision medicine strategy for psychiatric symptoms in tumor patients, which promises to enhance the efficacy of tumor therapy.
Sujet(s)
Tumeurs/traitement médicamenteux , Tumeurs/psychologie , Médecine de précision/méthodes , Stress psychologique/traitement médicamenteux , HumainsRÉSUMÉ
BACKGROUND: Thyroid cancer (THCA) is a malignancy affecting the endocrine system, which currently has no effective treatment due to a limited number of suitable drugs and prognostic markers. METHODS: Three Gene Expression Omnibus (GEO) datasets were selected to identify differentially expressed genes (DEGs) between THCA and normal thyroid samples using GEO2R tools of National Center for Biotechnology Information. We identified hub gene FN1 using functional enrichment and protein-protein interaction network analyses. Subsequently, we evaluated the importance of gene expression on clinical prognosis using The Cancer Genome Atlas (TCGA) database and GEO datasets. MEXPRESS was used to investigate the correlation between gene expression and DNA methylation; the correlations between FN1 and cancer immune infiltrates were investigated using CIBERSORT. In addition, we assessed the effect of silencing FN1 expression, using an in vitro cellular model of THCA. Immunohistochemical(IHC) was used to elevate the correlation between CD276 and FN1. RESULTS: FN1 expression was highly correlated with progression-free survival and moderately to strongly correlated with the infiltration levels of M2 macrophages and resting memory CD4+ T cells, as well as with CD276 expression. We suggest promoter hypermethylation as the mechanism underlying the observed changes in FN1 expression, as 20 CpG sites in 507 THCA cases in TCGA database showed a negative correlation with FN1 expression. In addition, silencing FN1 expression suppressed clonogenicity, motility, invasiveness, and the expression of CD276 in vitro. The correlation between FN1 and CD276 was further confirmed by immunohistochemical. CONCLUSION: Our findings show that FN1 expression levels correlate with prognosis and immune infiltration levels in THCA, suggesting that FN1 expression be used as an immunity-related biomarker and therapeutic target in THCA.
RÉSUMÉ
Background: Fatty acid transporters (FATPs) family play an important role in the uptake and metabolism regulation of long-chain fatty acids, which influence the occurrence and developing of multiple tumors. Fatty acid transporter 5(FATP5), a member of FATPs family, participates in fatty acid transport and lipid metabolism and is related to tumor development, whose mechanism in colorectal cancer (CRC) remains unclear. Methods: In this study, we comprehensively utilized a range of relevant bioinformatic tools along with multiple databases to analyze the expression of FATPs family and investigate the biological function and prognostic value of FATP5 in CRC. Besides, cell proliferation and cell cycle distribution analysis, western blotting and immunohistochemistry (IHC) further validated the conclusion of bioinformatics analysis. Results: FATP5 is the only member of FATPs family which was overexpressed in CRC. In the survival analysis based on the GSE39582 databases, the low expression of FATP5 predicts poor prognosis in CRC. Similar results were also observed in GSE17536, GSE28814 and TCGA colon cohorts. The potential function of DNA methylation regulated the abnormal expression of FATP5 in CRC. In addition, enrichment analysis indicated that FATP5 also participates in the regulation of cell cycle. Furthermore, Gene Set Enrichment Analysis (GSEA) showed a strong negative correlation between FATP5 and cell growth, implying that it may participate in regulating cancer cell proliferation by the regulation of cell cycle G2/M transition. At last, we identified that FATP5 was overexpressed in colorectal carcinoma tissues through immunohistochemistry staining, and played an important role in cell cycle by cell proliferation and cell cycle distribution analysis. Conclusion: This study suggested that FATP5 was overexpression in colorectal carcinoma and predicted favorable prognosis, indicating it as a novel appealing prognostic marker for CRC.
RÉSUMÉ
Background: Esophageal squamous cell carcinoma (ESCC) is one of the most fatal diseases worldwide. Because early diagnosis is difficult, ESCC is mostly diagnosed at an advanced stage, leading to a poor overall prognosis. The purpose of this study was to explore the differences between plasma metabolic profiles in ESCC patients and healthy controls and to establish a diagnostic model of ESCC. Methods: In this study, a cohort of 310 subjects, containing 140 ESCC patients and 170 healthy controls (HC), was recruited. Participants were randomly separated into a training set (80 ESCCs, 80 HCs) and a validation set (60 ESCCs, 90 HCs) and their plasma metabolomics profiles were analyzed by ultra-performance liquid chromatography-tandem quadruple time-of-flight mass spectrometry (UPLC-QTOF/MS) technique. Univariate statistical analysis and multivariate analysis (MVA) methods were used to identify differential metabolites. Finally, the dysregulated pathways associated with ESCC were further explored and the diagnostic performance of the biomarker panel was evaluated. Results: Metabolic analyses identified 34 significant metabolites involved in the metabolism of amino acids, phospholipids, fatty acids, purine, and choline. Farthermore, an effective diagnostic model for ESCC was constructed based on eight metabolites. This panel of biomarkers consisted of hypoxanthine, proline betaine, indoleacrylic acid, inosine, 9-decenoylcarnitine, tetracosahexaenoic acid, LPE (20:4), and LPC (20:5). The model was verified and evaluated in the validation set. The AUC value of the ROC curve was 0.991(95% CI: 0.981-1.000, CI, Confidence interval), with a sensitivity (SE) of 98.8% and a specificity (SP) of 94.9% for the training set and 0.965(95% CI: 0.936-0.993), with a SE of 88.3% and a SP of 88.9% for the validation set. Among them, three biomarkers, indoleacrylic acid, LPC (20:5), and LPE (20:4), exhibited a trend associated with the ESCC progression. Conclusions: Our study identified a novel plasma biomarker panel, which clearly distinguishes ESCC patients and provides insight into the mechanisms of ESCC. This finding may form the basis for the development of a minimally invasive method for ESCC detection.