12-hydroxy-5-8-10-14-eicosatetraenoic-acid and Adenoma

Colorectal cancer (CRC) is one of the main causes of cancer-related deaths worldwide. Sporadic CRC develops from normal mucosa via adenoma to adenocarcinoma, which provides a long screening window for clinical detection. However, early diagnosis of sporadic colorectal adenoma (CRA) and CRC using serum metabolic screening remains unclear. The purpose of this study was to identify some promising signatures for distinguishing the different pathological metabolites of colorectal mucosal malignant transformation. A total of 238 endogenous metabolites were elected. We found that CRA and CRC patients had 72 and 73 different metabolites compared with healthy controls, respectively. There were 20 different metabolites between CRA and CRC patients. The potential metabolites of tumor growth (including patients with CRA and CRC) were found, such as A-d-glucose, D-mannose, N-acetyl-D-glucosamine, L-cystine, Sarcosine, TXB 2, 12-Hete, and chenodeoxycholic acid. Compared with CRA, 3,4,5-trimethoxybenzoic acid was significantly higher in CRC patients. There results prompt us to use the potential serum signatures to screen CRC as the novel strategy. Serum metabolite screening is useful for early detection of mucosal intestinal malignancy. We will further investigate the roles of these promising biomarkers during intestinal tumorigenesis in future. SIGNIFICANCE: CRC is one of the main causes of cancer-related deaths worldwide. Sporadic CRC develops from normal mucosa via adenomas to adenocarcinoma, which provides a long screening window for about 5-10 years. We adopt the metabolic analysis of extensive targeted metabolic technology. The main purpose of the metabolic group analysis is to detect and screen the different metabolites, thereby performing related functional prediction and analysis of the differential metabolites. In our study, 30 samples are selected, divided into 3 groups for metabolic analysis, and 238 metabolites are elected. In 238 metabolites, we find that CRA patients have 72 different metabolites compared with health control. Compared with health control, CRC have 73 different metabolites. Compared with CRA and CRC patients, there are 20 different metabolites. The annotation results of the significantly different metabolites are classified according to the KEGG pathway type. The potential metabolites of tumor growth stage (including patients with CRA and CRC) are found, such as A-d-glucose, D-mannose, N-acetyl-D-glucosamine, L-cystine, sarcosine, TXB 2, 1

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Acetylglucosamine; Adenocarcinoma; Adenoma; Chenodeoxycholic Acid; Chromatography, High Pressure Liquid; Chromatography, Liquid; Colorectal Neoplasms; Cystine; Glucose; Humans; Mannose; Sarcosine; Tandem Mass Spectrometry

Insulin is known to modulate several functions in bovine adrenal cells, including steroidogenesis and growth. However, the role of insulin in regulating aldosterone synthesis in human adrenal glomerulosa cells has not been studied. In the present studies, we have examined the acute and chronic effects of insulin on angiotensin II (ANG II)-induced aldosterone synthesis in cultured normal and adenomatous human adrenal glomerulosa cells. Short-term insulin treatment (1.5 h) resulted in inhibition of ANG II-induced aldosterone synthesis. In contrast, chronic treatment (30 h) resulted in potentiation of ANG II action. The 12-lipoxygenase pathway of arachidonate metabolism has been shown to play a key role in ANG II-induced aldosterone synthesis. The acute inhibitory effects of insulin were in part mediated by inhibition of the 12-lipoxygenase pathway. The chronic stimulatory effect of insulin seemed to be due at least in part to the upregulation of cytochrome P-450 side-chain cleavage enzyme levels. These findings suggest that insulin has a differential temporal effect on ANG II action and therefore may be an important regulator of ANG II-induced aldosterone synthesis in the adrenal.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Adenoma; Adrenal Gland Neoplasms; Aldosterone; Angiotensin II; Antibodies; Cell Membrane; Cells, Cultured; Cholesterol Side-Chain Cleavage Enzyme; Humans; Hydroxyeicosatetraenoic Acids; Insulin; Insulin-Like Growth Factor I; Receptors, Somatomedin; Reference Values; Steroid 11-beta-Hydroxylase; Time Factors; Zona Glomerulosa