がん悪液質における中枢性代謝変化の解析

抄録

[Background]

Cancer cachexia is a systemic wasting syndrome, which is characterized by anorexia and the loss of body weight, adipose tissue, and skeletal muscle. This syndrome causes poor quality of life and poor responses to chemotherapy in advanced cancer patients. In this study, metabolic changes in the central nervous system (CNS) at the onset of cachexia was investigated.

[Methods]

Anesthetized 8-week-old male BALB/c-nu/nu mice were subcutaneously inoculated with a human gastric cancer cell line, 85As2. Body weight, tumor volume, and food consumption were evaluated weekly. Quantitative alteration of 113 kinds of hydrophilic metabolites in the cerebrum was determined using a capillary electrophoresis-time of flight mass spectrometry system.

[Results]

Subcutaneous implantation of 85As2 cells induced progressive tumor growth and significant body weight loss was observed in two weeks, accompanied by gradual decrease of food consumption. Metabolome analysis of the cerebrum collected two weeks after implantation showed lower amounts of purine nucleotides (IMP, AMP, ADP, ATP, GMP, GDP, and GTP) in cachexic mice than in control. On the other hand, quantification of the downstream metabolites revealed that the amounts of inosine, hypoxanthine, and uric acid were higher in cachexic mice.

[Conclusion]

These results suggest that the purine nucleotide metabolism in is activated at the onset of cancer cachexia (Uzu et al., 2019). Now, the changes of lipid metabolism are being investigated, and those results will be also presented.