C-CAT: The National Datacenter for Cancer Genomic Medicine in Japan.

SUMMARY: Since June 2019, under the umbrella of the national health insurance system, Japan has started cancer genomic medicine (CGM) with comprehensive genomic profiling (CGP) tests. The Ministry of Health, Labour and Welfare (MHLW) of Japan constructed a network of CGM hospitals (a total of 233 institutes as of July 1, 2022) and established the Center for Cancer Genomics and Advanced Therapeutics (C-CAT), the national datacenter for CGM. Clinical information and genomic data from the CGP tests are securely transferred to C-CAT, which then generates "C-CAT Findings" reports containing information of clinical annotation and matched clinical trials based on the CGP data. As of June 30, 2022, a total of 36,340 datapoints of clinical/genomic information are aggregated in C-CAT, and the number is expected to increase swiftly. The data are now open for sharing with not only the CGM hospitals but also other academic institutions and industries.

Investigation of the Factors Affecting Risk-Based Quality Management of Investigator-Initiated Investigational New-Drug Trials for Unapproved Anticancer Drugs in Japan.

BACKGROUND: With an increase in the complexity and cost of clinical trials and the advances in information technology, monitoring guidance issued by regulatory authorities recommends risk-adapted monitoring. To introduce the monitoring method for investigator-initiated investigational new drug (IND) trials using unapproved anticancer drugs, we performed exploratory retrospective analyses to identify risk factors for data quality. METHODS: To select investigator-initiated IND trials using unapproved anticancer drugs, we set the trial selection criteria. Data collection was performed by using audit trails and monitoring reports. Collected data were analyzed by univariate and multivariate analyses to identify the independent risk factors related to error. RESULTS: By trial selection criteria, 5 investigator-initiated IND trials using unapproved anticancer drugs were selected. The error rates of the total data, critical data, and noncritical data were 7.4%, 9.7%, and 5.9%, respectively. There was no difference between clinical research core hospitals certified by the Ministry of Health, Labour and Welfare and other hospitals in univariate analysis (odds ratio [OR], 1.00; 99% confidence interval [CI], 0.96-1.05; P = .9179). As the main independent risk factors related to error, critical data in the importance of data (OR, 1.28; 99% CI, 1.24-1.33; P < .0001) and groups with ≤3 patients after registration (OR, 1.12; 99% CI, 1.10-1.15; P < .0001) were significantly related to errors in multivariate analysis. CONCLUSIONS: The results of this research suggest that the feasibility of risk-based monitoring and sampling source data verification was indicated for noncritical data and patients after the third case.

Gene knockout and metabolome analysis of carnitine/organic cation transporter OCTN1.

PURPOSE: Solute carrier OCTN1 (SLC22A4) is an orphan transporter, the physiologically important substrate of which is still unidentified. The aim of the present study was to examine physiological roles of OCTN1. METHODS: We first constructed octn1 gene knockout (octn1 ( -/- )) mice. Metabolome analysis was then performed to identify substrates in vivo. The possible association of the substrate identified with diseased conditions was further examined. RESULTS: The metabolome analysis of blood and several organs indicated complete deficiency of a naturally occurring potent antioxidant ergothioneine in octn1 ( -/- ) mice among 112 metabolites examined. Pharmacokinetic analyses after oral administration revealed the highest distribution to small intestines and extensive renal reabsorption of [(3)H]ergothioneine, both of which were much reduced in octn1 ( -/- ) mice. The octn1 ( -/- ) mice exhibited greater susceptibility to intestinal inflammation under the ischemia and reperfusion model. The blood ergothioneine concentration was also much reduced in Japanese patients with Crohn's disease, compared with healthy volunteers and patients with another inflammatory bowel disease, ulcerative colitis. CONCLUSIONS: These results indicate that OCTN1 plays a pivotal role for maintenance of systemic and intestinal exposure of ergothioneine, which could be important for protective effects against intestinal tissue injuries, providing a possible diagnostic tool to distinguish the inflammatory bowel diseases.