Organoids derived from epithelial tumors have recently been utilized as a preclinical model in basic and translational studies. This model is considered to represent the original tumor in terms of 3D structure, genetic and cellular heterogeneity, but not tumor microenvironment. In this study, we established organoids and paired cancer-associated fibroblasts (CAFs) from surgical specimens of colorectal carcinomas (CRCs), and evaluated gene expression profiles in organoids with and without co-culture with CAFs to assess interactions between tumor cells and CAFs in tumor tissues. We found that the expression levels of several genes, which are highly expressed in original CRC tissues, were downregulated in organoids but re-expressed in organoids by co-culturing with CAFs. They comprised immune response- and external stimulus-related genes, e.g., REG family and dual oxidases (DUOXs), which are known to have malignant functions, leading tumor cells to proliferative and/or anti-apoptotic states and drug resistant phenotypes. In addition, the degree of differential induction of REG1 and DUOX2 in the co-culture system varied depending on CAFs from each CRC case. In conclusion, the co-culture system of CRC organoids with paired CAFs was able to partially reproduce the tumor microenvironment.

In order to clarify the level transboundary air pollution caused by polycyclic aromatic hydrocarbons (PAHs) and genotoxic substances, aerosols were collected from forest and suburban sites in Nagasaki, west Japan, for 6 years. The PAH concentration was measured, and the genotoxicity of the substances were evaluated using the umu test. The results showed no notable trends in the concentration or toxicity of either sites throughout the study period. The suburban and forest sites shared similar seasonal fluctuation patterns and quantitative values, suggesting that the western end of Japan might be affected by long-range transported pollutants, especially in winter. PAH concentration and genotoxicity showed the same seasonal patterns of increased levels in winter and lower levels in summer. This suggests that PAHs and genotoxic substances were correlated and share common sources. Back trajectory and source analyses were conducted using the diagnostic ratios of PAHs. It was predicted that air pollution by PAHs at the forest site arise predominantly as a result of biomass or coal combustion in continental regions, such as northern parts of China and the Korean Peninsula. This is particularly expected in winter. Therefore, genotoxic substances would also be strongly influenced by transboundary pollution from the continental region. In addition, it was estimated that the contribution of transboundary PAH pollution could reach 70% at the suburban site in winter.

Comprehensive genome profiling (CGP) serves as a guide for suitable genomically matched therapies for patients with cancer. However, little is known about the impact of the timing and types of cancer on the therapeutic benefit of CGP. A single hospital-based pan-cancer prospective study (TOP-GEAR; UMIN000011141) was conducted to examine the benefit of CGP with respect to the timing and types of cancer. Patients with advanced solid tumors (>30 types) who either progressed with or without standard treatments were genotyped using a single CGP test. The subjects were followed up for a median duration of 590 days to examine therapeutic response, using progression-free survival (PFS), PFS ratio, and factors associated with therapeutic response. Among the 507 patients, 62 (12.2%) received matched therapies with an overall response rate (ORR) of 32.3%. The PFS ratios (≥1.3) were observed in 46.3% (19/41) of the evaluated patients. The proportion of subjects receiving such therapies in the rare cancer cohort was lower than that in the non-rare cancer cohort (9.6% and 17.4%, respectively; P = 0.010). However, ORR of the rare cancer patients was higher than that in the non-rare cancer cohort (43.8% and 20.0%, respectively; P = 0.046). Moreover, ORR of matched therapies in the first or second line after receiving the CGP test was higher than that in the third or later lines (62.5% and 21.7%, respectively; P = 0.003). Rare cancer and early-line treatment were significantly and independently associated with ORR of matched therapies in multivariable analysis (P = 0.017 and 0.004, respectively). Patients with rare cancer preferentially benefited from tumor mutation profiling by increasing the chances of therapeutic response to matched therapies. Early-line treatments after profiling increase the therapeutic benefit, irrespective of tumor types.

In order to determine recent behaviors in atmospheric polycyclic aromatic hydrocarbon (PAH) concentrations at the west end of Japan and to reveal the causes of these behaviors, atmospheric PAH concentrations were measured in suburban and forest sites of Nagasaki, Japan from 2017 to 2021. The results showed that the total concentration of PAHs decreased considerably by 60% and 57% in suburban and forest sites, respectively, over this period. When analyzed by season, the rate of decrease in winter was markedly high. Therefore, the decreasing behavior in PAH concentrations in Nagasaki in recent years was considered to be mainly due to less PAHs originating from cold continental regions such as northern China. In particular, the reduction in coal and biomass combustion for winter heating in households, the efforts to improve air quality, and the limitation of economic activities in response to COVID-19 were likely responsible for the decrease in atmospheric PAH concentrations. In addition, although the PAH concentrations decreased, there was no significant change in the breakdown of the number of benzene rings in the PAH or in the attributes of their sources.