DNA Lesions Induced by Replication Stress Trigger Mitotic Aberration and Tetraploidy Development

During tumorigenesis, cells acquire immortality in association with the development of genomic instability. However, it is still elusive how genomic instability spontaneously generates during the process of tumorigenesis. Here, we show that precancerous DNA lesions induced by oncogene acceleration, which induce situations identical to the initial stages of cancer development, trigger tetraploidy/aneuploidy generation in association with mitotic aberration. Although oncogene acceleration primarily induces DNA replication stress and the resulting lesions in the S phase, these lesions are carried over into the M phase and cause cytokinesis failure and genomic instability. Unlike directly induced DNA double-strand breaks, DNA replication stress-associated lesions are cryptogenic and pass through cell-cycle checkpoints due to limited and ineffective activation of checkpoint factors. Furthermore, since damaged M-phase cells still progress in mitotic steps, these cells result in chromosomal mis-segregation, cytokinesis failure and the resulting tetraploidy generation. Thus, our results reveal a process of genomic instability generation triggered by precancerous DNA replication stress

Current state of therapeutic development for rare cancers in Japan, and proposals for improvement

This article discusses current obstacles to the rapid development of safe and effective treatments for rare cancers, and considers measures required to overcome these challenges. In order to develop novel clinical options for rare cancers, which tend to remain left out of novel therapeutic development because of their paucity, efficient recruitment of eligible patients, who tend to be widely dispersed across the country and treated at different centers, is necessary. For this purpose, it is important to establish rare cancer registries that are linked with clinical studies, to organize a central pathological diagnosis system and biobanks for rare cancers, and to consolidate patients with rare cancers to facilities that can conduct clinical studies meeting international standards. Establishing an all‐Japan cooperative network is essential. Clinical studies of rare cancers have considerable limitations in study design and sample size as a result of paucity of eligible patients and, as a result, the level of confirmation of the efficacy and safety shown by the studies is relatively low. Therefore, measures to alleviate these weaknesses inherent to external conditions need to be explored. It is also important to reform the current research environment in order to develop world‐leading treatment for rare cancers, including promotion of basic research, collaboration between industry and academia, and improvement of the infrastructure for clinical studies. Collaboration among a wide range of stakeholders is required to promote the clinical development of treatment for rare cancers under a nationwide consensus

General characterization of Antarctic micrometeorites collected by the 39th Japanese Antarctic Research Expedition: Consortium studies of JARE AMMs (III)

From November 1998 to January 1999,the 39th Japanese Antarctic Research Expedition (JARE-39) undertook Japanese first large-scale collection of Antarctic micrometeorites (AMMs), with sizes larger than 10μm, at the Meteorite Ice Field around the Yamato Mountains in Antarctica (at three different locations, for a total of 24 collection sites). The number of collected AMMs larger than 40μm is estimated to be about 5000. Here we present the general characterization (i.e., micro-morphology and surface chemical composition using SEM/EDS) of ∿810 AMMs chosen from 5 of the 24 sites. Additionally, the mineral composition of 61 out of 810 AMMs was determined by Synchrotron X-ray radiation. Preliminary results on mineralogical and chemical compositions show similarities with that of previous studies, even though a pronounced alteration of some AMMs is noticed. A correlation is found between the Mg/Si ratio at the sample\u27s surfaces of unmelted AMMs and the age of snow/ice in which the AMMs are embedded