In Japan, the social (medical) health‐care system is on the way to being developed to advance personalized medicine through the implementation of cancer genomic medicine, known as “cancer clinical sequencing,” which uses a next‐generation sequencer. However, no Japanese guidance for cancer genomic testing exists. Gene panel testing can be carried out to help determine patient treatment, confirm diagnosis, and evaluate prognostic predictions of patients with mainly solid cancers for whom no standard treatment is available. This guidance describes how to utilize gene panel testing according to the type of cancer: childhood cancer, rare cancer, carcinoma of unknown primary, and other cancers. The level of evidence classification for unified use in Japan is also detailed. This guidance establishes the basic principles of the quality control of specimens, requirements of medical institutions, informed consent, handling of data during the postanalysis stage, and treatment options based on the evidence level. In Japan, gene panel testing for cancer treatment and diagnosis is recommended to comply with this guidance. This is a collaborative work of the Japanese Society of Medical Oncology, Japan Society of Clinical Oncology, and the Japanese Cancer Association.
We investigated the influence of human activities on the spawning migration of the mud loach, Misgurnus anguillicaudatus. Mud loaches migrate from rivers to paddy fields for spawning. In this study, the number of adult loaches in paddy fields showed a peak in late May and rapidly decreased in July. In early July, water is discharged from paddy fields in order to allow the fields to dry for a few weeks, and water is again supplied later. The spawning season of the loaches probably spans from mid May to August; this was concluded by observing physiological indicators such as the gonad somatic index, oocyte maturity and serum levels of testosterone, estradiol-17b and 17a, 20b-dihydroxy-4-pregnen-3-one. When the loaches mature, they migrated to paddy fields if they could swim upward through the drainage ditches. However, the drainage ditches of modern paddy fields were reconstructed to deepen the water levels. The artificial drought of the rice culture management led to a discharge of water and loaches from the paddy fields during their spawning season. These results indicate that modern rice cultivation causes obstruction of the migration route and loss of spawning grounds; consequently, loaches use limited space and period of the paddy field for their spawning.
Amplification and/or overexpression of human epidermal growth factor receptor 2 (HER2) are observed in 15–20% of breast cancers (HER2+ breast cancers), and anti-HER2 therapies have significantly improved prognosis of patients with HER2+ breast cancer. One resistance mechanism to anti-HER2 therapies is constitutive activation of the phosphoinositide 3-kinase (PI3K) pathway. Combination therapy with small-molecule inhibitors of AKT and HER2 was conducted in HER2+ breast cancer cell lines with or without PIK3CA mutations, which lead to constitutive activation of the PI3K pathway. PIK3CA mutations played important roles in resistance to single-agent anti-HER2 therapy in breast cancer cell lines. Combination therapy of a HER2 inhibitor and an AKT inhibitor, as well as other PI3K pathway inhibitors, could overcome the therapeutic limitations associated with single-agent anti-HER2 treatment in PIK3CA-mutant HER2+ breast cancer cell lines. Furthermore, expression of phosphorylated 4E-binding protein 1 (p4EBP1) following the treatment correlated with the antiproliferative activities of the combination, suggesting that p4EBP1 may have potential as a prognostic and/or efficacy-linking biomarkers for these combination therapies in patients with HER2+ breast cancer. These findings highlight potential clinical strategies using combination therapy to overcome the limitations associated with single-agent anti-HER2 therapies in patients with HER2+ breast cancer.
Circadian changes in serum concentrations of testosterone (T), 11-ketotestosterone (11KT), estradiol-17beta (E2), 17alpha,20beta-dihydroxy-4-pregnen-3-one (DHP), 17alpha-hydroxyprogesterone (OHP), cortisol (F) and progesterone (P) were investigated in the spermiated/ovulated Japanese char Salvelinus leucomaenis for over three days using newly developed time-resolved fluoroimmunoassays. Testosterone and DHP in both sex and 11KT in male showed significantly (P<0.05) higher serum levels just before/after onset of darkness (15:00 or 18:00), and the levels during night and daytime were significantly (P<0.05) lower than those of the peak levels. Serum F levels in both sex during dark phase were significantly (P<0.05) higher than those levels during daytime. A surge of serum OHP concentrations in both sexes was observed at the time of twilight (03:00). The peak time of serum T, 11KT and DHP levels were approximately 6 hours prior to those of serum F and OHP levels. Serum E2 in female and P in both sex fluctuated intensely during sampling period, and did not show remarkable changes. These results strongly suggest the existence of circadian-like diel changes in serum T, DHP, F and OHP levels in both sex and 11KT in male, and no variations in serum E2 in female and P in both sex in spermiated/ovulated Japanese char under the stage of final maturation. Furthermore, relationship between circadian rhythms of steroid hormones and spawning behaviors are discussed in the present study.
Piscivorous largemouth bass (Micropterus salmoides) have been introduced in several regions outside of their native range in North America, resulting in significant disturbance to native fish communities. This species exhibits an ontogenetic diet shift from zooplanktivory to piscivory as juveniles. An early switch to piscivory allows 0+ bass to increase their growth rate prior to winter, resulting in reduced mortality. However, little is known about the dietary switch at the population level during the first year. We used carbon stable isotope analyses to examine the diets of age 0+ individuals in Lake Izunuma, Japan. The onset of the shift to piscivory occurred at a smaller size than in native or other nonnative areas [>40 mm total length (TL)]. We found a positive correlation between TL and δ 13 C throughout summer and autumn. Small individuals had δ 13 C values that were similar to those of zooplankton, whereas large individuals had δ 13 C values that were similar to those of cyprinid prey species. This suggests that the smaller 0+ individuals remain zooplanktivorous until late autumn, whereas the larger individuals shift to piscivory as early as June, soon after the breeding season ends. Our results also suggest that a significant number of 0+ bass failed to switch to piscivory until the winter of their first year, despite the smaller size threshold for the onset of piscivory.
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