Loss of histone H4K20 trimethylation predicts poor prognosis in breast cancer and is associated with invasive activity

INTRODUCTION: Loss of histone H4 lysine 20 trimethylation (H4K20me3) is associated with multiple cancers, but its role in breast tumors is unclear. In addition, the pathological effects of global reduction in H4K20me3 remain mostly unknown. Therefore, a major goal of this study was to elucidate the global H4K20me3 level in breast cancer tissue and investigate its pathological functions. METHODS: Levels of H4K20me3 and an associated histone modification, H3 lysine 9 trimethylation (H3K9me3), were evaluated by immunohistochemistry in a series of breast cancer tissues. Univariate and multivariate clinicopathological and survival analyses were performed. We also examined the effect of overexpression or knockdown of the histone H4K20 methyltransferases, SUV420H1 and SUV420H2, on cancer-cell invasion activity in vitro. RESULTS: H4K20me3, but not H3K9me3, was clearly reduced in breast cancer tissue. A reduced level of H4K20me3 was correlated with several aspects of clinicopathological status, including luminal subtypes, but not with HER2 expression. Multivariate analysis showed that reduced levels of H4K20me3 independently associated with lower disease-free survival. Moreover, ectopic expression of SUV420H1 and SUV420H2 in breast cancer cells suppressed cell invasiveness, whereas knockdown of SUV420H2 activated normal mammary epithelial-cell invasion in vitro. CONCLUSIONS: H4K20me3 was reduced in cancerous regions of breast-tumor tissue, as in other types of tumor. Reduced H4K20me3 level can be used as an independent marker of poor prognosis in breast cancer patients. Most importantly, this study suggests that a reduced level of H4K20me3 increases the invasiveness of breast cancer cells in a HER2-independent manner

A case of laparoscopic cholecystectomy for a woman with a symptomatic cholecystitis in the 20th week of pregnancy

We report a case of laparoscopic cholecystectomy for a woman with symptomatic cholecystitis in the ２０th week of pregnancy. A ２６ year old pregnant woman visited our hospital with sudden abdominal pain on the １５th week of pregnancy. She received a proton pomp inhibitor for suspecting acute gastritis. She visited our hospital again with the same complaint on the １９th week of pregnancy. With a diagnosis of symptomatic cholecystitis, she was referred to the department of Gastroenterology at our hospital. Her symptoms recovered following fasting and resting once. However, laparoscopic cholecystectomy was performed because of the recurrence of symptoms at the ２０th week of pregnancy. The postoperative courses of both mother and fetus were well. She was discharged on the ４th postoperative day. She delivered a bouncing baby on the ３７th week ４ day at natural childbirth

Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood

The nutritional environment to which animals are exposed in early life can lead to epigenetic changes in the genome that influence the risk of obesity in later life. Here, we demonstrate that the fibroblast growth factor-21 gene (Fgf21) is subject to peroxisome proliferator-activated receptor (PPAR) α–dependent DNA demethylation in the liver during the postnatal period. Reductions in Fgf21 methylation can be enhanced via pharmacologic activation of PPARα during the suckling period. We also reveal that the DNA methylation status of Fgf21, once established in early life, is relatively stable and persists into adulthood. Reduced DNA methylation is associated with enhanced induction of hepatic FGF21 expression after PPARα activation, which may partly explain the attenuation of diet-induced obesity in adulthood. We propose that Fgf21 methylation represents a form of epigenetic memory that persists into adulthood, and it may have a role in the developmental programming of obesity

pH measurement of tissues in living body-The trial examination of needle type pH microsenser applications-

Even today, pH measurement of living tissue in a clinical environment has been difficult. In this study, we succeeded in measuring the pH of　living tissue and observing changes over time using an optical fiber coated with a newly developed pH–reactive fluorescent substance. A standardized hole was made in the rat tibia, Poly Ether Ether Ketone (PEEK) and Commercially₇ days. As a result, it was confirmed that the pH of the tissue was increased with CP–tita-nium, in which osseointegration was confirmed, and with PEEK, which imparted surface wettability. In addition, a decrease in pH over time due to tissue damage was also confirmed. From the above, it was confirmed that a needle–type pH microsensor is suitable for measuring the pH of living tissue over time. With this method, the development of new implant materials can be expected. Pure (CP)–titanium were implanted, and the pH change was measured afte

多職種連携と患者特性に配慮したケアを行った高度肥満症の一例

A ４８-year-old man who weighed ２１６ kg was significantly overweight with a body mass index （BMI）of ７５．６kg/m２, and was unable to walk due to disuse syndrome. Because of the psychological and social problems in the background, a psychological examination was performed and the staff took time to build a trusting relationship with the patient, taking into account his characteristics. With diet and rehabilitation, he was able to lose weight to １２４kg and BMI ４３．９kg/m２ over ６００ days, and was able to walk with assistive devices and defecate by himself. The patient was discharged from our hospital after a series of multidisciplinary meetings with medical, nursing, welfare, and governmental agencies to create an environment for home recuperation. The reasons for the improvement to enable him to be discharged from the hospital were due to the multi-disciplinary meetings among the staff inside and outside the hospital, information sharing and advanced coordination, and smooth communication with the patient by taking into account his characteristics from a psychological standpoint

Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood

The nutritional environment to which animals are exposed in early life can lead to epigenetic changes in the genome that influence the risk of obesity in later life. Here, we demonstrate that the fibroblast growth factor-21 gene (Fgf21) is subject to peroxisome proliferator-activated receptor (PPAR) α–dependent DNA demethylation in the liver during the postnatal period. Reductions in Fgf21 methylation can be enhanced via pharmacologic activation of PPARα during the suckling period. We also reveal that the DNA methylation status of Fgf21, once established in early life, is relatively stable and persists into adulthood. Reduced DNA methylation is associated with enhanced induction of hepatic FGF21 expression after PPARα activation, which may partly explain the attenuation of diet-induced obesity in adulthood. We propose that Fgf21 methylation represents a form of epigenetic memory that persists into adulthood, and it may have a role in the developmental programming of obesity