ABSTRACT
A ketogenic diet is expected to be an effective support therapy for patients with cancer, but the degree and duration of carbohydrate restriction are unclear. We performed a case series study of a new ketogenic diet regimen in patients with different types of stage IV cancer. Carbohydrates were restricted to 10 g/day during week one, 20 g/day from week two for three months, and 30 g/day thereafter. A total of 55 patients participated in the study, and data from 37 patients administered the ketogenic diet for three months were analyzed. No severe adverse events associated with the diet were observed. Total ketone bodies increased significantly, and both fasting blood sugar and insulin levels were suppressed significantly for three months after completion of the study. Five patients showed a partial response on Positron emission tomography-computed tomography (PET-CT) at three months. Three and seven patients showed complete and partial responses, respectively at one year. Median survival was 32.2 (maximum: 80.1) months, and the three-year survival rate was 44.5%. After three months on the ketogenic diet, the serum Alb, BS, and CRP (ABC) score could be used to stratify the patients into groups with significantly different survival rates (p < 0.001, log-rank test). Our ketogenic diet regimen is considered to be a promising support therapy for patients with different types of advanced cancer.
Subject(s)
Diet, Ketogenic/mortality , Diet, Ketogenic/methods , Neoplasms/diet therapy , Neoplasms/mortality , Time Factors , Adult , Aged , Blood Glucose/analysis , Fasting/blood , Female , Humans , Insulin/blood , Ketone Bodies/blood , Male , Middle Aged , Neoplasm Staging , Neoplasms/blood , Positron Emission Tomography Computed Tomography , Survival Rate , Treatment OutcomeABSTRACT
In Japan, which is entering a super-aged society, the prevention of long-term care and bedridden caused by frailty and sarcopenia have been recognized as an urgent need. The pathology of frailty and sarcopenia includes broad problems of senility. A traditional herbal medicine is known to improve symptoms across the organs, many herbal medicines administered by examining the balance of mind and body are effective for frailty and sarcopenia. "The Safety Drug Therapy Guideline 2015 for the Elderly" was fully revised in 2015. In this guideline, traditional herbal medicines, which are suggested to be useful for the elderly, have been taken up, and the evidence of which is being accumulated. We regarded frailty and sarcopenia as 'kidney-Qi' deficiency, a concept that represents aging phenomenon in Kampo medicine and clarified the anti-sarcopenic effects of Go-sha-jinki-gan, a 'kidney-Qi'-tonifying medicine, using animal experimental models.
Subject(s)
Frailty , Sarcopenia , Aged , Animals , Frail Elderly , Humans , Japan , Medicine, Kampo , Sarcopenia/drug therapyABSTRACT
Maternal stress exerts long-lasting psychiatric and somatic on offspring, which persist into adulthood. However, the effect of maternal stress on the postnatal growth of pups has not been widely reported. In this study, we found that maternal immobilization stress (IS) during lactation resulted in low body weight of male mouse offspring, which persisted after weaning. Despite free access to chow, IS induced maternal malnutrition and decreased the serum insulin-like growth factor-1 (IGF-1) levels in the mothers and in the pups. mRNA expression analysis of anterior pituitary hormones in the pups revealed that growth hormone (GH) and prolactin (PRL), but no other hormones, were decreased by IS. Expression of the pituitary transcription factor PIT1 and isoforms of PITX2, which are essential for the development and function of GH-producing somatotropes and PRL-producing lactotropes, was decreased, whereas that of PROP1, which is critical for the earlier stages of pituitary development, was unchanged. Immunohistochemistry also showed a decrease in pituitary PRL protein expression. These results suggest that stress in a postpartum mother has persistent effects on the body weight of the offspring. Reduced PRL expression in the offspring's pituitary gland may play a role in these effects.
Subject(s)
Gene Expression Regulation, Developmental/physiology , Maternal Exposure , Pituitary Gland/metabolism , Prenatal Exposure Delayed Effects/pathology , Prenatal Exposure Delayed Effects/physiopathology , Prolactin/metabolism , Age Factors , Animal Nutritional Physiological Phenomena , Animals , Animals, Newborn , Behavior, Animal , Body Weight , Eating , Female , Growth Hormone/genetics , Growth Hormone/metabolism , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Male , Mice , Mice, Inbred ICR , Pregnancy , Prolactin/genetics , RNA, Messenger/metabolism , Stress, Psychological/psychology , Transcription Factors/genetics , Transcription Factors/metabolism , Homeobox Protein PITX2ABSTRACT
The p53 protein is a transcription factor that trans-activates various genes in response to DNA-damaging stress. To search for new p53-target genes, we applied a cDNA microarray system using two independent p53-inducible cell lines, followed by in silico analysis to detect p53 response elements. Here, we report on crystallin alpha B gene (CRYAB), which encodes alphaB-crystallin, and is one of the genes directly trans-activated by p53. We confirmed it is directly transcribed by p53 using promoter analysis, deletion reporter assay, ChIP assay and EMSA. alphaB-crystallin is also upregulated in a p53-dependent manner and binds to the DNA-binding domain of p53. Overexpression of alphaB-crystallin increased p53 protein and, in contrast, repression of alphaB-crystallin decreased p53 protein. Interestingly, both overexpression and repression of alphaB-crystallin reduced p53-dependent apoptosis. In conclusion, we identified that alphaB-crystallin was a novel p53-target gene and required for p53-dependent apoptosis using two independent p53-inducible cell lines. This is the first report associating p53 directly with a heat shock protein through trans-activation and physical interaction.
