Nutrition and Cancer Risk from the Viewpoint of the Intestinal Microbiome.

There are various important factors in reducing the risk of cancer development and progression; these factors may correct an unbalanced intake of nutrients to maintain the living body's homeostasis, detoxify toxic materials, acting as an external factor, and maintain and strengthen the body's immune function. In a normal cell environment, nutrients, such as carbohydrates, lipids, proteins, vitamins, and minerals, are properly digested and absorbed into the body, and, as a result, an environment in which cancer can develop and progress is prevented. It is necessary to prevent toxic materials from entering the body and to detoxify poisons in the body. If these processes occur correctly, cells work normally, and genes cannot be damaged. The most important factor in the fight against cancer and prevention of the development and progression of cancer is the immune system. This requires a nutritional state in which the immune system works well, allowing the intestinal microbiome to carry out all of its roles. In order to grow intestinal microbiota, the consumption of prebiotics, such as organic vegetables, fruits, and dietary fiber, and probiotics of effective intestinal microbiota, such as fermented foods and supplements, is required. Symbiosis, in which these organisms work together, is an effective means of reducing the risk of cancer. In addition, fecal microbiota transplantation (FMT) using ultrafine bubble water, produced specially by the Association for Clinical Research of Fecal Microbiota Transplantation Japan, is also useful for improving the nutritional condition and reducing the risk of cancer.

TAS0728, A Covalent-binding, HER2-selective Kinase Inhibitor Shows Potent Antitumor Activity in Preclinical Models.

Activated HER2 is a promising therapeutic target for various cancers. Although several reports have described HER2 inhibitors in development, no covalent-binding inhibitor selective for HER2 has been reported. Here, we report a novel compound TAS0728 that covalently binds to HER2 at C805 and selectively inhibits its kinase activity. Once TAS0728 bound to HER2 kinase, the inhibitory activity was not affected by a high ATP concentration. A kinome-wide biochemical panel and cellular assays established that TAS0728 possesses high specificity for HER2 over wild-type EGFR. Cellular pharmacodynamics assays using MCF10A cells engineered to express various mutated HER2 genes revealed that TAS0728 potently inhibited the phosphorylation of mutated HER2 and wild-type HER2. Furthermore, TAS0728 exhibited robust and sustained inhibition of the phosphorylation of HER2, HER3, and downstream effectors, thereby inducing apoptosis of HER2-amplified breast cancer cells and in tumor tissues of a xenograft model. TAS0728 induced tumor regression in mouse xenograft models bearing HER2 signal-dependent tumors and exhibited a survival benefit without any evident toxicity in a peritoneal dissemination mouse model bearing HER2-driven cancer cells. Taken together, our results demonstrated that TAS0728 may offer a promising therapeutic option with improved efficacy as compared with current HER2 inhibitors for HER2-activated cancers. Assessment of TAS0728 in ongoing clinical trials is awaited (NCT03410927).

[Evaluation of Basic Performance of "Point Strip ferritin-3000" for Simple and Rapid Quantification of Serum Ferritin].

Serum ferritin is an excellent marker for total iron content in the body and is essential for the diagnosis of iron deficiency or iron overload. Recently, a simple and rapid method, which utilizes immunochromatography for the quantification of serum ferritin, was developed. However, the range of measurement in previous reagents was limited (10-500 ng/mL). This range is rather narrow and is not fully helpful for the diagnosis of iron overload which sometimes occurs as a result of prolonged transfusions, or for monitoring iron contents during iron chelation therapy against iron overload. In the present study we evaluated the basic performance of the newly developed "Point Strip ferritin-3000", which can measure serum ferritin in the range of 300-3,000 ng/mL. Coefficient of variation (CV) s of within and inter-day assays were in the ranges of 7.3-11.1% and 2.1-5.2%, respectively. Using 87 serum samples obtained from the patients with written informed consents, the correlation coefficient was calculated to be 0.93 compared to the control method. In addition, the quantification of serum ferritin by "Point Strip ferritin-3000" was not influenced by bilirubin, hemoglobin, chyle, rheumatoid factor, or ascorbic acid. From our data, "Point Strip ferritin-3000" is reliable reagent in the range of 300-3,000 ng/mL, and is therefore considered to be useful for the diagnosis of iron overload, as well as for monitoring iron contents during iron chelation therapy. In addition, this quantification method can be easily performed using a small desktop equipment without any special technique, making this system applicable for epidemiological surveys and clinical studies.

cDNA cloning of the Sry-related gene Sox6 from rat with tissue-specific expression.

A cDNA encoding rat homologue of the previously characterized mouse Sox6 was isolated by a polymerase chain reaction (PCR) cloning strategy. Comparison of this eDNA with homologous mouse, human and rainbow trout cDNA exhibited an overall amino acid sequence identity of 99.6, 89.3 and 76.3% respectively. The leucine-zipper and HMG-box motif were almost completely conserved between these homologues. The expression of Sox6 was determined in rat by Northern hybridization and Real-time quantitative reverse transcription (RT)-PCR. rSox6 (rat Sox6) was specifically expressed in the neonatal brain and adult testis with Northern blotting. Real-time quantitative RT-PCR for the determination of Sox6 mRNA was examined. The rSox6 was expressed in the neonatal brain and adult testis as well as by Northern blotting and also expressed in the adult eyeball and slightly in the ovary.