p53 Expression in Pretreatment Specimen Predicts Response to Neoadjuvant Chemotherapy Including Anthracycline and Taxane in Patients with Primary Breast Cancer.

While clinical and pathologic responses are important prognostic parameters, biological markers from core needle biopsy (CNB) are needed to predict neoadjuvant chemotherapy (NAC) response, to individualize treatment, and to achieve maximal efficacy. We retrospectively evaluated the cases of 183 patients with primary breast cancer who underwent surgery after NAC (anthracycline and taxane) at the National Cancer Center Hospital (NCCH). We analyzed EGFR, HER2, and p53 expression and common clinicopathological features from the CNB and surgical specimens of these patients. These biological markers were compared between sensitive patients (pathological complete response;pCR) and insensitive patients (clinical no change;cNC and clinical progressinve disease;cPD). In a comparison between the 9 (5%) sensitive patients and 30 (16%) insensitive patients, overexpression of p53 but not overexpression of either HER2 or EGFR was associated with a good response to NAC. p53 (p＝0.045) and histological grade 3 (p＝0.011) were important and significant predictors of the response to NAC. The correspondence rates for histological type, histological grade 3, ER, PgR, HER2, p53, and EGFR in insensitive patients between CNB and surgical specimens were 70%, 73%, 67%, 70%, 80%, 93%, and 73%. The pathologic response was significantly associated with p53 expression and histological grade 3. The correspondence rate of p53 expression between CNB and surgical specimens was higher than that of other factors. We conclude that the level of p53 expression in the CNB was an effective and reliable predictor of treatment response to NAC

Neuroprotective Efficacy of YM872, an ␣-Amino-3-Hydroxy-5- Methylisoxazole-4-Propionic Acid Receptor Antagonist, after Permanent Middle Cerebral Artery Occlusion in Rats

ABSTRACT The neuroprotective efficacy of YM872, a novel, highly watersoluble ␣-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist, was investigated in rats subjected to permanent occlusion of the left middle cerebral artery. The rats were assessed either histologically or neurologically 24 hr or 1 wk after ischemia. YM872 was intravenously infused for either 4 or 24 hr at dose rates of 0 to 20 mg/kg/hr starting 5 min after ischemia to examine the effect of prolonged treatment. YM872 was then infused at 20 mg/kg/hr beginning 0 to 4 hr after ischemia to determine the efficacy time window. Additionally, a 20 mg/kg/hr dose rate of YM872 was infused for 4 hr in single day-or 5-day repetitive-administrations to evaluate long-term benefits of the drug. YM872 significantly reduced infarct volume in both 4-and 24-hr treatment groups measured 24 hr after ischemia. No difference was observed in the degree of protection between length of infusion. Significant neuroprotection was maintained even when drug administration was delayed up to 2 hr after ischemia. A single YM872-administration significantly improved neurological deficit and reduced infarct volume (30%, P Ͻ .01) measured 1 wk after ischemia. YM872 treatment did not induce such adverse effects as physiological changes, serious behavioral abnormalities or nephrotoxicity. These data suggest that the ␣-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor plays a crucial role in the progression of neuronal damage in the early phase of ischemia and that YM872 may be useful in treating acute ischemic stroke

Enhanced piezoelectric response of BaTiO3–KNbO3 composites

The piezoelectric response of solvothermally synthesized BaTiO3 (BT)–KNbO3 (KN) composites (the nominal BT/KN ratio was 1) with distinct interfaces was investigated. The x-ray diffraction pattern showed two distinct peaks began to merge into a singular broad peak at a two-theta position between (200) and (002) tetragonal-related peaks of BT. The transmission electron microscopy observation showed a heteroepitaxial interface region between BT single-crystal particles and deposited KN crystals. The large-field piezoelectric constant was 136 pC/N, which was three times larger than that of a sintered 0.5BT–0.5KN composite. The enhanced piezoelectric response was attributed to the strained epitaxial interface region

Polycystic Kidney Disease in the Medaka (Oryzias latipes) pc Mutant Caused by a Mutation in the Gli-Similar3 (glis3) Gene

Polycystic kidney disease (PKD) is a common hereditary disease in humans. Recent studies have shown an increasing number of ciliary genes that are involved in the pathogenesis of PKD. In this study, the Gli-similar3 (glis3) gene was identified as the causal gene of the medaka pc mutant, a model of PKD. In the pc mutant, a transposon was found to be inserted into the fourth intron of the pc/glis3 gene, causing aberrant splicing of the pc/glis3 mRNA and thus a putatively truncated protein with a defective zinc finger domain. pc/glis3 mRNA is expressed in the epithelial cells of the renal tubules and ducts of the pronephros and mesonephros, and also in the pancreas. Antisense oligonucleotide-mediated knockdown of pc/glis3 resulted in cyst formation in the pronephric tubules of medaka fry. Although three other glis family members, glis1a, glis1b and glis2, were found in the medaka genome, none were expressed in the embryonic or larval kidney. In the pc mutant, the urine flow rate in the pronephros was significantly reduced, which was considered to be a direct cause of renal cyst formation. The cilia on the surface of the renal tubular epithelium were significantly shorter in the pc mutant than in wild-type, suggesting that shortened cilia resulted in a decrease in driving force and, in turn, a reduction in urine flow rate. Most importantly, EGFP-tagged pc/glis3 protein localized in primary cilia as well as in the nucleus when expressed in mouse renal epithelial cells, indicating a strong connection between pc/glis3 and ciliary function. Unlike human patients with GLIS3 mutations, the medaka pc mutant shows none of the symptoms of a pancreatic phenotype, such as impaired insulin expression and/or diabetes, suggesting that the pc mutant may be suitable for use as a kidney-specific model for human GLIS3 patients

Stability and Metastability of Li3YCl6 and Li3HoCl6

[EN] Metastable solid electrolytes exhibit superior conductivity compared to stable ones, making them a subject of considerable interest. However, synthesis of the metastable phase is affected by multiple thermodynamic and kinetic parameters, leading to ambiguity in the organization of stability and metastability. In this study, we organized remnant and intermediate metastability based on temperature. The intermediate metastable phase, which is less stable than the temperature-independent stable phase, typically transforms into the stable phase(s) at high temperatures. In contrast, the remnant metastable phase is formed by first obtaining most stable phase at specific temperatures and then “trapping” it by rapidly changing the temperature. By investigating Li+ conducting chlorides, Li3MCl6 (M = Y and Ho), we demonstrated that heating starting materials to approximately 600 K produced low-temperature Li3MCl6 phase with one formula unit while further heating resulted in high-temperature Li3MCl6 phase with three formula units. Annealing quenched Li3MCl6 at 573 K resulted in a phase transition from the high-temperature to low-temperature phase, indicating that the high-temperature phase was remnant metastable at low temperatures.This research was partially supported by KAKENHI (Grant No. JP20KK0124), JST PRESTO (Grant Nos. JPMJPR21Q2 and JPMJPR21Q8), and Grant-in-Aid for JSPS Fellows (21J11152).N

Association of Lifelong Intake of Barley Diet with Healthy Aging: Changes in Physical and Cognitive Functions and Intestinal Microbiome in Senescence-Accelerated Mouse-Prone 8 (SAMP8)

Barley intake reportedly reduces the risk of cardiovascular disease, but effects on the systemic phenotypes during healthy aging have not yet been examined. Therefore, we examined the effects of barley on the lifespan; behavioral phenotypes, such as locomotor activity, and cognitive functions, and intestinal microbiome in the senescence-accelerated mouse-prone 8 (SAMP8) mouse. We prepared two mild high-fat diets by adding lard, in which the starch components of AIN-93G were replaced by rice or barley “Motchiriboshi.” SAMP8 (four weeks old, male) mice were fed AIN-93G until eight weeks old, and then rice (rice group) or barley diet (rice: barley = 1:4, barley group) until death. Changes in aging-related phenotypes, object and spatial recognition, locomotor and balancing activities, and the intestinal microbiome were recorded. Moreover, plasma cholesterol levels were analyzed at 16 weeks old. Barley intake prolonged the lifespan by approximately four weeks, delayed locomotor atrophy, and reduced balancing ability and spatial recognition. Barley intake significantly increased the medium and small particle sizes of high-density lipoprotein (HDL) cholesterol, which is associated with a reduced risk of total stroke. The Bacteroidetes to Firmicutes ratio in the barley group was significantly higher than that in the rice group during aging. Thus, lifelong barley intake may have positive effects on healthy aging

Influence of Housing Systems on Physical, Emotional, and Cognitive Functions with Aging in DBA/2CrSlc Mice

Environmental conditions, including enrichment and stress, affect animal behaviors, but limited information is available regarding the differences in animal functions between the chamber (ventilated system) vs. IVC (individually ventilated cages) housing systems. Therefore, the effects of different housing systems were examined on physical, emotional, and cognitive functions and the intestinal flora with aging. DBA/2CrSlc mice were divided into chamber and IVC groups. Differences in the structure of the two cages considered whether the mouse could dangle or not. Physical, emotional, and cognitive functions were examined using the open field, black and white box, object recognition, horizontal bar, wire hanging, balancing, footprint, and locomotor tests. The IVC group demonstrated significantly less food intake, higher body weight (by approximately 5 g), lower rectal core temperature, less muscle and balancing powers with aging, and fewer anxiety-like behaviors than the chamber group. No differences were observed in the cognitive function and intestinal microbiota between the groups. The housing environment affected the rodent basal temperature and body weight as well as the physical and emotional functions. Scientists should be attentive to the type of cages used in the housing system for an experiment, especially when comparing the results with animals reared in different systems