Low HER2 expression is a predictor of poor prognosis in stage I triple-negative breast cancer

IntroductionTriple-negative breast cancer (TNBC) is negative for hormone receptors and human epidermal growth factor receptor 2 (HER2). In stage I TNBC, adjuvant therapy or follow-up are performed according to risk factors, but clinical trial data is scarce. In recent years, it has been reported that HER2-low cases (1+/2+ and in situ hybridization negative) have different prognoses than HER2-0 cases. However, the risk of recurrence and risk factors in this HER2-low population for stage I TNBC have not yet been investigated.MethodsHerein, out of 174 patients with TNBC who underwent surgery from June 2004 to December 2009 at the National Cancer Center Hospital (Tokyo), we retrospectively examined 42 cases diagnosed as T1N0M0 TNBC after excluding those treated with preoperative chemotherapy.ResultsAll patients were female, the median age was 60.5 years, and 11 cases were HER2-low and 31 cases were HER2-0. The median follow-up period was 121 months. Postoperative adjuvant therapy was administered in 30 patients and recurrence occurred in 8 patients. HER2-low cases showed a significantly shorter disease-free survival (HR: 7.0; 95% CI: 1.2– 40.2; P=0.0016) and a trend towards shorter overall survival (hazard ratio [HR]: 4.2, 95% confidence interval [CI]: 0.58–31.4) compared with that of HER2-0 cases. HER2 was also identified as a factor for poor prognosis from the point- estimated values in univariate and multivariate analyses after confirming that there was no correlation between the other factors.ConclusionFor patients with stage I TNBC, the HER2-low population had a significantly worse prognosis than the HER2-0 population

Synthetic dietary inulin, Fuji FF, delays development of diet-induced obesity by improving gut microbiota profiles and increasing short-chain fatty acid production

Background Dietary fiber, including inulin, promotes health via fermentation products, such as short-chain fatty acids (SCFAs), produced from the fiber by gut microbiota. SCFAs exert positive physiological effects on energy metabolism, gut immunity, and the nervous system. Most of the commercial inulin is extracted from plant sources such as chicory roots, but it can also be enzymatically synthesized from sucrose using inulin producing enzymes. Studies conducted on rodents fed with a cafeteria diet have suggested that while increasing plasma propionic acid, synthetic inulin modulates glucose and lipid metabolism in the same manner as natural inulin. Therefore, this study aimed to determine the effects of a synthetic inulin, Fuji FF, on energy metabolism, fecal SCFA production, and microbiota profiles in mice fed with a high-fat/high-sucrose diet. Methods Three-week-old male C57BL/6J mice were fed a high-fat/high-sucrose diet containing cellulose or Fuji FF for 12 weeks, and the effects on energy metabolism, SCFA production, and microbiota profiles were evaluated. Results Body weight gain was inhibited by Fuji FF supplementation in high-fat/high-sucrose diet-fed C57BL/6J mice by reducing white adipose tissue weight while increasing energy expenditure, compared with the mice supplemented with cellulose. Fuji FF also elevated levels of acetic, propionic and butyric acids in mouse feces and increased plasma propionic acid levels in mice. Moreover, 16S rRNA gene amplicon sequencing of fecal samples revealed an elevated abundance of Bacteroidetes and a reduced abundance of Firmicutes at the phylum level in mice supplemented with Fuji FF compared to those supplemented with cellulose. Fuji FF also resulted in abundance of the family Bacteroidales S24-7 and reduction of Desulfovibrionaceae in the feces. Conclusion Long term consumption of Fuji FF improved the gut environment in mice by altering the composition of the microbiota and increasing SCFA production, which might be associated with its anti-obesity effects

A two-year survey of the oseltamivir-resistant influenza A(H1N1) virus in Yamagata, Japan and the clinical effectiveness of oseltamivir and zanamivir

Abstract Background Oseltamivir is the preferred antiviral drug for influenza, but oseltamivir-resistant A(H1N1) viruses have circulated worldwide since the 2007-2008 influenza season. We aimed to determine the rate of oseltamivir resistance among A(H1N1) isolates from Yamagata, Japan, to compare the virological characteristics between isolates from the 2007-2008 and 2008-2009 seasons, and to evaluate the clinical effectiveness of oseltamivir. Results Oseltamivir resistance, determined by detecting the H275Y mutation in the neuraminidase (NA) gene, was observed in 2.5% (2 of 79) and 100% (77 of 77) of isolates from the 2007-2008 and 2008-2009 seasons, respectively. Antigenic analysis suggested that antigenically different variants of A(H1N1) viruses circulated in the 2008-2009 season. Growth testing demonstrated that the ability of the 2008-2009 isolates to replicate in MDCK cells was similar to those of the oseltamivir-susceptible isolates from the 2007-2008 season. A phylogenetic analysis revealed that two oseltamivir-resistant viruses isolated in the 2007-2008 season were closely related to other oseltamivir-susceptible viruses in Yamagata but were different from oseltamivir-resistant viruses isolated in Europe and North America in the 2007-2008 season. The oseltamivir-resistant viruses isolated in Japan in the 2008-2009 season were phylogenetically similar to oseltamivir-resistant isolates from Europe and North America during the 2007-2008 season. Furthermore, the median duration of fever after the start of oseltamivir treatment was significantly longer in oseltamivir-resistant cases (2 days; range 1-6 days) than in oseltamivir-susceptible cases (1.5 days: range 1-2 days) (P = 0.0356). Conclusion Oseltamivir-resistant A(H1N1) isolates from Yamagata in the 2007-2008 season might have acquired resistance through the use of oseltamivir, and the 2008-2009 oseltamivir-resistant isolates might have been introduced into Japan and circulated throughout the country. Influenza surveillance to monitor oseltamivir-resistance would aid clinicians in determining an effective antiviral treatment strategy.</p