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

Investigation of Tumor Heterogeneity Using Integrated Single-Cell RNA Sequence Analysis to Focus on Genes Related to Breast Cancer-, EMT-, CSC-, and Metastasis-Related Markers in Patients with HER2-Positive Breast Cancer

Human epidermal growth factor receptor 2 (HER2) protein, which is characterized by the amplification of ERBB2, is a molecular target for HER2-overexpressing breast cancer. Many targeted HER2 strategies have been well developed thus far. Furthermore, intratumoral heterogeneity in HER2 cases has been observed with immunohistochemical staining and has been considered one of the reasons for drug resistance. Therefore, we conducted an integrated analysis of the breast cancer single-cell gene expression data for HER2-positive breast cancer cases from both scRNA-seq data from public datasets and data from our cohort and compared them with those for luminal breast cancer datasets. In our results, heterogeneous distribution of the expression of breast cancer-related genes (ESR1, PGR, ERBB2, and MKI67) was observed. Various gene expression levels differed at the single-cell level between the ERBB2-high group and ERBB2-low group. Moreover, molecular functions and ERBB2 expression levels differed between estrogen receptor (ER)-positive and ER-negative HER2 cases. Additionally, the gene expression levels of typical breast cancer-, CSC-, EMT-, and metastasis-related markers were also different across each patient. These results suggest that diversity in gene expression could occur not only in the presence of ERBB2 expression and ER status but also in the molecular characteristics of each patient

Highly active BaTi4O9/RuO2 photocatalyst by polymerized complex method

科研費報告書収録論文(課題番号:08455403・基盤研究(B)(2)・H8～H10/研究代表者:佐藤, 次雄/眉間包接半導体擬似分子の創製と光化学特性

Incomplete Selective Sweeps of Microcystis Population Detected by the Leader-End CRISPR Fragment Analysis in a Natural Pond

The freshwater cyanobacterium Microcystis aeruginosa frequently forms toxic massive blooms and exists in an arms race with its infectious phages in aquatic natural environments, and as a result, has evolved extremely diverse and elaborate antiviral defense systems, including the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated genes (Cas) system. Here, to assess Microcystis population dynamics associated with exogenous mobile genetic elements such as phages and plasmids, we examined the temporal variation in CRISPR genotypes (CTs) by analyzing spacer sequences detected in a natural pond between June and October 2013 when a cyanobacterial bloom occurred. A total of 463,954 high-quality leader-end CRISPR sequences were obtained and the sequences containing spacers were classified into 31 previously reported CTs and 68 new CTs based on the shared order of the leader-end spacers. CT19 was the most dominant genotype (32%) among the 16 most common CTs, followed by CT52 (14%) and CT58 (9%). Spacer repertoires of CT19 showed mainly two different types; CT19origin, which was identical to the CT19 spacer repertoire of previously isolated strains, and CT19new+, which contained a new spacer at the leader-end of the CRISPR region of CT19origin, which were present in almost equal abundance, accounting for up to 99.94% of CT19 sequences. Surprisingly, we observed the spacer repertoires of the second to tenth spacers of CT19origin at the most leader-end of proto-genotype sequences of CT19origin. These were observed during the sampling in this study and our previous study at the same ecosystem in 2010 and 2011, suggesting these CTs persisted from 2011 to 2013 in spite of phage pressure. The leader-end variants were observed in other CT genotypes. These findings indicated an incomplete selective sweep of Microcystis populations. We explained the phenomenon as follow; the abundance of Microcystis varied seasonally and drastically, resulting that Microcystis populations experience a bottleneck once a year, and thereby founder effects following a bottleneck mean that older CTs have an equal chance of increasing in prevalence as the CTs generated following acquisition of newer spacers

Multicenter study on hemorrhagic risk of heparin bridging therapy for periendoscopic thromboprophylaxis

Background: For endoscopic interventions, heparin bridging therapy is recommended in patients who are at high risk from interruption of antithrombotic therapy. Although heparin bridging has been reported to be effective in preventing thrombosis, several reports have raised concerns about increased risk of bleeding. The aim of this study was to clarify complications of hepari bridging therapy in therapeutic endoscopy. Methods: A nationwide multicenter survey using questionnaire was performed about patients undergoing therapeutic endoscopy with heparin bridging. Patients who underwent therapeutic endoscopy without heparin bridging therapy were considered as controls. Compliance scores of heparin bridging therapy guideline were employed, and association was analyzed between the score and occurrence of post-procedural bleeding. Results: The incidence of post-procedural bleeding was significantly higher (13.5 %, 33/245) in the heparin group compared with the control group (2.7 %, 299/11102)(p < 0.001). Thrombosis occurred in 1 patient each in the two groups. In the heparin group, post-procedural bleeding was more likely to be delayed bleeding. Dose adjustment of heparin was a significant factor contributing to bleeding. The compliance score of heparin bridging therapy guideline was significantly higher in those who suffered bleeding. Conclusions: Heparin bridging therapy significantly increased the risk of post-procedural bleeding compared with the control. The bleeding risk was associated with greater adherence with guidelines for heparin bridging therapy