Clinical relevance of apoptotic markers in breast cancer not yet clear

Currently, the mainly used characteristics to predict outcome or treatment response in patients with breast cancer are tumor size, N-status, histological grade and receptor status (ER/PgR). However, these conventional clinico-pathological characteristics are of limited value. More accurate determinators are needed to select patients who are most likely to benefit from treatment in terms of prognosis as well as treatment response. Proliferation and apoptosis are assumed to play a key role in tumor progression as well as response to treatment. Currently, an increasing number of molecular factors controlling apoptosis as well as proliferation is known. The clinical relevance of apoptotic tumor markers in the treatment strategy of patients with breast cancer is the subject of this review. In addition, potential future developments are discussed.     

Timing of surgery during the menstrual cycle and prognosis of breast cancer

There are conflicting reports on the differential effect of surgery performed during the two phases of the menstrual cycle, namely, follicular and luteal, and prognosis of operable breast cancer. A statistical meta-analysis of the published evidence suggests a modest survival benefit of 15+/-4% when the operation is performed during the luteal phase. Further research in this area might provide a novel avenue to understand the natural history of breast cancer. A spin off from these studies might be the understanding of the importance of events that occur at the time of surgery in determining long term prognosis.     

Early B-cell factors involve in the tumorigenesis and predict the overall survival of gastric cancer

Gastric cancer (GC) is a heavy health burden around the world, which is the fifth most frequent tumor and leads to the third most common cancer-related deaths. It is urgent to identify prognostic markers as the guideline for personalized treatment and follow-up. We accessed the prognostic value of Early B-cell factors (EBFs) in GC. A total of 415 GC tissues and 34 normal tissues from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) cohort, 616 external patients from {"type":"entrez-geo","attrs":{"text":"GSE15459","term_id":"15459"}}GSE15459, {"type":"entrez-geo","attrs":{"text":"GSE22377","term_id":"22377"}}GSE22377, {"type":"entrez-geo","attrs":{"text":"GSE51105","term_id":"51105"}}GSE51105, {"type":"entrez-geo","attrs":{"text":"GSE62245","term_id":"62245"}}GSE62245 were enrolled for analysis. Univariate and multivariate Cox regression analyses were employed to evaluate the sole and integrative prognostic value of EBFs, respectively. Genetic alterations, DNA methylation of EBFs were also evaluated, as well as the involved signaling pathways. We revealed that increased EBFs associated with the poor prognosis of GC patients, the prognostic model was established in TCGA-STAD cohort, and validated in Gene Expression Omnibus (GEO) cohorts, with effectiveness in both HER2 positive and negative patients. DNA methylation was involved in the impact on prognosis. Cell cycle, immune-associated, and MAPK pathways were influenced by EBFs. Anti-CTLA4 immunotherapy is more suitable for EBFs determining high-risk groups, but not anti-PD-1/PD-L1 therapy. 5-Fluorouracil, methotrexate, vorinostat are suitable to inhibit the function of EBFs. Our new findings provide novel insight into the prediction of prognosis and clinical treatment of GC patients based on EBFs.     

脑弥漫性轴索损伤的MRI征象及与GCS计分及预后的关系

目的：探讨脑弥漫性轴索损伤（DAI）的磁共振成像（MRI）征象及其与格拉斯哥昏迷量表评分（GCS）计分和预后的关系。方 法：回顾性分析2012 年1 月-2014 年7 月我院收集的30 例DAI 患者的临床病历资料,根据病灶累及部位分析其与GCS 计分和 临床预后的关系。结果：30 例患者共53 个病灶,17例多发病灶,13 例单发病灶;42 个病灶T1WI显示出低信号或者是等信号,11 个病灶T1WI显示为高信号;T2WI显示为高信号,FLAIR 序列以及弥散加权像（DWI）上表现出的信号更高,范围更清晰;病灶形 态呈条索状27 例,斑片状11 例,卵圆形8 例,不规则斑点状7 例;病灶未累及脑中线部位的患者临床预后优于病灶累及脑中线 部位的患者,差异有统计学意义（Z=-2.636,P=0.008）,病灶累及脑中线部位的患者GCS 计分情况比未累及组严重,计分更低,差 异有统计学意义（Z=-2.519,P=0.012）。结论：DAI病灶累及脑中线部位的患者GCS计分较低、预后差,MRI检查是诊断DAI 首选 的影像学方法,临床有重要的参考价值。     

MicroRNA and mRNA expression profiling in metastatic melanoma reveal associations with BRAF mutation and patient prognosis

The role of microRNAs (miRNAs) in melanoma is unclear. We examined global miRNA expression profiles in fresh‐frozen metastatic melanomas in relation to clinical outcome and BRAF mutation, with validation in independent cohorts of tumours and sera. We integrated miRNA and mRNA information from the same samples and elucidated networks associated with outcome and mutation. Associations with prognosis were replicated for miR‐150‐5p, miR‐142‐3p and miR‐142‐5p. Co‐analysis of miRNA and mRNA uncovered a network associated with poor prognosis (PP) that paradoxically favoured expression of miRNAs opposing tumorigenesis. These miRNAs are likely part of an autoregulatory response to oncogenic drivers, rather than drivers themselves. Robust association of miR‐150‐5p and the miR‐142 duplex with good prognosis and earlier stage metastatic melanoma supports their potential as biomarkers. miRNAs overexpressed in association with PP in an autoregulatory fashion will not be suitable therapeutic targets.     

Individualized medicine 2010

Molecular and cell biology have revolutionized not only diagnosis, therapy and prevention of human diseases but also greatly contributed to the understanding of their pathogenesis. Based on modern molecular and biochemical methods it is possible to identify on the one hand point mutations and single nucleotide polymorphisms. On the other hand, using high throughput array technologies, it is possible to analyse thousands of genes or gene products simultaneously, resulting in an individual gene or gene expression profile (signature). These data increasingly allow to define the individual risk for a given disease and to predict the individual prognosis of a disease as well as the efficacy of therapeutic strategies (individualized medicine). In the following sections some of the recent advances of predictive medicine and their clinical relevance will be addressed.     

Bmi1 Drives Stem-Like Properties and is Associated with Migration,Invasion, and Poor Prognosis in Tongue Squamous Cell Carcinoma

Bmi1 (B-cell-specific Moloney murine leukemia virus insertion site 1) had been found to involve in self -renewal of stem cells and tumorigenesis in various malignancies. The purpose of this study is to evaluate the role of Bmi1 in the development of tongue squamous cell carcinoma (TSCC) and its functional effect on the migration and invasion of TSCC. Initially, immunohistochemistry revealed that Bmi1 overexpression was a common event in premalignant dysplasia, primary TSCC, and lymph node metastases and was associated with a poor prognosis. A significant correlation between Bmi1 and SOD2 (manganese superoxide dismutase) expression was observed. Side population (SP) cells were used as cancer stem-like cells and further assessed by sphere and colony formation assays, and the expression of stem cell markers. TSCC cells with higher migration and invasion ability (UM1 cell lines) showed a higher proportion of SP cells and Bmi1 expression than TSCC cells with lower migration and invasion ability (UM2 cell lines). Knockdown of Bmi1 in UM1 or SP cells inhibited migration and invasion and decreased the sphere and colony formation, and the expression of stem cell markers and SOD2. Direct binding of C-myc to the Bmi1 promoter was demonstrated by chromatin immunoprecipitation and luciferase assays. Moreover, C-myc knockdown in SP cells inhibited their migration and invasion and decreased the expression of Bmi1 and SOD2. Our results indicate that the deregulation of Bmi1 expression is a frequent event during the progression of TSCC and may have a prognostic value for patients with this disease. The Bmi1-mediated migration and invasion of TSCC is related to cancer stem-like cells and involves the C-myc-Bmi1-SOD2 pathway.     

新发缺血性脑卒中患者实施单病种质量管理的预后评价

目的 调查分析上海市某三甲医院缺血性脑卒中单病种质量管理实施情况并评价其效果。方法 采用回顾性调查的方法,以NIHSS评分为疗效评价依据,对新发缺血性脑卒中单病种质量管理实施组和未实施组的预后情况进行分析评估。结果 在2组基线资料均衡的情况下,缺血性脑卒中单病种质量管理实施组的疗效显著优于未实施组,尤其是发病初始疾病严重程度一般者的疗效最好。结论 缺血性脑卒中单病种质量管理通过对诊疗过程的质量控制,规范了诊疗行为,改善了新发缺血性脑卒中患者的预后。