Classification of Diffuse Glioma Subtype from Clinical-Grade Pathological Images Using Deep Transfer Learning.

Diffuse gliomas are the most common primary brain tumors and they vary considerably in their morphology, location, genetic alterations, and response to therapy. In 2016, the World Health Organization (WHO) provided new guidelines for making an integrated diagnosis that incorporates both morphologic and molecular features to diffuse gliomas. In this study, we demonstrate how deep learning approaches can be used for an automatic classification of glioma subtypes and grading using whole-slide images that were obtained from routine clinical practice.

MicroRNA-29a activates a multi-component growth and invasion program in glioblastoma.

Background: Glioblastoma is a malignant brain tumor characterized by rapid growth, diffuse invasion and therapeutic resistance. We recently used microRNA expression profiles to subclassify glioblastoma into five genetically and clinically distinct subclasses, and showed that microRNAs both define and contribute to the phenotypes of these subclasses. Here we show that miR-29a activates a multi-faceted growth and invasion program that promotes glioblastoma aggressiveness.

Hybrid-Aware Model for Senior Wellness Service in Smart Home.

Smart home technology with situation-awareness is important for seniors to improve safety and security. With the development of context-aware computing, wearable sensor technology, and ubiquitous computing, it is easier for seniors to manage their health problem in smart home environment. For monitoring senior activity in smart home, wearable, and motion sensors-such as respiration rate (RR), electrocardiography (ECG), body temperature, and blood pressure (BP)-were used for monitoring movements of seniors.

Kazinol-E is a specific inhibitor of ERK that suppresses the enrichment of a breast cancer stem-like cell population.

Growing evidence shows that cancer stem-like cells (CSLCs) contribute to breast cancer recurrence and to its resistance to conventional therapies. The extracellular signal-regulated kinase (ERK) signaling pathway is a major determinant in the control of diverse cellular processes, including the maintenance of CSLCs. In this study, we found that Kazinol-E, an antioxidant flavan from Broussonetia kazinoki, decreased the CSLC population of a breast cancer cell line, MCF7.

Evodiamine selectively targets cancer stem-like cells through the p53-p21-Rb pathway.

In spite of the recent improvements, the resistance to chemotherapy/radiotherapy followed by relapse is the main hurdle for the successful treatment of breast cancer, a leading cause of death in women. A small population of breast cancer cells that have stem-like characteristics (cancer stem-like cells; CSLC) may contribute to this resistance and relapse. Here, we report on a component of a traditional Chinese medicine, evodiamine, which selectively targets CSLC of breast cancer cell lines MCF7 and MDAMB 231 at a concentration that does show a little or no cytotoxic effect on bulk cancer cells.

Cancer stem cell targeting: are we there yet?

Several decades after the first notion that cancer cells are heterogeneous, not only histologically but also at the level of tumorigenicity, the existence of a tumor initiation population (so-called cancer stem cells) is now widely accepted. Here, we review the historical background leading up to the identification of this special cancer cell population and its role in the resistance of tumors to conventional therapies. In addition, we briefly review the clinical targeting strategy of the specific signaling network for cancer stem cells.

Systemic approaches identify a garlic-derived chemical, Z-ajoene, as a glioblastoma multiforme cancer stem cell-specific targeting agent.

Glioblastoma multiforme (GBM) is one of the most common brain malignancies and has a very poor prognosis. Recent evidence suggests that the presence of cancer stem cells (CSC) in GBM and the rare CSC subpopulation that is resistant to chemotherapy may be responsible for the treatment failure and unfavorable prognosis of GBM. A garlic-derived compound, Z-ajoene, has shown a range of biological activities, including anti-proliferative effects on several cancers.

C. elegans RNA-binding protein GLD-1 recognizes its multiple targets using sequence, context, and structural information to repress translation.

Caenorhabditis elegans GLD-1, a maxi-KH motif containing RNA-binding protein, has various functions mainly during female germ cell development, suggesting that it likely controls the expression of a selective group of maternal mRNAs. To gain an insight into how GLD-1 specifically recognizes these mRNA targets, we identified 38 biochemically proven GLD-1 binding regions from multiple mRNA targets that are among over 100 putative targets co-immunoprecipitated with GLD-1. The sequence information of these regions revealed three over-represented and phylogenetically conserved sequence motifs.

Numb regulates glioma stem cell fate and growth by altering epidermal growth factor receptor and Skp1-Cullin-F-box ubiquitin ligase activity.

Glioblastoma contains a hierarchy of stem-like cancer cells, but how this hierarchy is established is unclear. Here, we show that asymmetric Numb localization specifies glioblastoma stem-like cell (GSC) fate in a manner that does not require Notch inhibition. Numb is asymmetrically localized to CD133-hi GSCs.

DNA methylation patterns of ulcer-healing genes associated with the normal gastric mucosa of gastric cancers.

Recent evidence suggests that gastric mucosal injury induces adaptive changes in DNA methylation. In this study, the methylation status of the key tissue-specific genes in normal gastric mucosa of healthy individuals and cancer patients was evaluated. The methylation-variable sites of 14 genes, including ulcer-healing genes (TFF1, TFF2, CDH1, and PPARG), were chosen from the CpG-island margins or non-island CpGs near the transcription start sites.

DNA methylation and expression patterns of key tissue-specific genes in adult stem cells and stomach tissues.

CpG-island margins and non-island-CpG sites round the transcription start sites of CpG-island-positive and -negative genes are methylated to various degrees in a tissue-specific manner. These methylation-variable CpG sites were analyzed to delineate a relationship between the methylation and transcription of the tissue-specific genes. The level of tissue-specific transcription was estimated by counting the number of the total transcripts in the SAGE (serial analysis of gene expression) database.

Chromosomal losses are associated with hypomethylation of the gene-control regions in the stomach with a low number of active genes.

Transitional-CpG methylation between unmethylated promoters and nearby methylated retroelements plays a role in the establishment of tissue-specific transcription. This study examined whether chromosomal losses reducing the active genes in cancers can change transitional-CpG methylation and the transcription activity in a cancer-type-dependent manner. The transitional-CpG sites at the CpG-island margins of nine genes and the non-island-CpG sites round the transcription start sites of six genes lacking CpG islands were examined by methylation-specific polymerase chain reaction (PCR) analysis.

Clinical implication of recurrent copy number alterations in hepatocellular carcinoma and putative oncogenes in recurrent gains on 1q.

To elucidate the pathogenesis of hepatocellular carcinoma (HCC) and develop useful prognosis predictors, it is necessary to identify biologically relevant genomic alterations in HCC. In our study, we defined recurrently altered regions (RARs) common to many cases of HCCs, which may contain tumor-related genes, using whole-genome array-CGH and explored their associations with the clinicopathologic features. Gene set enrichment analysis was performed to investigate functional implication of RARs.

PathCluster: a framework for gene set-based hierarchical clustering.

Motivation: Gene clustering and gene set-based functional analysis are widely used for the analysis of expression profiles. The development of a comprehensive method jointly combining the two methods would allow for greater biological insights.

Results: We developed a software package, PathCluster for gene set-based clustering via an agglomerative hierarchical clustering algorithm.

Transitional CpG methylation between promoters and retroelements of tissue-specific genes during human mesenchymal cell differentiation.

In general, methylation of the promoter regions is inversely correlated with gene expression. The transitional CpG area between the promoter-associated CpG islands and the nearby retroelements is often methylated in a tissue-specific manner. This study analyzed the relationship between gene expression and the methylation of the transitional CpGs in two human stromal cells derived from the bone marrow (BMSC) and adipose tissue (ATSC), both of which have a multilineage differentiation potential.

The 5'-end transitional CpGs between the CpG islands and retroelements are hypomethylated in association with loss of heterozygosity in gastric cancers.

Background: A loss of heterozygosity (LOH) represents a unilateral chromosomal loss that reduces the dose of highly repetitive Alu, L1, and LTR retroelements. The aim of this study was to determine if the LOH events can affect the spread of retroelement methylation in the 5'-end transitional area between the CpG islands and their nearest retroelements.

Methods: The 5'-transitional area of all human genes (22,297) was measured according to the nearest retroelements to the transcription start sites.

The length of CpG islands is associated with the distribution of Alu and L1 retroelements.

Alu and L1 retroelements have been suggested to initiate the spread of CpG methylation. In this study, the spread of CpG methylation was estimated based on the distance between the CpG islands and the nearest retroelements. All human genes (23,116) were examined and the correlations between the length of the CpG islands and the distance and density of the confronting retroelements were examined using nonoverlapping 5-kb windows.

Alu and L1 retroelements are correlated with the tissue extent and peak rate of gene expression, respectively.

We exploited the serial analysis of gene expression (SAGE) libraries and human genome database in silico to correlate the breadth of expression (BOE; housekeeping versus tissue-specific genes) and peak rate of expression (PRE; high versus low expressed genes) with the density distribution of the retroelements. The BOE status is linearly associated with the density of the sense Alus along the 100 kb nucleotides region upstream of a gene, whereas the PRE status is inversely correlated with the density of antisense L1s within a gene and in the up- and downstream regions of the 0-10 kb nucleotides. The radial distance of intranuclear position, which is known to serve as the global domain for transcription regulation, is reciprocally correlated with the fractions of Alu (toward the nuclear center) and L1 (toward the nuclear edge) elements in each chromosome.