Mortality Prediction Modeling for Patients with Breast Cancer Based on Explainable Machine Learning.

: Breast cancer is the most common cancer in women worldwide, requiring strategic efforts to reduce its mortality. This study aimed to develop a predictive classification model for breast cancer mortality using real-world data, including various clinical features. : A total of 11,286 patients with breast cancer from the National Cancer Center were included in this study.

The Cancer Clinical Library Database (CCLD) from the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) Project.

The common data model (CDM) has found widespread application in healthcare studies, but its utilization in cancer research has been limited. This article describes the development and implementation strategy for Cancer Clinical Library Databases (CCLDs), which are standardized cancer-specific databases established under the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) project by the Korean Ministry of Health and Welfare. Fifteen leading hospitals and fourteen academic associations in Korea are engaged in constructing CCLDs for 10 primary cancer types.

The Association of Estrogen Receptor Activity, Interferon Signaling, and MHC Class I Expression in Breast Cancer.

Purpose: The expression of major histocompatibility complex class I (MHC I) has previously been reported to be negatively associated with estrogen receptor (ER) expression. Furthermore, MHC I expression, level of tumor-infiltrating lymphocytes (TILs), and expression of interferon (IFN) mediator MxA are positively associated with one another in human breast cancers. This study aimed to investigate the mechanisms of association of MHC I with ER and IFN signaling.

IL-27 enhances IL-15/IL-18-mediated activation of human natural killer cells.

Background: Natural killer (NK) cells are an emerging new tool for cancer immunotherapy. To develop NK cell therapeutics from peripheral blood mononuclear cells (PBMCs) of healthy donors, substantial expansion of primary NK cells is necessary because of the very low number of these cells in peripheral blood. In this study, we aimed to investigate the effect of various cytokine alone or combinations, in expanded NK cells and to analyze the synergetic effect of cytokine combinations.

Minimally invasive surgical treatment using 'iliac pillar' screw for isolated iliac wing fractures in geriatric patients: a new challenge.

Purpose: There have been no prior case series of isolated iliac wing fracture (IIWF) due to low-energy trauma in geriatric patients in the literature. The aim of this study was to describe the characteristics of IIWF in geriatric patients, and to present a case series of IIWF in geriatric patients who underwent our minimally invasive screw fixation technique named 'iliac pillar screw fixation'.

Materials And Methods: We retrospectively reviewed six geriatric patients over 65  years old who had isolated iliac wing fracture treated with minimally invasive screw fixation technique between January 2006 and April 2016.

β-Arrestin-2-Dependent Signaling Promotes CCR4-mediated Chemotaxis of Murine T-Helper Type 2 Cells.

Allergic asthma is a complex inflammatory disease that leads to significant healthcare costs and reduction in quality of life. Although many cell types are implicated in the pathogenesis of asthma, CD4 T-helper cell type 2 (Th2) cells are centrally involved. We previously reported that the asthma phenotype is virtually absent in ovalbumin-sensitized and -challenged mice that lack global expression of β-arrestin (β-arr)-2 and that CD4 T cells from these mice displayed significantly reduced CCL22-mediated chemotaxis.

Clinical Impact of microRNAs Associated With Cancer Stem Cells as a Prognostic Factor in Ovarian Carcinoma.

Ovarian carcinoma is a highly lethal gynecological malignancy due to its frequent relapses and adoption of chemoresistance. To develop new biomarkers for disease progression in ovarian carcinoma, CSCs, which are considered to contribute to disease relapse and metastasis, were isolated from human ovarian carcinoma tissues, and differentially expressed microRNAs (miRNAs) in CSCs were identified and assessed the clinical implication of expression of these miRNAs. Primary cancer cells derived from human ovarian carcinomas were cultured and spheroid-forming cells (SFCs) were isolated.

Inhibition of interleukin-1β-mediated interleukin-1 receptor-associated kinase 4 phosphorylation by zinc leads to repression of memory T helper type 17 response in humans.

Zinc is an essential trace element that plays pivotal roles in multiple facets of the immune system. Besides its catalytic and structural roles, zinc also functions as an intracellular signalling molecule, and changes in zinc levels can cause both direct and indirect modulation of immune responses. Further, cytoplasmic levels of bioavailable zinc in immune cells are largely influenced by many extracellular stimuli.

Functional phenotype of synovial monocytes modulating inflammatory T-cell responses in rheumatoid arthritis (RA).

Monocytes function as crucial innate effectors in the pathogenesis of chronic inflammatory diseases, including autoimmunity, as well as in the inflammatory response against infectious pathogens. Human monocytes are heterogeneous and can be classified into three distinct subsets based on CD14 and CD16 expression. Although accumulating evidence suggests distinct functions of monocyte subsets in inflammatory conditions, their pathogenic roles in autoimmune diseases remain unclear.

A new neolignan and lignans from the stems of Lindera obtusiloba Blume and their anti-allergic inflammatory effects.

A new neolignan, linderin A (1), together with six known lignans, (+)-xanthoxyol (2), pluviatilol (3), actiforin (4), (+)-syringaresinol (5), (+)-(7S,8R,8'R)-acuminatolide (6), and (+)-9'-O-trans-feruloyl-5,5'-dimethoxylariciresinol (7) were isolated from the stems of Lindera obtusiloba Blume (Lauraceae). Their chemical structures were elucidated by a combination of spectroscopic analysis and chemical reaction, and the absolute configuration of 1 was determined by Mosher's esterification. The effect of compounds 1-7 on tumor necrosis factor (TNF)-α, interleukin(IL)-6, and their inhibitory activity of histamine release were examined using human mast cells.

Rhododendric acid A, a new ursane-type PTP1B inhibitor from the endangered plant Rhododendron brachycarpum G. Don.

In spite of the critical role of the natural products in drug discovery, surprising little attention has been placed on endangered and rare plant species that could play a pivotal role in pharmaceutical and fiber development. Protein tyrosine phosphatase-1B (PTP1B), which blocks insulin signaling, has been gaining interest to be a promising therapeutic target for the treatment of type 2 diabetes mellitus. Bioassay-guided fractionation on the leaves of Rhododendron brachycarpum G.

Santamarin, a sesquiterpene lactone isolated from Saussurea lappa, represses LPS-induced inflammatory responses via expression of heme oxygenase-1 in murine macrophage cells.

Saussurea lappa C.B. Clarke (Compositae) is indigenous to India and Pakistan.

The extracellular signal-regulated kinase mitogen-activated protein kinase/ribosomal S6 protein kinase 1 cascade phosphorylates cAMP response element-binding protein to induce MUC5B gene expression via D-prostanoid receptor signaling.

Mucus hypersecretion is a prominent feature of respiratory diseases, and MUC5B is a major airway mucin. Mucin gene expression can be affected by inflammatory mediators, including prostaglandin (PG) D(2,) an inflammatory mediator synthesized by hematopoietic PGD synthase (H-PGDS). PGD(2) binds to either D-prostanoid receptor (DP1) or chemoattractant receptor homologous molecule expressed on T-helper type 2 cells (CRTH2).

α-Melanocyte-stimulating hormone inhibits tumor necrosis factor α-stimulated MUC5AC expression in human nasal epithelial cells.

Mucin hypersecretion is an important clinical feature of several respiratory diseases, including asthma, cystic fibrosis, nasal allergy, rhinitis, and sinusitis. It has been shown that α-melanocyte-stimulating hormone (α-MSH), a proopiomelanocortin (POMC)-derived peptide, has immunomodulatory activities by inhibiting NF-κB activation induced by proinflammatory cytokines such as TNF-α. Because MUC5AC expression is known to be up-regulated by TNF-α via NF-κB activation, we evaluated the inhibitory effect of α-MSH on MUC5AC gene expression induced by TNF-α in normal human nasal epithelial (NHNE) cells.

AP2alpha is essential for MUC8 gene expression in human airway epithelial cells.

Mucins are high molecular weight proteins that make up the major components of mucus. Hypersecretion of mucus is a feature of several chronic inflammatory airway diseases. MUC8 is an important component of airway mucus, and its gene expression is upregulated in nasal polyp epithelium.

Suppression of prostaglandin E2-induced MUC5AC overproduction by RGS4 in the airway.

The mechanism by which E-prostanoid (EP) receptor is critically involved in PGE(2)-induced mucin 5AC (MUC5AC) gene expression in the airway has been unclear. Furthermore, there have been little reports regarding the negative regulatory mechanism and/or proteins that affect PGE(2)-induced MUC5AC overproduction. In the present study, we found that PGE(2) induced MUC5AC gene expression in a dose-dependent manner (EC(50): 73.

Signal pathway of 17beta-estradiol-induced MUC5B expression in human airway epithelial cells.

MUC5B is a major mucin of the human respiratory tract, and it is not clear how MUC5B expression is regulated in various airway diseases. The goal of this study was to determine the mechanisms by which 17beta-estradiol induces MUC5B gene expression in airway epithelial cells. It was found that E2, a sex hormone, stimulates MUC5B gene overexpression by interaction with estrogen receptor alpha (ERalpha) and by acting through extracellular signal-regulated kinase 1/2 (ERK1/2)-mitogen-activated protein kinase (MAPK).

An association between RRM1 haplotype and gemcitabine-induced neutropenia in breast cancer patients.

Purpose: We examined the pattern of single-nucleotide polymorphisms (SNPs) of gemcitabine metabolism-related and target genes in breast cancer patients and evaluated their association with drug response or toxicity.

Patients And Methods: SNPs in deoxycytidine kinase (dCK), deoxycytidine monophosphate deaminase (DCTD), and ribonucleotide reductase M1 polypeptide (RRM1) were analyzed with genomic DNA of 10 breast cancer cell lines, 74 peripheral blood mononuclear cell (PBMC) samples from advanced breast cancer patients treated with gemcitabine, and 56 PBMC samples from healthy volunteers.

Results: The incidences of SNPs of breast cancer patients were 1.

Different criteria for HER2 positivity by IHC can be applied in post-chemotherapy specimens in determining HER2 as a prognosticator in locally advanced breast cancer.

Purpose: We evaluated the clinical significance of HER2 in post-chemotherapy specimens after surgery in locally advanced breast cancer (LABC).

Methods: Thirty-four patients with LABC were treated with neoadjuvant chemotherapy, surgery, adjuvant chemotherapy, and radiotherapy. The HER2 status was determined using both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in the paraffin-embedded surgical specimens after neoadjuvant chemotherapy.

Identification of genes with correlated patterns of variations in DNA copy number and gene expression level in gastric cancer.

To identify DNA copy number changes that had a direct influence on mRNA expression in gastric cancer, cDNA microarray-based comparative genomic hybridization (aCGH) and gene expression profiling were performed using 17 K cDNA microarrays. A set of 158 genes showing Pearson correlation coefficients over 0.6 between DNA copy number changes and mRNA expression level variations was selected.

Ribonucleotide reductase M1 (RRM1) 2464G>A polymorphism shows an association with gemcitabine chemosensitivity in cancer cell lines.

Objectives: Significant variability in the efficacy and toxicity of an anticancer drug is observed in cancer patients. Currently, there are no standard tools for prediction of a patient's tumor response or his risk of adverse events to chemotherapy.

Methods: We investigate an association between polymorphisms of gemcitabine metabolism-related genes and its chemosensitivity in vitro using 62 human cancer cell lines of various origins.

Systematic analysis of cDNA microarray-based CGH.

cDNA microarray-based CGH (Microarray-CGH) is a useful technique for detecting genomic aberrations with a high resolution. However, the criteria for determining a genomic alteration have not been determined. We evaluated the genome-wide measurement of copy number of each gene in normal gastric and placenta tissues with both sex-matched, direct and sex-mismatched, indirect designs using 17K cDNA microarray.