Enhancing Clinical Applications by Evaluation of Sensitivity and Specificity in Whole Exome Sequencing.

The cost-effectiveness of whole exome sequencing (WES) remains controversial due to variant call variability, necessitating sensitivity and specificity evaluation. WES was performed by three companies (AA, BB, and CC) using reference standards composed of DNA from hydatidiform mole and individual blood at various ratios. Sensitivity was assessed by the detection rate of null-homozygote (N-H) alleles at expected variant allelic fractions, while false positive (FP) errors were counted for unexpected alleles.

Prognostic Model for High-Grade Neuroendocrine Carcinoma of the Lung Incorporating Genomic Profiling and Poly (ADP-ribose) Polymerase-1 Expression.

Purpose: High-grade neuroendocrine carcinoma (HGNEC) of the lung is an aggressive cancer with a complex biology. We aimed to explore the prognostic value of genetic aberrations and poly(ADP-ribose) polymerase-1 (PARP1) expression in HGNEC and to establish a novel prognostic model.

Materials And Methods: We retrospectively enrolled 191 patients with histologically confirmed HGNEC of the lung.

Effectiveness of a personalized digital exercise and nutrition-based rehab program for patients with gastric cancer after surgery: Study protocol for a randomized controlled trial.

Background: Patients with gastric cancer often encounter impaired quality of life and reduced tolerability to adjuvant treatments after surgery. Weight preservation is crucial for the overall prognosis of these patients, and exercise and supplemental nutrition play the main role. This study is the first randomized clinical trial to apply personalized, treatment stage-adjusted digital intervention with wearable devices in gastric cancer rehabilitation intervention for 12 months, commencing immediately after surgery.

Rapid Androgen-Responsive Proteome Is Involved in Prostate Cancer Progression.

Androgen exerts its functions by binding with an androgen receptor (AR). It can activate many signaling pathways that are important to the progression of castration-resistant prostate cancer (CRPC). Here, we characterized the rapid proteomic changes seen at 5, 15, 30, and 60 min after the androgen treatment of VCaP cells via the tandem mass tag (TMT) labeling strategy.

Local adenoviral delivery of soluble CD200R-Ig enhances antitumor immunity by inhibiting CD200-β-catenin-driven M2 macrophage.

CD200 is known as an immune checkpoint molecule that inhibits innate immune cell activation. Using a head and neck squamous cell carcinoma (HNSCC) model, we sought to determine whether localized delivery of adenovirus-expressing sCD200R1-Ig, the soluble extracellular domain of CD200R1, enhances antitumor immunity. Mouse-derived bone marrow cells and M1/M2-like macrophages were cocultured with tumor cells and analyzed for macrophage polarization.

Characterization of Proteins Regulated by Androgen and Protein Kinase a Signaling in VCaP Prostate Cancer Cells.

Androgen signaling via the androgen receptor (AR) is involved in normal prostate development and prostate cancer progression. In addition to androgen binding, a variety of protein kinases, including cyclic AMP-dependent protein kinase A (PKA), can activate the AR. Although hormone deprivation, especially that of androgen, continues to be an important strategy for treating prostate cancer patients, the disease ultimately progresses to castration-resistant prostate cancer (CRPC), despite a continuous hormone-deprived environment.

A Modular Mobile Health App for Personalized Rehabilitation Throughout the Breast Cancer Care Continuum: Development Study.

Background: Although many mobile health (mHealth) apps have evolved as support tools for self-management of breast cancer, limited studies have developed a comprehensive app and described the algorithms for personalized rehabilitation throughout the breast cancer care continuum.

Objective: This study aimed to develop a comprehensive mobile app and to describe an algorithm that adjusts personalized content to facilitate self-management throughout the breast cancer care continuum.

Methods: The development process of the modular mHealth app included the following 4 steps: (1) organizing expert teams, (2) defining evidence-based fundamental content and modules, (3) classifying user information for algorithms to personalize the content, and (4) creating the app platform and connectivity to digital health care devices.

Preclinical evaluation of radiation therapy of -associated mammary tumors using a mouse model.

Although germline mutations in highly predispose women towards breast and ovarian cancer, few substantial improvements in preventing or treating such cancers have been made. Importantly, BRCA1 function is closely associated with DNA damage repair, which is required for genetic stability. Here, we examined the efficacy of radiotherapy, assessing the accumulation of genetic instabilities, in the treatment of -associated breast cancer using a -mutant mouse model.

Phosphorylation of OCT4 Serine 236 Inhibits Germ Cell Tumor Growth by Inducing Differentiation.

Octamer-binding transcription factor 4 (Oct4) plays an important role in maintaining pluripotency in embryonic stem cells and is closely related to the malignancies of various cancers. Although posttranslational modifications of Oct4 have been widely studied, most of these have not yet been fully characterized, especially in cancer. In this study, we investigated the role of phosphorylation of serine 236 of OCT4 [OCT4 (S236)] in human germ cell tumors (GCTs).

CD200 Induces Epithelial-to-Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma via β-Catenin-Mediated Nuclear Translocation.

The membrane glycoprotein CD200 binds to its receptor CD200R1 and induces tolerance, mainly in cells of the myeloid lineage; however, information regarding its role in solid tumors is limited. Here, we investigated whether CD200 expression, which is enriched mainly in high-grade head and neck squamous cell carcinoma (HNSCC), correlates with cancer progression, particularly the epithelial-to-mesenchymal transition (EMT). The forced overexpression of CD200 in the HNSCC cell line, UMSCC84, not only increased the expression of EMT-related genes, but also enhanced invasiveness.

False-negative errors in next-generation sequencing contribute substantially to inconsistency of mutation databases.

Background: More than 11,000 laboratories and companies developed their own next-generation sequencing (NGS) for screening and diagnosis of various diseases including cancer. Although inconsistencies of mutation calls as high as 43% in databases such as GDSC (Genomics of Drug Sensitivity in Cancer) and CCLE (Cancer Cell Line Encyclopedia) have been reported, not many studies on the reasons for the inconsistencies have been published. Methods: Targeted-NGS analysis of 151 genes in 35 cell lines common to GDSC and CCLE was performed, and the results were compared with those from GDSC and CCLE wherein whole-exome- or highly-multiplex NGS were employed.

Inhibition of AKT suppresses the initiation and progression of -associated mammary tumors.

Despite the high incidence of -mutant breast cancer, few substantial improvements in preventing or treating such cancers have been made. Using a -mutant mouse model, we examined the contribution of AKT to the incidence and growth of -mutated mammary tumors. A haploinsufficiency of in -mutant mouse model significantly decreased mammary tumor formation from 54% in mice to 22% in mice.

Inhibition of Estrogen Signaling Reduces the Incidence of -associated Mammary Tumor Formation.

BRCA1-deficient breast cancer is a very well-known hereditary cancer. However, except for resection of normal mammary glands and ovaries, there is no acceptable measure for proactively preventing tumor development. Importantly, inherited mutations are closely associated with tumors in hormone-responsive tissues.

Farnesyl diphosphate synthase is important for the maintenance of glioblastoma stemness.

Glioblastoma is a highly malignant tumor that easily acquires resistance to treatment. The stem-cell-like character (stemness) has been thought to be closely associated with the treatment resistance of glioblastoma cells. In this study, we determined that farnesyl diphosphate synthase (FDPS), a key enzyme in isoprenoid biosynthesis, plays an important role in maintaining glioblastoma stemness.

Cyclin B1 stability is increased by interaction with BRCA1, and its overexpression suppresses the progression of BRCA1-associated mammary tumors.

Germline BRCA1 mutations predispose women to breast and ovarian cancer. BRCA1, a large protein with multiple functional domains, interacts with numerous proteins involved in many important biological processes and pathways. However, to date, the role of BRCA1 interactions at specific stages in the progression of mammary tumors, particularly in relation to cell cycle regulation, remains elusive.

OCT4 directly regulates stemness and extracellular matrix-related genes in human germ cell tumours.

Germ cell tumours (GCTs) are one of the most threatening malignancies in young men and women. Although several reports have suggested the importance of OCT4 in human GCTs, its role has not been clearly investigated on a molecular level. In this study, we revealed GCT-specific direct transcriptional target genes of OCT4.

Identification of somatic mutations using whole-exome sequencing in Korean patients with acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is a biologically and clinically heterogeneous cancer of the bone marrow that is characterized by the rapid growth of abnormal myeloid cells.

Methods: We performed a mutational analysis to identify AML somatic mutations using the whole-exome sequencing data of 36 tumor-normal sample pairs from Korean patients with de novo AML. We explored the functional impact of the genes identified in the mutational analyses through an integrated Gene Ontology (GO) and pathway analysis.

Migration and invasion of drug-resistant lung adenocarcinoma cells are dependent on mitochondrial activity.

A small proportion of cancer cells have stem-cell-like properties, are resistant to standard therapy and are associated with a poor prognosis. The metabolism of such drug-resistant cells differs from that of nearby non-resistant cells. In this study, the metabolism of drug-resistant lung adenocarcinoma cells was investigated.