PURPOSE: The purpose of this study is to investigate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and plasma cytokines and angiogenic factors (CAFs) as pharmacodynamic and prognostic biomarkers of bevacizumab monotherapy in colorectal cancer with liver metastasis (CRCLM). MATERIALS AND METHODS: From July 2011 to March 2012, 28 patients with histologically confirmed CRCLM received bevacizumab monotherapy followed by combined FOLFOX therapy. The mean age of the patients was 57 years (range, 30 to 77 years). DCE-MRI (K(trans) and IAUC₆₀) was performed at baseline, first follow-up (3 days after bevacizumab monotherapy), and second follow-up (3 days after combined therapy). CAF levels (vascular endothelial growth factor [VEGF], placental growth factor [PlGF], and interleukin-8) were assessed on the same days. Progression-free survival (PFS) time distributions were summarized using the Kaplan-Meier method and compared using log-rank tests. RESULTS: The median PFS period was 11.2 months. K(trans), IAUC₆₀, VEGF, and PlGF values on the first follow-up day were significantly different compared with baseline values. No differences were observed on the second follow-up day. A > 40% decrease in K(trans) from baseline to first follow-up was associated with a longer PFS (hazard ratio, 0.349; 95% confidence interval, 0.133 to 0.912; p=0.032). Changes in CAFs did not show correlation with PFS time. CONCLUSION: DCE-MRI parameters and CAFs are pharmacodynamic biomarkers of bevacizumab for CRCLM. In our study, change in K(trans) at 3 days after bevacizumab monotherapy was a favorable prognostic factor; however, the value of CAFs as a prognostic biomarker was not found.
Angiogenesis Inducing Agents ; Bevacizumab* ; Biomarkers ; Colorectal Neoplasms* ; Cytokines ; Disease-Free Survival ; Endothelial Growth Factors ; Follow-Up Studies ; Humans ; Liver* ; Magnetic Resonance Imaging* ; Methods ; Neoplasm Metastasis* ; Plasma ; Vascular Endothelial Growth Factor A

Purpose: Neuregulin 1 (NRG1) gene fusion is a potentially actionable oncogenic driver. The oncoprotein binds to ERBB3-ERBB2 heterodimers and activates downstream signaling, supporting a therapeutic approach for inhibiting ERBB3/ERBB2. However, the frequency and clinicopathological features of solid tumors harboring NRG1 fusions in Korean patients remain largely unknown. Materials and Methods: We reviewed archival data from next-generation sequencing panel tests conducted at a single institution, specifically selecting patients with in-frame fusions that preserved the functional domain. The clinicopathological characteristics of patients harboring NRG1 fusions were retrospectively reviewed. Results: Out of 8,148 patients, NRG1 fusions were identified in 22 patients (0.27%). The average age of the patients was 59 years (range, 32 to 78 years), and the male-to-female ratio was 1:1.2. The lung was the most frequently observed primary site (n=13), followed by the pancreaticobiliary tract (n=3), gastrointestinal tract (n=2, stomach and rectum each), ovary (n=2), breast (n=1), and soft tissue (n=1). Histologically, all tumors demonstrated adenocarcinoma histology, with the exception of one case of sarcoma. CD74 (n=8) and SLC3A2 (n=4) were the most frequently identified fusion partners. Dominant features included the presence of fewer than three co-occurring genetic alterations, a low tumor mutation burden, and low programmed death-ligand 1 expression. Various clinical responses were observed in patients with NRG1 fusions. Conclusion Despite the rarity of NRG1 fusions in Korean patients with solid tumors, identification through next-generation sequencing enables the possibility of new targeted therapies.

Dynamic contrast-enhanced MRI (DCE-MRI) is a noninvasive imaging technique used to evaluate tissue vascularity/permeability features through consecutive imaging acquisitions after gadolinium-based contrast agent administration. Over the past several decades, techniques and protocols for DCE-MRI have evolved, leading to growing applications of DCE-MRI for different neurological disorders. Although most established applications of DCE-MRI are for studying tumors, an increasing number of studies have been evaluating the use of this technique for neurodegenerative and other miscellaneous diseases. The purpose of this article was to provide an overview of DCE-MRI and its clinical applications in various neurological diseases.

Magnetic resonance elastography (MRE) is an emerging magnetic resonance imaging (MRI) technique capable of quantitatively evaluating the biomechanical properties of tissue. MRE has been widely used in the evaluation of chronic parenchymal liver diseases.However, numerous studies have suggested its applicability in evaluating other organs.The MRE data acquisition process consists of three main steps: 1) generation of mechanical waves in soft tissues; 2) adoption of a modified phase-contrast MRI sequence to capture tissue displacements produced by the propagation of applied waves; and 3) application of an inversion algorithm to transform the wave image into maps of viscoelastic properties. As efforts are made to standardize MRE terminology and protocols, more extensive clinical investigations using MRE are expected in the future.

Macrophages play essential roles in innate immune responses by producing various immune mediators. Therefore, modulating macrophage function is an attractive strategy to treat immune disorders. Aralia cordata var. continentalis (AC), known as “Dokwhal” in Korea, possesses various biological and medicinal functions, including immunomodulation. The present study investigated the effect of the hot water extract of AC (HAC) on RAW264.7 murine macrophages. When these cells were treated with HAC, nitric oxide production and inducible nitric oxide synthase expression was induced dose-dependently. In addition, HAC treatment triggered the secretion of innate immune cytokines, such as TNF-α and IL-6. Phagocytosis, measured by FITC-dextran internalization showed that HAC stimulated the phagocytic activity of macrophages. Furthermore, HAC promoted the production of reactive oxygen species in RAW264.7 cells, determined by CM-H2DCFDA. In addition, the immunoblot analysis of intracellular signaling proteins revealed that NF-kB and MAPK signaling pathways, which are important signaling mediators of inflammation, are upregulated by HAC. In conclusion, these findings suggested that HAC can stimulate macrophage activity, and NF-kB and MAPK signaling pathways might be involved in the immunostimulatory effects of HAC.
Aralia ; Cytokines ; Immune System Diseases ; Immunity, Innate ; Immunomodulation ; Inflammation Mediators ; Interleukin-6 ; Intracellular Signaling Peptides and Proteins ; Korea ; Macrophages ; NF-kappa B ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Phagocytosis ; Reactive Oxygen Species ; Water

In rodents, the circumvallate papilla (CVP), with its underlying minor salivary gland, the von Ebners' gland (VEG), is located on the dorsal surface of the posterior tongue. Detailed morphological processes to form the proper structure of CVP and VEG have not been properly elucidated. In particular, the specific localization patterns of taste buds in CVP and the branching formation of VEG have not yet been elucidated. To understand the developmental mechanisms underlying CVP and VEG formation, detailed histological observations of CVP and VEG were examined using a three-dimensional computer-aided reconstruction method with serial histological sections and pan-Cytokeratins immunostainings. In addition, to define the developmental processes in CVP and VEG formation, we examined nerve innervations and cell proliferation using microinjections of AM1-43 and immunostainings with various markers, including phosphoinositide 3-kinase, Ki-67, PGP9.5, and Ulex europaeus agglutinin 1 (UEA1). Results revealed specific morphogenesis of CVP and VEG with nerve innervations patterns, evaluated by the coincided localization patterns of AM1-43 and UEA1. Based on these morphological and immunohistochemical results, we suggest that nerve innervations and cell proliferations play important roles in the positioning of taste buds in CVP and branching morphogenesis of VEG in tongue development.
Animals ; Cell Proliferation ; Mice ; Microinjections ; Morphogenesis ; Rodentia ; Salivary Glands, Minor ; Taste Buds ; Tongue ; Ulex ; von Ebner Glands

Vaccination is the most efficient method for infectious disease prevention. Parenteral injections such as intramuscular, intradermal, and subcutaneous injections have several advantages in vaccine delivery, but there are many drawbacks. Thus, the development of a new vaccine delivery system has long been required. Recently, microneedles have been attracting attention as new vaccination tools. Microneedle is a highly effective transdermal vaccine delivery method due to its mechanism of action, painlessness, and ease of use. Here, we summarized the characteristics of microneedles and the possibilities as a new vaccine delivery route.
Communicable Diseases ; Injections, Subcutaneous ; Methods* ; Vaccination ; Vaccines*

Hemangioblastoma (HB) is a rare benign tumor that most commonly occurs in the cerebellum. HB is composed of neoplastic stromal cells and abundant small vessels. However, the exact origin of stromal cells is controversial. Extraneural HBs have been reported in a small series, and peripheral HBs arising in the adrenal gland are extremely rare. Herein, we report a case of sporadic adrenal HB in a 54-year-old woman. The tumor was a well-circumscribed, yellow mass measuring 4.2 cm in diameter. Histologically, the tumor was composed of small blood vessels and vacuolated stromal cells with clear cytoplasm. On immunohistochemical stain, the stromal cells were positive for S-100 protein, neuron-specific enolase, and synaptophysin. The tumor did not reveal mutation of VHL alleles. We herein present a case of HB of the adrenal gland and review of the literature.

This study was carried out to develop specific primers for PCR detection of Phellinus linteus. Diverse genomes of 15 Phellinus spp. including five Phellinus linteus isolates were fingerprinted by Primer Universal rice primer (URP)1F. The URP-PCR pattern differentiated P. linteus isolates from other phellinus spp. A polymorphic band (2.8 kb), which is unique for P. linteus isolates, was isolated and sequenced. Twenty four-oligonucleotide primer pairs were designed based on information of DNA sequence. The primer set (PLSPF2/PLSPR1) amplified single band (2.2 kb) of expected size with genomic DNA from seven Phellinus linteus, but not with that of other Phellinus species tested. The primers could be used identically in both DNA samples from mycelium and fruit bodies. This specific primers could offer a useful tool for detecting and identifying P. linteus rapidly.
Base Sequence ; Dermatoglyphics ; DNA ; Fruit ; Genome ; Mycelium ; Polymerase Chain Reaction*

Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare encephalopathy characterized by the coexistence of a perivascular inflammatory reaction in patients with cerebral amyloid angiopathy. CAA-RI diagnosis is challenging as its final diagnosis requires invasive procedures such as autopsy or brain biopsy. Therefore, multimodal imaging approaches with clinical considerations are essential for the probable diagnosis of CAA-RI. In particular, in the case of CAA-RI presented with uncommon clinical symptoms, the need for imaging in diagnosis is further highlighted by difficulties of clinical approaches. Herein, we report a case of CAA-RI with unusual clinical manifestation diagnosed using multimodal imaging including magnetic resonance imaging (MRI) and amyloid positron emission tomography-computed tomography (PET-CT). Multimodal imaging approaches using adequate MRI sequences and PET-CT scans could facilitate the diagnosis of CAA-RI without requiring invasive pathological confirmation.