Three-dimensional thermoluminescence (TL) spectra from MgAl2O4 irradiated with UV light were measured over 300~600 K and 300~800 nm. The peak positions of TL glow curves were shifted to lower temperature with increasing the exposure time of UV light. The 476 K TL glow curve is due to the second kinetics and its activation energy and escape frequency factor are calculated to be 0.85 eV and 1.92x10(6) sec(-1), respectively. The TL spectra were split into 530 nm and 700 nm emission bands which were associated with V(2+) and Cr(2+), respectively. The linearity range of 700 nm emission band is smaller than that of 530 nm emission band, but the saturation time of 700 nm emission band is longer than that of 530 nm emission band.
Aluminum* ; Kinetics ; Magnesium* ; Ultraviolet Rays ; United Nations

Locally advanced or metastatic disease accounts for two thirds of total patients with pancreatic cancer. Patients with pancreatic cancer are assessed as resectable, potentially resectable (borderline) or unresectable according to pre-operative examinations. The chances of resectability may be enhanced by using neoadjuvant systemic chemotherapy, radiotherapy or both. This case report presents a locally advanced pancreatic adenocarcinoma that was identified to be unresectable during surgical exploration. After receiving concurrent chemoradiotherapy, the patient was re-evaluated, identified as unresectable and received gemcitabine maintenance chemotherapy. Herein, we report the case of a patient with unresectable locally advanced pancreatic adenocarcinoma who achieved a complete response lasting for more than 32 months after receiving concurrent chmoradiotherapy followed by gemcitabine maintenance chemotherapy.
Adenocarcinoma ; Chemoradiotherapy ; Drug Therapy* ; Humans ; Maintenance Chemotherapy ; Pancreatic Neoplasms* ; Radiotherapy

Locally advanced or metastatic disease accounts for two thirds of total patients with pancreatic cancer. Patients with pancreatic cancer are assessed as resectable, potentially resectable (borderline) or unresectable according to pre-operative examinations. The chances of resectability may be enhanced by using neoadjuvant systemic chemotherapy, radiotherapy or both. This case report presents a locally advanced pancreatic adenocarcinoma that was identified to be unresectable during surgical exploration. After receiving concurrent chemoradiotherapy, the patient was re-evaluated, identified as unresectable and received gemcitabine maintenance chemotherapy. Herein, we report the case of a patient with unresectable locally advanced pancreatic adenocarcinoma who achieved a complete response lasting for more than 32 months after receiving concurrent chmoradiotherapy followed by gemcitabine maintenance chemotherapy.
Adenocarcinoma ; Chemoradiotherapy ; Drug Therapy* ; Humans ; Maintenance Chemotherapy ; Pancreatic Neoplasms* ; Radiotherapy

Manipulation of the sensory branches of the trigeminal nerve is known to cause autonomic changes, such as bradycardia or asystole, known as the trigemino-cardiac reflex. In this case, the patient underwent microvascular decompression due to trigeminal neuralgia and developed sudden bradycardia, followed by abrupt asystole with a concurrent fall in the systolic blood pressure. There was spontaneous return of cardiac rhythm and blood pressure, but two more episodes of sinus bradycardia occurred during the surgery.
Blood Pressure ; Bradycardia ; Heart Arrest* ; Humans ; Microvascular Decompression Surgery* ; Reflex, Trigeminocardiac ; Trigeminal Nerve ; Trigeminal Neuralgia*

To elucidate the roles of 8-hydroxydeoxyguanosine (oh8dG), the nucleoside of 8-hydroxyguanine (oh8Gua), we examined the effects of oh8dG upon LPS-induced intercellular adhesion molecule-1 (ICAM-1) expression and the underlying mechanisms in brain microglial cells. We found that oh8dG reduces LPS-induced reactive oxygen species (ROS) production, STAT3 activation, and ICAM-1 expression. oh8dG also suppresses pro-inflammatory cytokines, such as TNF-alpha, IL-6 and IFN-gamma. Overexpression of dominant negative STAT3 completely diminshed STAT3-mediated ICAM-1 transcriptional activity. Chromatin immunoprecipitation studies revealed that oh8dG inhibited recruitment of STAT3 to the ICAM-1 promoter, followed by a decrease in ICAM-1 expression. Using mice lacking a functional Toll-like receptor 4 (TLR4), we demonstrated that, while TLR4+/+ microglia were activated by LPS, TLR4-/-microglia exhibited inactivated STAT3 in response to LPS. Evidently, LPS modulates STAT3-dependent ICAM-1 induction through TLR4-mdiated cellular responses. Oh8dG apparently plays a role in anti-inflammatory actions via suppression of ICAM-1 gene expression by blockade of the TLR4-STAT3 signal cascade in inflammation-enhanced brain microglia. Therefore, oh8dG in the cytosol probably functions as an anti-inflammatory molecule and should be considered as a candidate for development of anti-inflammatory agents.
Toll-Like Receptor 4/genetics ; STAT3 Transcription Factor/physiology ; Reactive Oxygen Species/metabolism ; Microglia/*drug effects/metabolism ; Mice, Knockout ; Mice, Inbred C57BL ; Mice ; Male ; Lipopolysaccharides/*pharmacology ; Intercellular Adhesion Molecule-1/*metabolism ; Inflammation Mediators/metabolism ; Encephalitis/drug therapy ; Deoxyguanosine/*analogs & derivatives/pharmacology/therapeutic use ; Cytokines/biosynthesis ; Cell Survival/drug effects ; Brain/cytology/drug effects ; Anti-Inflammatory Agents, Non-Steroidal/*pharmacology ; Animals

STATs (signal transducers and activators of transcription) are proteins with dual functions: signal transducers in the cytoplasm and transcriptional activators in the nucleus. STAT proteins act as transcription factors activated by phosphorylation on its tyrosine residues upon stimulation by various cytokines. The phosphorylated STAT molecules then form homo- or heterodimers through SH2-mediated interaction and translocate into the nucleus to activate the transcription of various target genes. STAT5 recognizes the interferon-gamma activated site TTCNNNGAA (GAS sequence) in the promoter region of the beta-casein gene. Except for prolactin-dependent beta-casein production in mammary gland cells, the biological consequences of STAT5a activation in various systems are not clear. Here we showed that STAT5a was phosphorylated 10 min after desferrioxamine (DFO) treatment, and reached a maximum induction at 4 h in mammary epithelial cells (HC11) and transfected COS-7 cells. Under hypoxic conditions (2% O2), a maximal phosphorylation of STAT5a was observed within 6 h. EMSA (electrophoretic mobility shift assay) showed that DFO or hypoxia enhanced the binding activities of STAT5a DNA to beta-casein gene promoter in mammary epithelial cells (HC11) and transfected COS-7 cells. These results showed that DFO or hypoxia induces tyrosine phosphorylation of STAT5a and also increases the binding activity of STAT5a DNA in mammary epithelial cells. Our data suggest that the STAT5 may act as a mediator in hypoxia-mediated gene expression.
Animals ; Anoxia/*genetics/*metabolism ; Caseins/genetics ; Cell Line ; DNA/genetics/metabolism ; DNA-Binding Proteins/*metabolism ; Deferoxamine/pharmacology ; Epithelial Cells/drug effects/*metabolism ; Gene Expression Regulation ; Mammary Glands, Animal/cytology/*metabolism ; Mice ; Phosphorylation/drug effects ; Phosphotyrosine/metabolism ; Promoter Regions (Genetics)/genetics ; Protein Binding ; Response Elements/*genetics ; Support, Non-U.S. Gov't ; Trans-Activators/*metabolism

Hypoxia, a common consequence of solid tumor growth in breast cancer or other cancers, serves to propagate a cascade of molecular pathways which include angiogenesis, glycolysis, and various cellcycle control proteins. As we have shown previously, hypoxia activates STAT5 (signal transducer and activator of transcription 5) and increases its binding activity to the GAS element in mammary epithelial cells. In this study we attempted to elucidate the mechanism by which cyclin D1 is regulated by the STAT5 protein under hypoxic conditions. Our data demonstrate that hypoxia (2% O2) or desferrioxamine (DFO) induces tyrosine and serine phosphorylation of STAT5 in human breast cancer cells (MCF-7) and mammary epithelial cells (HC11). Imunoprecipitation and subsequent Western analysis showed that Jak2 leads to the tyrosine phosphorylation and activation of STAT5a or STAT5b under hypoxic conditions. Using a transfected COS-7 cell model system, we demonstrate that the activity of a cyclin D1 promoter-luciferase construct increased under hypoxic conditions or DFO treatment. The activity of the STAT5b/cyclin D1 promoter increased significantly by 12 h of hypoxia, whereas the activity of the STAT5a/cyclin D1 promoter was unaffected under hypoxic conditions. These increases in promoter activity are predominantly mediated by the Jak2/ STAT5b signaling pathway. We have shown by EMSA that hypoxia induces STAT5 to bind to the cyclin D1 promoter (GAS-1) in MCF-7 and HC11 cells. These data suggest that STAT5b may mediate the transcriptional activation of cyclin D1 after hypoxic stimulation.
Anaerobiosis/genetics ; Animals ; Breast Neoplasms/*genetics/metabolism ; COS Cells ; Cell Hypoxia/genetics ; Cercopithecus aethiops ; Cyclin D1/*genetics ; Deferoxamine/pharmacology ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Phosphorylation/drug effects ; Promoter Regions (Genetics) ; Protein-Tyrosine Kinase/*metabolism ; Proto-Oncogene Proteins/*metabolism ; Research Support, Non-U.S. Gov't ; Serine/metabolism ; Tumor Cells, Cultured ; Tyrosine/metabolism

The molecular mechanism underlying the initiation of somatic cell reprogramming into induced pluripotent stem cells (iPSCs) has not been well described. Thus, we generated single-cell-derived clones by using a combination of drug-inducible vectors encoding transcription factors (Oct4, Sox2, Klf4 and Myc) and a single-cell expansion strategy. This system achieved a high reprogramming efficiency after metabolic and epigenetic remodeling. Functional analyses of the cloned cells revealed that extracellular signal-regulated kinase (ERK) signaling was downregulated at an early stage of reprogramming and that its inhibition was a driving force for iPSC formation. Among the reprogramming factors, Myc predominantly induced ERK suppression. ERK inhibition upregulated the conversion of somatic cells into iPSCs through concomitant suppression of serum response factor (SRF). Conversely, SRF activation suppressed the reprogramming induced by ERK inhibition and negatively regulated embryonic pluripotency by inducing differentiation via upregulation of immediate early genes, such as c-Jun, c-Fos and EGR1. These data reveal that suppression of the ERK-SRF axis is an initial molecular event that facilitates iPSC formation and may be a useful surrogate marker for cellular reprogramming.

Purpose: K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods. Materials and Methods: Colorectal, breast, non–small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non–small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers). Results: In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively. Conclusion The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.