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Purpose The zinc finger protein, ZBTB48, is a telomere-associated protein. It was renamed as telomeric zinc finger-associated protein (TZAP) binding to elongated telomeres. However, its expression level was not measured in cancers. Patients and Methods We analyzed TZAP mRNA levels in 60 colorectal cancers (CRC) and its correlation with telomere length and TERT was studied. Results TZAP mRNA in CRC was higher statistically than that in paired non-cancerous tissues (p = 0.033). Higher TZAP was found in carcinoembryonic antigen (CEA)-positive CRCs (>5 ng/mL) (p = 0.012). Shorter telomere was found in CRCs with high TZAP expression than that with low TZAP expression (p = 0.010). According to quantitative correlation analysis, TZAP has a correlation with age (r = −0.349, p = 0.007), TERT (r = 0.279, p = 0.041) and telomere length (r = −0.305, p = 0.021). TZAP expression did not harbor prognostic value in CRC. Inhibition of TZAP expression by siRNA suppresses cell growth in HT29 cells; however, it resulted in increased cell viability in HCT116 cells. TZAP inhibition induces a decrease in mRNA levels of TERT in both HT29 and HCT116 cells. TCGA data analysis showed higher expression of TZAP showed poorer overall survival in colon cancer (p = 0.001); however, it did not have a significance in rectal cancer (p = 0.951). Conclusion We suggested that TZAP may be a possible biomarker for CRC.

The frequency of PIK3CA mutation and amplification was various and their clinical significances have not been clarified in Korean patients with invasive breast carcinoma (IBC). The study aimed to investigate the clinical and prognostic significances of PIK3CA mutation and amplification in IBC patients. DNA was isolated from paired normal and tumoral tissues in 128 IBC patients and the mutation and expression of PIK3CA gene were analyzed. PIK3CA mutation and expression was detected in 14.3% and 21.9% of IBC patients, respectively. And the level of PIK3CA expression was not different according to the presence of PIK3CA mutation (p = 0.775). PIK3CA mutation and expression were significantly associated with Luminal A type (p = 0.017 and p = 0.011, respectively). However, they did not have any clinical and prognostic values for IBC patients. This result suggested that alterations of PIK3CA pathway contribute to the pathogenesis of specific type of IBC.

Background and objectives: EZH2 is overexpressed in hepatocellular carcinoma (HCC) and is correlated with poor prognosis. However, its clinical significance and molecular mechanism have not been studied in HCC. In this study, clinical and prognostic values of EZH2 was studied using Total Cancer Genome Atlas (TCGA) data and then, these data were confirmed in Huh1 and HepG2 cell lines. Materials and Methods: We used the TCGA database from cBioPortal. In addition, we analyzed EZH2 mRNA levels in HCC cell lines and its correlation with STAT3 and EZH2. Results: According to TCGA, EZH2 had a prognostic value in various cancers, especially in HCC. Furthermore, EZH2 in HCC was correlated with N stage (p = 0.045) and alpha-fetoprotein (AFP) > 20 ng/mL (p < 0.01). However, a negative association between EZH2 and age (p = 0.027) was found. The overall survival result of HCC was significantly poorer in patients with high EZH2 expression. In addition, the recurrence rate was also significantly higher in patients with high expression of EZH2 than those with low expression (χ2 = 16.10, p < 0.001). EZH2 expression was negatively correlated with STAT3 expression among EZH2-associated genes (R = −0.163, p = 0.002). EZH2 expression level was down-regulated to 50% or less compared to the control group treated negative siRNA. MTT assays showed that EZH2-siRNA affected on the viability of HCC cell line significantly. Conclusions: In conclusion, the overexpression of EZH2 was an independent biomarker for poor outcomes of HCC. However, more in vivo studies are required to identify the downstream target genes in HCC to improve our understanding of the biological role of EZH2 in HCC.

Simple Summary Although the overexpression of CDCA8 is frequently observed in hepatocellular carcinoma (HCC) tissues, the functions of CDCA8 during HCC development remain to be clarified. The aim of our study was to investigate if targeting CDCA8 could affect liver tumor phenotypes in vitro and in vivo and to identify underlying molecular mechanisms to exert its therapeutic effect. We found that silencing of CDCA8 by siRNA inhibits the growth of parental cancer cell culture and mice tumors and suppresses stemness of CD133+ cancer stem cell population through the common responses of the upregulation of the tumor suppressive ATF3/GADD34 functional pathway and inactivation of the Akt/β–catenin signaling axis. These findings suggest CDCA8 as a novel therapeutic target for both primary HCC treatment and the prevention of metastasis or recurrence providing mode of action performed by a CDCA8 inhibitor. Abstract Big data analysis has revealed the upregulation of cell division cycle associated 8 (CDCA8) in human hepatocellular carcinoma (HCC) and its poorer survival outcome. However, the functions of CDCA8 during HCC development remain unknown. Here, we demonstrate in vitro that CDCA8 silencing inhibits HCC cell growth and long-term colony formation and migration through the accumulation of the G2/M phase cell population. Conversely, CDCA8 overexpression increases the ability to undergo long-term colony formation and migration. RNA sequencing and bioinformatic analysis revealed that CDCA8 knockdown led to the same directional regulation in 50 genes (25 down- and 25 upregulated). It was affirmed based on protein levels that CDCA8 silencing downregulates the levels of cyclin B1 and p-cdc2 and explains how it could induce G2/M arrest. The same condition increased the protein levels of tumor-suppressive ATF3 and GADD34 and inactivated AKT/β–catenin signaling, which plays an important role in cell growth and stemness, reflecting a reduction in sphere-forming capacity. Importantly, it was demonstrated that the extent of CDCA8 expression is much greater in CD133+ cancer stem cells than in CD133− cancer cells, and that CDCA8 knockdown decreases levels of CD133, p-Akt and β-catenin and increases levels of ATF3 and GADD34 in the CD133+ cancer stem cell (CSC) population. These molecular changes led to the inhibition of cell growth and sphere formation in the CD133+ cell population. Targeting CDCA8 also effectively suppressed tumor growth in a murine xenograft model, showing consistent molecular alterations in tumors injected with CDCA8siRNA. Taken together, these findings indicate that silencing CDCA8 suppresses HCC growth and stemness via restoring the ATF3 tumor suppressor and inactivating oncogenic AKT/β–catenin signaling, and that targeting CDCA8 may be the next molecular strategy for both primary HCC treatment and the prevention of metastasis or recurrence.

Telomere length is an important factor for the development of non-small cell lung cancer (NSCLC), and current articles focused on telomere associated genes. We studied the clinicopathological and prognostic implications of rs36115365 polymorphism of the TERT-CLPTM1L locus in NSCLC. The association between rs36115365 and telomere length was investigated in 176 NSCLCs.DNA was extracted from NSCLC tissues and polymorphism and telomere length were analyzed.The rs36115365 polymorphism showed the following frequencies according to the genotype: G/G in 81.8% of the patients, G/C in 14.2%, and C/C in 4.0%. Average telomere length in the tumor tissues were 3.06-fold longer than telomeres in paired non-tumor tissues (SD=1.87), and telomere length was not significantly different according to rs36115365 (These findings suggest that rs36115365 may contribute to the progression of NSCLC.

Background and Objectives: Telomere regulation have an association with colorectal cancer. Previous studies demonstrated its implication in colorectal carcinogenesis. This study aimed to identify the role of telomerase reverse transcriptase (TERT) in colorectal carcinogenesis and determine TERT expression and their associated genes in precancerous lesions. Materials and Methods: TERT expression in 93 colorectal precursor lesions was analyzed. This included 61 tubular adenomas (TAs) and 32 serrated polyps (SPs). Furthermore, KRAS and BRAF gene mutations and microsatellite instability were analyzed. Statistical tests were performed to analyze the relationship between variables. Results: TERT expression in TAs, when compared with those observed in paired adjacent nontumor tissues, was 0.92 &plusmn, 0.78. TERT expression levels were significantly lower in SPs (0.38 &plusmn, 0.14, p &lt, 0.001). KRAS and BRAF mutations were mutually exclusive in TAs and SPs (p &lt, 0.001). TERT expression tended to be associated with KRAS mutations (46.7% vs. 22.0%, p = 0.098) and low-grade tumors (35.0% vs. 16.0%, p = 0.096), but this difference was insignificant. Conclusions: TERT expression has a pivotal role in progression to TAs in colorectal tissue. Considering the association between TERT expression and KRAS mutation, therapeutic drugs targeting this pathway can be developed for cancer prevention.

The frequency of PIK3CA mutation and amplification was various and their clinical significances have not been clarified in Korean patients with invasive breast carcinoma (IBC). The study aimed to investigate the clinical and prognostic significances of PIK3CA mutation and amplification in IBC patients. DNA was isolated from paired normal and tumoral tissues in 128 IBC patients and the mutation and expression of PIK3CA gene were analyzed. PIK3CA mutation and expression was detected in 14.3% and 21.9% of IBC patients, respectively. And the level of PIK3CA expression was not different according to the presence of PIK3CA mutation (p = 0.775). PIK3CA mutation and expression were significantly associated with Luminal A type (p = 0.017 and p = 0.011, respectively). However, they did not have any clinical and prognostic values for IBC patients. This result suggested that alterations of PIK3CA pathway contribute to the pathogenesis of specific type of IBC.

Background and Objectives: RAD51 plays an essential role in DNA repair via homologous recombination. RAD51 facilitates strand transfer between interrupted sequences and their undamaged homologies. Therefore, we studied the RAD51 mRNA expression levels in colorectal cancer (CRC), and evaluated the clinicopathological and prognostic significance of RAD51. Materials and Methods: The RAD51 expression was examined in 48 CRCs and paired adjacent non-tumor tissues. We further evaluated the survival to determine the prognostic value of RAD51 in our CRC and The Cancer Genome Atlas (TCGA) data. Results: We confirmed that the RAD51 expression in tumor tissues, compared with that of paired non-tumor tissues, was upregulated 2.5-fold. Additionally, the RAD51 expression was significantly associated with the T stage (p = 0.027). According to a higher T stage, the RAD51 expression showed an increasing trend. However, the RAD51 expression did not show a prognostic value statistically. Conclusions: We confirmed that RAD51 was upregulated in tumors and was significantly associated with the T stage. Although there was no statistically significant prognostic value found in our samples and TGCA data, our study will provide new insight for RAD51 in CRC.

Mutations in the promoter region of telomerase reverse transcriptase (TERT) and alterations in telomere length (TL) have been the focus of research in various types of cancer. In the present study, the frequency and clinical characteristics of TERT promoter mutations and TL were studied in non-small cell lung cancers (NSCLC). TERT promoter mutations and TL were analyzed in 188 patients using DNA sequencing and the reverse transcription-quantitative polymerase chain reaction, respectively. The TERT promoter mutation rate was observed to be 2.2% (4/188 NSCLC cases), and it was significantly associated with regional lymph node invasion (P

Adenovirus (Ad)-mediated cancer gene therapy has been proposed as a promising alternative to conventional therapy for cancer. However, success of systemically administered naked Ad has been limited due to the immunogenicity of Ad and the induction of hepatotoxicity caused by Ad's native tropism. In this study, we synthesized an epidermal growth factor receptor (EGFR)-specific therapeutic antibody (ErbB)-conjugated and PEGylated poly(amidoamine) (PAMAM) dendrimer (PPE) for complexation with Ad. Transduction of Ad was inhibited by complexation with PEGylated PAMAM (PP) dendrimer due to steric hindrance. However, PPE-complexed Ad selectively internalized into EGFR-positive cells with greater efficacy than either naked Ad or Ad complexed with PP. Systemically administered PPE-complexed oncolytic Ad elicited significantly reduced immunogenicity, nonspecific liver sequestration, and hepatotoxicity than naked Ad. Furthermore, PPE-complexed oncolytic Ad demonstrated prolonged blood retention time, enhanced intratumoral accumulation of Ad, and potent therapeutic efficacy in EGFR-positive orthotopic lung tumors in comparison with naked Ad. We conclude that ErbB-conjugated and PEGylated PAMAM dendrimer can efficiently mask Ad's capsid and retarget oncolytic Ad to be efficiently internalized into EGFR-positive tumor while attenuating toxicity induced by systemic administration of naked oncolytic Ad.

Oncolytic adenovirus (Ad) holds great promise as a potential gene therapy for cancer. However, intravenously administered Ad may encounter difficulties due to unfavorable host responses, non-specific interactions, and the heterogeneity of the tumor cell population. As an approach to combine the advantages of oncolytic Ad and synthetic polymers and to address the associated difficulties, Ad was physically complexed with a pH-sensitive block copolymer, methoxy poly(ethylene glycol)- b -poly( l -histidine) (mPEG- b -pHis). The in vitro transduction efficiency at an acidic extracellular pH was remarkably enhanced in cancer cells when treated with the Ad expressing green fluorescent protein (GFP) coated with mPEG- b -pHis (c-dE1/GFP) as compared to that of naked Ad (n-dE1/GFP). Time-lapse total internal reflection fluorescence microscopic imaging revealed a significantly enhanced cellular uptake rate of c-dE1/GFP at acidic tumor pH when compared with that at neutral pH or naked cognate Ad (n-dE1/GFP). In addition, c-dE1/GFP remained relatively stable in human serum-containing media, and considerably reduced both the innate and adaptive immune response against Ad. Moreover, the therapeutic efficacy and survival benefit of mPEG- b -pHis-complexed oncolytic Ad (c-H5mT/Luc) by systemic treatment was significantly enhanced compared to that with naked oncolytic Ad (n-H5mT/Luc) in both coxsackie and adenovirus receptor-positive and -negative tumors. Whole-body bioluminescence imaging showed 7.3-fold higher luciferase expression at the tumor site and 23.0-fold less luciferase expression in liver tissue for c-H5mT/Luc relative to that for naked oncolytic Ad (n-H5mT/Luc). Considering the heterogeneity of tumor tissue, these results are important for guiding the development of more potent and specific treatment of devastating metastatic cancers using this viral system. Statement of significance Although adenoviral systems have shown considerable promise and undergone extensive evaluation attempts to specifically target Ad vectors to cancer cells have met limited success. This shortcoming is due to the strong immune response stimulated by Ad and the hepatotoxicity of the viral particles. To overcome restricted vector issues, we generated Ad/mPEG- b -pHis for tumor microenvironment-targeting hybrid vector systems, an oncolytic Ad coated with a pH-responsive polymer, mPEG- b -pHis. The Ad/mPEG- b -pHis exhibited pH-dependent transduction efficiency and cancer-cell killing effects. Moreover, systemic administration of oncolytic Ad/mPEG- b -pHis led to marked suppression of tumor growth and tumor-specific viral replication. Ad successfully avoided the innate and adaptive immune responses and liver accumulation with the help of mPEG- b -pHis on its surface.

Adenovirus (Ad) is a widely used vector for cancer gene therapy but its therapeutic efficacy is limited by low coxsackievirus and adenovirus receptor (CAR) expression in tumors and non-specifically targeted infection. Ad infectivity and specificity can be markedly improved by creating Ad-magnetic nanoparticles cluster complexes and directing their migration with an external magnetic field (MGF). We electrostatically complexed GFP-expressing, replication-incompetent Ad (dAd) with PEGylated and cross-linked iron oxide nanoparticles (PCION), generating dAd-PCION complexes. The dAd-PCION showed increased transduction efficiency, independent of CAR expression, in the absence or presence of an MGF. Cancer cell killing and intracellular oncolytic Ad (HmT)-PCION replication significantly increased with MGF exposure. Site-directed, magnetically-targeted delivery of the HmT-PCION elicited significantly greater therapeutic efficacy versus treatment with naked HmT or HmT-PCION without MGF in CAR-negative MCF7 tumors. Immunohistochemical tumor analysis showed increased oncolytic Ad replication in tumors following infection by HmT-PCION using an MGF. Whole-body bioluminescence imaging of tumor-bearing mice showed a 450-fold increased tumor-to-liver ratio for HmT-PCION with, versus without, MGF. These results demonstrate the feasibility and potential of external MGF-responsive PCION-coated oncolytic Ads as smart hybrid vectors for cancer gene therapy.

A Case Report of Sequela of Operation of Hallux ValgusSoo-Jung Jung 1 , Kyung-Mi Park 1 , Yu-Rim Song 1 Seong-Hee Cho 1 , Seung-Jeong Yang 1 , Young-Hun Ma 21 Dept. of Korean Gynecology and Obstetrics, College of Korean Medicine, Dong-Shin University 2 Dept. of Korean Internal Medicine, College of Korean Medicine, Dong-Shin UniversityObjectives: This study aims to report the effect of Korean medicine treatme nts on a sequela of operation of hallux valgus. Methods: The patient was treated with Dangkisoosan-gami, Acupuncture treatment including Herbal-Acupuncture and physical therapy. We evaluated treatment effects by circumference of foot and ankle, Edema index score by Body Composition Analyzer, Ankle-Brachial Index (ABI) and Visual Analogue Scale (VAS). Results: After 25 days of treatment, the symptoms such as lower extremity edema, foot pain and ankle pain were improved. Conclusions: In this case, Korean medicine treatments for a sequela of oper ation of hallux valgus was effective. But further studies are require d to confirm the effect of these methods. Key Words: Hallux Valgus, Lower extremity edema, Visual analogue scale (VAS), Dangkisoosan-gami

Telomere shortening is associated with colorectal carcinogenesis and recent studies have focused on its characteristics in both normal mucosa and tumor tissues. To clarify the role of telomeres in colorectal carcinogenesis, we analyzed telomere shortening in normal and tumor regions of 93 colorectal precursor lesions. Telomere length was examined in 61 tubular adenomas (TAs) and 32 serrated polyps (SPs), and PIK3CA expression, KRAS mutation, BRAF mutation, and MSI were also analyzed. Telomere length was similar in normal and tumor tissues of TAs and SPs. In normal tissues of TAs, telomere shortening was associated with PIK3CA amplification (81.3% vs. 18.8%, p < 0.001), whereas it was associated with BRAF mutation in normal tissues of SPs (66.7% vs. 23.1%, p = 0.060). According to the analysis on tumor tissues, KRAS and BRAF mutations were mutually exclusive in TAs and SPs (p < 0.001), and telomere shortening was associated with mitochondrial microsatellite instability (63.6% vs. 36.4%, p = 0.030). These data suggested a pivotal role of telomere shortening in normal colorectal tissue for proceeding to TAs or SPs along with PIK3CA amplification and BRAF mutation, respectively. Moreover, telomeres in TAs may collaborate with mitochondrial instability for disease progression.

A positive correlation between telomere length and mitochondrial DNA (mtDNA) copy number has previously been observed in healthy individuals, and in patients with psychiatric disorders. In the present study, telomere length and mtDNA copy number were evaluated in gastric cancer (GC) tissue samples. DNA was extracted from 109 GC samples (including 82 intestinal, and 27 diffuse cases), and the telomere length and mtDNA copy number were analyzed using a quantitative-polymerase chain reaction assay. The relative telomere length and mtDNA copy number in tumor tissue, as compared with in normal tissue, (mean ± standard deviation) in all GC samples were 11.48±1.14 and 14.86±1.35, respectively. Telomere length and mtDNA copy number were not identified as exhibiting clinical or prognostic value for GC. However, positive correlations between telomere length and mitochondrial DNA copy number were identified in GC (r=0.408, P

Promoter mutations in telomerase reverse transcriptase (TERT) and telomere length have been studied in various tumors. In the present study, the frequency and clinical characteristics of TERT promoter mutation and telomere length were studied in hepatocellular carcinoma (HCC). TERT promoter mutation and telomere length were analyzed in 162 tumor samples of the patients with HCC by sequencing and real-time PCR, respectively. The TERT promoter mutation rate was 28.8% (46/160) in HCC and was associated with males (P = 0.027). The telomere length was not significantly different in the presence of a TERT promoter mutation but was shorter in high-grade tumor stages (P = 0.048). Survival analyses showed that poor overall survival was associated with longer telomere length (P = 0.013). However, the TERT promoter mutation did not have a prognostic value for HCC. Multivariate survival analyses demonstrated that the telomere length was an independent prognostic marker for poor overall survival (hazard ratio = 1.75, 95% confidence interval: 1.046–2.913, P = 0.033). These data demonstrated that TERT promoter mutation is a frequent event in HCC; however, telomere length, but not the presence of a TERT promoter mutation, might have potential value as a prognostic indicator of HCC.

Positive association between telomere length and mitochondrial DNA (mtDNA) copy number were introduced in healthy and patients with psychiatric disorder. Based on frequent genetic changes of telomere and mitochondria in colorectal carcinomas (CRC), we studied their clinical characteristics and their association in colorectal carcinogenesis. DNA was extracted from 109 CRCs, 64 colorectal tubular adenomas (TAs), and 28 serrated polyps (SPs), and then, telomere length and mtDNA copy number were analyzed in these legions by using a real-time PCR assay. Telomere length and mtDNA copy number (mean ± S.D) in CRCs was 1.87 ± 1.52 and 1.61 ± 1.37, respectively. In TAs and SPs, relative mtDNA copy number was 0.92 ± 0.71 and 1.84 ± 1.06, respectively, shoing statistical difference (p = 0.017). However, telomere length was similar in these precancerous legions. Telomere length and mtDNA copy number did not show clinical and prognostic values in CRCs, however, positive correlation between telomere length and mitochondrial DNA copy number were found in CRC (r = 0.408, p

The objective of this study was to study the effect of magnetized water on porcine cumulus cell-oocyte complexes (COCs). Oocytes obtained from female pig were cultured in a medium magnetized at 0, 2000, 4000, and 6000 Gauss (G) for 5 minutes using the neodymium magnet. Subsequently, intracellular hydrogen peroxide (H₂O₂) concentration, glutathione (GSH) activity, oocyte membrane integrity, anti-apoptosis factor Bcl-xL expression, and nuclear maturation were analyzed. The intracellular H₂O₂ levels in COCs cultured for 44 hours were not significantly different among the variously magnetized samples. However, GSH activity were significantly higher in the magnetized samples compared to the 0 G sample. The Bcl-xL mRNA expression in COCs cultured for 44 hours was higher in the 4000 G sample than other treatment groups. Membrane damage in COCs cultured for 22 and 44 hours was significantly lower in 4000 G group than control group. On the other hand, nuclear stages as maturation indicator significantly increased in 2000, 4000, and 6000 G groups compared to 0 G group. These results indicate that incubation of porcine oocytes and cumulus cells in magnetized medium improves intracellular GSH levels, membrane integrity and nuclear maturation, and inhibits apoptosis in vitro.

Despite the favorable therapeutic outcomes reported in differentiated thyroid cancer (DTC), a significant proportion of DTC patients present with refractory behavior to conventional therapy. The sirtuin (Sirt) family has recently been implicated in the maintenance of cellular homeostasis under genotoxic stress. Here, we investigated the induction of Sirt1 expression by etoposide-induced genotoxic stress to gain insights into thyroid carcinogenesis and identify novel therapeutic targets. Immunohistochemical staining analyses of Sirt1 and Sirt3 were performed using human thyroid cancer tissues and matched normal tissues, and bioinformatic analyses were done using public repositories, including the Human Protein Atlas, BioGPS, NCBI Gene Expression Omnibus (GEO) profiles, and GeneNetwork. TPC1, FTC133 and FRO cells were used for molecular biological experiments including apoptosis assays, MTT, immunofluorescence staining and qRT-PCR assays. The IHC data and public repositories data consistently showed variable Sirt1 and Sirt3 expression patterns in normal thyroid follicular cells and papillary thyroid cancer cells. The induction of Sirt1 and Sirt3 was cell type-specific and the expression levels of these genes correlated with apoptotic cell death and cell viability after etoposide-induced genotoxic stress. Sirt1‑Foxp3 signaling-mediated regulation of Bax and p21 mRNA expression was a signature molecular event in TPC1 cells, which showed remarkable resistance to etoposide-induced genotoxic stress. The induction of Sirt1 and Sirt3 may be a determinant of thyroid cancer cell survival under genotoxic stress conditions. Further examination of the Sirt1-Foxp3 signal may improve our understanding of thyroid carcinogenesis and help identify new druggable targets.

Review of Experimental Studies on Antithrombotic in Oriental Medicine-Within Articles in The Journal of Oriental Obstetrics & Gynecology Since 2001’- Soo-Jung Jung 1 , Young-Hun Ma 2 , Seung-Bum Choi 2 , Kyung-Mi Park 11 Dept. of GY&OB, Dong-Shin Mokdong Oriental Medical Hospital 2 Dept. of Internal Medicine, Dong-Shin Mokdong Oriental Medical Hospital Purpose: The purpose of this study is to compare with the result of exp erimental study about antithrombotic effect by reviewing recent oriental medicine journals that have been published since 2001‘ in Korea. Methods: Articles on antithrombotic effect that have been published from 2001’ to 2013’ in oriental medicine journals registered Nationa l Research Foundation of Korea were searched. After that, 12 articles using same ‘thrombosis condition model’ were selected and reviewed. Results: The results were as follows. 1. If there is no limit drug concentrations, platelet aggregati on induced by adenosine diphosphate (ADP) in hyulbuchukeo-tanggamibang (HBCT) was the largest aggregation inhibitory effect and platelet aggregation induced by epinephrine in Saegeum-san (SGS), Jogan-tanggagambang (JGTG), hyulbuchukeo-tanggamibang (HBCT) had a large inhibitory effect on aggregation. 2. At the lowest concentration, Mokdan-san (MDS) of the inhibition of platelet aggregation induced by ADP and Hyunhosaik-san (HHS) of the inhibition of platelet aggregation induced by epinephrine were effective. 3. Pulmonary embolism induced by collagen and epinephrine in Neungasojeok-tang (NSJT) has the highest antithrombotic effect. 4. Pathological conditions of extravasated blood by dextran, Jogan-tanggagambang (JGTG) has the highest inhibitory effect on decrease in platele t numbers. Compared to the rest of the experimental drug, Saegeum-san (SGS), Heanggyonghonghwa-tang (HGTHHT), Wusl-san (WSS), Mokdan-san (MDS) showed significant inhibitory effect on the prothrombin time (PT) increases. Honghwadanggui-san (HDS), Saegeum-san (SGS) showed significant inhibitory effect on increase in activ ated partial thromboplastin time (APTT) and Jogan-tanggagambang (JGTG), Heanggyonghonghwa-tang (HGTHHT) showed significant inhi bitory effect on decrease in fi brinogen. Conclusions: This result will provide useful information for the prescripti ons of antithrombotic medicine in the field of Oriental medicine. W e will have to carry out further studies that will compare each herb used in the diseases caused by extravasated blood. Key Words: Antithrombotic, Oriental Medicine, Extravasated Blood

Disasters like mountain landslides and collapse in cutting areas claim many a life and cause economic losses, involving much effort and expenses for their recovery. This study has surveyed and analyzed incident of disasters that had occurred on the sloping sides in Korea for the past 13 years in an effort to relieve damage caused by disasters on the sloping sides. The analysis confirms that while the major cause of disasters on the sloping side was storms in the past, frequency of disasters on sloping sides caused by local downpour is steadily on the rise. In addition, while disasters were concentrated in Gangwon Province, a mountainous region of the country, frequency of disasters occurring on the sloping sides is steadily increasing recently on the sloping sides in downtown areas in Seoul, Gyeonggi-do and so forth, attributing a large percentage of disasters to sloping sides. Data surveyed and analyzed in this study are thought to be applicable as basic data for the establishment of effective measures for the prevention of disasters occurring on the sloping sides in the days to come.

Products of the eruption of Mt. Baekdusan are identified as volcanic materials at the estuaries of the Songhuagang river to north, the Dumangang river to east and the Amnokgang river to west. More speficially, pyroclastic flows, lahars and volcanic floods can affect an area of 400km in radius, centering around Lake Cheonji caldera. However, unlike the millenium eruption, the flow situation has been changed. Because multi-purpose dams and reserviors with a combined pondage of mora than 2 billion tons of water have been built in the rivers of which sources are originated from Lake Cheonji caldera. In addition, the flow of fluids expected to take place when the volcano has erupted is thought to be affected by artificial constructions in both direct and indirect ways. This study calculates the direction of fluids flow by using numerical analyses of pyroclastic flows, lahars and volcanic floods that can occur when the volcano of Mt. Baekdusan has erupted. We also estimate the scope of damages by pyroclastic flows, lahars, volcanic flooding caused by the pondage of the dams and water storages in and around Mt. Baekdusan. Pyroclastic flows transported over the steep slopes at the early times of eruptions move over the mountain slopes, affecting airplanes, and lahars due to leaks of Lake Cheonji could reach as far as major rivers and streams near Mt. Baekdusan. Unlike historical accounts, volcanic flood is expected to be limited in its scope of influence to reservoirs bigger than Lake Cheonji in pondage.

Gantzer’s muscle (GM) is an additional muscle in the forearm, which develops as an accessory head of the flexor pollicis longus or the flexor digitorum profundus. The study aimed to determine the topography of the GM and to define the topographical relationship between the GM and the neurovascular structures surrounding it. After confirming the presence of GM, its topography and the neurovascular structures were analyzed to determine the correlation between them in 73 upper limbs. The incidence of GM was 47.95% (35/73) and the average insertion point of GM was identified at 49.33 ± 7.47‰ (119.82 ± 20.80 mm) on the reference line between the medial epicondyle and the pisiform bone. And the branching points of the median nerve and the ulnar artery were located 19.91 ± 11.23‰ (52.21 ± 24.67 mm), 17.45 ± 8.39‰ (42.53 ± 20.54 mm) on the reference line, respectively. The presence of GM had no significant correlation with the position of the nerve branches. On the other hand, the branching point of the ulnar artery was distally located in the cases with the presence of the GM (17.35 ± 8.65 vs 19.42 ± 10.87, p = 0.031). There was a significant positive correlation between the point of arterial bifurcation and the length of the GM (r = 0.407, p = 0.015). This study suggested that the GM has a topographical relation with the arterial structures, perhaps for embryological reasons.

The purpose of this study is to estimate and compare suction stress between sand and silt sampled from the coast of Korea. The water content and matric suction of sand (Joomunjin) and silt (Saemangeum) were first examined using an automated soil–water characteristic curve (SWCC) apparatus based on the axis translation technique. SWCCs were then estimated from the test results using the van Genuchten (1980) model. At equal matric suction, the corresponding water content of silt was higher than that of sand. Moreover, the saturated water content and air-entry value (AEV) of silt were larger than those of sand. Using the fitting SWCC parameters, suction stress characteristic curves (SSCCs) were estimated according to the method proposed by Lu and Likos (2006). The SSCC behavior for sand and silt was different and significantly depended on the material properties, particularly pore size and pore size distribution. For sand, the suction stress exhibited rapid variation with changes in matric suction, but for silt, the suction stress approached a constant value as the matric suction increased. In addition, when the matric suction was smaller than the AEV of soil, the suction stress was equal to the magnitude of the matric suction. In contrast, when the matric suction exceeded the AEV of soil, suction stress had a nonlinear shape with respect to the matric suction.

Pancreatic cancer is highly aggressive, malignant, and notoriously difficult to cure using conventional cancer therapies. These conventional therapies have significant limitations due to excessive extracellular matrix (ECM) of pancreatic cancer and poor cancer specificity. The excess ECM prevents infiltration of drugs into the inner layer of the solid tumor. Therefore, novel treatment modalities that can specifically target the tumor and degrade the ECM are required for effective therapy. In the present study, we used ECM-degrading and Wnt signal-disrupting oncolytic adenovirus (oAd/DCN/LRP) to achieve a desirable therapeutic outcome against pancreatic cancer. In addition, to overcome the limitations in systemic delivery of oncolytic Ad (oAd) and to specifically target pancreatic cancer, neurotensin peptide (NT)-conjugated polyethylene glycol (PEG) was chemically crosslinked to the surface of Ad, generating a systemically injectable hybrid system, oAd/DCN/LRP-PEG-NT. We tested the targeting and therapeutic efficacy of oAd/DCN/LRP-PEG-NT toward neurotensin receptor 1 (NTR)-overexpressing pancreatic cancer cells, both in vitro and in vivo. The oAd/DCN/LRP-PEG-NT elicited increased NTR-selective cancer cell killing and transduction efficiency when compared with a cognate control lacking NT (oAd/DCN/LRP-PEG). Furthermore, systemic administration of oAd/DCN/LRP-PEG-NT significantly decreased induction of innate and adaptive immune responses against Ad, and blood retention time was markedly prolonged by PEGylation. Moreover, NTR-targeting oAd elicited greater in vivo tumor growth suppression when compared with naked oAd and 9.5 × 10(6)-fold increased tumor-to-liver ratio. This significantly enhanced antitumor effect of oAd/DCN/LRP-PEG-NT was mediated by active viral replication and viral spreading, which was facilitated by ECM degradation and inhibition of Wnt signaling-related factors (Wnt, β-catenin, and/or vimentin) in the tumor tissues. Taken together, these results demonstrate that oAd/DCN/LRP-PEG-NT has strong therapeutic potential for systemic treatment of NTR-overexpressing pancreatic cancer due to its NTR-targeting ability, enhanced therapeutic efficacy, and safety.

Although oncolytic adenoviruses (Ads) are an attractive option for cancer gene therapy, the intravenous administration of naked Ad still encounters unfavorable host responses, non-specific interactions, and heterogeneity in targeted cancer cells. To overcome these obstacles and achieve specific targeting of the tumor microenvironment, Ad was coated with the pH-sensitive block copolymer, methoxy poly(ethylene glycol)-b-poly(L-histidine-co-L-phenylalanine) (PEGbPHF). The physicochemical properties of the generated nanocomplex, Ad/PEGbPHF, were assessed. At pH 6.4, GFP-expressing Ad/PEGbPHF induced significantly higher GFP expression than naked Ad in both coxsackie and adenovirus receptor (CAR)-positive and -negative cells. To assess the therapeutic efficacy of the Ad/PEGbPHF complex platform, VEGF promoter-targeting transcriptional repressor zinc-finger protein-expressing oncolytic Ad (KOX) was used to form complexes. At pH 6.4, KOX/PEGbPHF significantly suppressed VEGF gene expression, cancer cell migration, vessel sprouting, and cancer cell killing effect compared to naked KOX or KOX/PEGbPHF at pH 7.4, demonstrating that KOX/PEGbPHF can overcome the lack of CAR that is frequently observed in tumor tissues. The antitumor activity of KOX/PEGbPHF systemically administered to a tumor xenograft model was significantly higher than that of naked KOX. Furthermore, KOX/PEGbPHF showed lower hepatic toxicity and did not induce an innate immune response against Ad. Altogether, these results demonstrate that pH sensitive polymer coated Ad complex significantly increase net positive charge upon exposure to hypoxic tumor microenvironment, allowing it to passive target to tumor site. It may offer superior potential for systemic therapy, due to its improved tumor selectivity, increased therapeutic efficacy, and lower toxicity compared to naked KOX.

Although oncolytic adenoviruses (Ads) are an attractive option for cancer gene therapy, the intravenous administration of naked Ad still encounters unfavorable host responses, non-specific interactions, and heterogeneity in targeted cancer cells. To overcome these obstacles and achieve specific targeting of the tumor microenvironment, Ad was coated with the pH-sensitive block copolymer, methoxy poly(ethylene glycol)-b-poly(l-histidine-co-l-phenylalanine) (PEGbPHF). The physicochemical properties of the generated nanocomplex, Ad/PEGbPHF, were assessed. At pH 6.4, GFP-expressing Ad/PEGbPHF induced significantly higher GFP expression than naked Ad in both coxsackie and adenovirus receptor (CAR)-positive and -negative cells. To assess the therapeutic efficacy of the Ad/PEGbPHF complex platform, an oncolytic Ad expressing VEGF promoter-targeting transcriptional repressor (KOX) was used to form complexes. At pH 6.4, KOX/PEGbPHF significantly suppressed VEGF gene expression, cancer cell migration, vessel sprouting, and cancer cell killing effect compared to naked KOX or KOX/PEGbPHF at pH 7.4, demonstrating that KOX/PEGbPHF can overcome the lack of CAR that is frequently observed in tumor tissues. The antitumor activity of KOX/PEGbPHF systemically administered to a tumor xenograft model was significantly higher than that of naked KOX. Furthermore, KOX/PEGbPHF showed lower hepatic toxicity and did not induce an innate immune response against Ad. Altogether, these results demonstrate that pH-sensitive polymer-coated Ad complex significantly increases net positive charge upon exposure to hypoxic tumor microenvironment, allowing passive targeting to the tumor tissue. It may offer superior potential for systemic therapy, due to its improved tumor selectivity, increased therapeutic efficacy, and lower toxicity compared to naked KOX.

The sewage treatment efficiency of hybrid constructed wetlands (CWs) was evaluated under different ventilation methods. The removal efficiencies of biochemical oxygen demand (BOD), total nitrogen (TN), and total phosphorus (TP) in the vertical flow( VF-) horizontal flow (HF) CWs using an electric fan air blower by the renewable energy of solar and wind power were higher than those by natural ventilation, excluding only suspended solids (SS). The TN treatment efficiency in the CW using the air blower especially increased rapidly by 16.6% in comparison with the CW employing natural ventilation, since the VF bed provided suitable conditions (aerobic) for nitrification to occur. The average removal efficiencies of BOD, SS, TN, and TP in the effluent were 98.8, 97.4, 58.0, and 48.3% in theCWusing an electric fan air blower, respectively. The treatment performance of the CWs under different ventilation methods was assessed, showing TN in the CW using an electric fan air blower to be reduced by 57.5 similar to 58.6% for inlet TN loading, whereas reduction by 19.0 similar to 53.3% was observed in the CW with natural ventilation. Therefore, to increase the removal of nutrients in CWs, an improved ventilation system, providing ventilation via an electric fan air blower with the renewable energy, is recommended.

Culture conditions for CO 2 fixation by a chemoautotrophic microorganism, strain YN-1, were optimized by statistical analysis using factorial design. Statistical analysis was performed by SAS software and then predicted the levels of four factors, H 2 ( X 1 ), O 2 ( X 2 ), CO 2 ( X 3 ) concentration and pH ( X 4 ) which were required to obtain the optimum culture conditions. For the fractional factorial design 3 4−1 , total 27 experimental runs by combination of each factor were carried out in a 5 L-jar fermentor, and the three-dimensional response surfaces were plotted to find out the optimum level of each factor for maximum CO 2 fixation. Dry cell weight in optimized culture condition was predicted as 11.4 g/L in 48 h under the condition of 37.5 × 10 −3 mol/min H 2 , 9.38 × 10 −3 mol/min O 2 , 4.91 × 10 −3 mol/min CO 2 , and pH 6.7. As compared with CO 2 fixation rate before optimizing culture conditions, the improvement of CO 2 fixation rate under optimized culture conditions was experimentally confirmed.

As a biochemical approach to decrease the amount of biological sludge, the sludge solubilization by repeatedly changing the microbial environments from aerobic to anaerobic was studied. The sludge reduction amount in batch operation was related to the degradation of intracellular materials released through sludge solubilization. The shorter the operation cycle time was, the more effective the sludge amount reduction was. On the other hand, under the cycle time of 3–24 h, longer anaerobic period compared to aerobic period was effective in removing nitrogenous compounds. This was partly ascribed to the excretion of enzyme such as protease and lipase.

As a biochemical approach to reduce the amount of excess sludge from wastewater treatment process, sludge solubilization induced by changing the sludge environment by alternating aerobic and anaerobic operations has been proposed. The sludge solubilization leads to the release of carbonaceous and nitrogenous compounds, which is to be reduced time by time due to the energy consumption by the repeated microbial assimilation. Batch experiments were carried out under various operating conditions alternating aerobic and anaerobic period to characterize the behavior of nitrogenous compounds in the sludge solubilization. Nitrogenous compounds among intracellular matters released by the lysis were successively transformed biochemically, finally having been removed completely under an optimal condition. However, under the conditions out of the optimum, the released nitrogen such as ammonia and nitrate is accumulated in the system. Ammonia accumulation was found to be due to the higher protease activity associated with the protein hydrolysis originated from cell lysis.

Pancreatic cancer is highly aggressive, malignant, and notoriously difficult to cure using conventional cancer therapies. These conventional therapies have significant limitations due to excessive extracellular matrix (ECM) of pancreatic cancer and poor cancer specificity. The excess ECM prevents infiltration of drugs into the inner layer of the solid tumor. Therefore, novel treatment modalities that can specifically target the tumor and degrade the ECM are required for effective therapy. In the present study, we used ECM-degrading and Wnt signal-disrupting oncolytic adenovirus (oAd/DCN/LRP) to achieve a desirable therapeutic outcome against pancreatic cancer. In addition, to overcome the limitations in systemic delivery of oncolytic Ad (oAd) and to specifically target pancreatic cancer, neurotensin peptide (NT)-conjugated polyethylene glycol (PEG) was chemically crosslinked to the surface of Ad, generating a systemically injectable hybrid system, oAd/DCN/LRP-PEG-NT. We tested the targeting and therapeutic efficacy of oAd/DCN/LRP-PEG-NT toward neurotensin receptor 1 (NTR)-overexpressing pancreatic cancer cells, both in vitro and in vivo. The oAd/DCN/LRP-PEG-NT elicited increased NTR-selective cancer cell killing and increased transduction efficiency when compared with a cognate control lacking NT (oAd/DCN/LRP-PEG). Furthermore, systemic administration of oAd/DCN/LRP-PEG-NT significantly decreased induction of innate and adaptive immune responses against Ad, and blood retention time was markedly prolonged by PEGylation. Moreover, NTR-targeting oAd elicited greater in vivo tumor growth suppression when compared with naked oAd, and 9.5×106-fold increased tumor-to-liver ratio. This significantly enhanced antitumor effect of oAd/DCN/LRP-PEG-NT was mediated by active viral replication and viral spreading, which was facilitated by ECM degradation and inhibition of Wnt signaling-related factors (Wnt, β-catenin, and/or vimentin) in tumor tissues. Taken together, these results demonstrate that oAd/DCN/LRP-PEG-NT has strong therapeutic potential for systemic treatment of NTR-overexpressing pancreatic cancer, due to its NTR-targeting ability, enhanced therapeutic efficacy, and safety.

This study intends to find out what manmade elements in typical moderately disturbed coastal landscape are most adversely affecting its aesthetic quality. Simulation photos including a combination of five most common manmade structures (houses, roads, power lines, embankments, and aquaculture facilities) found on coastal areas were made, and thirty eight subjects in the field of landscape architecture and forty eight average subjects were asked to evaluate their visual preferences of the 32 simulation photos using seven levels of Likert scale. Overall, average and professional subjects did not show significant differences in their evaluations. Visual preferences were greatly influenced by the presence of the manmade structures. A natural coastal landscape without any manmade structures was most preferable, and a disturbed coastal landscape by all five manmade structures was least preferable. Power lines had the most serious negative impact on the landscape, and followed by the embankment. In coastal landscape restoration works and management, priority needs to be given to these manmade structures which have bigger negative landscape impacts.

Adenovirus (Ad) vectors show promise as cancer gene therapy delivery vehicles, but immunogenic safety concerns and coxsackie and adenovirus receptor (CAR)-dependency have limited their use. Alternately, biocompatible and bioreducible nonviral vectors, including arginine-grafted cationic polymers, have been shown to deliver nucleic acids through a cell penetration peptide (CPP) and protein transduction domain (PTD) effect. We utilized the advantages of both viral and nonviral vectors to develop a hybrid gene delivery vehicle by coating Ad with mPEG-PEI-g-Arg-S-S-Arg-g-PEI-mPEG (Ad/PPSA). Characterization of Ad/PPSA particle size and zeta potential showed an overall size and cationic charge increase in a polymer concentration-dependent manner. Ad/PPSA also showed a marked transduction efficiency increase in both CAR-negative and -positive cells compared to naked Ad. Competition assays demonstrated that Ad/PPSA produced higher transgene expression levels than naked Ad and achieved CAR-independent transduction. Oncolytic Ad (DWP418)/PPSA was able to overcome the nonspecificity of polymer-only therapies by demonstrating cancer-specific killing effects. Furthermore, the DWP418/PPSA nanocomplex elicited a 2.24-fold greater antitumor efficacy than naked Ad in vivo. This was supported by immunohistochemical confirmation of Ad E1As accumulation in MCF7 xenografted tumors. Lastly, intravenous injection of DWP418/PPSA elicited less innate immune response compared to naked Ad, evaluated by interleukin-6 cytokine release into the serum. The increased antitumor effect and improved vector targeting to both CAR-negative and -positive cells make DWP418/PPSA a promising tool for cancer gene therapy.

Oncolytic adenoviruses (Ads) have shown great promise in cancer gene therapy but their efficacy has been compromised by potent immunological, biochemical, and specific tumor-targeting limitations. To take full advantage of the innate cancer-specific killing potency of oncolytic Ads but also exploit the subtleties of the tumor microenvironment, we have generated a pH-sensitive and bio-reducible polymer (PPCBA)-coated oncolytic Ad. Ad-PPCBA complexes showed higher cellular uptake at pH 6.0 than pH 7.4 in both high and low coxsackie and adenovirus receptor-(CAR)-expressing cells, thereby demonstrating Ad-PPCBA's ability to target the low pH hypoxic tumor microenvironment and overcome CAR dependence for target cell uptake. Endocytic mechanism studies indicated that Ad-PPCBA internalization is mediated by macropinocytosis instead of the CAR-dependent endocytic pathway that internalizes naked Ad. VEGF-specific shRNA-expressing oncolytic Ad complexed with PPCBA (RdB/shVEGF-PPCBA) elicited much more potent suppression of U87 human brain cancer cell VEGF gene expression in vitro, and human breast cancer MCF7 cell/Matrigel plug vascularization in a mouse model, when cancer cells had been previously infected at pH 6.0 versus pH 7.4. Moreover, intratumorally and intravenously injected RdB/shVEGF-PPCBA nanocomplexes elicited significantly higher therapeutic efficacy than naked virus in U87-tumor mouse xenograft models, reducing IL-6, ALT, and AST serum levels. These data demonstrated PPCBA's biocompatibility and capability to shield the Ad surface to prevent innate immune response against Ad after both intratumoral and systemic administration. Taken together, these results demonstrate that smart, tumor-specific, oncolytic Ad-PPCBA complexes can be exploited to treat both primary and metastatic tumors.

Adenovirus (Ad) is a widely used vector for cancer gene therapy but its therapeutic efficacy is limited on the lacked expression of the coxsackievirus and adenovirus receptor (CAR) in tumor tissues as well as specificity of targeted infection. Ad infectivity and specificity can be markedly improved by creating Ad-magnetic nanoparticles cluster complexes and subjecting them to an external magnetic field. First, we characterized the PEGylated and cross-linked iron oxide nanoparticles (PCION) through NMR, transmission electron microscope, and cytotoxicity assay. Then, we electrostatically complexed GFP-expressing replication-incompetent Ad (dE1/GFP, or dAd) with PCION, generating dAd/PCION complex. dAd/PCION showed increased transduction efficiency, independent of CAR in the absence or presence of an external magnetic field (MGF). The size distribution and zeta potential of the polyelectrolyte complex (dAd/PCION) were shown 182.3 and 24.6, respectively, compared with naked Ad (74.6 and -22.6). Due to the magnetic properties of the clustered magnetic nanoparticles, we attributed the markedly enhanced transduction efficiency to be primarily mediated by the MGF. Cancer cell killing effect was significantly increased Hmt/PCION+MGF system compared to that of HmT or HmT/PCION, independent of CAR expression. Importantly, in MCF7 tumor xenograft models, the magnetofection-mediated HmT/PCION complex displayed significantly enhanced anti-tumor efficacy in the presence of an external magnetic field by 2.74- and 2.10- fold than cancer cell killing effects in the absence of an MGF and Ad alone, respectively. These results demonstrate that magnetofection-mediated oncolytic Ad infection is able to overcome CAR-dependent infectivity while producing higher antitumor efficacy.