• Journal of Gastric Cancer
• /
• v.17 no.2
• /
• pp.132-144
• /
• 2017

Purpose: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. Materials and Methods: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. Results: Of 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64-0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. Conclusions: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.

• Economic and Environmental Geology
• /
• v.39 no.5 s.180
• /
• pp.555-566
• /
• 2006

Major, trace and rare earth elements data of the Cretaceous Jindong granitic rocks were investigated in order to constrain the magma source characteristics and to establish the paleotectonic environment of the southwestern part of the Gyeongsang Basin. Geochemical signatures of the granitic rocks from the study area indicate that all of the rocks have characteristics of calc-alkaline series in the subalkaline field, and progressively shift from metaluminous to peraluminous with differentiation. In the variation diagrams, the overall geochemical features of the granites show systematic variations in major and trace elements. Chondrite normalized REE patterns show generally enriched LREE((La/Yb)c=4.2-12.8) and slight negative to flat Eu anomalies. Rb-Sr isotope data of the Jindong granites show that the whole rock age and Sr initial ratio are $114.6{\pm}9.1Ma$ and 0.70457, respectively. The Sr initial ratio of the Jindong granites is very similar to those of the Creataceous granites from Masan, Kimhae and Busan area($^{87}Sr/^{86}Sr=0.7049-0.707$). These results suggest that the magma have the mantle signature and intruded into the area during the early Cretaceous age. The Jindong granites have higher $Al_{2}O_{3},\;Na_{2}O$, Sr and lower $K_{2}O$, Y concentrations compared with typical calc-alkaline granitic rocks. These adakitic signatures are similar to those of adakitic pluton on Kyushu Island, southwest Japan arc. On the ANK vs. ACNK and tectonic discrimination diagrams, parental magma type of the granites corresponds to I-type, VAG granite. Interpretations of the geochemical characteristics of the granitic rocks favor their emplacement at continental margin during the subduction of Izanagi plate.

• Korean Journal of Food Science and Technology
• /
• v.48 no.4
• /
• pp.378-383
• /
• 2016

The glasswort is an edible halophyte demonstrating various physiological effects including anti-inflammatory activity. In the present study, the effects of glasswort extracts on inflammatory events and interactions of THP-1 monocytes with intestinal epithelial cells were investigated. Five solvent fractions, including the ethylether fraction (Fr.E), were prepared from a 70% methanol extract of glasswort. THP-1 monocytes underwent differentiation by phorbol 12-myristate 13-acetate treatment and were then activated by lipopolysaccharide (LPS), which induced cyclooxygenase (COX)-2 expression. None of the glasswort fractions tested alone induced COX-2 in differentiated THP-1 cells. Fr.E, however, enhanced LPS-induced COX-2 expression in differentiated THP-1 cells. Culture media of THP-1 cells treated with each fraction stimulated the growth of normal intestinal INT-407 cells more prominently than that of HT-29 colon cancer cells. COX-2 expression in HT-29 cells was inhibited when the cells were exposed to the THP-1 culture medium treated with Fr.E. Thus, glasswort could modulate the interaction between immune cells and intestinal cells.

• Journal of Animal Science and Technology
• /
• v.52 no.4
• /
• pp.265-270
• /
• 2010

Adipogenesis has been one of the most intensely studied models of cellular differentiation. During adipogenesis, differential expression of many adipogenesis related genes lead to profound changes in cellular, morphological, and physiological characteristics of the differentiating cells. The aim of the present study was to examine the expression levels of adipogenic candidate genes, cAMP early repressor (ICER), nephroblastoma over-expressed protein (NOV), heat shock protein beta 1 (HSPB1) and succinate dehydrogenase (SDH), during adipogenesis of bovine mesenchymal stem cells (BMSC). The BMSC were cultured in DMEM / low glucose medium with adipogenic inducers for 6 days and the expression of various candidate genes which seemed related to adipogenesis were measured by real-time PCR. This study showed that the expression of peroxisome proliferator activated receptor ${\gamma}$(PPAR${\gamma}$) and fatty acid binding protein 4 (FABP4) genes as adipogenic indicators were increased to 3.11 and 3.11 folds on day 6 than on day 0, respectively (p<0.05). To determine whether candidate genes were related to adipogenesis, the expression levels of ICER, NOV, HSPB1, and SDH genes were measured during adipogenesis in BMSC. Our results showed that the expression level of ICER gene was significantly increased to 4.12 folds (0.01729 vs. 0.07138; p<0.05), whereas NOV, HSPB1, and SDH genes were decreased to 2.89, 3.18 and 2.36 folds, respectively, on day 6 when compared to day 0. These results suggest that these candidate genes have stimulatory or inhibitory effects on adipogenesis in BMSC, indicating that these genes may be directly or indirectly related to the adipogenic event of adipose precursor cells.

• Tuberculosis and Respiratory Diseases
• /
• v.59 no.6
• /
• pp.631-637
• /
• 2005

Background : Transcriptional factors of the CREB(cAMP Response Element Binding Protein) are involved in the regulation of gene expression in response to a variety of signaling pathways. Proteins produced by the CREB genes play key roles in many physiological processes, including memory and long-term potentiation. The retinoic acid receptor (RAR) axis mediates epithelial cell differentiation and proliferation in many tissues including the lung. Material and method : The RAR and CREB expression levels were examined in 60 adenocarcinomas and 60 squamous cell carcinomas of the lung using immunohistochemical staining. Results : 1) RAR protein expression was found in 58.3%(35/60) of adenocarcinomas and 36.7%(22/60) of squamous cell carcinomas(P<0.05). 2) RAR protein expression was found in 80%(16/20) of well differentiated adenocarcinomas, 60%(12/20) of moderately differentiated adenocarcinomas, and 35%(7/20) of poorly differentiated adenocarcinomas (P<0.01). 3) RAR protein expression was found in 45%(9/20) of well differentiated squamous cell carcinomas, 35%(7/20) of moderately differentiated squamous cell carcinomas, and 30%(6/20) of poorly differentiated squamous cell carcinomas (P>0.05). 4) CREB expression was found in 61.7%(37/60) of adenocarcinomas and 40%(24/60) of squamous cell carcinomas( P<0.05). 5) CREB expression was found in 85%(17/20) of well differentiated adenocarcinomas, 60%(12/20) of moderately differentiated adenocarcinomas, and 40%(8/20) of poorly differentiated adenocarcinomas (P<0.01). 6) CREB expression was found in 45%(9/20) of well differentiated squamous cell carcinomas, 35%(7/20) of moderately differentiated squamous cell carcinomas, and 35%(8/20) of poorly differentiated squamous cell carcinomas(P>0.05). 7) RAR and CREB expression was found in 68.5% of lung cancers, and there was a significant correlation between them(P<0.05). Conclusion : RAR and CREB expression can be used to indirectly determine the malignant potentiality of a cell.

• Radiation Oncology Journal
• /
• v.11 no.2
• /
• pp.267-275
• /
• 1993

Eighty five patients of oral cavity cancer, treated with radiation at the Department of Therapeutic Radiology, Korea Cancer Center Hospital, during the period from March 1985 to September 1990 were analyzed retrospectively. Among 85 patients, 37 patients were treated with radiation only and 48 patients were treated with radiation following surgery. And 70 patients received external irradiation only by $^{60}Co$ with or without electron, the others were 7 patients for external irradiation plus interstitial implantation and 8 patients for external irradiation plus oral cone electron therapy. Primary sites were mobile tongue for 40 patients, mouth floor for 17 patients, palate for 12 patients, gingiva including retromolar trigone for 10 patients, buccal mucosa for 5 patients, and lip for 1 patient. According to pathologic classification, squamous cell carcinoma was the most common (77 patients). According to AJC TNM stage, stage I + II were 28 patients and stage III+IV were 57 patients. Acturial overall survival rate at 3 years was $43.9\%,$ 3 year survival rates were $60.9\%$ for stage I + II, and $23.1\%$ for stage III+IV, respectively. As a prognostic factor, primary T stage was a significant factor (p<0.01). The others, age, location, lymph node metastasis, surgery, radiation dose, and cell differentiation were not statistically significant. Among those factors, radiation plus surgery was more effective than radiation only in T3+T4 or in any N stage although it was not statistically sufficient (p<0.1). From those results, it was conclusive that definitive radiotherapy was more effective than surgery especially In the view of pertainig of anatomical integrity and function in early stage, and radiation plus surgery was considered to be better therapeutic tool in advanced stage.

• Korean Journal of Ecology and Environment
• /
• v.38 no.1 s.110
• /
• pp.73-82
• /
• 2005

This study was conducted, based on the field survey and laboratory observations, to elucidate egg developmental processes and their characteristics of the Korean slender gudgeon, Squalidus gracilis majimae. For the experiments, the mature adults were collected at the Woongcheon-Cheon Stream and Boreung Reservoir located in Boreung City, Chungnam Province and eggs were obtained from the natural spawning area. Morphological characteristics of the egg and embryonic development were summarized as follows: The shape of the fertilized egg was spherical, adhesive and transparent. The fertilized egg was 2.9${\pm}$0.3 mm (n = 30) in mean diameter under water temperature of $26{\pm}1.5^{\circ}C$, light white in color and had no oil droplets. After 20 minutes from the time of fertilization, a blastodisc was formed and divided into two cells at 48 minutes after fertilization. The blastular stage occurred at 5 hours 40 minutes after fertilization and the gastrular stage was detected at 8 hours 41 minutes after fertilization. The beginning of embryo formation was observed at 12 hours 58 minutes after fertilization and optic vesicles and 9 somites were discovered at 17 hours 05 minutes after fertilization. Differentiation of brains and embryo wiggling were observed at 37 hours 27 minutes after fertilization. Heart beating and the formation of melanophores in optic vesicles were detected at 44 hours 46 minutes after fertilization. The formation of pectoral fins and melanophores in the body were discovered at 50 hours 36 minutes after fertilization. Hatching occurred at 57 hours 49 minutes after fertilization. The newly hatched larvae were 3.3${\pm}$0.2 mm (n = 120) in total length. We believe that these results may contribute the species and population conservations under the situation of accelerated water pollution and the decreases of its diversity.

• Development and Reproduction
• /
• v.12 no.3
• /
• pp.289-296
• /
• 2008

BPES (Blepharophimosis/Ptosis/Epicanthus inversus Syndrome) is an autosomal dominant disorder caused by mutations in FOXL2. Affected individuals have premature ovarian failure (POF) in addition to small palpebral fissures, drooping eyelids, and broad nasal bridge. FOXL2 is a member of the forkhead family transcription factors. In FOXL2-deficient ovaries, granulosa cell differentiation dose not progress, leading to arrest of folliculogenesis and oocytes atresia. Using yeast two-hybrid screening of rat ovarian cDNA library with FOXL2 as bait, we found that small ubiquitin-related modifier (SUMO)-conjugating E2 enzyme UBE2I protein interacted with FOXL2 protein. UBE2I also known as UBC9 is an essential protein for processing SUMO modification. Sumoylation is a form of post-translational modification involved in diverse signaling pathways including the regulation of transcriptional activities of many transcriptional factors. In the present study, we confirmed the protein-protein interaction between FOXL2 and UBE2I in human cells, 293T, by in vivo immunoprecipitation. In addition, we generated truncated FOXL2 mutants and identified the region of FOXL2 required for its association with UBE2I using yeast-two hybrid system. Therefore, the identification of UBE2I as an interacting protein of FOXL2 further suggests a presence of novel regulatory mechanism of FOXL2 by sumoylation.

• Clinical and Experimental Reproductive Medicine
• /
• v.35 no.1
• /
• pp.39-48
• /
• 2008

Objective: The aim of this study was to investigate whether multipotent germline stem cells (MGSCs) can be established from neonatal mouse testis. Methods: Various cells containing MGSCs were collected from neonatal testis of ICR mice and allocated to plates for in vitro culture. After 7 days in culture, the cells were passed to a fresh culture plate and continuously cultured. From the third or fourth passage, the presumed MGSCs were cultured and maintained on mitomycin C-inactivated STO feeder cells. The MGSCs were cultured in a condition where mouse embryonic stem cells (ESCs) are cultured. Characteristics of the MGSCs were evaluated by RT-PCR, immunocytochemistry, alkaline phosphatase activity, karyotyping, and transmission electron microscopy. Results: Two MGSCs lines were established from 9 pooled sets of neonatal testicular cells. MGSCs colonies were morphologically undistinguishable from ESCs colonies and both MGSC lines as well as ESCs expressed undifferentiated stem cell markers, such as Thy-1, Oct-4, Nanog, Sox2 and alkaline phosphatase. Fine structure of undifferentiated MGSCs were similar to those of ESCs and 60% of MGSCs (12/20) had normal karyotype at passage 10. They were able to form embryoid bodies (EBs) and MGSC-derived EBs expressed marker genes of three germ layers. Conclusion: We could establish the MGSCs from neonatal mouse testis and they were differentiated to multipotent lineages of three germ layers. Molecular characteristics of MGSCs were similar to those of ESCs. Our results suggest a possibility that multipotent stem cells derived from testis, the MGSCs, could replace the ESCs in biotechnology and regenerative medicine.

• Korean Journal of Microbiology
• /
• v.47 no.4
• /
• pp.281-288
• /
• 2011

To screen downstream genes of Aspergillus nidulans MsnA showing amino acid sequence similarity to the zinc finger region of Msn2/4 stress response transcription factors in Saccharomyces cerevisiae, differentially expressed genes (DEG) in MsnA overexpressed or msnA null mutant strains compared to wild type have been isolated. The cognate gene IDs were identified by DNA sequencing of the selected DEGs. Among those, DEG6 was known as mstB encoding a putative monosaccharide transporter. Expression level of mstB mRNA was increased in MsnA overproducing strains and MsnA bound directly to the promoter region of mstB in vitro. MstB containing twelve transmembrane domains exhibited 80% of amino acid sequence identities to A. niger MstA a high-affinity monosaccharide transporter. A null mutant of mstB was phenotypically undistinguishable to wild type. On the other hand, forced overexpression of MstB caused the increased formation of sexual structure cleistothecia in 0.1% glucose condition where wild type showed almost no cleistothecia. This result implies that mstB is involved in transport of monosaccharide required for sexual differentiation.