• Journal of Gastric Cancer
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• v.9 no.4
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• pp.246-255
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• 2009

Purpose: The objectives of this study were to investigate the impact of the number of resected lymph nodes on the survival of gastric cancer patients who underwent curative resection, and to evaluate the cut-off values that can have an influence on survival on the tumor stage-stratified analysis. Materials and Methods: The subjects were 949 gastric cancer patients who underwent curative resection at Korea University Medical Center from 1992 to 2002. They were classified according to the depth of tumor invasion, and the influence of the number of resected lymph nodes on survival was investigated. The cut-off value for the number of resected lymph nodes was determined as the smallest value that showed a significant survival difference. Results: The tumor size, location, lymph node stage, the number of metastatic lymph nodes and the number of resected lymph nodes were significantly different according to the tumor stage. The average number of resected lymph nodes was about 39, and it showed linear correlation with the number of metastatic lymph nodes. On the Cox proportional hazard model, the cut-off values of the number of resected lymph nodes, as corrected by the number of metastatic lymph nodes, was 14 for all the patients, 15 for the pT1 patients, 28 for the pT2 patients and 37 for the pT3 patients, respectively. Conclusion: Retrieving a number of lymph nodes that is more than the cut-off value could improve the survival of gastric cancer patients. Surgeons should also make efforts to perform an exact and thorough D2 lymph node dissection. Therefore, we urge surgeons to perform D2 dissection and pathologists should examine an certain exact number of lymph nodes.

• Journal of Gastric Cancer
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• v.5 no.4 s.20
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• pp.281-287
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• 2005

Purpose: This study was conducted to evaluate the effectiveness and the role of post-operative adjuvant chemoradiation therapy in a stage-II (UICC, 1997) primary gastric cancer. Materials and Methods: From September 1994 to December 2004, 954 stage-II gastric-cancer patients were seen, and all of them underwent a curative resection with extensive (D2) lymph-node dissection. The chemotherapy consisted of fluorouracil $(400mg/m^2)$ plus leucovorin $(20mg/m^2)$ for 5 days, followed by 4,500 cGy of radiotherapy for 5 weeks with fluorourcil and leucovorin on the first 4 days and the last 3 days of radiotherapy. Two five-day cycles of chemotherapy were given four weeks after the completion of radiotherapy. The Kaplan-Meier method was used to estimate the survival rates. To assess the importance of potential prognostic factors, we performed univariate and multivariate analyses using a log-rank test and Cox's proportional hazards regression model. A P value <0.05 was considered significant. Results: Univariate analysis revealed that age, tumor size, gross type, surgical method, and postoperative adjuvant therapy had statistical significance. Among these factors, age, surgical method, tumor size, surgical method, and postoperative adjuvant therapy were found to be independent prognostic factors by using a multivariate analysis. The postoperative adjuvant chemotherapy group and the chemoradiation therapy group had survival benefit compared to the surgery-only group. However the chemoradiation therapy group had no significant survival benefit compared to the chemotherapy group. Conclusion: The postoperative adjuvant therapy in stage-II gastric-cancer patients had significant benefit. Therefore, postoperative adjuvant chemoradiation therapy has an acceptable effect. A large-scale, randomized study is needed to evaluate the effectiveness and the role of postoperative radiation therapy.

• Tuberculosis and Respiratory Diseases
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• v.47 no.4
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• pp.451-459
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• 1999

Background : In sepsis, excessive generation of reactive oxygen species plays key roles in the pathogenesis of acute lung injury. The serum antioxidants such as catalase and MnSOD are elevated in sepsis and considered as predictors of acute respiratory distress syndrome(ARDS) and prognostic factors of sepsis. Peroxiredoxin(Prx) has recently been known as an unique and major intracellular antioxidant. In this study, we evaluated the expression of Prx I and Prx II in mouse monocyte-macrophage cells(RAW 267.7) after treatment of oxidative stress and endotoxin and measured the amount of Prx I, Prx II and thioredoxin(Trx) in peritoneal and bronchoalveolar lavage fluid of septic animal model. Methods : Using immunoblot analysis with specific antibodies against Prx I, Prx II and Trx, we evaluated the distribution of Prx I and Prx II in human neutrophil, alveolar macrophage and red blood cell. We evaluated the expression of Prx I and Prx II in mouse monocyte-macrophage cells after treatment of $5\;{\mu}M$ menadione and $1\;{\mu}g/ml$ lipopolysaccharide(LPS) and measured the amount of Prx I, Prx II and Trx in peritoneal lavage fluid of intraperitoneal septic animals(septic animal model induced with intraperitoneal 6 mg/Kg LPS injection) and those in bronchoalveolar lavage fluid of intraperitoneal septic animals and intravenous septic animals(septic animal model induced with intravenous 5 mg/Kg LPS injection) and compared with the severity of lung inflammation. Results : The distribution of Prx I and Prx II were so different among human neutrophil, alveolar macrophage and red blood cell. The expression of Prx I in mouse monocyte-macrophage cells was increased after treatment of $5\;{\mu}M$ menadione and $1\;{\mu}g/ml$ lipopolysaccharide but that of Prx II was not increased. The amount of Prx I, Prx II and Trx were increased in peritoneal lavage fluid of intraperitoneal septic animals but were not increased in bronchoalveolar lavage fluid of intraperitoneal and intravenous septic animals regardless of the severity of lung inflammation. Conclusion : As intracellular antioxidant, the expression of Prx I is increased in mouse monocyte-macrophage cells after treatment of oxidative stress and endotoxin. The amount of Prx I, Prx II and Trx are increased in local inflammatory site but not increased in injured lung of septic animal model.

• Journal of Life Science
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• v.32 no.7
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• pp.532-541
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• 2022

Obesity induced by high-fat diet (HFD) is verified as a strong risk factor and negative prognostic factor for prostate cancer in several genetically engineered mice although it was not examined in the normal mice. To investigate whether HFD-induced obesity can affect the development and progression of cancer in the prostate of normal mice, alterations in the weight and histological structure of the prostate as well as the expression of cancer-related proteins were analyzed in obese C57BL/6N mice fed with 60% HFD for 16 weeks. First, HFD-induced obesity, including an increase in organ weight, body weight, fat accumulation, and serum lipid profile, was successfully induced in C57BL/6N mice after HFD treatment. The total weight of the prostate significantly increased HFD-induced obesity in the model mice compared with the control group. Among the four lobes of the prostate, the weight of the ventral prostate (VP) and anterior prostate (AP) were higher in HFD-induced obesity model mice than in the control group, although the weights of the lateral prostate (DLP) and seminal vesicle (SV) were constantly maintained. In addition, the incidences of hyperplasia and non-hodgkin's lymphoma (NHL) in the histological structure were remarkably increased in HFD-induced obesity model mice, while the epithelial thickness was higher in the same group. A significant increase in the phosphorylation levels of key proteins in the AKT (protein kinase B) signaling pathway was detected in HFD-induced obesity model mice. Therefore, these results suggest that HFD-induced obesity can promote hyperplasia and NHL in the prostates of C57BL/6N mice through the activation of the AKT signaling pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8383-8390
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• 2014

Background: Although the predictive value of the excision repair cross-complementing group 1 (ERCC1) C118T polymorphism in clinical outcomes of patients with colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy has been evaluated in numerous published studies, the conclusions are conflicting. Therefore, we performed the present meta-analysis to determine the precise role of the ERCC1 C118T polymorphism in this clinical situation and help optimize individual chemotherapy. Materials and Methods: A multiple search strategy was used to identify eligible studies. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were used to estimate objective response and oxaliplatin-induced toxicity, with hazard ratios (HRs) with 95%CIs for progression-free survival (PFS) and overall survival (OS). Results: A total of 22 studies including 2,846 CRC patients were eligible in the analysis. Overall, no significant correlation was found between the ERCC1 C118T polymorphism and objective response to oxaliplatin-based chemotherapy, in all patients or in the Asian and Caucasian subgroups. However, the pooled analysis showed that the PFS and OS were significantly shorter in patients who carried T/T or T/C genotypes of ERCC1 C118T as compared to the C/C genotype. On stratified analysis by ethnicity, the ERCC1 118T allele was associated with a favorable prognosis in Caucasians (PFS, HR=0.58, 95%CI: 0.24-1.44; OS, HR=0.38, 95%CI: 0.22-0.64) but an unfavorable prognosis in Asians (PFS, HR=2.49, 95%CI: 1.87-3.33; OS, HR=2.63, 95%CI: 1.87-3.69) based on a dominant model. In addition, we failed to find a statistically significant impact of ERCC1 C118T polymorphism on oxaliplatin-induced toxicity. Conclusions: The ERCC1 C118T polymorphism may have prognostic value in patients with CRC undergoing oxaliplatin-based chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4637-4642
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• 2014

Background: Hypoxia-inducible factor $1{\alpha}$ (HIF-$1{\alpha}$) plays an important role in regulating cell survival and angiogenesis, which are critical for tumor growth and metastasis. Genetic variations of HIF1A have been shown to influence the susceptibility to many kinds of human tumors. Increased expression of HIF-$1{\alpha}$ has also been demonstrated to be involved in tumor progression. However, the prognostic value of single nucleotide polymorphisms (SNPs) inthe HIF1A gene remains to be determined in most cancer types, including colorectal cancer (CRC). In this study, we sought to investigate the predictive role of HIF1A SNPs in prognosis of CRC patients and efficacy of chemotherapy. Materials and Methods: We genotyped two functional SNPs in HIF1A gene using the Sequenom iPLEX genotyping system and then assessed their associations with clinicopathological parameters and clinical outcomes of 697 CRC patients receiving radical surgery using Cox logistic regression model and Kaplan Meier curves. Results: Generally, no significant association was found between these 2 SNPs and clinical outcomes of CRC. In stratified analysis of subgroup without adjuvant chemotherapy, patients carrying CT/TT genotypes of rs2057482 exhibited a borderline significant association with better overall survival when compared with those carrying CC genotype [Hazard ratio (HR), 0.47; 95% confidence interval (95% CI): 0.29-0.76; P < 0.01]. Moreover, significant protective effects on CRC outcomes conferred by adjuvant chemotherapy were exclusively observed in patients carrying CC genotype of rs2057482 and in those carrying AC/CC genotype of rs2301113. Conclusions: Genetic variations in HIF1A gene may modulate the efficacy of adjuvant chemotherapy after surgery in CRC patients.

• Journal of Trauma and Injury
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• v.24 no.2
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• pp.89-94
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• 2011

Purpose: A few studies have assessed the factors affecting the prognoses for major trauma patients and those improving the circumstances when dealing with the trauma system. In that light, we analyzed factors, such as pre-hospital factors, the time to admission, the length of stay in the emergency department (ED) and emergency operation, influencing the outcomes for trauma patients. Methods: The patients who visited our emergency department from April 1, 2009, to February 29, 2011, due to major trauma were enrolled in the study. The inclusion criterion was a revised trauma score (RTS) < 7 or injury severity score (ISS) ${\geq}$ 16. We used reviews of medical records, to analyze each step of emergency medical care with respect to patients' sex, age, visit time and visit date. Continuous variables were described as a median with an interquartile range, and we compared the variables between the survival and the mortality groups by using the Mann-Whitney U test. Fisher's exact test was used for nominal variables. Using the variables that showed statistical significance in univariate comparisons, we performed a logistic regression analysis, and we tested the model's adequacy by the using the Hosmer-Lemeshow method. Results: A total of 261 patients with major trauma satisfied either the RTS score criterion or the ISS score criterion. Excluding 12 patients with missing data, 249 patients were included in this study. The overall mortality rate was 16.9%. Time to ED arrival, time to admission, time of ED stay, RTS, ISS, and visit date being a holiday showed statistically significant differences between the survival and the mortality groups in the univariate analysis. RTS, ISS, length of ED stay, and visit date being a holiday showed statistical significance in the multivariate analysis. Conclusion: The mortality rate did not show a significant relationship with the time to ED arrival, use of 119, on time to admission. Rather, it elicited a quite significant correlation with the trauma scoring system (RTS and ISS), the time of ED stay, and the visit date being a holiday.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9699-9706
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• 2014

Background: The predictive value of the xeroderma pigmentosum group D (XPD) Lys751Gln polymorphism regarding clinical outcomes of patients with colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy has been evaluated in numerous published studies, but the results remain inconclusive. Therefore, we performed a meta-analysis to determine the precise role of the XPD Lys751Gln polymorphism in this clinical situation and optimize individual chemotherapy. Materials and Methods: A multiple search strategy was used to identify eligible studies. Pooled odds ratios (ORs), generalized odds ratio (ORG) and their 95% confidence intervals (CIs) were used to estimate the objective response, while hazard ratios (HRs) with 95%CIs were used for progression-free survival (PFS) and overall survival (OS). Results: A total of 17 studies including 2,286 patients met the inclusion criteria. Overall, the XPD 751Gln allele was associated with a non-significant reduced objective response to oxaliplatin-based chemotherapy in all patients or in the Asian and Caucasian subgroups. However, poor PFS and OS of CRC patients treated with oxaliplatin-based regimens were significantly related to the XPD 751Gln allele in the dominant model (PFS: HR=2.10, 95%CI: 1.65-2.67; OS: HR=3.18, 95%CI: 1.57-6.47). On stratified analysis by ethnicity, these relationships were more pronounced in Asians (PFS: HR=2.49, 95%CI: 1.79-3.47; OS: HR=5.25, 95%CI: 3.46-7.94) than in Caucasians (PFS: HR=1.73, 95%CI: 1.22-2.46; OS: HR=1.78, 95%CI: 1.06-2.99). Conclusions: The XPD Lys751Gln polymorphism may have prognostic value in patients with CRC undergoing oxaliplatin-based chemotherapy.

• BMB Reports
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• v.51 no.5
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• pp.255-260
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• 2018

Wntless/GPR177 functions as WNT ligand carrier protein and activator of $WNT/{\beta}$-catenin signaling, however, its molecular role in gastric cancer (GC) has remained elusive. We investigated the role of GPR177 in gastric tumorigenesis and provided the therapeutic potential of a clinical development of anti-GPR177 monoclonal antibodies. GPR177 mRNA expression was assessed in GC transcriptome data sets (GSE15459, n = 184; GSE66229, n = 300); protein expression was assessed in independent patient tumor tissues (Yonsei TMA, n = 909). GPR177 expression were associated with unfavorable prognosis [log-rank test, GSE15459 (P = 0.00736), GSE66229 (P = 0.0142), and Yonsei TMA (P = 0.0334)] and identified as an independent risk predictor of clinical outcomes: GSE15459 [hazard ratio (HR) 1.731 (95% confidence interval; CI; 1.103-2.715), P = 0.017], GSE66229 [HR 1.54 (95% CI, 1.10-2.151), P = 0.011], and Yonsei TMA [HR 1.254 (95% CI, 1.049-1.500), P = 0.013]. Either antibody treatment or GPR177 knockdown suppressed proliferation of GC cells and sensitized cells to apoptosis. And also inhibition of GPR177 suppresses in vitro and in vivo tumorogenesis in GC cells and inhibits $WNT/{\beta}$-catenin signaling. Finally, targeting and inhibition of GPR177 with antibody suppressed tumorigenesis in PDX model. Together, these results suggest GPR177 as a novel candidate for prognostic marker as well as a promising target for treatment of GC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6449-6453
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• 2014

Background: Prior studies showed a relationship between serum albumin and the albumin to globulin ratio with different types of cancer. We aimed to evaluate the predictive value of the albumin-globulin ratio (AGR) for survival of patients with lung adenocarcinoma. Materials and Methods: This retrospective study included 240 lung adenocarcinoma patients. Biochemical parameters before chemotherapy were collected and survival status was obtained from the hospital registry. The AGR was calculated using the equation AGR=albumin/(total protein-albumin) and ranked from lowest to highest, the total number of patients being divided into three equal tertiles according to the AGR values. Furthermore, AGR was divided into two groups (low and high tertiles) for ROC curve analysis. Cox model analysis was used to evaluate the prognostic value of AGR and AGR tertiles. Results: The mean survival time for each tertile was: for the $1^{st}$ 9.8 months (95%CI:7.765-11.848), $2^{nd}$ 15.4 months (95%CI:12.685-18.186), and $3^{rd}$ 19.9 months (95%CI:16.495-23.455) (p<0.001). Kaplan-Meier curves showed significantly higher survival rates with the third and high tertiles of AGR in comparison with the first and low tertiles, respectively. At multivariate analysis low levels of albumin and AGR, low tertile of AGR and high performance status remained an independent predictors of mortality. Conclusions: Low AGR was a significant predictor of long-term mortality in patients with lung adenocarcinoma. Serum albumin measurement and calculation of AGR are easily accessible and cheap to use for predicting mortality in patients with lung adenocarcinoma.