• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2987-2991
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• 2015

Background: The prognostic role of thyroid transcription factor-1 (TTF-1) expression in lung cancer has been assessed but with inconsistent results. The present study aimed to evaluate the prognostic value of TTF1 expression in advanced non-squamous non-small cell lung cancer (NSCLC). Materials and Methods: In this retrospective study, patients with stage IIIB-IV non-squamous NSCLC were enrolled. Progression free survival (PFS) and overall survival (OS) were assessed according to TTF1 expression status, age categories (${\leq}60$ vs >60 years), gender, performance status (PS) (0-2 vs 3-4), type of 1st line chemotherapy (pemetrexed containing vs others) and EGFR status. Results: A total of 120 patients were included. In univariate analysis, PFS was improved in patients with PS 0-2 (7.0 vs 2.0 months, p=0.002) and those who received pemetrexed-containing chemotherapy (9.2 vs 5.8 months, p=0.004). OS was improved in female patients (23.0 vs 8.7 months, p<0.0001), PS 0-2 (14.4 vs 2.0 months, p<0.0001), those with pemetrexed-containing chemotherapy (17.0 vs 11.0 months, p=0.019), TTF1-positive (12.8 vs 5.8 months, p=0.011) and EGFR- mutant patients (23.0 vs 11.7 months, p=0.006). In multivariate analysis, male gender (HR=2.34, p=0.025) and non-pemetrexed containing therapy (HR=2.24, p=0.022) were independent predictors of worse PFS. Wild EGFR status (HR=2.49, p=0.015) and male gender (HR=2.78, p=0.008) were predictors of worse OS. Conclusions: Pemetrexed-containing therapy significantly improved PFS while OS was improved in EGFR mutant patients. Female patients had better PFS and OS. TTF1 expression was not a prognostic marker in advanced non-squamous NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.347-350
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• 2013

The aim of the present study was to determine whether allogeneic red blood cell transfusions showed a deleterious effect and what might be preoperative risk factors for blood transfusion in patients with TNM stage II colon cancer. Total 470 patients who fulfilled inclusion criteria were selected for a further 10-year follow-up study. We found that there were statistical significance between non-transfused and transfused group in mortality (P=0.018), local recurrence (P=0.000) and distant metastasis (P=0.040). Local recurrence and distant metastasis between 1 to 3 units and more than 3 units group did not show any significant differences. There was no difference in survival rate between non-transfused and 1 to 3 units group (log rank=0.031, P=0.860). The difference between different blood transfusion volume in transfused patients was found (78.77% vs 63.83%, P=0.006). Meanwhile, the significant difference of survival rate was existed between non-transfused group and more than 3 units group (84.83% vs 63.83%, P=0.002 ). Univariate analysis showed the following 3 variables to be associated with an increased risk of allogeneic blood transfusions: preoperative CEA level (P<0.05), location of tumor (P<0.01) and diameter of tumor (P<0.01). Multivariate analysis revealed that location of tumor and diameter of tumor are two independent factors for requirement of perioperative transfusions. Therefore, allogeneic transfusion increase the postoperative tumor mortality, local recurrence and distant metastasis in patients with stage II colon cancer. The postoperative tumor mortality, local recurrence and distant metastasis were not associated with the blood transfusion volume. The blood transfusion volume was associated with the survival rate. Location of tumor and diameter of tumor were the independent preoperative risk factors for blood transfusion.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1889-1894
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• 2013

Background: Basaloid squamous cell carcinoma of the esophagus (BSCCE) is a rare and distinctive tumor with no standard treatment. This study aimed to explore treatment in relation to prognosis of the disease. Methods: A total of 142 patients with BSCCE that underwent treatment in our hospital from March 1999 to July 2010 were retrospectively analyzed. All patients received surgery, 42 postoperative radiotherapy and 28 patients chemotherapy. Results: There were 26 patients included in stage I, 60 in stage II, 53 in stage III and 3 in stage IV. The clinical symptoms and macroscopic performances of BSCCE did not differ from those of typical esophageal squamous cell carcinoma. Among 118 patients receiving endoscopic biopsy, only 12 were diagnosed with BSCCE. The median survival time (MST) of the entire group was 32 months, with 1-, 3- and 5-year overall survival (OS) of 81.4%, 46.8% and 31.0%, respectively. The 5-year OS of stage I and II patients was significantly longer than that of stages III/IV, at 60.3%, 36.1% and 10.9%, respectively (p<0.001, p=0.001). The MST and 5-year OS were 59.0 months and 47.4% in patients with tumors located in the lower thoracic esophagus, and 27.0 months and 18.1% in those with lesions in the upper/middle esophagus (p=0.002). However, the survival was not significantly improved in patients undegoing adjunctive therapy. Multivariate analysis showed TNM stage and tumor location to be independent prognostic factors. Furthermore, distant metastasis was the most frequent failure pattern, with a median recurrence time of 10 months. Conclusion: BSCCE is an aggressive disease with rapid progression and a propensity for distant metastasis. It is difficult to make a definitive diagnosis via preoperative biopsy. Multidisciplinary therapy including radical esophagectomy with extended lymphadenectomy should be recommended, while the effectiveness of radiochemotherapy requires further validation for BSCCE.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5271-5276
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• 2014

Mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3 (MEKK3) is an important protein kinase and a member of the MAPK family, which regulates cellular responses to environmental stress and serves as key integration points along the signal transduction cascade that not only link diverse extracellular stimuli to subsequent signaling molecules but also amplify the initiating signals to ultimately activate effector molecules and induce cell proliferation, differentiation and survival. To explore the relationship between MEKK3 and cell apoptosis, clinicopathology and prognosis, we characterize the expression of MEKK3 and survivin in cervical cancer. MEKK3 and survivin expression was measured by RT-PCR and Western blotting of fresh surgical resections from 30 cases of cervical cancer and 25 cases of chronic cervicitis. Protein expression was detected by tissue microarray and immunochemistry (En Vision) in 107 cases of cervical cancer, 86 cases of cervical intraepithelial neoplasia (CIN), and 35 cases of chronic cervicitis. Expression patterns were analyzed for their association with clinicopathological factors and prognosis in cervical cancer. Expression of MEKK3 and survivin mRNA was significantly higher in cervical cancer than in the controls (p<0.05). MEKK3 and survivin expression differed significantly between cervical carcinoma, CIN, and cervicitis (p<0.05) and correlated with clinical stage, infiltration depth, and lymph node metastasis (p<0.05). MEKK3 expression was positively correlated with survivin (p<0.05). Kaplan-Meier survival analysis showed that MEKK3 and survivin expression, lymph node metastasis, depth of invasion, and FIGO stage reduce cumulative survival. Cox multivariate regression analysis showed that MEKK3, survivin, and clinical staging are independent prognostic factors in cervical cancer (p<0.05). Expression of MEKK3 and survivin are significantly increased in cervical cancer, their overexpression participating in the occurrence and development of cervical cancer, with protein expression and clinical staging acting as independent prognostic factors for patients with cervical cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1471-1477
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• 2015

Background: Adding taxanes to adjuvant antracycline and cyclophosphamide (AC) in combination may provide significant improvement in node-positive and high risk node-negative breast cancer (BC) patients. However, the optimal dose and the role of dose-dense (DD) chemotherapy have yet to be determined. The aim of this study was to compare the efficacy of a DD paclitaxel (P)-AC combination with conventional weekly P-AC or docetaxel D-AC combinations in patients with node-positive breast cancer. Materials and Methods: Newly diagnosed 280 node-positive BC patients diagnosed from 1998 to 2013 in three clinics were retrospectively analyzed. Demographic and medical data were collected from the medical charts. Patients were categorized to 3 groups according to treatment arms: arm A, ddAC-P; arm B, weekly P and AC combination; and arm C; T and AC combination. Adjuvant trastuzumab was added for HER2-positive patients. Kaplan-Meier survival analysis was carried out for disease free survival (DFS) and overall survival (OS). The log-rank test was used to examine the statistical significance of the differences observed between the groups. Two-sided P values <0.05 were considered statistically significant. Results: Of the total of 280 patients, 101 were in arm A, 114 in arm B and 65 in arm C.The median ages were 49, 50 and 46, respectively (p=0.11). Median follow-up was 39 (3-193) months. Stage, lymphovascular and perineural invasion, receptor patern, and menopausal status were similar in the 3 treatment arms, but HER2 positivity was significantly lower in arm A, compared to arms B and C (25.7%, 53.1%, 41.5% in arms A, B and C, respectively; p<0.001). Also grade 3 tumors were significantly less frequent in treatment arm A compared to arm B and C (27.3%, 56.8% and 49.2%, respectively, p=0.01). Afterunivariate and multivariate analysis were performed, 3-year DFS rates were 89%, 81%, and 75%, respectively (p=0.12) and three year OS rates were 96.6%, 89%, and 75% (p=0.62). Conclusions: In this study, no significant difference was found between adjuvant dose dense and conventional taxane treatment regimens.

• Radiation Oncology Journal
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• v.37 no.1
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• pp.37-42
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• 2019

Purpose: To identify prognostic factors influencing progression-free survival (PFS) of aggressive fibromatosis (AF) after postoperative radiotherapy (PORT) and assess correlations between immunohistochemistry (IHC) features of β-catenin/smooth muscle actin (SMA) and PFS. Materials and Methods: Records of 37 patients with AF treated by PORT from 1984 to 2015 were retrospectively reviewed. Fifteen patients underwent wide excision for AF and 22 patients received debulking operation. The median total dose of PORT was 59.4 Gy. IHC staining results of β-catenin and SMA were available for 11 and 12 patients, respectively. Results: The median follow-up duration was 105.9 months. Five-year PFS rate was 70.9%. Tumor size or margin status was not related to PFS in univariate analysis (p = 0.197 and p = 0.716, respectively). Multivariate analysis showed that increased interval from surgery to PORT (>5.7 weeks) was a marginal risk factor for PFS (p = 0.054). Administration of PORT at the initial diagnosis resulted in significantly improved PFS compared to deferring PORT after recurrence (p = 0.045). Patient with both risk factors of deferring PORT after recurrence and interval from surgery to PORT >5.7 weeks had significantly lower 5-year PFS than patients without risk factor (34.1% vs. 100.0%; p = 0.012). Nuclear β-catenin intensity tended to inversely correlate with 5-year PFS, although it did not reach statistical significance (62.5% at low vs. 100.0% at high; p = 0.260). SMA intensity was not related to PFS (p = 0.700). Conclusion: PORT should be performed immediately after surgery irrespective of margin status or tumor size especially in recurrent case. Nuclear β-catenin staining intensity of IHC might correlate with local recurrence.

• Journal of Gastric Cancer
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• v.12 no.2
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• pp.113-119
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• 2012

Purpose: The aim of this study is to compare the characteristics of tumor and prognosis, depending on the status of resection margin involvement, on the frozen section diagnosis in gastric cancer. Materials and Methods: This study was conducted retrospectively, in 83 margin-positive patients on the frozen section diagnosis, who underwent gastrectomy from July 1995 to September 2006. The control group was selected by matching the age, gender, TNM stage and status of adjuvant chemoradiotherapy, among those who had shown clear resection margins. The characteristics of tumor and patient survival are investigated, and they were analyzed between the two groups. Results: The tumor size was significantly larger in the study group than that of the control group (P=0.037). There was significant difference between the two groups in location of the tumors (P=0.003). Multivariate analysis indicated that only the location and Lauren's classification are independent factors, which affected the resection margin involvement. Median survival was $41.0{\pm}11.5$ months in the study group and $93.0{\pm}30.3$ months in the control group (P=0.049). In the survival analysis, it was investigated that TNM stage and the resection margin involvement of the frozen section diagnosis were the critical variables. Conclusions: When the tumor is located at the middle or the upper third, or the Lauren's indeterminate type, they are highly likely to show the resection margin involvement on the frozen section diagnosis, and it can, therefore, have negative effects on the prognosis. It is considered as good to perform more extensive resection as possible, during the initial resection.

• Journal of Gastric Cancer
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• v.9 no.4
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• pp.238-245
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• 2009

Purpose: Treatment strategies for early gastric carcinoma (EGC) should be based on achieving a complete cure, but clear indications for limited surgery have not been established. We investigated surgical outcomes for early gastric cancer to determine the optimal? treatment strategy for EGC. Materials and Methods: Subjects included 881 patients who underwent curative surgery for EGC between 1986 and 2003. Retrospective uni & multi-variate analysis for prognostic factors, factors affecting lymph node metastasis, and risk factors for cancer recurrence were analyzed. Results: In multivariate survival analyses, age, operation method, macroscopic appearance and lymph node stage proved to be independent prognostic factors. Lymph node metastasis, depth of tumor invasion, tumor size, lymphatic and venous invasion were also significant risk factors in multivariate analyses. In multivariate analyses for cancer recurrence, depth of tumor invasion and lymph node metastasis proved to be significant risk factors. Conclusion: Appropriate surgical treatment with lymph node dissection is necessary for EGC patients with risk factors for lymph node metastasis.

• Korean Circulation Journal
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• v.53 no.10
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• pp.710-719
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• 2023

Background and Objectives: In previous studies, high homocysteine levels were associated with high cardiovascular mortality. However, these results were inconsistent with those of randomized controlled trials. We aimed to evaluate the causal role of homocysteine on allcause and cardiovascular mortality using Mendelian randomization (MR) analysis. Methods: This study included the 10,005 participants in the Namwon Study. In conventional observational analysis, age, sex, survey years, lifestyles, body mass index, comorbidities, and serum folate level were adjusted using multivariate Cox proportional regression. MR using 2-stage least squares regression was used to evaluate the association between genetically predicted plasma homocysteine levels and mortality. Age, sex, and survey years were adjusted for each stage. The methylenetetrahydrofolate reductase (MTHFR) polymorphism was used as an instrumental variable for predicting plasma homocysteine levels. Results: Observed homocysteine levels were positively associated with all-cause (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.26-1.54) and cardiovascular (HR, 1.62; 95% CI, 1.28-2.06) mortality when plasma homocysteine levels doubled. However, these associations were not significant in MR analysis. The HRs of doubling genetically predicted plasma homocysteine levels for all-cause and cardiovascular mortality were 0.99 (95% CI, 0.62-1.57) and 1.76 (95% CI, 0.54-5.77), respectively. Conclusions: This MR analysis did not support a causal role for elevated plasma homocysteine concentrations in premature deaths.

• Journal of Preventive Medicine and Public Health
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• v.30 no.3 s.58
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• pp.630-642
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• 1997

The purpose of this study was to examine the mortality risk associated with cognitive impairment among the rural elderly. The subjective of study was 558 of 'A Study on the Depression and Cognitive Impairment in the Rural Elderly' of Jung Ae Rhee and Hyang Gyun Jung's study(1993). Cognitive impairment and other social and health factors were assessed in 558 elderly rural community residents. For this study, a Korean version of the Mini-Mental State Examination(MMSEK) was used as a global indicator of cognitive functioning. And mortality risk factors for each cognitive impairment subgroup were identified by univariate and multivariate Cox regression analysis. At baseline 22.6% of the sample were mildly impaired and 14.2% were severely impaired. As the age increased, the cognitive function was more impaired. Sexual difference was existed in the cognitive function level. Also the variables such as smoking habits, physical disorders had the significant relationship with cognitive function impairment. Across a 3-year observation period the mortality rate was 8.5% for the cognitively unimpaired, 11.1% for the mildly impaired, and 16.5% for the severly impaired respendents. And the survival probability was .92 for the cognitively unimpaired, .90 for the mildly impaired, and .86 for the severly impaired respondents. Compared to survival curve for the cognitively unimpaired group, each survival curve for the mildly and the severely impaired group was not significantly different. When adjustments models were not made for the effects of other health and social covariates, each hazard ratio of death of mildly and severely impaired persons was not significantly different as compared with the cognitively unimpaired. But, as MMSEK score increased, significantly hazard ratio of death decreased. Employing Cox univariate proportional hazards model, statistically other significant variables were age, monthly income, smoking habits, physical disorders. Also when adjustments were made for the effects of other health and social covariates, there was no difference in hazard ratio of death between those with severe or mild impairment and unimpaired persons. And as MMSEK score increased, significantly hazard ratio of death did not decrease. Employing Cox multivariate proportional hazards model, statistically other significant variables were age, monthly income, physical disorders. Employing Cox multivariate proportional hazards model by sex, at men and women statistically significant variable was only age. For both men and women, also cognitive impairment was not a significant risk factor. Other investigators have found that cognitive impairment is a significant predictor of mortality. But we didn't find that it is a significant predictor of mortality. Even though the conclusions of our study were not related to cognitive impairment and mortality, early detection of impaired cognition and attention to associated health problems could improve the quality of life of these older adults and perhaps extend their survival.