Goyang, South Korea
Goyang, South Korea

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Park J.-W.,Hospital National Cancer Center | Kim S.C.,Ewha Womans University | Kim D.Y.,Hospital National Cancer Center | Oh J.H.,Hospital National Cancer Center | Cho J.Y.,Sungkyunkwan University
BMC Cancer | Year: 2014

Background: Resistance to 5-fluorouracil (5-FU) in patients with colorectal cancer prevents effective treatment and leads to unnecessary and burdensome chemotherapy. Therefore, prediction of 5-FU resistance is imperative.Methods: To identify the proteins linked to 5-FU resistance, two-dimensional gel electrophoresis-based proteomics was performed using the human colon cancer cell line SNU-C4R with induced 5-FU resistance. Proteins showing altered expression in SNU-C4R were identified by matrix-associated laser desorption/ionization-time-of-flight analysis, and their roles in susceptibility to 5-FU or radiation were evaluated in various cell lines by transfection of specific siRNA or creation of overexpression constructs. Changes in cellular signaling and expression of mitochondrial apoptotic factors were investigated by Western Blot analysis. A mitochondrial membrane potential probe (JC-1 dye) and a flow cytometry system were employed to determine the mitochondrial membrane potential. Finally, protein levels were determined by Western Blot analysis in tissues from 122 patients with rectal cancer to clarify whether each identified protein is a useful predictor of a chemoradiation response.Results: We identified mitochondrial phosphoenolpyruvate carboxykinase (mPEPCK) as a candidate predictor of 5-FU resistance. PEPCK was downregulated in SNU-C4R compared with its parent cell line SNU-C4. Overexpression of mPEPCK did not significantly alter the susceptibility to either 5-FU or radiation. Suppression of mPEPCK led to a decrease in both the cellular level of phosphoenolpyruvate and the susceptibility to 5-FU and radiation. Furthermore, the cellular levels of phosphoenolpyruvate (an end product of PEPCK and a substrate of pyruvate kinase), phosphorylated AKT, and phosphorylated 4EBP1 were decreased significantly secondary to the mPEPCK suppression in SNU-C4. However, mPEPCK siRNA transfection induced changes in neither the mitochondrial membrane potential nor the expression levels of mitochondrial apoptotic factors such as Bax, Bcl-2, and Bad. Downregulation of total PEPCK was observed in tissues from patients with rectal cancer who displayed poor responses to preoperative 5-FU-based radiation therapy.Conclusion: Our overall results demonstrate that mPEPCK is a useful predictor of a response to chemoradiotherapy in patients with rectal cancer. © 2014 Park et al.; licensee BioMed Central Ltd.

Jho H.J.,Hospital National Cancer Center | Myung S.-K.,Hospital National Cancer Center | Chang Y.-J.,Hospital National Cancer Center | Chang Y.-J.,National Cancer Control Institute | And 2 more authors.
Supportive Care in Cancer | Year: 2013

Purpose: Patient education has been considered as one of the important strategies to improve cancer pain control. However, randomized controlled trials (RCTs) have reported inconsistent findings on this issue. This study aims to evaluate the overall efficacy of pain education on improving pain management in cancer patients by using a meta-analysis of RCTs. Methods: We searched PubMed, EMBASE, and the Cochrane Library in February 2012. Two evaluators independently reviewed and selected trials based on the predetermined selection criteria. Out of 213 articles meeting initial criteria, 12 RCTs involving 2,169 participants (1,069 intervention group and 1,100 control group), were included in the final analysis. Results: In the meta-analysis of all 12 RCTs, compared with the control group, the intervention group showed a small significant lower pain intensity (standardized mean difference [SMD], -0.11; 95 % confidence interval [CI], -0.20 to -0.02). In the subgroup meta-analysis by various factors, a beneficial effect of pain education was observed for patients with an estimated prognosis of at least 3 months, a follow-up within 2 weeks after pain education, multiple sessions, measured worst pain, tailored education, general pain management, education by medical staff, and usual care for a control group. However, in the subgroup meta-analyses of trials using attention control as a control group and high-quality trials, there was no significant effect of pain education. Conclusions: Further large, high-quality RCTs using a placebo control such as attention control are required to investigate whether pain education has a true efficacy on pain control or is a placebo effect. © 2013 Springer-Verlag Berlin Heidelberg.

Kim Y.-S.,Seoul National University | Kwak S.M.,Sungkyunkwan University | Myung S.-K.,Hospital National Cancer Center
Neuroepidemiology | Year: 2015

Background: Observational epidemiological studies such as cross-sectional, case-control, and cohort studies have reported inconsistent findings regarding the association between caffeine intake from coffee or tea and the risk of cognitive disorders such as dementia, Alzheimer's disease, cognitive impairment, and cognitive decline. Methods: We searched PubMed and EMBASE in September 2014. Three evaluators independently extracted and reviewed articles, based on predetermined selection criteria. Results: Out of 293 articles identified through the search and bibliographies of relevant articles, 20 epidemiological studies from 19 articles, which involved 31,479 participants (8,398 in six cross-sectional studies, 4,601 in five case-control studies, and 19,918 in nine cohort studies), were included in the final analysis. The pooled odds ratio (OR) or relative risk (RR) of caffeine intake from coffee or tea for cognitive disorders (dementia, Alzheimer's disease, cognitive impairment, and cognitive decline) was 0.82 (95% confidence interval [CI], 0.67-1.01, I2 = 63.2%) in a random-effects meta-analysis. In the subgroup meta-analysis by caffeine sources, the summary OR or RR of coffee intake was 0.83 (95% CI, 0.70-0.98; I2 = 44.8%). However, in the subgroup meta-analysis by study design, the summary estimates (RR or OR) of coffee intake for cognitive disorders were 0.70 (95% CI, 0.50-0.98; I2 = 42.0%) for cross-sectional studies, 0.82 (95% CI, 0.55-1.24; I2 = 33.4%) for case-control studies, and 0.90 (95% CI, 0.59-1.36; I2 = 60.0%) for cohort studies. Conclusions: This meta-analysis found that caffeine intake from coffee or tea was not associated with the risk of cognitive disorders. © 2015 S. Karger AG, Basel.

Jo S.J.,Seoul National University | Shin H.,Dongguk University | Jo S.,Seoul National University | Kwon O.,Seoul National University | Myung S.-K.,Hospital National Cancer Center
Clinical and Experimental Dermatology | Year: 2015

Summary Background Hand-foot syndrome (HFS) is a common cutaneous side effect of certain systemic chemotherapeutic agents. Aim To assess the efficacy of pyridoxine supplements in the management of HFS. Methods We searched PubMed, EMBASE and the Cochrane Central Register of Controlled Trials for studies reporting the efficacy of pyridoxine supplements to manage HFS. We performed a meta-analysis using HFS incidence and improvement rates to measure the preventive and treatment efficacy of pyridoxine supplementation. Results We assessed eight studies [two retrospective studies, two prospective comparative trials and four randomized controlled trials (RCTs)] for preventive efficacy and three studies (one RCT and two non-RCTs) for treatment efficacy. A random-effects meta-analysis did not find any significant association between prophylactic pyridoxine supplementation and HFS development [relative risk (RR) = 0.95; 95% CI 0.87-1.05) or any significant preventive efficacy against HFS in subgroup meta-analyses of study design, chemotherapeutic agents, pyridoxine dose, HFS severity, publication year or observation period. However, pyridoxine did show significant efficacy in treating HFS (RR = 1.75; 95% CI 1.09-2.80), but did not show efficacy in the only RCT (RR = 1.12; 95% CI 0.58-2.14). Conclusions We found no clinical evidence to support the use of pyridoxine supplements to prevent HFS during chemotherapy. © 2014 British Association of Dermatologists.

Kim B.C.,Hospital National Cancer Center | Chang H.J.,Hospital National Cancer Center | Su Han K.,Hospital National Cancer Center | Sohn D.K.,Hospital National Cancer Center | And 5 more authors.
Endoscopy | Year: 2011

Background and study aims: Laterally spreading tumors (LST) are classified into two subtypes, with the nongranular type harboring a higher risk of (pre)malignant changes than the granular type. Further subdifferentiation into two subgroups each has been suggested, but the clinical significance of such a subdifferentiation has not previously been studied in detail in larger numbers. Patients and methods: Out of 6499 patients diagnosed with colorectal adenomas between January 2006 and November 2008, 153 patients (2.35 %) had 158 LSTs, 96 with a granular and 62 with a nongranular pattern. The former group was subdivided into homogeneous and nodular mixed, the latter group into flat elevated and pseudodepressed. Clinical and histopathological parameters were compared among the four subtypes. Results: Parameters were variably distributed between the four groups, with nodular mixed tumors being larger than the other three types (P < 0.0001). As in other studies, malignant transformation and premalignant lesion (HGIN/CIS) were more frequent in nodular mixed than in homogeneous tumors (45.0 % vs. 5.6 %, P < 0.001), and also more common in pseudodepressed than in flat elevated tumors (41.7 % vs. 13.2 %, P = 0.011). Submucosal invasive cancer was present in 8.3 % of nodular mixed tumors, 7.9 % of flat elevated, and 12.5 % of pseudodepressed, while it was absent in homogeneous tumors. Serrated adenoma was identified in 10.8 % of all LSTs, and sessile serrated adenoma tended to be more common in flat elevated tumors. Conclusions: Further subdifferentiation of the LST lesions to identify lesions at risk of malignant transformation makes most sense in the granular type. Among nongranular LSTs, both subtypes carry a significant risk. © Georg Thieme Verlag KG Stuttgart - New York.

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