Moon-Won Yoo

Functional links between clustered microRNAs: suppression of cell-cycle inhibitors by microRNA clusters in gastric cancer

microRNAs (miRNAs) play integral roles in diverse processes including tumorigenesis. miRNA gene loci are often found in close conjunction, and such clustered miRNA genes are transcribed from a common promoter to generate polycistronic primary transcript. The primary transcript (pri-miRNA) is then processed by two RNase III proteins to release the mature miRNAs. Although it has been speculated that the miRNAs in the same cluster may play related biological functions, this has not been experimentally addressed. Here we report that the miRNAs in two clusters (miR-106b∼93 ∼ 25 and miR-222 ∼ 221) suppress the Cip/Kip family members of Cdk inhibitors (p57Kip2, p21Cip1 and p27Kip1). We show that miR-25 targets p57 through the 3′-UTR. Furthermore, miR-106b and miR-93 control p21 while miR-222 and miR-221 regulate both p27 and p57. Ectopic expression of these miRNAs results in activation of Cdk2 and facilitation of G1/S phase transition. Consistent with these results, both clusters are abnormally upregulated in gastric cancer tissues compared to the corresponding normal tissues. Ectopic expression of miR-222 cluster enhanced tumor growth in the mouse xenograft model. Our study demonstrates the functional associations between clustered miRNAs and further implicates that effective cancer treatment may require a combinatorial approach to target multiple oncogenic miRNA clusters.

Diagnostic accuracy of T and N stages with endoscopy, stomach protocol CT, and endoscopic ultrasonography in early gastric cancer

Preoperative accurate diagnosis of the T and N stages in early gastric cancer (EGC) is important in determining the application of various limited treatments. The aim of this study is to analyze the accuracy of T and N staging of EGC with esophagogastroduodenoscopy (EGD), Stomach protocol CT (S‐CT), and endoscopic ultrasonography (EUS), and the factors influencing the accuracy.

Synchronous and metachronous cancers in patients with gastric cancer

The purpose of this study is to investigate characteristics of synchronous and metachronous cancer in gastric cancer and to suggest appropriate methods of treatment management.

Increased morbidity rates in patients with heart disease or chronic liver disease following radical gastric surgery.

The aim of this study was to investigate possible associations between (i) comorbid disease and (ii) perioperative risk factors and morbidity following radical surgery for gastric cancer.

Long-Term Surgical Outcome of 1057 Gastric GISTs According to 7th UICC/AJCC TNM System: Multicenter Observational Study From Korea and Japan.

AbstractThe aim of this study was to evaluate the treatment and prognosis of gastric gastrointestinal stromal tumors (GISTs) according to the 7th UICC/AJCC tumor-node-metastasis (TNM) system and the modified National Institutes of Health (NIH) risk classification. The study cohort consisted of 1057 patients with gastric GIST who underwent surgery between January 2000 and December 2007 from 13 institutions in Korea and 2 in Japan. Clinicopathologic characteristics, surgical outcomes, recurrence, and 5-year recurrence-free survival were evaluated.The mean age of the patients was 58.6 years. Thirty patients (2.8%) had distant metastasis preoperatively. Median tumor size was 4.0 cm. Complete resection (R0 resection) was achieved in 1018 patients (96.3%). Eighty-six patients (8.1%) had postoperative complications, and 2 patients (0.2%) died within 30 days after surgery. According to the 7th UICC/AJCC TNM system, 5-year recurrence-free survival rates were 95% to 99% in stage I, 94.1% in stage II, 74.1% in stage IIIA, 48.6% in stage IIIB, and 50.0% in stage IV patients. On survival analysis of high-risk patients according to the TNM system, the 5-year recurrence-free survival rates were 91.6% in stage II, 74.1% in stage IIIA, and 48.6% in stage IIIB patients. Independent factors of recurrence following surgery for gastric GIST were gender, tumor size, mitotic count, and radicality on multivariate analysis.The treatment outcome and prognosis of gastric GIST in Korea and Japan seem more favorable compared to those in Western countries. Compared to the modified NIH risk classification, the 7th UICC/AJCC TNM system is more reflective of the 5-year recurrence-free survival of patients with gastric GIST.

Phase II Study of Induction Chemotherapy with Docetaxel, Capecitabine, and Cisplatin Plus Bevacizumab for Initially Unresectable Gastric Cancer with Invasion of Adjacent Organs or Paraaortic Lymph Node Metastasis

Purpose The purpose of this study was to evaluate the efficacy and safety of induction chemotherapy with docetaxel, capecitabine, and cisplatin (DXP) plus bevacizumab (BEV) on initially unresectable locally advanced gastric cancer (LAGC) or paraaortic lymph node (PAN) metastatic gastric cancer (GC). Materials and Methods Patients with LAGC or unresectable PAN metastatic GC received six induction chemotherapy cycles (60 mg/m2 docetaxel intravenously on day 1, 937.5 mg/m2 capecitabine orally twice daily on days 1-14, 60 mg/m2 cisplatin intravenously on day 1, and 7.5 mg/kg BEV intravenously on day 1 every 3 weeks), followed by conversion surgery. The primary endpoint was R0 resection rate. Results Thirty-one patients with invasion to adjacent organs but without PAN metastasis (n=14, LAGC group) or with PAN metastasis regardless of invasion (n=17, PAN group) were enrolled between July 2010 and December 2014. Twenty-seven patients (87.1%) completed six chemotherapy cycles. The most common grade ≥ 3 toxicities were neutropenia (71%), neutropenia with fever/infection (22.6%/3.2%), and stomatitis (16.1%). The clinical response and R0 resection rates were 64.3% (95% confidence interval [CI], 46.6 to 82.0) and 64.5% (LAGC group, 71.4%; PAN group, 58.8%), respectively. The pathological complete regression rate was 12.9%. After a median follow-up of 44.5 months (range, 39.4 to 49.7 months), the median progression-free survival and overall survival were 13.1 months (95% CI, 8.9 to 17.3) and 38.6 months (95% CI, 22.0 to 55.1), respectively. Conclusion Induction chemotherapy with DXP+BEV displayed antitumor activities with encouraging R0 resection rate and manageable toxicity profiles on patients with LAGC or PAN metastatic GC.

Calibration of Thomson scattering system on VEST

The Thomson scattering system has been recently installed on Versatile Experiment Spherical Torus (VEST) to measure the electron temperature and the density of the core plasmas. Since the calibration of the system is required for the accurate measurement of these parameters, a polychromator and the system efficiency are calibrated. The bias voltage of the detector is optimized and the relative responsivity of the polychromator is measured to analyse the spectral broadening. The tendency of decreasing responsivity because of the ambient temperature change is addressed together. The efficiencies of the alignments using HeNe laser and Nd:YAG laser are compared. After the alignment using Rayleigh scattering, it is improved ~ 7 times while the peak signal of the stray light is decreased. To evaluate the efficiencies of the alignment using HeNe laser, it is compared with the efficiency of the fine alignment by Rayleigh scattering. After absolute calibration is done, the Thomson scattering signal is estimated theoretically. The Bayesian analysis is tried using the synthetic data, and the results show that the input temperature and the density are inside the contour of the 90% confident level. The calibrated Thomson scattering system will provide the meaningful information of the core plasma of the VEST.

Comparison of long-term outcomes of endoscopic submucosal dissection and surgery for esophagogastric junction adenocarcinoma.

144Background: Endoscopic submucosal dissection (ESD) has been accepted as standard treatment for early gastric cancer. However, comparative outcomes of ESD and surgery have not been evaluated for adenocarcinoma in the esophagogastric junction (EGJ). We investigated the long-term outcomes of ESD compared with surgery for adenocarcinoma in the EGJ. Methods: Subjects who underwent ESD or surgery for Siewert type II adenocarcinoma which met absolute and expanded criteria between 2005 and 2010 were eligible for this study. Clinical features and treatment outcomes were retrospectively reviewed using medical records. Results: Among 79 patients included, 40 underwent ESD and 39 underwent surgery. During the median follow-up period of 60.9 months (range: 13.1-125.4 months), the 5-year overall survival rates were 93.9% and 97.3% for ESD and surgery groups, respectively (p= 0.376). There was no gastric cancer-related deaths in either groups. Adverse events occurred in 11 patients (13.9%) overall and the incidence o...