• Journal of Microbiology
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• v.41 no.4
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• pp.340-344
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• 2003

The group I intron from Tetrahymena thermophila has been demonstrated to employ splicing reactions with its substrate RNA in the trans configuration. Moreover, we have recently shown that the transsplicing group I ribozyme can replace HCV-specific transcripts with a new RNA that exerts anti-viral activity. In this study, we explored the potential use of RNA replacement for cancer treatment by developing trans-splicing group I ribozymes, which could replace tumor-associated RNAs with the RNA sequence attached to the 3' end of the ribozymes. Thymidine phosphorylase (TP) RNA was chosen as a target RNA because it is known as a valid cancer prognostic factor. By performing an RNA mapping strategy that is based on a trans-splicing ribozyme library, we first determined which regions of the TP RNA are accessible to ribozymes, and found that the leader sequences upstream of the AUG start codon appeared to be particularly accessible. Next, we assessed the ribozyme activities by comparing trans-splicing activities of several ribozymes that targeted different regions of the TP RNA. This assessment was performed to verify if the target site predicted to be accessible is truly the most accessible. The ribozyme that could target the most accessible site, identified by mapping studies, was the most active with high fidelity in vitro. Moreover, the specific trans-splicing ribozyme reacted with and altered the TP transcripts by transferring an intended 3' exon tag sequence onto the targeted TP RNA in mammalian cells with high fidelity. These results suggest that the Tetrahymena ribozyme can be utilized to replace TP RNAs in tumors with a new RNA harboring anti-cancer activity, which would revert the malignant phenotype.

• Childhood Kidney Diseases
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• v.24 no.2
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• pp.91-97
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• 2020

Purpose: Alport syndrome (AS) is one of the most common inherited renal diseases caused due to mutations of genes encoding specific proteins of the type IV collagen family, and its major clinical manifestations include progressive renal failure, sensorineural deafness, and ocular abnormalities. We investigated the clinical characteristics and long-term prognosis of AS in Korean pediatric and adult populations. Methods: We conducted a retrospective review of medical records of 33 children and adults who had been diagnosed or treated with AS from 1985 to 2019. Results: The mean age of the 33 patients diagnosed with AS was 16.2±13.6 years, and the male-to-female ratio was 2:1. At the first visit, recurrent gross hematuria was the most common initial symptom. In 10 of 33 patients (30.3%), sensorineural hearing loss (SNHL) was diagnosed, but none had ophthalmic problems. Moreover, 11 of 33 patients (33.3%) had advanced to end-stage renal disease (ESRD), and a significant difference was observed in the age of the patients who progressed to ESRD based on the presence or absence of SNHL (P=0.035). Conclusion: SNHL in AS can be an important prognostic factor for long-term deterioration of renal function. Further investigation is required to confirm the clinical course and the genetic characteristics of AS in Korea through prospective national cohort studies.

• Molecules and Cells
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• v.40 no.5
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• pp.363-370
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• 2017

Extrahepatic cholangiocarcinoma (ECC), a malignant tumor of biliary origin, has a poor prognosis with limited treatment options. The KRAS oncogene is the most commonly mutated gene in ECC and one of the factors that predicts a poor prognosis and low survival rate. L1 cell adhesion molecule (L1CAM) is expressed in ECC cells and acts as an independent poor prognostic factor in predicting patient survival. In this study we investigate the functional significance of L1CAM in ECC cells with activating KRAS mutation. We selected an ECC cell line, EGI-1, with activating KRAS mutation, and then confirmed its expression of L1CAM by RT-PCR, western blot analysis, and flow cytometry. The suppression of L1CAM expression (using a specific lentivirus-delivered shRNA) significantly decreased the migratory and invasive properties of EGI-1 cells, without altering their proliferation or survival. Analyses of signaling effectors in L1CAM-depleted and control EGI-1 cells indicated that L1CAM suppression decreased the levels of both phosphorylated MKK4 and total MKK4, together with c-Jun N-terminal kinase (JNK) phosphorylation. Further, exposure to a JNK inhibitor (SP600125) decreased migration and invasion of EGI-1 cells. These results suggest that L1CAM promotes cellular migration and invasion via the induction of MKK4 expression, leading to JNK activation. Our study is the first to demonstrate a functional role for L1CAM in ECC carrying the activating KRAS mutation. Given that KRAS is the most commonly mutated oncogene in ECC, L1CAM may serve as an attractive therapeutic target for ECC cells with activating KRAS mutation.

• Korean Journal of Head & Neck Oncology
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• v.13 no.1
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• pp.3-8
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• 1997

Malignant melanoma has a very poor prognosis compared to other cancers. There are no specific tumor markers other than clinical staging and depth of invasion to predict the prognosis of the malignant melanoma. The nm23 has been known to inhibit the metastasis of the malignant melanoma, some studies showed that it is highly expressed in the malignant melanoma cell line which has a relatively weak metastatic potential. In this study, we compared the expression of nm23 in mucosal type with that in cutaneous type of the malignant melanoma in the head and neck according to the stage and survival rate to identify the role of nm23 expression as a prognostic factor in mucosal melanoma of the head and neck. Six out of eight cases in mucosal type and seven out of 11 cases in cutaneous type expressed nm23, which showed no significant differences. Between the two groups there were no significant differences in expression of nm23 according to clinicopathologic staging or two year survival rate. However, in cases with low cliniopathological staging and those surviving more than two years the expression was significantly increased which suggests that expression of nm23 can be used as an aid in determining the prognosis of mucosal melanoma.

• Journal of Korean Neurosurgical Society
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• v.39 no.4
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• pp.271-276
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• 2006

Objective : Despite the recent progress that has been made in intracerebral monitoring, it is still difficult to quantify the exact extent of primary brain damage after severe head injury. In this work, we investigate the role of S-100B protein as a serum marker of brain damage after severe head injury. Methods : 21 patients with severe head injury [GCS score <9] were selected for this prospective study. A venous blood sample was taken as soon as possible after head injury and the serum concentration of S-100B protein was measured daily for five consecutive days. The serum level of S-100B protein was compared with the patients' outcome. The outcome was measured twice, at hospital discharge and after 6 months of follow-up using the Glasgow Outcome Scale[GOS]. Results : Those patients who died within two weeks [after head injury] had a significantly higher serum S-100B value than those who survived [median, 9.64ug/L versus 2.91ug/L]. Seven [78%] of the nine patients who died had a maximum S-100B value of 2ug/L or higher, while three [25%] of the twelve surviving patients showed a maximum S-100B protein value of more than 2ug/L [P<005]. Conclusion : These results indicate that S-100B protein appears to be the most reliable index for estimating the extent of brain damage.

• Journal of Korean Neurosurgical Society
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• v.60 no.4
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• pp.456-464
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• 2017

Objective : Although little is known about its origins, neck pain may be related to several associated anatomical pathologies. We aimed to characterize the incidence and features of chronic neck pain and analyze the relationship between neck pain severity and its affecting factors. Methods : Between March 2012 and July 2013, we studied 216 patients with chronic neck pain. Initially, combined tramadol (37.5 mg) plus acetaminophen (325 mg) was administered orally twice daily (b.i.d.) to all patients over a 2-week period. After two weeks, patients were evaluated for neck pain during an outpatient clinic visit. If the numeric rating scale of the patient had not decreased to 5 or lower, a cervical medial branch block (MBB) was recommended after double-dosed previous medication trial. We classified all patients into two groups (mild vs. severe neck pain group), based on medication efficacy. Logistic regression tests were used to evaluate the factors associated with neck pain severity. Results : A total of 198 patients were included in the analyses, due to follow-up loss in 18 patients. While medication was successful in reducing pain in 68.2% patients with chronic neck pain, the remaining patients required cervical MBB. Lateral cervical curvature, such as a straight or sigmoid type curve, was found to be significantly associated with the severity of neck pain. Conclusion : We managed chronic neck pain with a simple pharmacological management protocol followed by MBB. We should keep in mind that it may be difficult to manage the patient with straight or sigmoid lateral curvature only with oral medication.

• Clinical and Experimental Pediatrics
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• v.64 no.5
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• pp.229-238
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• 2021

Background: Bronchial hyperresponsiveness (BHR), an important physiological feature of asthma, is a prognostic marker of childhood asthma. Purpose: We aimed to investigate the factors associated with BHR in adolescents with childhood asthma. Methods: Two hundred and fifteen adolescents (≥13 years of age; 149 males, 66 females) who were diagnosed with asthma during childhood were enrolled, underwent methacholine challenge tests, and were divided into the BHR group (<25 mg/mL of provocation concentration causing a 20% fall in forced expiratory volume in 1 second [FEV₁] [PC₂₀], n=113) or non-BHR group (≥25 mg/mL of PC₂₀, n=102). We examined longitudinal changes in BHR and the risk factors for its persistence in the 108 adolescents for whom baseline data, including methacholine PC₂₀ at age 6 years, were available. Multivariate logistic regression analyses were performed to assess the factors associated with BHR in adolescents. Results: Mold sensitization (adjusted odds ratio [aOR], 5.569; P=0.005) and increased blood eosinophil count (aOR, 1.002; P=0.026) were independently associated with BHR in boys but not girls. The odds of BHR decreased by 32% with each 1-year increase in age in boys (aOR, 0.683; P=0.010) but not girls. A reduced FEV₁/forced vital capacity ratio (<90%) was independently related with BHR in female patients only (aOR, 7.500; P=0.007). BHR decreased with age throughout childhood. A low methacholine PC₂₀ at age 6 years was independently associated with persistent BHR throughout childhood in male and female patients, whereas early mold sensitization was a risk factor for persistent BHR in male patients only (aOR, 7.718; P=0.028). Conclusion: Our study revealed sex-specific differences in the factors associated with BHR in adolescents with childhood asthma. Our findings suggest the risk factors that might affect asthma transition from childhood to adolescence and adulthood.

• Journal of Yeungnam Medical Science
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• v.36 no.2
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• pp.115-123
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• 2019

Background: This study aimed to assess the in-field lymph node (LN) failure rate according to LN size and to investigate effect of LN size on the survival outcome of patients with locally advanced cervical carcinoma treated with concurrent chemoradiotherapy (CCRT). Methods: A total of 310 patients with locally advanced cervical carcinoma treated with CCRT were enrolled in retrospective study. LN status was evaluated by magnetic resonance imaging. All patients received conventional external beam irradiation and high-dose rate brachytherapy, and concurrent cisplatin-based chemotherapy. In-field LN failure rate according to LN size was analyzed. Results: The median follow-up period was 83 months (range, 3-201 months). In-field LN failure rate in patients with pelvic LN size more than 10 mm was significantly higher than that in patients with pelvic LN size less than 10 mm (p<0.001). A similar finding was observed in the infield para-aortic LN (PALN) failure rate (p=0.024). The pelvic and PALN size (${\geq}10mm$) was a significant prognostic factor of overall-survival (OS) and disease-free survival rate in univariate and multivariate analyses. The OS rate was significantly different between groups according to LN size (<10 mm vs. ${\geq}10mm$). Conclusion: A LN of less than 10 mm in size in an imaging study is controlled by CCRT. On the other hand, in LN of more than 10 mm in size, the in-field LN failure rate increase and the prognosis deteriorate. Therefore, a more aggressive treatment strategy is needed.

• Journal of Chest Surgery
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• v.52 no.5
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• pp.360-367
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• 2019

Background: Primary chest wall sarcoma is a rare disease with limited reports of surgical resection. Methods: This retrospective review included 41 patients with primary chest wall sarcoma who underwent chest wall resection and reconstruction from 2001 to 2015. The clinical, histologic, and surgical variables were collected and analyzed by univariate and multivariate Cox regression analyses for overall survival (OS) and recurrence-free survival (RFS). Results: The OS rates at 5 and 10 years were 73% and 61%, respectively. The RFS rate at 10 years was 57.1%. Multivariate Cox regression analysis revealed old age (hazard ratio [HR], 5.16; 95% confidence interval [CI], 1.71-15.48) as a significant risk factor for death. A surgical resection margin distance of less than 1.5 cm (HR, 15.759; 95% CI, 1.78-139.46) and histologic grade III (HR, 28.36; 95% CI, 2.76-290.87) were independent risk factors for recurrence. Conclusion: Long-term OS and RFS after the surgical resection of primary chest wall sarcoma were clinically acceptable.

• Journal of Gastric Cancer
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• v.19 no.2
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• pp.202-211
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• 2019

Purpose: Poor physiological reserve for withstanding major cancer surgery in older adults is an important concern in the selection of patients for oncologic gastrectomy. The present study aimed to analyze mortality patterns among patients who underwent gastrectomy for cancer according to age groups. The primary outcomes of this study were early- and middleterm results: 30-day and 3-, 6-, 12-, and 36-month mortality rates. Materials and Methods: A retrospective review of 288 patients who underwent surgical resection for gastric cancer in two centers was carried out. Patients were stratified into four groups according to age: 29-50 years (group I, n=27), 51-65 years (group II, n=117), 66-75 years (group III, n=81), and 76-92 years (group IV, n=58). Statistical calculations focused on the differences in the survival rates between groups I and II as well as between groups II and IV. Results: The middle-aged patients (group II) had significantly better 3-year survival than either the youngest (group I) or the oldest patients (group IV). The 6-month mortality rates were 16.9% in group III and 29.3% in group IV. Two-thirds of the patients from groups III and IV who died between 2 and 6 months after surgery had an uneventful postoperative course. Conclusions: Age is an important prognostic factor of middle-term survival after gastrectomy for cancer. Geriatric assessment and better patient selection for major surgery for cancer are required to improve the outcome of gastrectomy for cancer in patients aged over 75 years.