• Journal of Chest Surgery
• /
• v.47 no.3
• /
• pp.262-268
• /
• 2014

Background: The development of diagnostic techniques and an awareness of health examinations can bring about an early diagnosis of lung cancer. However, appropriate postoperative management and adjuvant chemotherapy remain under debate in postoperative therapeutic strategy. The present study was conducted to assess the clinicopathologic factors that influence recurrence and prognosis after complete resection of lung cancer. Methods: The present study analyzed 62 patients with lung cancer who underwent complete resection of diagnosed adenocarcinoma between 1994 and 2007. In addition to conventional factors, which include staging factor and histological evaluation, the present study also performed univariate and multivariate analyses to consider claudin, a cell adhesion molecule, as a prognostic factor by immunohistochemical staining. Results: There was no correlation between conventional factors, including lymphatic and vascular invasion, and recurrence. However, there was a significant correlation between high expression of claudin 4 and cancer recurrence. In particular, there was a correlation between high expressions of claudin 1, 4, and 5 and a reduction of disease-free survival. Conclusion: Increased expressions of claudin 4 were negative prognostic factors in adenocarcinoma of the lung and thus could be used to identify high-risk patients for adjuvant chemotherapy, even if they had early-stage lung cancer. The present findings collectively suggest that consideration of claudin as a prognostic factor in the active postoperative treatment in patients at high risk will lead to better therapeutic outcomes with fewer side effects.

• Radiation Oncology Journal
• /
• v.35 no.4
• /
• pp.332-339
• /
• 2017

Purpose: This study aimed to evaluate the prognostic effects of lymphovascular invasion (LVI) in triple-negative breast cancer (TNBC) patients who underwent surgical resection. Materials and Methods: A total of 63 non-metastatic TNBC patients who underwent surgical resection were retrospectively investigated from 2007 to 2016 in Inje University Busan Paik Hospital. Pathological tests revealed that 12 patients (19.0%) had LVI. Approximately 61.9% (n = 39) of the patients' samples stained positive for p53. Additional chemotherapy and radiotherapy (RT) were performed in 53 (84.1%) and 47 (74.6%) patients, respectively. Results: The median follow-up period was 39.5 months (range, 5.9 to 123.0 months). The pathological T stage (p = 0.008), N stage (p = 0.014), and p53 positivity (p = 0.044) were associated with LVI. Overall, the 3-year disease-free survival (DFS) rate and overall survival (OS) rate were 85.4% and 90.2%, respectively. Ten patients (15.9%) experienced relapse. LVI (n = 12) was associated with relapses (p = 0.016). p53 positivity was correlated with poor DFS (p = 0.048). Furthermore, LVI was related to poor DFS (p = 0.011) and OS (p = 0.001) and considered as an independent prognostic factor for DFS (p = 0.039). The 3-year DFS of patients with LVI (n = 12) was only 58.3%. Adjuvant RT minimized the negative prognostic effect of LVI on DFS (p = 0.068 [with RT] vs. p = 0.011 [without RT]). Conclusion: LVI was related to the detrimental effects of disease progression and survival of TNBC patients. Thus, a more effective treatment strategy is needed for TNBC patients with LVI.

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

• Biomolecules & Therapeutics
• /
• v.17 no.2
• /
• pp.162-167
• /
• 2009

Adipocytes undergo adipocyte stress in the excessive presence of lipid. Adipocyte stress accompanies the typical signs of endoplasmic reticulum (ER) stress: unfolded protein response and overexpression of molecular chaperones. Apoptotic induction in adipocytes is known as a good strategy for treating obesity. The drug "tunicamycin" was tested for its therapeutic potential in inducing apoptosis on differentiating adipocytes of 3T3-L1. When the 3T3-L1 cells, stimulated for adipogenesis, were treated with tunicamycin, they showed typical ER stress symptoms. Despite progression in ER stress, however, the differentiated 3T3-L1 hardly proceeded to apoptosis based on the CHOP protein expression and FACS analysis. This is very different from C2C12, the myogenic counterpart of 3T3-L1, which showed significant apoptosis along with ER stress. This study also characterizes a potential mechanism whereby adipocyte may avoid apoptosis to sustain the pathological state of obesity. The level of GRP94 expression significantly upholds in 3T3-L1 under tunicamycin treatment compared to preadipocytes and C2C-12. When GRP94 expression was inhibited by siRNA, 3T3-L1 showed a higher level of CHOP expression compared to C2C12 cells. In conclusion, adipocytes exert an anti-apoptotic mechanism under ER stress caused by tunicamycin; thus, apoptotic induction in adipocyte is not a viable anti-obesity option. The unusual level of GRP94 may serve as a key role whereby adipocytes reach to the obesity level circumventing the apoptosis.

• Biomolecules & Therapeutics
• /
• v.28 no.1
• /
• pp.110-118
• /
• 2020

Migration presents a substantial social and public health issue. However, it is unclear whether diabetes is worse among Asian migrants than natives of South Korea over time. This longitudinal study investigated the nationwide population, including 2,680,495 adults aged 20 years and older (987,214 Asian migrants and 1,693,281 natives), who received health check-ups, using the Korean National Health Insurance Service data (2009-2015). Joinpoint regression was used to estimate the annual percentage change of diabetes, and multivariable logistic regression was used to examine differences in incident type 2 diabetes between Asian migrants and natives adjusting for age, sex, economic status, body mass index, smoking status, any alcohol use, and physical activity. The age-adjusted prevalence of diabetes increased among native men (from 8.8% in 2009 to 9.7% in 2015, APC=1.64, p<0.05) compared to Asian migrant men, and the age-adjusted prevalence of diabetes increased among native women (from 6.0% in 2009 to 6.7% in 2015, APC=1.88, p<0.05) compared to Asian migrant women. In the multivariate analyses, Asian migrants were less likely to get type 2 diabetes than natives (odds ratio, 0.82; 95% CI, 0.78 to 0.86) between the first and last health check-ups. However, the odds ratio for developing type 2 diabetes was 1.15 (95% CI, 1.10 to 1.20) among low-income levels compared to high-income levels, regardless of whether they were Asian migrants or natives. The results could help to establish a new strategy for prevention, treatment, and management of diabetes among the Asian population.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.5 no.2
• /
• pp.206-211
• /
• 2002

Wilson's disease is a treatable autosomal recessive inherited disorder of copper metabolism due to mutation of the copper transporting gene. The basic strategy of treatment is to reduce the amount of copper in the liver and other tissues by administering both a low copper diet and copper-chelating agents. D-penicillamine is the first choice as a copper-chelating agent. Some serious side effects could occur in 3~5% of all patients following D-penicillamine therapy. We report a 19 year-old male with Wilson's disease who developed nephrotic syndrome 6 months after the initiation of D-penicillamine therapy. Prednisolone was administered to control nephrotic syndrome and D-penicillamine was switched to trientine. Urinary remission was achieved within a week and maintained thereafter. Nephrotic syndrome was proven to be MCNS by kidney biopsy.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.20 no.4
• /
• pp.222-226
• /
• 2017

Purpose: Celiac disease, an autoimmune enteropathy triggered by exposure to gluten, is not uncommon in South Jordan. However, its prevalence is underestimated due to lack of physician awareness of the diversity of disease presentation. The clinical spectrum includes classic gastrointestinal manifestations, as well as rickets, iron-deficiency anemia, short stature, elevated liver enzymes, and edema. Our goal was to evaluate celiac disease presentation in clinically diagnosed children. Methods: Retrospective study included all children diagnosed with celiac disease between September 2009 and September 2015. Hospital charts were reviewed. Demographic data, clinical characteristics, and follow-up were recorded. Results: Thirty-five children were diagnosed with celiac disease during the study period. Mean age${\pm}$standard deviation was $6.7{\pm}3.8$ years (range, 2.0-14 years). There were 17 (48.6%) female patients. The average duration between onset of symptoms and diagnosis was $16.3{\pm}18.7$ months. Fifteen (42.9%) patients presented with classic malabsorption symptoms, whereas 7 (20.0%) patients presented with short stature. Positive tissue transglutaminase antibodies (tTg)-immunoglobulin A (IgA) was seen in 34 (97.1%) patients. The one patient with negative tTg-IgA had IgA deficiency. Although tTG-IgA values were not available for objective documentation of compliance, clinical data (resolution of presenting abnormalities and growth improvement) assured acceptable compliance in 22 (62.9%) patients. Conclusion: CD in children may present with diverse picture. Although of the small number, the non-classical presentations are not uncommon in our rural community. Gluten-free diet is the main strategy for treatment and associated with usually correction of laboratory abnormalities and improvement of growth.

• Horticultural Science & Technology
• /
• v.19 no.1
• /
• pp.43-47
• /
• 2001

This study was conducted to investigate the integrated control strategy against pear black leaf spot disease. Using indicator plant PS-95 we selected six virus-free trees (cv. Niitaka) from commercial orchards in the major pear production area. Disease symptom by pear black leaf spot in the shoot of pear (Niitaka) has been successfully inhibited by heat treatments for 3 weeks at temperature of $40^{\circ}C$ (day) and $32^{\circ}C$ (night) or 4 weeks at $37^{\circ}C$ and $30^{\circ}C$, respectively. However, survival rate of the shoot tips on stocks was low. Seven cultivars Niitaka, Imamura- aki, Waseaka, Nijisseiki, Wasenijisseiki, Shinsetsu and Whangkeumbae produced visible symptoms in the first year after inoculation with the virus. Other 11 selections remained symptomless. Two resistant cultivars Suwhangbae and Gamcheonbae were selected, which showed high fruit quality. It is recommended that these cultivars could be top-grafted onto the infected Niitaka trees to overcome the damage caused by the disease in the orchard.

• Journal of Radiation Industry
• /
• v.10 no.4
• /
• pp.181-187
• /
• 2016

Selective ${\beta}_1$-agonist and antagonists are used for the treatment of cardiac diseases including congestive heart failure, angina pectoris and arrhythmia. Selective ${\beta}_1$-antagonists including nebivolol have high binding affinity on ${\beta}_1$-adrenergic receptor, not ${\beta}_2$-receptor mainly expressed in smooth muscle. Nebivolol is one of most selective ${\beta}_1$-blockers in clinically used ${\beta}_1$-blockers including atenolol and bisoprolol. We tried to develop clinically useful cardiac PET tracers using a selective ${\beta}_1$-blocker. Nebivolol is $C_2$-symmetric and has two chromane moiety with a secondary amino alcohol and aromatic fluorine. We adopted the general synthetic strategy using epoxide ring opening reaction. Unlike formal synthesis of nebivolol, we prepared two chromane building blocks with fluorine and iodine which was transformed to diaryliodonium salt for labelling of $^{18}F$. Two epoxide building blocks were readily prepared from commercially available chromene carboxylic acids (1, 8). Then, the amino alcohol building block (15) was prepared by ammonolysis of epoxide (14) followed by coupling reaction with the other building block, epoxide (7). Diaryliodonium salt, a precursor for $^{18}F$-aromatic substitution, was synthesized in moderate yield which was readily subjected to $^{18}F$-aromatic substitution to give $^{18}F$-labelled nebivolol.

• Gut and Liver
• /
• v.12 no.6
• /
• pp.633-640
• /
• 2018

Background/Aims: Obesity is a risk factor for gastroesophageal reflux disease (GERD), with several studies demonstrating positive associations between body mass index (BMI) and GERD symptoms. However, little is known about the effect of BMI changes on erosive esophagitis (EE). In this study, we investigated whether BMI reduction could resolve EE. Methods: A retrospective cohort study was performed to assess the natural course of EE according to changes in BMI. Participants undergoing health check-ups from 2006 to 2012 were enrolled, and 1,126 subjects with EE were included. The degree of esophagitis was measured by upper endoscopy and serially checked over a 5-year follow-up. Logistic regression and Cox proportional hazards models were used to investigate the association between BMI reduction and EE resolution. Results: Substantial weight loss is associated with EE resolution. The adjusted odds ratio for EE resolution was 1.44 (95% confidence interval [CI], 1.09 to 1.92) among participants with a decrease in BMI compared to those with no decrease in BMI. The EE resolution rate was related to the degree of BMI reduction. The effect of weight loss on EE resolution was higher among subjects who lost more weight. Compared with subjects with no decrease in BMI, the hazard ratios for EE resolution were 1.09 (95% CI, 0.89 to 1.35), 1.31 (95% CI, 1.01 to 1.72) and 2.12 (95% CI, 1.44 to 3.12) in subjects with BMI reductions of ${\leq}1$, 1-2, and >$2kg/m^2$, respectively. Conclusions: EE resolution is associated with a decrease in BMI, and weight loss is potentially an effective GERD treatment.