• Journal of Gastric Cancer
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• 제18권1호
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• pp.20-29
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• 2018

Purpose: Pre-operative lymph node (LN) size is a valuable parameter for determining treatment strategy for gastric cancer. However, a correlation between LN size and metastasis has not been established. Materials and Methods: Thirty-six LN-positive (LNP) and matched 36 LN-negative (LNN) patients were included, and pathology slides of the LNs of these patients were reviewed. All the LNs were measured along the long-axis (LA) and short-axis (SA), manually. Results: Average retrieved LNs were $37.3{\pm}19.8$ and $40.5{\pm}11.6$ in the LNN and LNP groups, respectively. In total 2,800 LNs, including 136 metastatic LNs (MLNs) and 2,664 non-metastatic LNs (nMLNs), were evaluated. Mean length was significantly more in MLNs along both, the LA and SA (MLN_LA vs. nMLN_LA: $4.97{\pm}3.84$ vs. $3.37{\pm}2.40mm$, MLN_SA vs. nMLN_SA: $3.86{\pm}3.19$ vs. $2.43{\pm}1.59mm$; P<0.001). However, 92.6% (126/136) and 95.6% (130/136) of MLNs were <10 mm along the LA and SA, respectively. In addition, only 22.2% of the LNP group exhibited an MLN as the largest LN. Conclusions: Pre-operative multi-detector computed tomography has limited ability in estimating the presence of metastasis in LNs because most MLNs are less than 10 mm, and only a small proportion of the LNP group exhibits an MLN as the largest MLN.

• Asian Pacific Journal of Cancer Prevention
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• 제13권10호
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• pp.5069-5074
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• 2012

Objectives: The purpose of this study was to determine the relationship between methylation status of the Dact1 gene and MTHFR a1298c polymorphic forms in transitional cell carcinoma tissues in a Chinese population. Methods: Polymorphisms of folate metabolism enzyme gene MTHFR were assessed by restrictive fragment length polymorphism (RFLP) methods and PCR-based DNA methylation analysis was used to determine the CpG island methylation status of the Dact1 gene. Associations between the methylation status of the Dact1 gene and clinical characteristics, as well as MTHFR a1298c polymorphisms, were analyzed. Results: aberrant methylation of the Dact1 gene was found in 68.3% of cancer tissues and 12.4% of normal tissues,. The methylation rate of the Dact1 gene in cancer tissues was significantly higher in patients with lymph node metastasis than in those without lymph node metastasis (46.3% vs. 17.2%, P = 0.018). No association was found between aberrant DNA methylation and selected factors including sex, age, tobacco smoking, alcohol consumption and green tea consumption. After adjusting for potential confounding variables, variant allele of MTHFR a1298c was found to be associated with methylation of the Dact1 gene. Compared with wild type CC, the odds ratio was 4.33 (95% CI: 1.06-10.59) for AC and 4.95 (95% CI: 1.18-12.74) for AA. The N stage in TNM staging and the occurrence of lymph node metastasis were associated with an MTHFR 1298 AA+AC genotype (P<0.05). Conclusion: MTHFR 1298 AC and AA genotypes might help maintain a normal methylation status of the Dact1 gene, aberrant CpG island methylation of which is closely related to the genesis and progression of transitional cell carcinoma.

• Radiation Oncology Journal
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• 제35권1호
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• pp.39-47
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• 2017

Purpose: The purpose of this study was to analyze clinical outcomes from cervical cancer and stratify patients into risk groups for prognostic factors for early-stage disease. Materials and Methods: We retrospectively reviewed patients with stage IB or IIA cervical cancer treated with adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) following primary surgery at Samsung Medical Center from 2001 to 2011. Adjuvant RT was added for patients with intermediate-risk factors, and adjuvant CCRT was performed on high-risk patients after surgery. Results: We reviewed 247 patients-149 in the high-risk group and 98 in intermediate-risk group. The median follow-up was 62 months. Loco-regional failure (LRF) alone occurred in 7 patients (2.8%), distant metastasis alone in 37 patients (15.0%) and LRF with DM in 4 patients (1.6%). The 5-year disease-free survival (DFS) and overall survival (OS) rates for both groups were 79.7% and 87.6%, respectively. In the high-risk group, the 5-year DFS and OS probabilities were 72.5% and 81.9%, respectively. Histologic type, pathologic tumor size, and the number of pelvic lymph node (PLN) metastasis were significant prognostic factors for DFS and OS. We suggest a scoring system (0-3) using these prognostic factors to predict poor prognosis in high-risk patients. Using this system, patients with higher scores have higher recurrence and lower survival rates. Conclusion: In the high-risk cervical-cancer group who received primary surgery and adjuvant CCRT, non-squamous type, large tumor size and the number of PLN metastasis were significant prognostic factors, and the number of these factors was associated with survival rates.

• Food Science and Biotechnology
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• 제18권6호
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• pp.1423-1429
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• 2009

Rhizopus oryzae KSD-815 was isolated from nuruk that has been used to make Korean traditional wines. This study was performed to investigate the effect of cultures of R. oryzae KSD-815 on cardiovascular disorders and cancer metastasis. Firstly, these cultures were sequentially fractionationed with n-hexane (TAHe), ethylacetate (TAE), n-butanol (TAB), and $H_2O$ (TAW). The TAE inhibited the activity of angiotensin-converting enzyme (ACE) and TAB suppressed platelet aggregation in vitro. TAE and TAB inhibited cell motility of human breast cancer cells. Furthermore, TAW interrupted the formation of neovasculature and tube-like structure, and down-regulated the expression of angiogenic factors, basic fibroblast growth factor (bFGF), tumor necrosis factor-$\alpha$ (TNF-$\alpha$), and hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) in breast cancer cells. These results indicated that cultures of R. oryzae KSD-815 display the inhibitory activities on hypertension, platelet aggregation, and metastasis, and suggest that these cultures might be further probed for the purposes as therapeutic agents or dietary supplements.

• 대한기관식도과학회지
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• 제8권1호
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• pp.81-86
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• 2002

Background and objectives : There may be frequent lymphatic neck metastasis among supraglottic cancer patients after their primary surgery. The aim of this study was to evaluate the effectiveness of prophylactic neck dissections in supraglottic cancer patients to lower the neck metastasis. Material and method : The authors retrospectively reviewed medical records of 52 patients (7 females. 45 males) who had received the operations for the supraglottic cancer from 1995 to 2000. They were preoperatively examined with Computer Tomographic images, and also examined by the cervical neck palpations. Postoperative pathologic specimens were reviewed and the Pathologic stagings were confirmed by the pathologist. Results : Among 52 patients who received surgery for supraglottic carcinoma, 5 patients received ipsilateral neck dissection, 12 patients received ipsilateral neck dissection with postoperative radiation therapy, 10 Patients received bilateral neck dissection and 25 patients received bilateral neck dissection with postoperative radiation treatment. In comparison of the data of N0 to N+ conversion rate of neck, there were 11 ipsilateral T3 N0 patients and 2 patients(18%) were converted to N+ status, and there were 8 Patients with T4 N0 stages, and 3 patients(38%) were converted to N+ status. In comparing the data of contralateral neck dissection on N0 patient, there were 8 patients of T3 N0 patients, and there was 1 patient (13%) who showed recurrence. There were 5 patients of T4 N0 stages and there was 1(20%) patient with recurrences. When the ipsilateral N stages were N2a, and N2b, there 1 case of contraleral N+ conversions, respectively. In recurrences, there were 2 patients of N2b staged patients and 1 patient of N2c patient that showed recurrence during the follow up period. Conclusion : This data shows that at least an ipsilateral neck dissection is necessary in order to prevent the recurrences, and also suggests that bilateral neck dissection is necessary for the higher T stage. Since the higher N staged patients showed higher rate of recurrence, so that neck dissection is mandatory for the higher N staged patients.

• Radiation Oncology Journal
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• 제34권2호
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• pp.96-105
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• 2016

Purpose: The standard radiation dose for patients with locally rectal cancer treated with preoperative chemoradiotherapy is 45-50 Gy in 25-28 fractions. We aimed to assess whether a difference exists within this dose fractionation range. Materials and Methods: A retrospective analysis was performed to compare three dose fractionation schedules. Patients received 50 Gy in 25 fractions (group A), 50.4 Gy in 28 fractions (group B), or 45 Gy in 25 fractions (group C) to the whole pelvis, as well as concurrent 5-fluorouracil. Radical resection was scheduled for 8 weeks after concurrent chemoradiotherapy. Results: Between September 2010 and August 2013, 175 patients were treated with preoperative chemoradiotherapy at our institution. Among those patients, 154 were eligible for analysis (55, 50, and 49 patients in groups A, B, and C, respectively). After the median follow-up period of 29 months (range, 5 to 48 months), no differences were found between the 3 groups regarding pathologic complete remission rate, tumor regression grade, treatment-related toxicity, 2-year locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, or overall survival. The circumferential resection margin width was a prognostic factor for 2-year locoregional recurrence-free survival, whereas ypN category was associated with distant metastasis-free survival, disease-free survival, and overall survival. High tumor regression grading score was correlated with 2-year distant metastasis-free survival and disease-free survival in univariate analysis. Conclusion: Three different radiation dose fractionation schedules, within the dose range recommended by the National Comprehensive Cancer Network, had no impact on pathologic tumor regression and early clinical outcome for locally advanced rectal cancer.

• 대한한방내과학회지
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• 제40권5호
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• pp.841-850
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• 2019

Objective: The aim of this study was to report the effects of traditional Korean medicine as a treatment for the pain of a compression fracture in a patient with metastatic prostate cancer. Methods: A 60-year-old male patient with a compression fracture was treated with herbal medicines, acupuncture, and pharmacopuncture for 25 days. His chief complaints were severe low back pain, pain and numbness in both legs, and right groin pain. The effect of treatment was evaluated by the numerical rating scale (NRS) score for pain, the Oswestry Disability Index (ODI) score, and blood test results (CBC-diff count, CRP, ESR, etc.). Results: After 25 days of inpatient treatment, the patient's pain was controlled. The NRS and ODI scores were lower and most pathological symptoms had decreased. Conclusions: Traditional Korean medicine can be a solution for patients with compression fractures arising from metastasis of prostate cancer to the spine.

• Molecules and Cells
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• 제45권4호
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• pp.202-215
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• 2022

The androgen receptor (AR) is an important therapeutic target for treating prostate cancer (PCa). Moreover, there is an increasing need for understanding the AR-independent progression of tumor cells such as neuroendocrine prostate cancer (NEPC). Menin, which is encoded by multiple endocrine neoplasia type 1 (MEN1), serves as a direct link between AR and the mixed-lineage leukemia (MLL) complex in PCa development by activating AR target genes through histone H3 lysine 4 methylation. Although menin is a critical component of AR signaling, its tumorigenic role in AR-independent PCa cells remains unknown. Here, we compared the role of menin in AR-positive and AR-negative PCa cells via RNAi-mediated or pharmacological inhibition of menin. We demonstrated that menin was involved in tumor cell growth and metastasis in PCa cells with low or deficient levels of AR. The inhibition of menin significantly diminished the growth of PCa cells and induced apoptosis, regardless of the presence of AR. Additionally, transcriptome analysis showed that the expression of many metastasis-associated genes was perturbed by menin inhibition in AR-negative DU145 cells. Furthermore, wound-healing assay results showed that menin promoted cell migration in AR-independent cellular contexts. Overall, these findings suggest a critical function of menin in tumorigenesis and provide a rationale for drug development against menin toward targeting high-risk metastatic PCa, especially those independent of AR.

• Journal of Gastric Cancer
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• 제22권1호
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• pp.24-34
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• 2022

Purpose: Total gastrectomy (TG) with lymph node (LN) dissection is recommended for early gastric cancer (EGC) but is not indicated for endoscopic resection (ER). We aimed to identify patients who could avoid TG by establishing a scoring system for predicting lymph node metastasis (LNM) in proximal EGCs. Materials and Methods: Between January 2003 and December 2017, a total of 1,025 proximal EGC patients who underwent TG with LN dissection were enrolled. Patients who met the absolute ER criteria based on pathological examination were excluded. The pathological risk factors for LNM were determined using univariate and multivariate logistic regression analyses. A scoring system for predicting LNM was developed and applied to the validation group. Results: Of the 1,025 cases, 100 (9.8%) showed positive LNM. Multivariate analysis confirmed the following independent risk factors for LNM: tumor size >2 cm, submucosal invasion, lymphovascular invasion (LVI), and perineural invasion (PNI). A scoring system was created using the four aforementioned variables, and the areas under the receiver operating characteristic curves in both the training (0.85) and validation (0.84) groups indicated excellent discrimination. The probability of LNM in mucosal cancers without LVI or PNI, regardless of size, was <2.9%. Conclusions: Our scoring system involving four variables can predict the probability of LNM in proximal EGC and might be helpful in determining additional treatment plans after ER, functioning as a good indicator of the adequacy of treatments other than TG in high surgical risk patients.

• Journal of Gastric Cancer
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• 제22권4호
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• pp.319-338
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• 2022

Purpose: Gastric cancer (GC) has high morbidity and mortality, the cure rate of surgical treatment and drug chemotherapy is not ideal. Therefore, development of new treatment strategies is necessary. We aimed to identify the mechanism underlying Sp1 regulation of GC progression. Methods and Methods: The levels of Sp1, β-catenin, SET domain bifurcated 1 (SETDB1), and 15-hydroxyprostaglandin dehydrogenase (HPGD) were detected by quantitative reverse transcription polymerase chain reaction and western blot analysis. The targets of SETDB1 were predicted by AnimalTFDB, and dual-luciferase reporter assay was used for confirming the combination of Sp1, β-catenin, and SETDB1. HGC27 or AGS cells (1×10⁶ cells/mouse) were injected into mice via the caudal vein for GC model establishment. The level of Ki67 was detected using immunohistochemistry, and hematoxylin and eosin staining was performed for evaluating tumor metastasis in mice with GC. Results: HPGD was inhibited, while the protein levels of Sp1, β-catenin, and SETDB1 were up-regulated in GC tissues and cell lines. HPGD overexpression or SETDB1 silencing inhibited the proliferation, invasion, and migration of GC cells, and Sp1 regulated the proliferation, invasion, and migration of GC cells in a β-catenin-dependent manner. Furthermore, HPGD served as a target of SETDB1, and it was negatively regulated by SETDB1; additionally, Sp1 and β-catenin bound to the SETDB1 promoter and negatively regulated HPGD expression. We proved that Sp1 regulated GC progression via the SETDB1/HPGD axis. Conclusions: Our findings revealed that Sp1 transcriptionally inhibited HPGD via SETDB1 in a β-catenin-dependent manner and promoted the proliferation and metastasis of GC cells.