• Journal of Gastric Cancer
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• 제10권3호
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• pp.91-98
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• 2010

Purpose: Silent mating-type information regulation 2 homologue 1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase. SIRT1 plays an important role in the regulation of cell death/survival and stress response in mammals. The aim of this study was to investigate whether the SIRT1 gene is involved in the development or progression of gastric cancers. Materials and Methods: SIRT1 and p53 genes in 86 gastric cancers were examined for genetic alterations by PCR-single strand conformation polymorphism sequencing, as well as SIRT1 protein expression in 170 gastric cancers by immunohistochemistry. Results: In the genetic analysis, we found SIRT1 and p53 mutations in two and 12 cases, respectively. Two missense mutations, c.599 C>T (T200I) and c.1258 G>A (E420K), were detected in the SIRT1 gene coding region. The SIRT1 and p53 mutation were found in mutually exclusive gastric cancers. The immunohistochemistry revealed that SIRT1 overexpression was found in 95 (55.9%) of 170 gastric cancers. Altered SIRT1 expression was not statistically associated with clinicopathological parameters, including tumor differentiation, location, lymph node metastasis, or p53 expression. Two cases with an SIRT1 mutation showed increased SIRT1 expression. Conclusions: These results suggest that genetic alterations and overexpression of the SIRT1 gene may contribute to gastric cancer development.

• BMB Reports
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• 제54권7호
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• pp.368-373
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• 2021

The vertebrate genome contains an endogenous retrovirus that has been inherited from the past millions of years. Although approximately 8% of human chromosomal DNA consists of sequences derived from human endogenous retrovirus (HERV) fragments, most of the HERVs are currently inactive and noninfectious due to recombination, deletions, and mutations after insertion into the host genome. Several studies suggested that Human endogenous retroviruses (HERVs) factors are significantly related to certain cancers. However, only limited studies have been conducted to analyze the expression of HERV derived elements at protein levels in certain cancers. Herein, we analyzed the expression profiles of HERV-K envelope (Env) and HERV-R Env proteins in eleven different kinds of cancer tissues. Furthermore, the expression patterns of both protein and correlation with various clinical data in each tissue were analyzed. The expressions of both HERV-K Env and HERV-R Env protein were identified to be significantly high in most of the tumors compared with normal surrounding tissues. Correlations between HERV Env expressions and clinical investigations varied depending on the HERV types and cancers. Overall expression patterns of HERV-K Env and HERV-R Env proteins were different in every individual but a similar pattern of expressions was observed in the same individual. These results demonstrate the expression profiles of HERV-K and HERV-R Env proteins in various cancer tissues and provide a good reference for the association of endogenous retroviral Env proteins in the progression of various cancers. Furthermore, the results elucidate the relationship between HERV-Env expression and the clinical significance of certain cancers.

• 한국간담췌외과학회지
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• 제27권4호
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• pp.415-422
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• 2023

Backgrounds/Aims: Although cancer survivors are at higher risk of developing second primary malignancies, cancer surveillance strategies for them have not yet been established. This study aimed to identify first primary cancers that had high risks of developing second primary exocrine pancreatic cancer (EPC). Methods: Data on individuals diagnosed with primary cancers between 1993 and 2017 were obtained from the Korea Central Cancer Registry. The standardized incidence ratios (SIRs) of second primary EPCs were analyzed according to the primary tumor sites and follow-up periods. Results: Among the 3,205,840 eligible individuals, 4,836 (0.15%) had second primary EPCs, which accounted for 5.8% of the total EPC patients in Korea. Between 1 and 5 years after the diagnosis of first primary cancers, SIRs of second primary EPCs were increased in patients whose first primary cancers were in the bile duct (males 2.99; females 5.03) in both sexes, and in the small intestine (3.43), gallbladder (3.21), and breast (1.26) in females. Among those who survived 5 or more years after the diagnosis of first primary cancers, SIRs of second primary EPCs were elevated in patients whose first primary cancers were in the bile duct (males 2.61; females 2.33), gallbladder (males 2.29; females 2.22), and kidney (males 1.39; females 1.73) in both sexes, and ovary (1.66) and breast (1.38) in females. Conclusions: Survivors of first primary bile duct, gallbladder, kidney, ovary, and female breast cancer should be closely monitored for the occurrence of second primary EPCs, even after 5 years of follow-up.

• Korean Journal of Radiology
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• 제21권9호
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• pp.1027-1035
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• 2020

Objective: To assess the appropriate follow-up interval, and rate and timepoint of cancer detection in women with Breast Imaging Reporting and Data System (BI-RADS) 3 lesions on screening ultrasonography (US) according to the type of institution. Materials and Methods: A total of 1451 asymptomatic women who had negative or benign findings on screening mammogram, BI-RADS 3 assessment on screening US, and at least 6 months of follow-up were included. The median follow-up interval was 30.8 months (range, 6.8-52.9 months). The cancer detection rate, cancer detection timepoint, risk factors, and clinicopathological characteristics were compared between the screening and tertiary centers. Nominal variables were compared using the chi-square or Fisher's exact test and continuous variables were compared using the independent t test or Mann-Whitney U test. Results: In 1451 women, 19 cancers (1.3%) were detected; two (0.1%) were diagnosed at 6 months and 17 (1.2%) were diagnosed after 12.3 months. The malignancy rates were both 1.3% in the screening (9 of 699) and tertiary (10 of 752) centers. In the screening center, all nine cancers were invasive cancers and diagnosed after 12.3 months. In the tertiary center, two were ductal carcinomas in situ and eight were invasive cancers. Two of the invasive cancers were diagnosed at 6 months and the remaining eight cancers newly developed after 13.1 months. Conclusion: One-year follow-up rather than 6-month follow-up may be suitable for BI-RADS 3 lesions on screening US found in screening centers. However, more caution is needed regarding similar findings in tertiary centers where 6-month follow-up may be more appropriate.

• 보험의학회지
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• 제29권2호
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• pp.8-17
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• 2010

• Asian Pacific Journal of Cancer Prevention
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• 제15권11호
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• pp.4689-4695
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• 2014

Background: A great number of studies have shown that cytochrome P450 1A1 (CYP1A1) genetic polymorphisms, CYP1A1 Msp I and CYP1A1 Ile/Val, might be risk factors for digestive tract cancers, including esophageal cancer (EC), gastric cancer (GC), hepatic carcinoma (HC), as well as colorectal cancer (CC), but the results are controversial. In this study, a meta-analysis of this literature aimed to clarify associations of CYP1A1 genetic polymorphisms with digestive tract cancers susceptibility in Chinese populations. Materials and Methods: Eligible case-control studies published until December 2013 were retrieved by systematic literature searches from PubMed, Embase, CBM, CNKI and other Chinese databases by two investigators independently. The associated literature was acquired through deliberate search and selection based on established inclusion criteria. Fixed-effects or random-effects models were used to estimate odds ratios (ORs and 95%CIs). The meta-analysis was conducted using Review Manager 5.2 and Stata 12.0 softwares with stability evaluated by both stratified and sensitivity analyses. Moreover, sensitivity analysis and publication bias diagnostics confirmed the reliability and stability. Results: Eighteen case-control studies with 1,747 cases and 2,923 controls were selected for CYP1A1 MspI polymorphisms, and twenty case-control studies with 3, 790 cases and 4, 907 controls for the CYP1A1 Ile/Val polymorphisms. Correlation associations between CYP1A1 Ile/Val polymorphisms and digestive tract cancers susceptibility were observed in four genetic models in the meta-analysis (GG vs AA:OR= 2.03, 95%CI =1.52- 2.72; AG vs AA: OR=1.26, 95%CI =1.07-1.48; [GG+AG vs AA] :OR =1.42, 95%CI=1.20-1.68, [GG vs AA+AG]:OR=1.80, 95%CI =1.40-2.31). There was no association between CYP1A1 Msp I polymorphisms and digestive tract cancers risk. Subgroup analysis for tumor type showed a significant association of CYP1A1 Ile/Val genetic polymorphisms with EC in China. However, available data collected by the study failed to reveal remarkable associations of GC or HC with CYP1A1 Ile/Val genetic polymorphisms and EC, GC or CC with CYP1A1 MspI genetic polymorphisms. Conclusions: Our results indicated that CYP1A1 Ile/Val genetic polymorphisms, but not CYP1A1 Msp I polymorphisms, are associated with an increased digestive tract cancers risk in Chinese populations. Additional well-designed studies, with larger sample size, focusing on different ethnicities and cancer types are now warranted to validate this finding.

• Radiation Oncology Journal
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• 제1권1호
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• pp.55-60
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• 1983

To evaluate the usefulness of computed tomography (CT) in radiotherapy treatment planning in malignant tumors of thoracic cage, the computer generated dose distributions were compared between plans based on conventional studies and those based on CT scan. 22 cases of thoracic malignancies, 15 lung cancers and 7 esophageal cancers, diagnosed and treated in Department of Therapeutic Radiology of Seoul National University Hospital from September, 1982 to April, 1983, were analyzed. In lung cancers, dose distribution in plans using AP, PA parallel opposing ports with posterior spinal cord block and in plans using box technique both based on conventional studies were compared with dose distribution using AP, PA and two oblique ports based on CT scan. In esophageal cancers, dose distribution in plans based on conventional studies and those based on CT scans, both using 3 port technique were compared. The results are as follows: 1. Parallel opposing field technique were inadequate in all cases of lung cancers, as portion of primary tumor in 13 of 15 cases and portion of mediastinum in all were out of high dose volume. 2. Box technique was inadequate in 5 of 15 lung cancers as portion of primary tumor was not covered and in every case the irradiated normal lung volume was quite large. 3. Plans based on CT scan were superior to those based on conventional studies as tumor was demarcated better with CT and so complete coverage of tumor and preservation of more normal lung volume could be made. 4. In 1 case of lung cancer, tumor localization was nearly impossible with conventional studies, but after CT scan tumor was more clearly defined and localized. 5. In 1 of 7 esophageal cancers, the radiation volume should be increased for marginal coverage after CT scan. 6. Depth dose correction for tissue inhomogeneity is possible with CT, and exact tumor dose can be calculated. As a result radiotherapy treatment planning based on CT scan has a pteat advantage over that based on conventional studies.

• 대한두경부종양학회지
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• 제15권2호
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• pp.162-165
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• 1999

Background and Objectives: Multiple primary tumors of the upper aerodigestive tract are not unusual. We examined head and neck cancer patients to discover the presence of second primary cancer in their upper gastrointestinal tract, using esophagogastroscopy. Materials and Methods: Endoscopic examination of the upper gastrointestinal tract was performed on 51 patients whose head and neck cancers were treated at department of therapeutic radiology from August 1996 to April 1999. Two of all patients had been studied by barium swallowing study. In 51 patients, twenty-four had a primary tumor in the larynx, 8 in the oropharynx, 6 in the nasopharynx, 6 in the oral cavity, 6 in the hypopharynx, and 1 in the nasal cavity. Endoscopically pathologic lesions were biopsied. In control group, endoscopy was performed on 1097 patients who didn't complain any symptoms. Results: Endoscopy showed early malignant lesions in 4 cases(7.7%). Histology of esophageal cancers showed squamous cell carcinoma. Malignant lesions of stomach in 2 cases were histologically identified as adenocarcinoma. Two esophageal cancers occurred in patients whose primary lesions had oropharynx and hypopharynx. Two cases of gastric cancer were also accompanied by oropharynx and hypopharynx. The incidence of second primary cancer was 2 in oropharynx and 2 in hypopharynx. In all cases, second primary cancers were found simultaneously. In control group, 9(0.8%) of 1097 patients were confirmed as early esophageal and gastric cancers. Conclusion: The majority of esophageal and gastric cancer detected by endoscopy were early stage in both head and neck cancer and control group. The incidence of esophageal and gastric cancer of head and neck cancer patients was 10 times as high as that of control group. Although followup period was short, all second primary cancers were detected simultaneously. We would recommend that endoscopic evaluation be included in the workup and followup of all patients with newly diagnosed head and neck cancer.

• Biomolecules & Therapeutics
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• 제29권5호
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• pp.551-561
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• 2021

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2249-2254
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• 2013

The study was conducted to determine the effect of Malaysian jungle Tualang Honey (TH) on development of breast cancer induced by the carcinogen 7,12-dimethylbenz(${\alpha}$)anthracene (DMBA) in rats. Forty nulliparous female Sprague-Dawley rats were given 80 mg/kg DMBA then randomly divided into four groups: Group 1 served as a Control while Groups 2, 3 and 4 received 0.2, 1.0 or 2.0 g/kg bodyweight/day of TH, respectively, for 150 days. Results showed that breast cancers in the TH-treated groups had slower size increment and smaller mean tumor size (${\leq}2cm^3$) compared to Controls (${\leq}8cm^3$). The number of cancers developing in TH-treated groups was also significantly fewer (P<0.05). Histological grading showed majority of TH-treated group cancers to be of grade 1 and 2 compared to grade 3 in controls. There was an increasing trend of apoptotic index (AI) seen in TH-treated groups with increasing dosage of Tualang Honey, however, the mean AI values of all TH-treated groups were not significantly different from the Control value (p>0.05). In conclusion, Tualang Honey exerted positive modulation effects on DMBA-induced breast cancers in rats in this preliminary study.