• 한국방사선학회논문지
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• 제15권4호
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• pp.507-518
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• 2021

자기공명영상(MRI)은 뇌의 구조적 및 기능적 연구에서 핵심 기술로 필요성이 증가하고 있다. Tractography 분석을 이용하는 뇌지도(Connectome)는 MRI를 통해 뇌의 구조적 연결성을 확인하고 연결성의 변동성을 이용해 질병 병리학에 대한 이해를 높이는 방법으로 인간을 대상으로 활발한 연구가 진행되고 있다. 하지만 마우스 같은 작은 동물의 경우 분석 방법의 표준화가 부족하고 영상에 대한 정확한 전처리 전략 및 아틀라스 기반 신경 정보학에 대한 과학적 합의가 없다. 또한, 인간의 뇌에 비해 마우스의 뇌는 매우 작기 때문에 높은 해상도를 갖는 영상을 획득하는 것에도 어려움이 있다. 연구에서는 구조적 영상과 확산 텐서 영상을 이용해 구조 영역 세분화를 포함한 구조적 연결성 분석을 가능하게 하고 마우스 뇌 데이터를 처리하는 Allen Mouse Brain Atlas 기반 영상 데이터 분석 파이프라인을 제시한다. 각 분석 방법은 마우스 뇌 영상 데이터의 분석을 가능하게 하고 이미 인간 영상데이터로 검증된 소프트웨어를 이용해 신뢰성을 가질 수 있게 하였다. 또한, 연구에서 제시되는 파이프라인은 복잡한 분석 과정과 다양한 기능들 중 마우스 Tractography에 필요한 기능들을 정리하여 사용자가 효율적으로 데이터 처리를 하는데 최적화되었다.

• BMB Reports
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• 제36권1호
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• pp.49-59
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• 2003

Platelet-derived growth factor (PDGF) is a critical regulator of mesenchymal cell migration and proliferation. The vital functions of PDGFs for angiogenesis, as well as development of kidney, brain, cardiovascular system and pulmonary alveoli during embryogenesis, have been well demonstrated by gene knock-out approaches. Clinical studies reveal that aberrant expression of PDGF and its receptor is often associated with a variety of disorders including atherosclerosis, fibroproliferative diseases of lungs, kidneys and joints, and neoplasia. PDGF contributes to cancer development and progression by both autocrine and paracrine signaling mechanisms. In this review article, important features of the PDGF isoforms and their cell surface receptor subunits are discussed, with regards to signal transduction, PDGF-isoform specific cellular response, and involvement in angiogenesis, and tumorstromal interactions.

• 대한한방내과학회지
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• 제29권3호
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• pp.827-834
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• 2008

Papillary thyroid carcinoma is the most common type of thyroid malignancy. It has better prognosis and rarer incidence of distant metastasis than other types of thyroid malignancy. However, once distant metastasis happens, its result will be bad. They mostly spread to the lungs and bones. and rarely to the brain. We report a patient with a papillary thyroid carcinoma metastasis to the lymph nodes. the ribs. the brain, and the lungs. The patient underwent total thyroidectomy, radioiodine ablation, rib partial resection, and lung wedge resection. However, upon progress of metastasis. the patient insisted on being treated with traditional Korean medical treatment using allergen-removed Rhus Verniciflua Stokes (A-RVS) instead of the conventional treatment including chemotherapy. The size of the tumor partly decreased, and the patient showed no side effects. This case report brings forth the importance of a thorough study in papillary thyroid carcinomas and their metastasis from the traditional Korean medical point of view, along with the long-term effect of allergen-removed Rhus Verniciflua Stokes (A-RVS).

• BMB Reports
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• 제55권6호
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• pp.281-286
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• 2022

Hepatocellular carcinoma is a major health burden, and though various treatments through much research are available, difficulties in early diagnosis and drug resistance to chemotherapy-based treatments render several ineffective. Cancer stem cell model has been used to explain formation of heterogeneous cell population within tumor mass, which is one of the underlying causes of high recurrence rate and acquired chemoresistance, highlighting the importance of CSC identification and understanding the molecular mechanisms of CSC drivers. Extracellular CSC-markers such as CD133, CD90 and EpCAM have been used successfully in CSC isolation, but studies have indicated that increasingly complex combinations are required for accurate identification. Pseudogene-derived long non-coding RNAs are useful candidates as intracellular CSC markers - factors that regulate pluripotency and self-renewal - given their cancer-specific expression and versatile regulation across several levels. Here, we present the use of microarray data to identify stemness-associated factors in liver cancer, and selection of sole pseudogene-derived lncRNA ZNF204P for experimental validation. ZNF204P knockdown impairs cell proliferation and migration/invasion. As the cytosolic ZNF204P shares miRNA binding sites with OCT4 and SOX2, well-known drivers of pluripotency and self-renewal, we propose that ZNF204P promotes tumorigenesis through the miRNA-145-5p/OCT4, SOX2 axis.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5761-5767
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• 2013

The potential correlation of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism with hepatocellular carcinoma (HCC) susceptibility is ambiguous. Taking account of inconsistent results of previous meta-analyses and new emerging literatures, we conducted a meta-analysis covering 15 case-control datasets to evaluate the relationship. Relevant studies from Medline, Embase and CNKI were retrieved. A fixed-effect model or a random-effect model, depending on between-study heterogeneity, were applied to estimate the association between XRCC1 polymorphism Arg399Gln and HCC risk with the results presented as odds ratios (ORs) and 95% confidence intervals (95% CIs). In accordance with Hardy-Weinberg equilibrium, 15 studies with data for 6,556 individuals were enrolled in this systematic review. For overall HCC,thr XRCC1 polymorphism Arg399Gln was significantly associated with HCC susceptibility in a homozygote model as well as in a dominant model (G/G vs. A/A, OR=1.253, p=0.028; G/G+A/G vs. A/A, OR= 1.281, p=0.047, respectively), but not in a heterozygote model (A/G vs. A/A, OR=1.271, p=0.066) or a recessive model (G/G vs. A/G + A/A, OR= 1.049, p=0.542). Similar results were also observed on stratification analysis by ethnicity (A/G vs. A/A, OR=1.357, p=0.025; G/G vs. A/A, OR=1.310, p=0.011; G/G+A/G vs. A/A, OR= 1.371, p=0.013). However, no potential contribution of XRCC1 Arg399Gln polymorphism to HCC susceptibility in HBV/HCV subgroups was identified. No publication bias was found in this study. In conclusion, the XRCC1 Arg399Gln polymorphism contributes to HCC susceptibility. Due to the lack of studies in Western countries, further large-sample and rigorous studies are needed to validate the findings.

• Korean Journal of Radiology
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• 제22권4호
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• pp.584-595
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• 2021

Objective: Immune checkpoint inhibitor (ICI) therapy has shown activity against melanoma brain metastases. Recently, promising results have also been reported for ICI combination therapy and ICI combined with radiotherapy. We aimed to evaluate radiologic response and adverse event rates of these therapeutic options by a systematic review and meta-analysis. Materials and Methods: A systematic literature search of Ovid-MEDLINE and EMBASE was performed up to October 12, 2019 and included studies evaluating the intracranial objective response rates (ORRs) and/or disease control rates (DCRs) of ICI with or without radiotherapy for treating melanoma brain metastases. We also evaluated safety-associated outcomes. Results: Eleven studies with 14 cohorts (3 with ICI combination therapy; 5 with ICI combined with radiotherapy; 6 with ICI monotherapy) were included. ICI combination therapy {pooled ORR, 53% (95% confidence interval [CI], 44-61%); DCR, 57% (95% CI, 49-66%)} and ICI combined with radiotherapy (pooled ORR, 42% [95% CI, 31-54%]; DCR, 85% [95% CI, 63-95%]) showed higher local efficacy compared to ICI monotherapy (pooled ORR, 15% [95% CI, 11-20%]; DCR, 26% [95% CI, 21-32%]). The grade 3 or 4 adverse event rate was significantly higher with ICI combination therapy (60%; 95% CI, 52-67%) compared to ICI monotherapy (11%; 95% CI, 8-17%) and ICI combined with radiotherapy (4%; 95% CI, 1-19%). Grade 3 or 4 central nervous system (CNS)-related adverse event rates were not different (9% in ICI combination therapy; 8% in ICI combined with radiotherapy; 5% in ICI monotherapy). Conclusion: ICI combination therapy or ICI combined with radiotherapy showed better local efficacy than ICI monotherapy for treating melanoma brain metastasis. The grade 3 or 4 adverse event rate was highest with ICI combination therapy, and the CNS-related grade 3 or 4 event rate was similar. Prospective trials will be necessary to compare the efficacy of ICI combination therapy and ICI combined with radiotherapy.

• International Journal of Stem Cells
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• 제16권4호
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• pp.438-447
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• 2023

Recently, ex-vivo gene therapy has emerged as a promising approach to enhance the therapeutic potential of mesenchymal stem cells (MSCs) by introducing functional genes in vitro. Here, we explored the need of using selection markers to increase the gene delivery efficiency and evaluated the potential risks associated with their use in the manufacturing process. We used MSCs/CD that carry the cytosine deaminase gene (CD) as a therapeutic gene and a puromycin resistance gene (PuroR) as a selection marker. We evaluated the correlation between the therapeutic efficacy and the purity of therapeutic MSCs/CD by examining their anti-cancer effect on co-cultured U87/GFP cells. To simulate in vivo horizontal transfer of the PuroR gene in vivo, we generated a puromycin-resistant E. coli (E. coli/PuroR) by introducing the PuroR gene and assessed its responsiveness to various antibiotics. We found that the anti-cancer effect of MSCs/CD was directly proportional to their purity, suggesting the crucial role of the PuroR gene in eliminating impure unmodified MSCs and enhancing the purity of MSCs/CD during the manufacturing process. Additionally, we found that clinically available antibiotics were effective in inhibiting the growth of hypothetical microorganism, E. coli/PuroR. In summary, our study highlights the potential benefits of using the PuroR gene as a selection marker to enhance the purity and efficacy of therapeutic cells in MSC-based gene therapy. Furthermore, our study suggests that the potential risk of horizontal transfer of antibiotics resistance genes in vivo can be effectively managed by clinically available antibiotics.

• Radiation Oncology Journal
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• 제12권2호
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• pp.165-173
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• 1994

목적 : 폐암환자에 있어서 뇌전이는 심각한 문제이며 또한 장기간 생존을 기대할 수가 없다. 종양억제효과를 증가시키는 동시에 만발 장애를 감소시켜 전체 치료기간을 가능한 단축시키기 위하여 비소세포성 폐암화자의 뇌전이에 대한 다분할 조사법인 급속분할조사법을 시행하였다. 재료 및 방법 : 1991년부터 1993년까지 비소세포성 폐암으로 확진되어 뇌전이가 발생한 24명의 환자에게 6시간 간격으로 2Gy씩 하루 2회로 총 48Gy를 전뇌에 조사하였다. 단일 병소는 전뇌에 40Gy 조사후 치료범위를 축소하여 8Gy를 추가하였다. 총 26예증 신경증상이 점차 진행되는 양상을 보인 2명은 방사선치료를 중단하였다. 결과 : 방사선치료 도중에 3명은 급성 방사선효과로 오심과 구토를 호소하였으나, 방사선량 증가로 인한 심각한 부작용은 없었다. 통상적인 치료방법인 2주에 30Gy를 조사한 경우(4.5개월)보다 48Gy의 급속분할조사에 의한 방사선치료법이 중간생존기간을 향상시켰으나(7개월)통계학적 의의는 없었다(p>0.05). 뇌에 국한된 전이 환자와 활동수행 상태가 양호한 군이 다발성 전이나 활동수행상태가 불량한 군보다 중간생존기간과 반년생존율에 있어서 유의한 증가를 나타내었다(p<0.01). 결론 : 뇌전이 단독소견과 양호한 활동수행능력 상태등 양호한 예후인자를 가진 환자는 생존기간 향상이 기대된다. 본 연구결과로 환자의 quaility of life를 고려하여 하후 1회 치료법과 2또는 3회치료법을 비교하는 다자간의 전향적인 연구가 필요하리라 생각된다.

• Journal of Yeungnam Medical Science
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• 제33권2호
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• pp.142-145
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• 2016

Gastric cancer is the most common cancer in Korean males and can easily spread to distant organs such as the liver, lungs, brain, or bones. However, skin metastasis, particularly of the eye, is rare. Metastatic eyelid cancer is extremely rare; metastases from internal organs have not been reported so far. We recently experienced a patient with metastatic eyelid cancer from adenocarcinoma of the stomach. A 62-year-old female was admitted with a right upper eyelid mass and foreign body sensation. She had a history of stomach cancer of 3 years. She was treated by chemotherapy and radiotherapy for pathologic fracture. After receiving supportive care for 2 years, the mass appeared on her right pupil. Punch-biopsy of the mass was performed and histological examination revealed adenocarcinoma, the same as the initial histological result. We report this case with a review of related literature.

• Safety and Health at Work
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• 제8권3호
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• pp.258-266
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• 2017

Background: Welders are exposed to many known and suspected carcinogens. An excess lung cancer risk among welders is well established, but whether this is attributable to welding fumes is unclear. Excess risks of other cancers have been suggested, but not established. We investigated welding cancer risks in the population-based Canadian Census Health and Environmental Cohort. Methods: Among 1.1 million male workers, 12,845 welders were identified using Standard Occupational Classification codes and followed through retrospective linkage of 1991 Canadian Long Form Census and Canadian Cancer Registry (1992-2010) records. Hazard ratios (HRs) were calculated using Cox proportional hazards models based on estimated risks of lung cancer, mesothelioma, and nasal, brain, stomach, kidney, and bladder cancers, and ocular melanoma. Lung cancer histological subtypes and risks by industry group and for occasional welders were examined. Some analyses restricted comparisons to blue-collar workers to minimize effects of potential confounders. Results: Among welders, elevated risks were observed for lung cancer [HR: 1.16, 95% confidence interval (CI): 1.03-1.31], mesothelioma (HR: 1.78, 95% CI: 1.01-3.18), bladder cancer (HR: 1.40, 95% CI: 1.15-1.70), and kidney cancer (HR: 1.30, 95% CI: 1.01-1.67). When restricted to blue-collar workers, lung cancer and mesothelioma risks were attenuated, while bladder and kidney cancer risks increased. Conclusion: Excess risks of lung cancer and mesothelioma may be partly attributable to factors including smoking and asbestos. Welding-specific exposures may increase bladder and kidney cancer risks, and particular sources of exposure should be investigated. Studies that are able to disentangle welding effects from smoking and asbestos exposure are needed.