• BMB Reports
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• 제55권6호
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• pp.267-274
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• 2022

Molecular imaging is used to improve the disease diagnosis, prognosis, monitoring of treatment in living subjects. Numerous molecular targets have been developed for various cellular and molecular processes in genetic, metabolic, proteomic, and cellular biologic level. Molecular imaging modalities such as Optical Imaging, Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), and Computed Tomography (CT) can be used to visualize anatomic, genetic, biochemical, and physiologic changes in vivo. For in vivo cell imaging, certain cells such as cancer cells, immune cells, stem cells could be labeled by direct and indirect labeling methods to monitor cell migration, cell activity, and cell effects in cell-based therapy. In case of cancer, it could be used to investigate biological processes such as cancer metastasis and to analyze the drug treatment process. In addition, transplanted stem cells and immune cells in cell-based therapy could be visualized and tracked to confirm the fate, activity, and function of cells. In conventional molecular imaging, cells can be monitored in vivo in bulk non-invasively with optical imaging, MRI, PET, and SPECT imaging. However, single cell imaging in vivo has been a great challenge due to an extremely high sensitive detection of single cell. Recently, there has been great attention for in vivo single cell imaging due to the development of single cell study. In vivo single imaging could analyze the survival or death, movement direction, and characteristics of a single cell in live subjects. In this article, we reviewed basic principle of in vivo molecular imaging and introduced recent studies for in vivo single cell imaging based on the concept of in vivo molecular imaging.

• BMB Reports
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• 제55권10호
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• pp.506-511
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• 2022

Advanced hepatocellular carcinoma (HCC) is among the most challenging cancers to overcome, and there is a need for better therapeutic strategies. Among the different cancer drugs that have been used in clinics, sorafenib is considered the standard first-line drug for advanced HCC. Here, to identify a chemical compound displaying a synergistic effect with sorafenib in HCC, we screened a focused chemical library and found that MG149, a histone acetyltransferase inhibitor targeting the MYST family, exhibited the most synergistic anticancer effect with sorafenib on HCC cells. The combination of sorafenib and MG149 exerted a synergistic anti-proliferation effect on HCC cells by inducing apoptotic cell death. We revealed that cotreatment with sorafenib and MG149 aggravated endoplasmic reticulum (ER) stress to promote the death of HCC cells rather than adaptive cell survival. In addition, combined treatment with sorafenib and MG149 significantly increased the intracellular levels of unfolded proteins and reactive oxygen species, which upregulated ER stress. Collectively, these results suggest that MG149 has the potential to improve the efficacy of sorafenib in advanced HCC via the upregulation of cytotoxic ER stress.

• Biomolecules & Therapeutics
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• 제31권1호
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• pp.116-126
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• 2023

Mainly due to the slanted focus on the mechanism and regulation of neuronal aging, research on astrocyte aging and its modulation during brain aging is scarce. In this study, we established aged astrocyte culture model by long-term culturing. Cellular senescence was confirmed through SA-β-gal staining as well as through the examination of morphological, molecular, and functional markers. RNA sequencing and functional analysis of astrocytes were performed to further investigate the detailed characteristics of the aged astrocyte model. Along with aged phenotypes, decreased astrocytic proliferation, migration, mitochondrial energetic function and support for neuronal survival and differentiation has been observed in aged astrocytes. In addition, increased expression of cytokines and chemokine-related factors including plasminogen activator inhibitor -1 (PAI-1) was observed in aged astrocytes. Using the RNA sequencing results, we searched potential drugs that can normalize the dysregulated gene expression pattern observed in long-term cultured aged astrocytes. Among several candidates, minoxidil, a pyrimidine-derived anti-hypertensive and anti-pattern hair loss drug, normalized the increased number of SA-β-gal positive cells and nuclear size in aged astrocytes. In addition, minoxidil restored up-regulated activity of PAI-1 and increased mitochondrial superoxide production in aged astrocytes. We concluded that long term culture of astrocytes can be used as a reliable model for the study of astrocyte senescence and minoxidil can be a plausible candidate for the regulation of brain aging.

• 문화기술의 융합
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• 제9권1호
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• pp.457-462
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• 2023

윤종빈 감독의 드라마 <수리남>은 2022년 넷플릭스를 통해 스트리밍 되어 드라마 순위 1위에 올랐다. <수리남>은 윤종빈 감독이 이전부터 추구해 온 한국사회 남성 서사의 계보를 잇고 있다. <수리남>에서 주인공들은 한국사회를 벗어나 타국에서 생존을 모색하는 디아스포라 행보를 선택한다. <수리남>의 두 남성 주인공은 적대적인 관계로 설정되어 있지만 근본적으로 "생존"을 위해 돈을 추구한다는 공통점이 있다. 이들은 1980~90년대 한국사회의 공적권력의 횡포를 피해 디아스포라를 선택했지만, 수리남은 사적 폭력과 공적 권력이 유착된 최악의 장소였다. 거기서 한 명은 마약왕이 되고, 한 명은 한국의 국익을 위해 행동한다. 상이한 둘의 선택은 디아스포라의 명암을 보여주는 사례라 할 수 있다. 윤종빈 감독은 <수리남>에서 '가족'과 '폭력'이라는 기존 작품들의 주제를 계승하면서, 자신이 탐구해 온 한국 남성 서사의 지리적 영역을 확장시켰다.

• 치위생과학회지
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• 제23권3호
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• pp.216-224
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• 2023

Background: Smilax glabra has various pharmacological activities and is widely used as a herbal medicine. Although the incidence of oral cancer is low, the recurrence rate is high, and the 5-year survival rate is poor. It is necessary to search for anticancer drugs that increase the effect of cancer chemotherapy on heterogeneous oral tissues and reduce the side effects on normal cells. This study aimed to investigate the effects and mechanism of ethanol extract of Smilax glabra (EESG) as an anticancer drug for oral cancer. Methods: Smilax glabra root components extracted with 70% ethanol were used to analyze their effects on cancer cells. A 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide assay was performed for cytotoxicity analysis. Flow cytometry was performed to determine the cell cycle phase distribution. To observe apoptotic cells, terminal deoxynucleotidyl transferase dUTP nick end labeling and γH2AX were detected by fluorescence microscope. The protein levels of cleaved PARP and caspase were analyzed using western blotting. The activation of procaspase-3 was confirmed by measuring caspase-3 activity. Results: EESG was no cytotoxic to normal gingival fibroblast but was high in YD10B oral squamous cell carcinoma (OSCC) cells. EESG treatment increased the subdiploid DNA content of YD10B cells by assessing DNA content distribution. Chromatin condensation and DNA strand breaks increased in YD10B cells treated with EESG. EESG-treated YD10B cells had high Annexin V and low propidium iodide levels, confirming that early apoptosis was induced. In addition, increased levels of γH2AX foci, a marker of DNA damage, were observed in the nuclei of EESG-treated YD10B cells. The EESG-treated YD10B cells also exhibited decreased procaspase-3 and procaspase-9 levels, increased PARP cleavage and caspase-3 activity. Conclusion: These results indicate that EESG inhibited cancer cell proliferation by inducing apoptosis in YD10B OSCC cells.

• Advances in nano research
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• 제15권5호
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• pp.451-466
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• 2023

Gastrointestinal cancer (GC) is a prevalent malignant tumor of the digestive system that poses a severe health risk to humans. Due to the specific organ structure of the gastrointestinal system, both endoscopic and MRI diagnoses of GIC have limited sensitivity. The primary factors influencing curative efficacy in GIC patients are drug inefficacy and high recurrence rates in surgical and pharmacological therapy. Due to its unique optical features, good biocompatibility, surface effects, and small size effects, nanotechnology is a developing and advanced area of study for the detection and treatment of cancer. Because of its deep location and complex surgery, diagnosing and treating gastrointestinal cancer is very difficult. The early diagnosis and urgent treatment of gastrointestinal illness are enabled by nanotechnology. As diagnostic and therapeutic tools, nanoparticles directly target tumor cells, allowing their detection and removal. XGBoost was used as a classification method known for achieving numerous winning solutions in data analysis competitions, to capture nonlinear relations among many input variables and outcomes using the boosting approach to machine learning. The research sample included 300 GC patients, comprising 190 males (72.2% of the sample) and 110 women (27.8%). Using convolutional neural networks (CNN) and artificial neural networks (ANN)-EXtreme Gradient Boosting (XGBoost), the patients mean± SD age was 50.42 ± 13.06. High-risk behaviors (P = 0.070), age at diagnosis (P = 0.037), distant metastasis (P = 0.004), and tumor stage (P = 0.015) were shown to have a statistically significant link with GC patient survival. AUC was 0.92, sensitivity was 81.5%, specificity was 90.5%, and accuracy was 84.7 when analyzing stomach picture.

• 한국군사과학기술학회지
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• 제27권1호
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• pp.107-115
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• 2024

Various vaccines were rapidly developed during the COVID-19 pandemic to prevent and treat infections but global infections continue, and concerns about new mutations and infectious diseases persist. Thus, active research focuses on developing, producing, and supplying vaccines and treatments for various infectious diseases and potential pandemics. Natural killer(NK) cells, as innate immune cells, can recognize and eliminate abnormal cells like virus-infected and cancer cells. Hence, their development as anticancer and antiviral treatments is rapidly advancing. In this study, optimal short-term culture conditions were identified for allogeneic NK cells by simplifying the culture process through the isolation of NK cells(referred to as NKi cells) and eliminating CD3+ cells(referred to as CD3- cells). NK cells demonstrated reduced viral titer in injection of NK cells into SARS-CoV-2 infected ACE-tg mice increased survival. The study's findings could form the basis for an antiviral treatment platform that swiftly responds to new viral disease pandemics.

• 생명과학회지
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• 제26권1호
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• pp.109-116
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• 2016

면역에 대한 관심은 점차 증가하는 추세이며, 식물유래 천연물을 이용한 면역기능 증강에 관련된 연구 역시 활발히 진행되고 있다. 왕느릅나무 껍질은 줄기 혹은 뿌리의 껍질을 뜻하며 전통적으로 동·서양 할 것 없이 항염, 진통, 항암, 상처치료에 사용되어 왔다. 본 연구는 왕느릅나무 열수 추출물(Ulmus macrocarpa water extract, UMWE)이 면역기능에 끼치는 영향을 조사하기 위해 실시되었다. 실험은 UMWE를 농도 100 mg/kg 또는 200 mgkg로 식이한 군, UMW를 농도 100 mg/kg 또는 200 mg/kg으로 식이하면서 면역억제물질인 cyclophosphamide(CY, 120 mg/kg)를 투여한 군, CY만을 투여한 군, 아무 것도 처리하지 않은 비처리군, 총 6개 군으로 나누어 2주간 매일 식이하면서 진행하였다. 각 군에서 획득한 비장지수와 비장세포 지수를 비교하였을 때 UMWE 식이가 CY에 의한 비장세포의 감소를 완화시키는 것으로 나타났으며, in vitro 실험에서 MTT방법과 7-amino-actinomycin D 방법을 통해 비장세포의 생존을 유지하며 사멸을 지연하는 것이 확인되었다. 또한, UMWE는 YAC-1에 대한 비장 NK 세포 활성을 면역억제제 CY가 존재하는 조건에서도 정상적으로 유지시켜 면역기능 유지에 영향을 주는 것으로 나타났다.

• Radiation Oncology Journal
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• 제23권1호
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• pp.51-60
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• 2005

목적 : 분자 표적의 선택적 억제가 방사선 세포 살상 효과를 증진시키는 것으로 알려져 있으므로 선택적 COX-2 억제제와 EGF 수용체 차단제를 HeLa 세포주에 처리한 후 방사선 효과의 상승작용을 알아보고자 하였다. 대상 및 방법 : 자궁경부암 세포주인 HeLa세포에서 EGF 수용체 차단제 AG 1478, 선택적 COX-2 억제제 NS 398과 방사선을 복합 투여하여 세포성장 억제 분석(cell graph inhibition assay)과 세포사멸 분석(apoptosis assay)을 시행하였고, 방사선 감수성 변화를 살펴보기 위해 세포생존 분석(clonogenic survival assay)을 시행하였다. 방사선 감수성 인자로는 2 Gy에서의 세포생존분획($SF_2$)과 linear-quadratic model을 이용한 dose enhancement ratio (DER)를 사용하였다. 방사선 감수성에 대한 작용기전 분석을 위해 flow cytometry로 세포주기 분석(cell cycle analysls)을 시행하였고, western blot 분석을 통하여 bcl-2와 bax 단백질의 발현 변화를 살펴보았다. 결과 : HeLa세포에 NS 398과 AG 1478을 방사선과 함께 복합 투여한 실험 군에서 세포사멸 정도가 가장 높게 나타났다($8.49\%$ vs. $22.70\%$). 세포주기 분석 결과, 방사선과 복합 약물 처리군에서 $G_0/G_l$ 세포주기 정체와 5 세포 분획 소실이 나타났으며 이러한 변화는 72시간 이후까지 지속되었다 세포생존 분석 결과로는 방사선과 AG 1478군에서 $SF_{2}0.68{\pm}0.07$, DER 1.12를 보인 반면, 방사선과 복합약물처리군에서는 $SF_{2}0.12{\pm}0.01,\;DER\;3.00$으로 나타났다. Western blot분석에서는 방사선과 복합약물처리군에서 bcl-2와 bax 단백질 발현이 모두 감소하는 양상을 보였다. 결론 : 신호전달 체계를 억제하는 분자 표적 약제인 선택적 COX-2 억제제와 EGF 수용체 차단제를 방사선과 복합투여함으로써 HeLa세포의 방사선 감수성이 증가됨을 확인하였다.

• Tuberculosis and Respiratory Diseases
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• 제57권4호
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• pp.351-357
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• 2004

연구배경 : 최근 항암화학요법과 방사선요법의 병용치료는 국소진행성 비소세포폐암 치료에 있어서 표준치료방법으로 자리잡고 있으며 동시요법이 순차적요법에 비해 치료반응율에 있어서 우수하다고 알려져 있다. 본 연구는 비소세포폐암 치료에 있어서 우수한 효과를 보이고 방사선감작 효과가 있다고 알려진 paclitaxel (60 $mg/m^2$) 매주투여와 동시 방사선요법의 III병기 비소세포폐암 환자에서의 치료효과와 독성을 조사하기 위하여 시행하였다. 방 법 : III병기 비소세포폐암 환자 22명 (IIIA:6, IIIB:16)을 대상으로 paclitaxel (60 $mg/m^2$)을 제 1, 8, 15, 22, 29, and 36일째에 매주 투여하고 동시에 54 Gy의 방사선 치료를 시행하였다. 초기 동시치료를 종료하고 paclitaxel (175 $mg/m^2$)/cisplatin (75 $mg/m^2$) 혹은 paclitaxel (175 $mg/m^2$)/carboplatin (6AUC) regimen 으로 보강화학요법을 3주 간격으로 2주기 시행하였다. 결 과 : 전반적 치료반응율은 81.8% (18/22)로서 완전관해가 9.1% (2/22), 부분관해가 72.7% (16/22)의 결과를 보였다. 두명의 (9.1%) 환자가 치료종료 후 방사선폐장염의 합병증으로 사망하였다. 3도 이상의 독성 반응은 방사선폐장염 (22.7%), 식도염 (22.7%), 신경병증 (13.6%), 및 백혈구감소증 (13.6%)의 결과를 나타내었다. 중앙생존기간은 15개월이었고 1년 및 2년 생존율은 각각 63.6%와 31.8%였다. 결 론 : 국소진행성 비소세포폐암 환자에서 paclitaxel 매주 투여에 의한 동시 방사선요법은 우수한 종양반응율을 나타내지만 치명적인 방사선폐장염의 발생 위험이 있으므로 향후 보완연구가 필요할 것으로 사료된다.