• Tuberculosis and Respiratory Diseases
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• 제86권1호
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• pp.1-13
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• 2023

Lung cancer ranks first in cancer mortality in Korea and cancer incidence in Korean men. More than half of Korean lung cancer patients undergo chemotherapy, including adjuvant therapy. Cytotoxic agents, targeted therapy, and immune checkpoint inhibitors are used in chemotherapy according to the biopsy and genetic test results. Among chemotherapy, the one that has developed rapidly is targeted therapy. The National Comprehensive Cancer Network (NCCN) guidelines have been updated recently for targeted therapy of multiple gene mutations, and targeted therapy is used not only for chemotherapy but also for adjuvant therapy. While previously targeted therapies have been developed for common genetic mutations, recently targeted therapies have been developed to overcome uncommon mutations or drug resistance that have occurred since previous targeted therapy. Therefore, this study describes recent, rapidly developing targeted therapies.

• Asian Pacific Journal of Cancer Prevention
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• 제15권12호
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• pp.4915-4918
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• 2014

Background and Aims: Advances in the treatment of cervical cancer over the last decade have predominantly involved the development of genes directed at molecular targets. Gene therapy is recognized to be a novel method for the treatment of cervical cancer. Genes can be administered into target cells via nanocarriers. This study aimed to develop systemically administrable nano-vectors. Floate (Fa) containing gene loaded nanoparticles (NPs) could target HeLa human cervical cancer cells through combination with receptors on the cells to increase the nuclear uptake of genetic materials. Methods: Fa was linked onto Poly (ethylene glycol)-b-poly (D, L-lactide) (PEG-PLA) to form Fa-PEG-PLA, and the resulting material was used to load plasmids of enhanced green fluorescence protein (pEGFP) to obtain gene loaded nanoparticles (Fa-NPs/DNA). Physical-chemical characteristics, in vitro release and cytotoxicity of Fa-NPs/DNA were evaluated. The in vitro transfection efficiency of Fa-NPs/DNA was evaluated in HeLa cells and human umbilical vein endothelial cells (HUVEC). PEG-PLA without Fa was used to load pEGFP from NPs/DNA as a control. Results: Fa-NPs/DNA has a particle size of 183 nm and a gene loading quantity of 92%. After 72h of transfection, Fa-NPs/DNA displayed over 20% higher transfection efficiency than NPs/DNA and 40% higher than naked DNA in HeLa cells. However, in HUVECs, no significant difference appeared between Fa-NPs/DNA and NPs/DNA. Conclusions: Fa-PEG-PLA NPs could function as excellent materials for gene loading. This nano-approach could be used as tumor cell targeted medicine for the treatment of cervical cancer.

• Molecules and Cells
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• 제37권12호
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• pp.857-864
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• 2014

Astrocyte elevated gene-1 (AEG-1) is a recently discovered oncogene that has been reported to be highly expressed in various types of malignant tumors, including renal cell carcinoma. However, the precise role of AEG-1 in renal cancer cell proliferation and apoptosis has not been clarified. In this study, we transfected the renal cancer cell line Caki-1 with a plasmid expressing AEG-1 short hairpin RNA (shRNA) and obtained cell colonies with stable knockdown of AEG-1. We found that AEG-1 down-regulation inhibited cell proliferation and colony formation and arrested cell cycle progression at the sub-G1 and G0/G1 phase. Western blot analysis indicated that the expression of proliferating cell nuclear antigen (PCNA), cyclin D1 and cyclin E were significantly reduced following AEG-1 down-regulation. In addition, AEG-1 knockdown led to the appearance of apoptotic bodies in renal cancer cells, and the ratio of apoptotic cells significantly increased. Expression of the antiapoptotic factor Bcl-2 was dramatically reduced, whereas the pro-apoptotic factors Bax, caspase-3 and poly (ADPribose) polymerase (PARP) were significantly activated. Finally, AEG-1 knockdown in Caki-1 cells remarkably suppressed cell proliferation and enhanced cell apoptosis in response to 5-fluorouracil (5-FU) treatment, suggesting that AEG-1 inhibition sensitizes Caki-1 cells to 5-FU. Taken together, our data suggest that AEG-1 plays an important role in renal cancer formation and development and may be a potential target for future gene therapy for renal cell carcinoma.

• Journal of Microbiology and Biotechnology
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• 제20권4호
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• pp.821-827
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• 2010

Gene delivery that provides targeted delivery of therapeutic genes to the cells of a lesion enhances therapeutic efficacy and reduces toxic side effects. This process is especially important in cancer therapy when it is advantageous to avoid unwanted damage to healthy normal cells. Incorporating cancer-specific ligands that recognize receptors overexpressed on cancer cells can increase selective binding and uptake and, as a result, increase targeted transgene expression. In this study, we investigated whether a peptide capable of homing to hepatocellular carcinoma (HCC) could facilitate targeted gene delivery by cationic liposomes. This homing peptide (HBP) exhibited selective binding to a human hepatocarcinoma cell line, HepG2, at a concentration ranging from 5 to 5,000 nM. When conjugated to a cationic liposome, HBP substantially increased cellular internalization of plasmid DNA to increase the transgene expression in HepG2 cells. In addition, there was no significant enhancement in gene transfer detected for other human cell lines tested, including THLE-3, AD293, and MCF-7 cells. Therefore, we demonstrate that HBP provides targeted gene delivery to HCC by cationic liposomes.

• 폴리머
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• 제31권5호
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• pp.454-459
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• 2007

본 연구에서는 folic acid(FA)가 복합화된 저분자량 수용성 키토산(LMWSC) 나노입자(water soluble chitosan-folic acid nanoparticle, WSCFA)를 제조하고, 또한 DNA와 나노복합체 합성 및 특성을 분석함으로써 in vitro에서 세포내 독성을 평가하였다. WSCFA 합성을 확인하기 위하여 분광학적 분석 방법을 사용하여 분석하였으며, WSCFA 나노입자는 110 nm 이하의 입자 크기인 구형의 형태를 가지고 있음을 알 수 있었다. In vitro 세포내 독성 실험에서, WSCFA-DNA 복합체는 세포내 독성을 전혀 나타내지 않음으로 높은 세포 생존율을 보여주었다. 전기영동 실험을 통해 WSCFA의 DNA 응축능력을 확인하였고, in vitro에서의 전이효율은 형광 광도계에 의해 평가하였다.

• Biotechnology and Bioprocess Engineering:BBE
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• 제7권5호
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• pp.303-310
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• 2002

Cell therapy applied to wound healing or tissue regeneration presents a revolutionary realm to which principles of gene engineering and delivery may be applied. One promising application is the transplantation of cells into the wounded tissue to help the tissue repair. However, when cells are transplanted from in vitro to in vivo, immune rejection occurs due to the immune response triggered by the activation of T-cell, and the transplanted cells are destroyed by the attack of activated T-cell and lose their function. Immune suppressant such as FK506 is commonly used to suppress immune rejection during transplantation. However, such kind of immune suppressants not only suppresses immune rejection in the periphery of transplanted cells but also suppresses whole immune response system against pathogenic infection. In order to solve this problem, we developed a method to protect the desired cells from immune rejection without impairing whole immune system during cell transplantation. Previously, we reported the success of constructing glomerular epithelial cells for removal of immune complex, in which complement receptor of type 1 (CR1) was over-expressed on the membrane of renal glomerular epithelial cells and could bind immune complex of DNA/anti-DNA-antibody to remove immune complex through phagocy-tosis [1]. Attempting to apply the CR1-expressing cells to cell therapy and evade immune rejection during cell transplantation, we constructed three plasmids containing genes encoding a soluble fusion protein of cytolytic T lymphocyte associated antigen-4 (CTLA4Ig) and an enhanced green fluorescent protein (EGFP). The plasmids were transfected to the above-mentioned glomerular epithelial cells to express both genes simultaneously. Using the clone cells for cell transplantation showed that mice with autoimmune disease prolonged their life significantly as compared with the control mice, and two injections of the cells at the beginning of two weeks resulted in remarkable survivability, whereas it requires half a year and 50 administrations of proteins purified from the same amount of cells to achieve the same effect.

• 대한한방부인과학회지
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• 제19권2호
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• pp.199-213
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• 2006

Purpose : This study was aimed to investigate the inhibitory effect of Sparganii Rhizoma on the proliferation of human uterine leiomyoma cells and the expression of gene related the mechanism of cell apoptosis. Methods : This study was evaluated the number of death cells treated with indicated concentration of Sparganii Rhizoma and investigated cell death rate by MTS assay. Furthermore, fluorescence-activated cell sorter analysis and DNA fragmentation assay were used to dissect between necrosis and apoptosis. and then we observed the differential gene expression by western blot analysis. Results :1) The inhibitory effect on the growth of uterine leiomyoma cell treated with Sparganii Rhizoma was increased in a dose dependent manner. 2) As the result of FACS analysis, subG1 phase incrase was observed 23.49% inuterine leiomyoma cell treated with Sparganii Rhizoma at $500\;{\mu}g/ml$ compared to control.. 3) The gene expression of p53, p21 related cell apoptosis was increased according to increasing concentration but p27 was none exchanged. 4) The expression of cyclin A, D and E was decreased in a concentration proportional and then the dephosphorylation of pRb was increased. 5) The character of apoptosis, DNA fragmentation was significantly observed according to increasing concentration. 6) The expression of pro-caspase3 were decreased dependent on treatment concentration and activated PARP took place. Conclusion : The inhibitory effect of Sparganii Rhizoma on the proliferation of human uterine leiomyoma cells was observed with apoptosis and cell cycle arrest. These data suggest that Sparganii Rhizoma might be candidate of medical therapy for uterine leiomyoma.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2003년도 학술발표대회 발표논문초록집
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• pp.74-74
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• 2003

Embryonic stem cells have several characteristics suitable for cell replacement therapy. To investigate a possibility of using human embryonic stem cell (hESC) as a carrier of therapeutic gene(s), hESC (MB03) was co-transfected with cDNAS coding for tyrosine hydroxylase (TH) and GTP cyclohydrolase Ⅰ (GTPCH Ⅰ) and bulk-selected using neomycin and hygromycin-B. Successful transfection was confirmed by western immunoblotting and RT-PCR. The genetically modified hESC (bk-THGC) relieved apomorphine-induced asymmetric motor behavior by approximately 54% when grafted into striatum of 6-OHDA-denervated rat brain. The number of rotation, however, increased up to 176+18% in 6 weeks when sham-grafted compared with number of rotation before graft. Immunohistochemical staining revealed that the grafted hESC survived and expressed TH for at least 6 weeks while the experiment was continued.

• Tuberculosis and Respiratory Diseases
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• 제44권1호
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• pp.162-174
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• 1997

연구배경 : HSVtk 유전자를 암세포에 이입하여 GCV에 대해 선택적으로 감수성을 증가시키는 HSVtk/GCV 유전자치료에서 bystander effect는 모든 암세포에 유전자를 이입하지 않고도 치료효과를 얻을 수 있도록 한다. 그러나 현존하는 viral vector는 유전자이입 효율이 낮아 임상적으로 치료효과를 기대하는데는 한계가 있다. 따라서 유전자의 이입효율이 높은 새로운 vector의 개발과 함께 bystander effect의 극대화를 통해 치료효과를 증가시킬 수 있는 방법 등이 요구된다. 최근 gap junction을 통한 세포간의 metablic cooperation이 bystander effect의 주요기전임이 밝혀졌고 retinoids는 gap junction을 통한 세포간의 communication을 증가시킨다고 보고되었다. 저자들은 HSVtk/GCV 유전자치료에서 bystander effect에 미치는 retinoids의 효과를 조사하였다. 방 법 : Adenovus와 retrovirus vector를 이용하여 connexin 43를 발현하는 악성중피종세포와 connexin 43를 발현하지 않는 SKHep-J 세포주에 HSVtk 유전자를 이입한 후 HSVtk 유전자가 이입된 세포와 HSVtk 유전자가 이입되지 않은 세포들을 여러가지 비율로 혼합한 mixing study를 시행하였으며 $10^{-10}M-10^{-6}M$ RA 처리 유무에 따른 bystander effect에 의한 살상효과를 비교하였다. 그리고 gap junction을 통한 세포간의 communication에 대한 retinoids의 영향을 조사하기 위해 retinoids 처리에 따른 세포간 communication을 FACS를 이용하여 double-dye transfer study로 측정하였다. 결 과 : Connexin 43를 발현하지 않는 SKHep-J 세포주에서는 RA 처리유무에 따른 bystander effect에 의한 살상효과의 차이가 없었다. 그러나 connexin 43를 발현하는 악성중피종 세포주에서는 $10^{-8}M-10^{-6}M$ RA처리시 세포간의 communication과 bystander effect가 RA를 처리하지 않은 대조군에 비해 유의하게 증가되었다. 결 론 : RA는 gap junction을 통한 세포간의 communication을 증가시켜 HSVtk/GCV 유전자치료에서 bystander effect에 의한 살상효과를 증가시켰다. 이러한 결과는 HSVtk/GCV 유전자치료의 효과를 증가시킬 수 있는 새로운 방법이 될 수 있을 것으로 생각된다.

• 대한핵의학회지
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• 제38권2호
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• pp.143-151
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• 2004

Recent progress in the development of non-invasive imaging technologies continues to strengthen the role of molecular imaging biological research. These tools have been validated recently in variety of research models, and have been shown to provide continuous quantitative monitoring of the location(s), magnitude, and time-variation of gene expression. This article reviews the principles, characteristics, categories and the use of radionuclide reporter gene imaging technologies as they have been used in imaging cell trafficking, imaging gene therapy, imaging endogenous gene expression and imaging molecular interactions. The studios published to date demonstrate that reporter gene imaging technologies will help to accelerate pre-clinical model validation as well as allow for clinical monitoring of human diseases.