• IMMUNE NETWORK
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• 제9권5호
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• pp.158-168
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• 2009

Tumor therapy using cytokines has been developed for last two decades. Several recombinant cytokines and tumor cell vaccines produced by cytokine gene transfer have been in clinical trials, but several side effects hamper routine clinical applications. Many cytokines are originally expressed as membrane-bound form and then processed to secretory form exerting paracrine effects. Though functional differences of these two types of cytokines are elusive yet, the membrane-bound form of cytokine may exert its effects on restricted target cells as a juxtacrine, which are in physical contacts. With the efforts to improve antitumor activities of cytokines in cancer patients, developing new strategies to alleviate life-threatening side effects became an inevitable goal of tumor immunologists. Among these, tumor cell vaccines expressing cytokines as membrane-bound form on tumor cell surface have been developed by genetic engineering techniques with the hope of selective stimulation of the target cells that are in cell-to-cell contacts. In this review, recent progress of tumor cell vaccines expressing membrane-bound form of cytokines will be discussed.

• Radiation Oncology Journal
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• 제11권2호
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• pp.431-437
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• 1993

방사선 수술에 있어서 선량 형태를 변형시키기 위한 조사변수들의 선택은 중요한 문제이다. 선형가속기를 이용한 뇌정위적 방사선 수술은 통상 원형 조사면과 다중 arc를 이용하여 구형 형태의 선량을 얻는 방법을 이용하고 있다. 그러나, 병소가 임의의 형태인 경우 구형의 선량으로서는 병소 이외에 정상조직도 많은 선량이 가해지게 된다. 현재 병소형태의 선량을 얻기 위한 방법으로 multiple isocenters를 이용하거나, 각 arc에 달리 weights를 주는 방법을 사용하고 있다. 본 논문에서는 병소의 beam's eye view를 이용하여 조사 위치에서 조사면을 shaping하는 새로운 방법에 대하여 논의하고자 한다. 이러한 conformal조사 방법은 병소와 정상조직의 가시적인 3차원 선량분포와 dose volume histogram의 분석 방법을 통하여 검증되었다. conformal 방법을 이용한 경우 multiple isocenter를 이용한 경우보다 적은 arc 수를 가지고도 상응하는 dose gradient와 더 나은 선량의 균질성을 얻을 수 있었다.

• 대한방사선치료학회:학술대회논문집
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• 대한방사선치료학회 2000년도 제1차 학술발표회
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• pp.14-14
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• 2000

• 대한방사선치료학회지
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• 제27권1호
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• pp.31-43
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• 2015

목 적 : 정위적체부방사선치료(Stereotatic body radiation therapy, SBRT)는 원발성 종양과 전이성 종양의 치료법으로 이용되어진다. SBRT는 높은 선량을 전달하기 때문에 MU(Monitor unit)의 증가로 치료시간이 길어지고 치료계획용적(Planning Target Volume, PTV) 주변의 정상장기를 효과적으로 보호할 수 있는 치료계획이 필요하다. 특히 다중표적의 경우 SBRT를 여러 번에 나누어 치료해야하거나 선량 겹침으로 인한 고 선량 영역(Hot spot)이 생길수도 있다. 본 연구는 다중표적 간암에서 TrueBeam STx(Varian, USA)의 무편평화여과기선질(Flattening filter free, FFF) beam을 이용한 용적변조회전치료(Volumetric modulated arc therapy, VMAT)의 유용성을 평가하고자 한다. 대상 및 방법 : 다중표적 간암의 SBRT를 시행하는 5명의 환자를 대상으로 TrueBeam STx의 10MV FFF beam을 이용한 VMAT과 15MV 편평화여과기선질(Flattening filter, FF) beam을 이용한 입체조형치료(conformal radiotherapy, CRT)계획을 세웠다. 두 치료계획을 비교하기 위하여 선량용적히스토그램(Dose Volume Histogram, DVH)을 이용하여 치료계획용적(Planning Target Volume, PTV), 간, 십이지장, 장, 식도, 척수에 들어가는 선량을 평가하고 전체 MU 값을 비교하였다. 또한 두 치료계획의 치료시간을 비교하기 위하여 Beam on time을 평가하였다. 결 과 : PTV에 대한 처방선량지수(Conformity Index, CI), 선량균질지수(Homogeneity index, HI), 처방선량포함지수(Paddick's Conformity Index, PCI)의 평균값은 VMAT에서 각각 $1.006{\pm}0.028$, $1.098{\pm}0.016$, $1.132{\pm}0.084$, CRT에서 $1.381{\pm}0.419$ $1.136{\pm}0.042$, $1.534{\pm}0.465$로 평가되었다. 정상장기에 대한 선량은 CRT에서 VMAT 보다 약 1.8배 높은 선량으로 평가되었다. 전체 MU값은 VMAT에서 약 1.3배 높게 평가되었고 VMAT과 CRT 두 치료계획의 평균 Beam on time은 각각 6.8분, 21.3분으로 평가되었다. 결 론 : 다중표적 간암의 정위적체부방사선치료에서 FFF Beam을 이용한 VMAT을 적용하면 선량 겹침 없이 다중표적을 한 번에 치료할 수 있으며 PTV의 선량포함을 만족하면서 주위의 정상장기를 더 효과적으로 보호할 수 있는 치료계획이 가능하다. 또한 FFF Beam의 높은 선량률(Dose rate)을 이용하여 치료시간을 단축시켜 치료 중 발생할 수 있는 오차를 감소시킬 수 있다.

• 한국콘텐츠학회논문지
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• 제15권8호
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• pp.416-423
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• 2015

본 연구에서는 내부표적체적을 통한 방사선치료계획을 분석하여 호흡연동방사선치료에 주로 이용되는 호기상태의 치료계획체적과 비교 분석하여 정상조직이 받은 선량을 알아보았다. 2013년 12월부터 2014년 6월까지 모 대학교병원 방사선종양학과에서 복부부위에 호흡연동방사선치료를 받은 환자 25명을 대상으로 하였으며, 암의 종류는 liver(64%), CBD(8%), gastric(8%), GB(8%), pancreas(8%), SMA(4%)이었다. ITV와 PTV 체적의 평균치는 $471.44cm^3$, $425.48cm^3$ 로 체적의 증가를 알 수 있었고, PTV구간에서 ITV구간으로 선택한 구간의 증가로 인해 정상조직체적 또한 증가함을 알 수 있었다. 그리고 정상조직체적의 증가, target volume 증가, 치료조사야 면적증가의 차이와 정상조직이 받은 선량평균치의 차이에서는 right kidney가 유의한 증가를 보였다. 호흡평균치에 따른 정상조직이 받은 선량평균치의 차이는 없었고 target moving과 정상조직의 선량평균치의 차이에서는 both kidney가 유의한 차이를 나타내었다. 결론적으로 PTV구간과 ITV구간 체적 설정을 통한 치료방법이 모두 정상조직의 보호선량에 적합하였으며, 처방선량의 95% 이상이 분포하였으므로 환자의 치료목적에 따라 선택적으로 사용되어도 무방할 것이라 사료된다.

• 대한의생명과학회지
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• 제24권3호
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• pp.157-167
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• 2018

The concept of gene therapy is to treat a disease by transferring therapeutic nucleic acids to a patient's cells. It took several decades from the basic theoretical proposal of gene therapy to the current promising treatment option for some important human diseases. The encountered adverse effects in the early clinical studies boosted the development of sophisticated vectors and elaborate clinical designs. The gene therapy is now considered to have the potential to cure many diseases that are incurable with conventional medications. By the end of 2017, about 2,600 clinical trials of gene therapy have been performed or are ongoing for a variety of diseases such as cancers, monogenic diseases, cardiovascular diseases and neurological diseases etc. Here, we present a brief introduction of technical achievement in relation to gene therapy development, and a review of the current status of global gene therapy clinical development.

• 한국발생생물학회지:발생과생식
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• 제18권1호
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• pp.65-71
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• 2014

Cell cycle process is regulated by a number of protein kinases and among them, serine/threonine kinases carry phosphate group from ATP to substrates. The most important three kinase families are Cyclin-dependent kinase (Cdk), Polo-like kinase (Plk), and Aurora kinase. Polo-like kinase family consists of 5 members (Plk1-Plk5) and they are involved in multiple functions in eukaryotic cell division. It regulates a variety of aspects such as, centrosome maturation, checkpoint recovery, spindle assembly, cytokinesis, apoptosis and many other features. Recently, it has been reported that Plks are related to tumor development and over-expressed in many kinds of tumor cells. When injected the anti-Plk antibody into human cells, the cells show aneuploidy, and if inhibit Plks, most of the mitotic cell division does not proceed properly. For that reasons, many inhibitors of Plk have been recently emerged as new target for remedy of the cancer therapeutic research. In this paper, we reviewed briefly the characteristics of Plk families and how Plks work in regulating cell cycles and cancer formation, and the possibilities of Plks as target for cancer therapy.

• Molecules and Cells
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• 제38권6호
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• pp.475-481
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• 2015

Programmable nucleases, which include zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and RNA-guided engineered nucleases (RGENs) repurposed from the type II clustered, regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system are now widely used for genome editing in higher eukaryotic cells and whole organisms, revolutionising almost every discipline in biological research, medicine, and biotechnology. All of these nucleases, however, induce off-target mutations at sites homologous in sequence with on-target sites, limiting their utility in many applications including gene or cell therapy. In this review, we compare methods for detecting nuclease off-target mutations. We also review methods for profiling genome-wide off-target effects and discuss how to reduce or avoid off-target mutations.

• 한양메디칼리뷰
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• 제33권1호
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• pp.59-64
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• 2013

Cancer remains the leading cause of death worldwide despite intense efforts in developing innovative treatments. Current approaches in cancer therapy are mainly directed to a selective targeting of cancer cells to avoid potential side effects associated with conventional therapy. In this respect, Natural killer (NK) cells have gained growing attention and are now being considered as promising therapeutic tools for cancer therapy owing to their intrinsic ability to rapidly recognize and kill cancer cells, while sparing normal healthy cells. NK cells play a key role in the first line of defense against transformed and virus-infected cells. NK cells sense their target through a whole array of receptors, both activating and inhibitory. Functional outcome of NK cell against target cells is determined by the balance of signals transmitted from diverse activating and inhibiting receptors. Despite significant progress made in the role of NK cells attack as a pivotal sentinel in tumor surveillance, the molecular has been that regulate NK cell responses remain unclear, which restricts the use of NK cells as a therapeutic measure. Accordingly, current efforts for NK cell-based cancer therapy have largely relied on the strategies that are based on the manipulation of inhibitory receptor function. However, if we better understand the mechanisms governing NK cell activation, including those mediated by diverse activating receptors, this knowledge can be applied to the development of optimal design for cancer immunotherapy by targeting NK cells.

• BMB Reports
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• 제57권1호
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• pp.2-11
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• 2024

Advancements in gene and cell therapy have resulted in novel therapeutics for diseases previously considered incurable or challenging to treat. Among the various contributing technologies, genome editing stands out as one of the most crucial for the progress in gene and cell therapy. The discovery of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and the subsequent evolution of genetic engineering technology have markedly expanded the field of target-specific gene editing. Originally studied in the immune systems of bacteria and archaea, the CRISPR system has demonstrated wide applicability to effective genome editing of various biological systems including human cells. The development of CRISPR-based base editing has enabled directional cytosine-to-thymine and adenine-to-guanine substitutions of select DNA bases at the target locus. Subsequent advances in prime editing further elevated the flexibility of the edit multiple consecutive bases to desired sequences. The recent CRISPR technologies also have been actively utilized for the development of in vivo and ex vivo gene and cell therapies. We anticipate that the medical applications of CRISPR will rapidly progress to provide unprecedented possibilities to develop novel therapeutics towards various diseases.