• 한국방사선학회논문지
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• 제11권3호
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• pp.147-151
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• 2017

HFL-I 세포를 이용하여 immediate assay를 시행하였다. 발생한 repair의 양이 없기 때문에 $LogSn=-n{\gamma}({\alpha}d+{\beta}d^2$)에서 ${\gamma}$의 값은 1이며 이는 LQ model과 같다. 그리고 세포생존율의 데이터를 바탕으로 ${\alpha}$, ${\beta}$, ${\alpha}/{\beta}$의 값을 얻었다. 또한 12시간, 36시간, 48시간 후 delayed assay를 시행하여 marchese model 통해 ${\gamma}$값을 도출한 후 Pot entially lethal damage repair (PLDR)가 발생한 양을 확인하였다. delay time이 길어질수록 ${\gamma}$값은 감소함으로써 PLDR의 양이 증가함을 확인하였고 이에 따라 세포생존율은 상승됨을 보였다. 탄소빔의 1분할, 2분할, 3분할, 4분할 조사 시 각각의 interval 시간동안 나타나는 ${\gamma}$값 역시 감소하고 있음을 확인하여 PLDR의 발생을 확인할 수 있었지만 ${\gamma}$값만 감안한 marchese model을 surviving fraction값에 적용 시 오류 발생함을 보였다. 이는 탄소빔 분할조사 시 다른 회복의 매커니즘이 존재함을 뜻하여 이를 적용할 수 있는 새로운 파라미터가 고려되어져야 할 것이다.

• 한국방사선학회논문지
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• 제11권4호
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• pp.177-181
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• 2017

방사선 생물학적 효과(Radio biological effectiveness, RBE)를 선량에 대부분 의존하는 X선과 달리 탄소빔의 경우 LET의 변화량은 반드시 고려되어야할 사항이다. 이는 X선 과는 극히 대조적인 선량 분포도를 갖고 있기 때문이며 LET의 변화량이 중요한 이유가 된다. 따라서 기존의 LQ 모델이나 회복생존모델의 경우 이러한 점이 감안되지 않아 탄소빔의 분할 조사 시 문제점을 보이며 오류를 보이고 있다. 본 연구에서는 약 $75keV/{\mu}m$의 고LET 탄소빔 분할 조사 시 Potentially Lethal Damage Repair (PLDR)의 발생양을 확인하고 약 $13keV/{\mu}m$ 저LET 조사와 비교하여 현저히 감소하였음을 확인하였다. PLDR의 감소에 따라 생존율 또한 감소하였다. 따라서 탄소빔의 생물리학적 모델 개발에 LET의 변화량은 반드시 고려되어져야 할 것으로 보인다.

• Archives of Reconstructive Microsurgery
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• 제16권2호
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• pp.57-62
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• 2007

Non-vascularized free composite graft is one of the simple and effective reconstructive options, but its clinical use has been limited due to questionable survival rate. Early vascularization is essential for graft survival and is mainly carried out via recipient bed or repaired sites. This study was designed to investigate the effect of the lateral marginal approximations on the survival of the free composite flap using a model of skin-subcutaneous composite graft in rats. Thirty 1.5 ${\times}$ 1.5 $cm^2$ sized square shape composite flaps were elevated freely and reposed in place immediately on the dorsum of five Sprague-Dawley rats, and divided into five groups of six flaps. In all groups, graft bed was isolated with silastic sheet. In the group I, all sides of flap were repaired with blockage of silastic sheet insertion. Three, two, and one sides of flap were treated with same method in the group II, III, and IV respectively. Other sides of flaps were repaired without blockage, so all sides of flap were repaired in the group V. At 14 days later, the survived rate of each flap was evaluated according to the numbers of the repair sites. Histological examination was done for the evaluation of new vessel development quantitatively. Overall survived rates were increased with the number of repaired sites, but the group V only showed increased survival rate up to more than fifty percentile of the flap size with a significant difference statistically. New vessels were also increased in proportion with the number of repaired sites, and the repair site more than two had significant effect on the increased number of new vessels. In conclusion, at least more than three-fourth of flap circumference should be repaired in order to increase flap survival effectively under the condition of bed isolation.

• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10917-10922
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• 2015

Background: This study was conducted to determine DEPDC1 expression in hepatocelluar carcinomas (HCCs) and to reveal its potential role in diagnosis and prognosis of affected patients. Materials and Methods: DEPDC1 expression at the mRNA level was detected by quantitative real-time PCR (qRT-PCR) in 205 cases of HCC and paired adjacent normal liver tissues, and by semi-quantitative RT-PCR in 20 cases. Survival curves were obtained by using Kaplan-Meier method and Log-rank test. Independent predictors associated with regard to disease free survival (DFS) and overall survival (OS) were identified using the Cox proportional hazard model. Results: High DEPDC1 mRNA levels were detected in 144 out of 205 cases (70.24%) of HCC, significantly associated with clinicopathological parameters, including tumor size (${\geq}4cm$), alpha-fetoprotein (${\geq}100ng/ml$), B-C of BCLC stage and recurrence. Kaplan-Meier survival analysis revealed that HCC patients with high DEPDC1 expression had poor OS and DFS. Multivariate analysis demonstrated that high DEPDC1 expression was an independent predictor for OS (HR=1.651; 95% 95%CI, 1.041-2.617; p=0.033) and DFS (HR=1.583; 95%CI, 1.01-2.483; p=0.045). Conclusions: Our results indicate DEPDC1 might be a novel diagnostic marker and an independent prognostic predictor for HCC patients.

• Radiation Oncology Journal
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• 제7권2호
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• pp.171-183
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• 1989

Roesch의 생존 방정식속에 세포증식으로 일어나는 생존증가를 가장 일반적 형식으로 포함시킨 식을 유도하고 이 식으로부터 저선량률 방사선에만 적용되는 동결과선량식 (Isoeffect formula)을 유도하였다. 이 저선량률식이 파라메터 하나로 결정해주는 총선량은 Paterson과 Green에 의하여 얻어진 실험 임상결과와 일치한다. 이 파라메터와 선량률 효과 사이의 관계의 의의를 논하였다. 또한 고선량률 분절(fractionation) 치료와 동저선량률 계속치료를 연락하는 동결과 선량식을 유도 사용하여, Ellis가 잰 실험결과와 비교하였다. 그 결과, Ellis와 Paterson이 쓴 'tolerance'의 표준이 $\alpha/\beta$의 비 4Gy에 해당하는 것임이 밝혀졌다. 그러므로 이들의 'tolerance'의 표준은 'early effect'에만 두고 본 것이 아님을 알 수 있다. 개념적인 면에서도, 아래와 같은 새로운 견해가 나올 수 있다. KHT sarcoma의 생존선도 (survival curve)에 선량률 효과가 보이지 않는 이유로 $\alpha/\beta$의 비가 큰 점을 들을 수 있다. 이것은 이 survival curve에 어께 (shoulder)가 보이지 않는 것으로도 증명이 된다. Pierquin이 선량률에 무관하게 head and neck tumor치료에 같은 총선량을 쓴 것을 정당화시킬 수 있다.

• International Journal of Stem Cells
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• 제17권1호
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• pp.70-79
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• 2024

The efficacy of adipose-derived stem cells (ASCs) on myocardial infarction is limited due to poor survival and engraftment. Integrin-mediated cell adhesion is a prerequisite for its survival and homing. ASCs expressed insufficient integrin 𝛼₄, limiting their homing capacity. This study aims to characterize integrin 𝛼₄⁺ ASC subpopulation and investigate their therapeutic efficacy in myocardial infarction. We used fluorescence-activated cell sorting to harvest integrin 𝛼₄⁺ ASCs subpopulation, which were characterized in vitro and transplanted into myocardial infarction model. Positron emission tomography imaging were performed to measure infarction size. Cardiac cine magnetic resonance imaging was used to evaluate heart contractile function. Compared with the unfractionated ASCs, integrin 𝛼₄⁺ ASCs subpopulation secreted a higher level of angiogenic growth factors, migrated more rapidly, and exhibited a stronger anti-apoptotic capacity. Vascular cell adhesion molecule-1 was obviously up-regulated at 3 days after myocardial infarction, which interacted with integrin α₄ receptor on the surface of ASCs to enhance the survival and adhesion. Thus, we implanted unfractionated ASCs or integrin α₄⁺ ASCs subpopulation into the 3-day infarcted myocardium. Integrin α₄⁺ ASCs subpopulation exhibited more robust engraftment into the infarcted myocardium. Integrin α₄⁺ ASCs subpopulation more effectively decreased infarct size and strengthen cardiac function recovery than did the unfractionated ASCs. Integrin α₄⁺ ASCs subpopulation is superior to unfractionated ASCs in ameliorating ischemic myocardial damage in animal model. Mechanistically, their more robust engraftment into the infarct area, higher migratory capacity and their increased release of paracrine factors contribute to enhanced tissue repair.

• Archives of Plastic Surgery
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• 제35권6호
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• pp.637-644
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• 2008

Purpose: The survival of bone marrow derived stem cell was reported several times. But the survival of adipose tissue derived stem cells(hASCs) was not mentioned on. We studied the adipose tissue derived stem cell's survival and effect on articular cartilage in rabbits. Methods: Osteoarthritis was induced in twenty New Zealand white rabbits by intraarticular injection of monosodium iodoacetate(MIA). After four weeks, hASCs were also injected into the knee joints space without any vehicle, but the control group received phosphate buffered saline only. The histologic grade of articular cartilage was measured in 4 and 8 weeks after the transplantation of hASC and the viability of injected stem cells measured by Fluorescent in situ Hybridization (FISH) examination. Results: After 4 and 8 weeks from hASCs transplantation, histologic grade was not significantly difference between two groups(p>0.05), and the Y chromosome of the transplanted hASCs was not detected in articular cartilage. Conclusion: We found that direct injection of hASC in joint space didn't work on damaged articular cartilage repair.

• Biomolecules & Therapeutics
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• 제20권6호
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• pp.544-549
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• 2012

To examine the neuroprotective effects of ginsenoside R0, we investigated the effects of ginsenoside R0 in PC12 cells under an anoxic or oxidative environment with Edaravone as a control. PC12 neuroendocrine cells were used as a model target. Anoxic damage or oxidative damage in PC12 cells were induced by adding sodium dithionite or hydrogen peroxide respectively in cultured medium. Survival ratios of different groups were detected by an AlamarBlue assay. At the same time, the apoptosis of PC12 cells were determined with flow cytometry. The putative neuroprotective effects of ginsenoside R0 is thought to be exerted through enhancing the activity of antioxidant enzymes Superoxide dismutases (SOD). The activity of SOD and the level of malondialdehyde (MDA) and intracellular reactive oxygen species (ROS), were measured to evaluate the protective and therapeutic effects of ginsenoside R0. Ginsenoside R0 treated cells had a higher SOD activity, lower MDA level and lower ROS, and their survival ratio was higher with a lower apoptosis rate. It is suggested that ginsenoside R0 has a protective effect in the cultured PC12 cells, and the protection efficiency is higher than Edaravone. The protective mechanisms of these two are different. The prevent ability of ginsenoside R0 is higher than its repair ability in neuroprotection in vitro.

• 한국의학물리학회지:의학물리
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• 제11권2호
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• pp.157-165
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• 2000

목적: 방사선조사에 의해 형성된 DNA 손상정도가 산소에 의해 변화되는 추세을 이론적 모델을 이용하여 평가 및 분석하였다. 방법 및 대상: Water radiolysis(물의 방사성분해)시 생성되는 유리기 들간의 반응, 손상된 DNA의 형성, 손상의 복구, 및 산소에 의한 손상의 고정들을 시간 미분 방정식을 이용하여 표현하였다. 문헌에 나와 있는 반응상수(rate constants)들은 그대로 사용되었고 알려지지 않은 상수들은 실험에서 얻어진 데이터에서 얻은 곡선을 대입하여 얻었다. 화학반응상수 변화와 산소농도변화에 따른 세포 생존도를 구하였다. 모델을 통해 얻어진 세포 생존도와 방사선량의 상관관계를 세포 생존곡선으로 표시하였다. 산소에 의한 손상의 fixation(고착화)과정과 산소농도가 세포생존에 미치는 영향을 분석하여 보았다. 산소가 세포생존에 미치는 정도를 정량화 하기 위하여 산소증가효과비(Oxygen Ehhancement Ratio, OER)를 계산하여 실험치와 이론치를 비교하였다. 결과: 산소에 대한 민감성 연구에서 DNA생존도는 산소의 농도와 화학반응속도상수에 영향을 받았다. 산소의 농도가 0에서 1.0 $\times$ $10^{7}$ 으로 변화할 때 세포 생존도에는 변화가 없었다. 그러나 1.0 x $10^{7}$ 에서 1.0 $\times$ $10^{10}$ 변화할 경우 세포의 생존률이 감소하였다. 모의연구에서 얻은 OER치는 10% 세포생존시에는 2.32, 45% 세포생존시에는 1.9 이었다. 결론: 산소의 감수성 연구에서 보여주듯이 방정식을 이용하여 얻어진 새포생존곡선은 실험에서 얻어진 세포생존곡선을 재연할 수 있었다 또한 방사선조사시 생성되는 손상된 세포의 양은 산소 반응상수가 가장 크고 산소농도가 증가되는 경우에 증가됨을 알수있었다. 모의연구에서 얻은 산소증가효과비는 세포생존이 low level인 경우 높은 일치성을 보여 주었다 따라서 본 연구는 세포살해시 산소의 효과를 semi-empirical 모델을 사용하여 예측할수 있다는 것을 보여주고 있다.

• Journal of Veterinary Science
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• 제22권1호
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• pp.7.1-7.13
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• 2021

Background: Niemann-Pick disease type C (NPC) is caused by the mutation of NPC genes, which leads to the abnormal accumulation of unesterified cholesterol and glycolipids in lysosomes. This autosomal recessive disease is characterized by liver dysfunction, hepatosplenomegaly, and progressive neurodegeneration. Recently, the application of induced neural stem cells (iNSCs), converted from fibroblasts using specific transcription factors, to repair degenerated lesions has been considered a novel therapy. Objectives: The therapeutic effects on NPC by human iNSCs generated by our research group have not yet been studied in vivo; in this study, we investigate those effects. Methods: We used an NPC mouse model to efficiently evaluate the therapeutic effect of iNSCs, because neurodegeneration progress is rapid in NPC. In addition, application of human iNSCs from NPC patient-derived fibroblasts in an NPC model in vivo can give insight into the clinical usefulness of iNSC treatment. The iNSCs, generated from NPC patientderived fibroblasts using the SOX2 and HMGA2 reprogramming factors, were transplanted by intracerebral injection into NPC mice. Results: Transplantation of iNSCs showed positive results in survival and body weight change in vivo. Additionally, iNSC-treated mice showed improved learning and memory in behavior test results. Furthermore, through magnetic resonance imaging and histopathological assessments, we observed delayed neurodegeneration in NPC mouse brains. Conclusions: iNSCs converted from patient-derived fibroblasts can become another choice of treatment for neurodegenerative diseases such as NPC.