• Title/Summary/Keyword: Repair survival model

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Change of Surviving Fractions based on the Recovery of Potentially Lethal Damage in HFL-I Cell Line (HFL-I 세포의 잠재적 치사 손상 회복에 따른 세포 생존율 변화)

  • Choi, Eunae
    • Journal of the Korean Society of Radiology
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    • v.11 no.3
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    • pp.147-151
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    • 2017
  • Potentially lethal damage repair (PLDR) in HFL-I was investigated by delayed plating experiments. The surviving fraction data were fitted to the linear Quadratic equation ($LogSn=-n{\gamma}({\alpha}d+{\beta}d^2$) where ${\gamma}=1$ for immediate plating). And a repair factor ${\gamma}$ was developed to compare survival for immediate and delayed plating. When we only took into account the repair factor of PLDR ${\gamma}$ which was derived from the delay assay, the cell survival response th fractionated carbon ion irradiation was not fully matched. This gap suggested that consideration of another repair process is necessary. So this suggests that the various repair process plays an important role in the fractionated irradiations.

Comparison of Parameter Using the Repair Survival Model Irradiated High-LET (LET 증가에 따른 회복 생존 모델의 파라미터 값 비교)

  • Choi, Eunae
    • Journal of the Korean Society of Radiology
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    • v.11 no.4
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    • pp.177-181
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    • 2017
  • Dose response curves using absorbed dose to the biological effect are usually available in case of conventional X beam. However, absorbed dose is not consider in treatment planning for carbon beam such as heavy ions. Because the biological effects also depend on other quantities such as the local variation, which is often characterized by the linear energy transfer (LET). So LQ model cannot explain the entire response of fractionated carbon beam irradiation. The variation in LET with penetration depth leads to substantial differences in biological effect of carbon beam. And it is therefore essential in treatment planning to calculate not only the absorbed dose but also the LET to estimate the biological outcome of the radiation of interest. LET variation plays an important role in the fractionated irradiations. It is suggested that consideration of LET is necessary in biophysical model.

The Effect of Lateral Approximations on the Survival of the Free Composite Flap (이식편의 측면접합이 복합조직이식의 생존에 미치는 영향)

  • Kim, Deok-Woo;Park, Seung-Ha;Lee, Byung-Ihl
    • Archives of Reconstructive Microsurgery
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    • v.16 no.2
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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.

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DEP Domain Containing 1 is a Novel Diagnostic Marker and Prognostic Predictor for Hepatocellular Carcinoma

  • Yuan, Sheng-Guang;Liao, Wei-Jia;Yang, Jian-Jun;Huang, Guo-Jin;Huang, Zhao-Quan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.24
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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.

Dose-Rate Effects Generated from Repair and Regeneration (재생과 증식에 기인하는 선량률 효과)

  • Yi Pon Nyong;Cho Kwan Ho;Marks Richard D.;Kim Jae Ho
    • Radiation Oncology Journal
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    • v.7 no.2
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    • pp.171-183
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    • 1989
  • A general effect for cell proliferation has been incorporated into Roesch's survival equation (Accumulation Model). From this an isoeffect formula for the low dose-rate regimen is obtained. The prediction for total doses equivalent to 60Gy delivered at the constant dose-rate over 7 days agrees well with the dose-time data of Paterson and of Green, when the parameter ratio A/B (${\approx}{\alpha{\mu}}/2{\beta}\;where\;{\mu}$ is the repair rate) is chosen to be 0.7Gy/h. When a constant proliferation rate and known facts of division delay are assumed, an isoeffect relation between low dose-rate treatment and acute dose-rate treatment can be derived. This formula in the regimens where proliferation is negligible predicts exactly the data of Ellis that 8 fractions of 5 Gy/day for 7 days are equivalent to continuously applied 60Gy over 7days, provided the A/B ratio is 0.7 Gy/h and the $\alpha/\beta$ ratio is 4Gy. Overall agreement between the clinical data and the predictions made by the formula at the above parameter values suggests that the biologcal end points used as the tolerance level in the studies by Paterson, Green, and Ellis all agree and they are not entirely the early effects as generally assumed. The absence of dose-rate effects observed in the mouse KHT sarcoma can better be explained in terms of a large value for the A/B ratio. Similarly, the same total dose used independently of the dose-rate to treat head and neck tumors by Pierquin can be justified.

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Integrin 𝛼4 Positive Subpopulation in Adipose Derived Stem Cells Effectively Reduces Infarct Size through Enhanced Engraftment into Myocardial Infarction

  • Zihui Yuan;Juan Tan;Jian Wang
    • International Journal of Stem Cells
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    • v.17 no.1
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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.

The Effects of Human Adipose Tissue-derived Stem Cells on Degenerative Change of Knee in Rabbit Model (가토 모델에서 인체지방유래 줄기세포가 슬관절의 퇴행성 변화에 미치는 영향)

  • Jeong, Ki-Hwan;Kim, Seok-Kwun;Jeong, Jae-Oo;Heo, Jeong;Kwon, Yong-Seok;Lee, Keun-Cheol
    • Archives of Plastic Surgery
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    • v.35 no.6
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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.

Protective Effect of Ginsenoside R0 on Anoxic and Oxidative Damage In vitro

  • Jiang, Zhou;Wang, Yuhui;Zhang, Xiaoyun;Peng, Tao;Li, Yanqing;Zhang, Yi
    • Biomolecules & Therapeutics
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    • v.20 no.6
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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.

A Theoretical Study for Estimation of Oxygen Effect in Radiation Therapy (방사선 조사시 산소가 세포에 미치는 영향의 이론적 분석)

  • Rena J. Lee;HyunSuk Suh
    • Progress in Medical Physics
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    • v.11 no.2
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    • pp.157-165
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    • 2000
  • Purpose: For estimation of yields of l)NA damages induced by radiation and enhanced by oxygen, a mathematical model was used and tested. Materials and Methods: Reactions of the products of water radiolysis were modeled as an ordinary time dependant equations. These reactions include formation of radicals, DNA damage, damage repair, restitution, and damage fixation by oxygen and H-radical. Several rate constants were obtained from literature while others were calculated by fitting an experimental data. Sensitivity studies were performed changing the chemical rate constant at a constant oxygen number density and varying the oxygen concentration. The effects of oxygen concentration as well as the damage fixation mechanism by oxygen were investigated. Oxygen enhancement ratio(OER) was calculated to compare the simulated data with experimental data. Results: Sensitivity studies with oxygen showed that DNA survival was a function of both oxygen concentration and the magnitude of chemical rate constants. There were no change in survival fraction as a function of dose while the oxygen concentration change from 0 to 1.0 x 10$^{7}$ . When the oxygen concentration change from 1.0 $\times$ 107 to 1.0 $\times$ 101o, there was significant decrease in cell survival. The OER values obtained from the simulation study were 2.32 at 10% cell survival level and 1.9 at 45% cell survival level. Conclusion: Sensitivity studies with oxygen demonstrated that the experimental data were reproduced with the effects being enhanced for the cases where the oxygen rate constants are largest and the oxygen concentration is increased. OER values obtained from the simulation study showed good agreement for a low level of cell survival. This indicated that the use of the semi-empirical model could predict the effect of oxygen in cell killing.

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Induced neural stem cells from human patient-derived fibroblasts attenuate neurodegeneration in Niemann-Pick type C mice

  • Hong, Saetbyul;Lee, Seung-Eun;Kang, Insung;Yang, Jehoon;Kim, Hunnyun;Kim, Jeyun;Kang, Kyung-Sun
    • Journal of Veterinary Science
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    • v.22 no.1
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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.