• Title/Summary/Keyword: preclinical model

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Anti-cancer Activity of Paclitaxel, Lenvatinib and Radiation Combination Therapy on Anaplastic Thyroid Cancer in Vitro and in Vivo (Paclitaxel, Lenvatinib 및 방사선 병용 요법의 역형성 갑상선암에서의 항암 작용)

  • Jun, Shiyeol;Kim, Soo Young;Kim, Seok-Mo;Park, Ki Cheong;Kim, Hee Jun;Chang, Ho Jin;Lee, Yong Sang;Chang, Hang-Seok;Park, Cheong Soo
    • Korean Journal of Head & Neck Oncology
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    • v.35 no.2
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    • pp.19-25
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    • 2019
  • Background/Objectives: Although anaplastic thyroid carcinoma (ATC) is rare, it is one of the deadliest forms of thyroid cancer. The fatality rate for ATC is high, and the survival rate at one year after diagnosis is <20%. The present study aimed to investigate the anti-tumor activities of paclitaxel, radiation, and tyrosine kinase inhibitor (TKI) combined therapy in anaplastic thyroid cancer cells both in vitro and in vivo and explore its effects on apoptotic cell death pathways. Materials & Methods: ATC cell line was exposed to TKI, lenvatinib in the presence or absence of paclitaxel with radiation, and cell viability was determined by MTT assay. Effects of the combined treatment on cell cycle and intracellular signaling pathways were assessed by flow cytometry and western blot analysis. The ATC cell line xenograft model was used to examine the anti-tumor activity in vivo. Results: Our data revealed that the combined administration of paclitaxel, TKI, and radiation decreased cell viability in ATC cells, and also significantly increased apoptotic cell death in these cells, as demonstrated by the cleavage of caspase-3 and DNA fragmentation. This combination therapy reduced anti-apoptotic factor levels in ATC cells, while significantly decreasing tumor volume and increasing survival in ATC xenografts. Conclusion: These results indicate that administering the combination of paclitaxel, TKI, and radiation therapy may exert significant anticancer effects in preclinical models, potentially suggesting a new clinical approach for treating patients with ATC.

Repeated irradiation by light-emitting diodes may impede the spontaneous progression of experimental periodontitis: a preclinical study

  • Hyemee Suh;Jungwon Lee;Sun-Hee Ahn;Woosub Song;Ling Li;Yong-Moo Lee;Yang-Jo Seol;Ki-Tae Koo
    • Journal of Periodontal and Implant Science
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    • v.53 no.2
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    • pp.120-134
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    • 2023
  • Purpose: We investigated whether repeated irradiation with light-emitting diodes (LEDs) at a combination of 470 nm and 525 nm could suppress the progression of experimental periodontitis. Methods: A experimental periodontitis model was established in the second, third, and fourth premolars of the mandible in beagle dogs for 2 months. The spontaneous progression of periodontitis was monitored under the specified treatment regimen for 3 months. During this period, the animals were subjected to treatments of either plaque control only (control) or plaque control with LED application (test) at 2-week intervals. The clinical parameters included the probing pocket depth (PPD), gingival recession (GR), and the clinical attachment level (CAL). Histomorphometric analysis was performed using measurements of the length of the junctional epithelium, connective tissue (CT) zone, and total soft tissue (ST). Results: There were significant differences in PPD between the control and test groups at baseline and 12 weeks. When the change in PPD was stratified based on time intervals, it was shown that greater differences occurred in the test group, with statistical significance for baseline to 12 weeks, 6 to 12 weeks, and baseline to 6 weeks. There was no significant difference in GR between the control and test groups at any time points. Likewise, no statistically significant differences were found in GR at any time intervals. CAL showed a statistically significant difference between the control and test groups at baseline only, although significant differences in CAL were observed between baseline and 12 weeks and between 6 and 12 weeks. The proportion of CT to ST was smaller for both buccal and lingual areas in the control group than in the test group. Conclusions: Repeated LED irradiation with a combination of 470-nm and 525-nm wavelengths may help suppress the progression of periodontal disease.

Protective Effect of Enzymatically Modified Stevia on C2C12 Cell-based Model of Dexamethasone-induced Muscle Atrophy (덱사메타손으로 유도된 근위축 C2C12 모델에서 효소처리스테비아의 보호 효과)

  • Geon Oh;Sun-Il Choi;Xionggao Han;Xiao Men;Se-Jeong Lee;Ji-Hyun Im;Ho-Seong Lee;Hyeong-Dong Jung;Moon Jin La;Min Hee Kwon;Ok-Hwan Lee
    • Journal of Food Hygiene and Safety
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    • v.38 no.2
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    • pp.69-78
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    • 2023
  • This study aimed to investigate the protective effect of enzymatically modified stevia (EMS) on C2C12 cell-based model of dexamethasone (DEX)-induced muscle atrophy to provide baseline data for utilizing EMS in functional health products. C2C12 cells with DEX-induced muscle atrophy were treated with EMS (10, 50, and 100 ㎍/mL) for 24 h. C2C12 cells were treated with EMS and DEX to test their effects on cell viability and myotube formation (myotube diameter and fusion index), and analyze the expression of muscle strengthening or degrading protein markers. Schisandra chinensis Extract, a common functional ingredient, was used as a positive control. EMS did not show any cytotoxic effect at all treatment concentrations. Moreover, it exerted protective effects on C2C12 cell-based model of DEX-induced muscle atrophy at all concentrations. In addition, the positive effect of EMS on myotube formation was confirmed based on the measurement and comparison of the fusion index and myotube diameter when compared with myotubes treated with DEX alone. EMS treatment reduced the expression of muscle cell degradation-related proteins Fbx32 and MuRF1, and increased the expression of muscle strengthening and synthesis related proteins SIRT1 and pAkt/Akt. Thus, EMS is a potential ingredient for developing functional health foods and should be further evaluated in preclinical models.

Ex vivo Morphometric Analysis of Coronary Stent using Micro-Computed Tomography (미세단층촬영기법을 이용한 관상동맥 스텐트의 동물 모델 분석)

  • Bae, In-Ho;Koh, Jeong-Tae;Lim, Kyung-Seob;Park, Dae-Sung;Kim, Jong-Min;Jeong, Myung-Ho
    • Journal of the Korean Society of Radiology
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    • v.6 no.2
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    • pp.93-98
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    • 2012
  • Micro-computed tomography (microCT) is an important tool for preclinical vascular imaging, with micron-level resolution. This non-destructive means of imaging allows for rapid collection of 2D and 3D reconstructions to visualize specimens prior to destructive analysis such as pathological analysis. Objectives. The aim of this study was to suggest a method for ex vivo, postmortem examination of stented arterial segments with microCT. And ex vivo evaluation of stents such as bare metal or drug eluting stents on in-stent restenosis (ISR) in rabbit model was performed. The bare metal stent (BMS) and drug eluting stent (DES, paclitaxel) were implanted in the left or right iliac arteries alternatively in eight New Zealand white rabbits. After 4 weeks of post-implantation, the part of iliac arteries surrounding the stent were removed carefully and processed for microCT. Prior to microCT analysis, a contrast medium was loaded to lumen of stents. All samples were subjected to an X-ray source operating at 50 kV and 200 ${\mu}A$ by using a 3D isotropic resolution. The region of interest was traced and measured by CTAN analytical software. Objects being exposed to radiation had different Hounsfield unit each other with values of approximately 1.2 at stent area, 0.12 ~ 0.17 at a contrast medium and 0 ~ 0.06 at outer area of stent. Based on above, further analyses were performed. As a result, the difference of lengths and volumes between expanded stents, which may relate to injury score in pathological analysis, was not different significantly. Moreover, ISR area of BMS was 1.6 times higher than that of DES, indicating that paclitaxel has inhibitory effect on cell proliferation and prevent infiltration of restenosis into lumen of stent. And ISR area of BMS was higher ($1.52{\pm}0.48mm^2$) than that of DES ($0.94{\pm}0.42mm^2$), indicating that paclitaxel has inhibitory effect on cell proliferation and prevent infiltration of restenosis into lumen of stent. Though it was not statistically significant, it showed that the extent of neointema of mid-region of stents was relatively higher than that of anterior and posterior region in parts of BMS as showing cross-sectional 2-D image. suggest that microCT can be utilized as an accessorial tool for pathological analysis.

Efficacy and Safety of a Newly Developed Self-Expanding Open-Cell Type Nitinol Stent for Peripheral Arteries: A Preclinical Study in Minipigs (새로 개발된 말초동맥용 자가팽창성 개방형 니티놀 스텐트의 유효성 및 안전성 평가: 미니피그 전임상실험)

  • Min Uk Kim;Jae Hwan Lee;Chang Jin Yoon;Won Seok Choi;Saebeom Hur;Jin Wook Chung
    • Journal of the Korean Society of Radiology
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    • v.81 no.4
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    • pp.899-911
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    • 2020
  • Purpose To evaluate the safety and efficacy of the newly designed open-cell type self-expandable nitinol stent (NiTi-stent) for peripheral arteries. Materials and Methods Twenty-eight limbs of 14 minipigs were randomly assigned to the NiTistent group or conventional nitinol stent group. Stents were symmetrically implanted into the iliac arteries of each animal using carotid artery approach and were observed for 1 month (n = 5) and 6 months (n = 9). The angiographic lumen diameter (ALD), late lumen loss, angiographic stenosis, histomorphometric lumen area, neointimal area, and area stenosis were analyzed and compared between the groups. Results Stent migration, stent fracture, or thrombus formation were not observed in either group. At the 1-month follow-up, the neointimal area (p = 0.008) and area stenosis (p = 0.016) were significantly smaller in the NiTi-stent group than in the control group. At the 6-months followup, the NiTi-stent group showed significantly larger ALD (p = 0.014), less late lumen loss (p = 0.019), less angiographic stenosis (p = 0.014), larger lumen area (p = 0.040), and smaller neointimal area and area stenosis (p = 0.004 and p = 0.014, respectively) compared with the control group. Conclusion The NiTi-stent is as safe and effective as the conventional nitinol stent and induces less neointimal hyperplasia in a minipig iliac artery model.