• Title/Summary/Keyword: preclinical model

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Mouse models of breast cancer in preclinical research

  • Park, Mi Kyung;Lee, Chang Hoon;Lee, Ho
    • Laboraroty Animal Research
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    • v.34 no.4
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    • pp.160-165
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    • 2018
  • Breast cancer remains the second leading cause of cancer death among woman, worldwide, despite advances in identifying novel targeted therapies and the development of treating strategies. Classification of clinical subtypes (ER+, PR+, HER2+, and TNBC (Triple-negative)) increases the complexity of breast cancers, which thus necessitates further investigation. Mouse models used in breast cancer research provide an essential approach to examine the mechanisms and genetic pathway in cancer progression and metastasis and to develop and evaluate clinical therapeutics. In this review, we summarize tumor transplantation models and genetically engineered mouse models (GEMMs) of breast cancer and their applications in the field of human breast cancer research and anti-cancer drug development. These models may help to improve the knowledge of underlying mechanisms and genetic pathways, as well as creating approaches for modeling clinical tumor subtypes, and developing innovative cancer therapy.

Precise System Models using Crystal Penetration Error Compensation for Iterative Image Reconstruction of Preclinical Quad-Head PET

  • Lee, Sooyoung;Bae, Seungbin;Lee, Hakjae;Kim, Kwangdon;Lee, Kisung;Kim, Kyeong-Min;Bae, Jaekeon
    • Journal of the Korean Physical Society
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    • v.73 no.11
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    • pp.1764-1773
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    • 2018
  • A-PET is a quad-head PET scanner developed for use in small-animal imaging. The dimensions of its volumetric field of view (FOV) are $46.1{\times}46.1{\times}46.1mm^3$ and the gap between the detector modules has been minimized in order to provide a highly sensitive system. However, such a small FOV together with the quad-head geometry causes image quality degradation. The main factor related to image degradation for the quad-head PET is the mispositioning of events caused by the penetration effect in the detector. In this paper, we propose a precise method for modelling the system at the high spatial resolution of the A-PET using a LOR (line of response) based ML-EM (maximum likelihood expectation maximization) that allows for penetration effects. The proposed system model provides the detection probability of every possible ray-path via crystal sampling methods. For the ray-path sampling, the sub-LORs are defined by connecting the sampling points of the crystal pair. We incorporate the detection probability of each sub-LOR into the model by calculating the penetration effect. For comparison, we used a standard LOR-based model and a Monte Carlo-based modeling approach, and evaluated the reconstructed images using both the National Electrical Manufacturers Association NU 4-2008 standards and the Geant4 Application for Tomographic Emission simulation toolkit (GATE). An average full width at half maximum (FWHM) at different locations of 1.77 mm and 1.79 mm are obtained using the proposed system model and standard LOR system model, which does not include penetration effects, respectively. The standard deviation of the uniform region in the NEMA image quality phantom is 2.14% for the proposed method and 14.3% for the LOR system model, indicating that the proposed model out-performs the standard LOR-based model.

Preclinical application of 188Re-Tin colloid for treatment of mouse tumor model with peritoneal effusion

  • Jin, Yong Nan;Lee, Yong Jin;Kim, Young Joo;Lee, Yun-Sang;Jeong, Jae Min
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.3 no.2
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    • pp.80-84
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    • 2017
  • Re-188 is an excellent and practical radioisotope produced by W-188/Re-188-generator for therapy. We prepared Re-188-tin colloid for therapy of various diseases and tried to treat peritoneal effusion in animal model. Sarcoma-180 cells were injected into ICR mice to induce peritoneal effusion and the mice were grown for 3 d. Re-188-tin colloids (0.25, 0.5, and 1 mCi/mL per 30 g body weight) were injected into the mice and the mice were grown for 90 d. Planar gamma scintigraphy showed even distribution of Re-188-tin colloid radioactivity. Bax expression was found to be dose dependent to Re-188-tin colloid. Normal saline treated group showed the shortest survival time. Among the treated groups, 0.5 mCi dose group showed the longest survival time. In conclusion, Re-188-tin colloid was prepared successfully and showed the feasibility to use as a peritoneal effusion treatment in mice.

Developmental competence and Effects of Coculture after Crypreservation of Blastomere-Biopsied Mouse Embryos as a Preclinical Model for Preimplantation Genetic Diagnosis (착상 전 유전진단 기술 개발의 동물실험 모델로서 할구 생검된 생쥐 배아에서 동결보존 융해 후 배아 발생 양상과 공배양 효과에 관한 연구)

  • Kim, Seok-Hyun;Kim, Hee-Sun;Ryu, Buom-Yong;Choi, Sung-Mi;Pang, Myung-Geol;Oh, Sun-Kyung;Jee, Byung-Chul;Suh, Chang-Suk;Choi, Young-Min;Kim, Jung-Gu;Moon, Shin-Yong;Lee, Jin-Yong;Chae, Hee-Dong;Kim, Chung-Hoon
    • Clinical and Experimental Reproductive Medicine
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    • v.27 no.1
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    • pp.47-57
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    • 2000
  • Objective: The effects of cryopreservation with or without coculture on the in vitro development of blastomere-biopsied 8-cell mouse embryos were investigated. This experimental study was originally designed for the setup of a preclinical mouse model for the preimplantation genetic diagnosis (PGD) in human. Methods: Eight-cell embryos were obtained after in vitro fertilization (IVF) from F1 hybrid mice (C57BL(표현불가)/CBA(표현불가)). Using micromanipulation, one to four blastomeres were aspirated through a hole made in the zona pellucida by zona drilling (ZD) with acid Tyrode's solution (ATS). A slow-freezing and rapid-thawing protocol with 1.5M dimethyl sulfoxide (DMSO) and 0.1M sucrose as cryoprotectant was used for the cryopreservation of blastomere- biopsied 8-cell mouse embryos. After thawing, embryos were cultured for 110 hours in Ham's F-10 supplemented with 0.4% bovine serum albumin (BSA). In the coculture group, embryos were cultured for 110 hours on the monolayer of Vero cells in the same medium. The blastocyst formation was recorded, and the embryos developed beyond blastocyst stage were stained with 10% Giemsa to count the total number of nuclei in each embryo. Results: The survival rate of embryos after cryopreservation was significantly lower in the blastomere-biopsied (7/8, 6/8, 5/8, and 4/8 embryos) groups than in the non-biopsied, zona intact (ZI) group. Without the coculture, the blastocyst formation rate of embryos after cryopreservation was not significantly different among ZI, the zona drilling only (ZD), and the balstomere-biopsied groups, but it was significantly lower than in the non-cryopreserved control group. The mean number of cells in embryos beyond blastocyst stage was significantly higher in the control group ($50.2{\pm}14.0$) than in 6/8 ($26.5{\pm}6.2$), 5/8 ($25.0{\pm}5.5$), and 4/8 ($17.8{\pm}7.8$) groups. With the coculture using Vero cells, the blastocyst formation rate of embryos after cryopreservation was significantly lower in 5/8 and 4/8 groups, compared with the control, 7/8, and 6/8 groups. The mean number of cells in embryos beyond blastocyst stage was also significantly lower in 4/8 group ($25.9{\pm}10.2$), compared with the control ($50.2{\pm}14.0$), 7/8 ($56.0{\pm}22.2$), and 6/8 ($55.3{\pm}25.5$) groups. Conclusion: After cryopreservation, blastomere-biopsied mouse embryos have a significantly impaired developmental competence in vitro, but this detrimental effect might be prevented by the coculture with Vero cells in 8-cell mouse embryos biopsied one or two blastomeres. Biopsy of mouse embryos after ZD with ATS is a safe and highly efficient preclinical model for PGD of human embryos.

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Effects of Coculture on Development of Biopsied Mouse Embryos as a Preclinical Model for Preimplantation Genetic Diagnosis of Human Embryos (생쥐 모델을 이용한 배아의 할구 생검법과 할구가 생검된 배아의 배양시 공배양 효과에 관한 연구: 인간에서의 착상 전 유전진단 기술 개발을 위한 동물실험 모델의 개발)

  • Kim, S.H.;Ryu, B.Y.;Jee, B.C.;Choi, S.M.;Kim, H.S.;Pang, M.G.;Oh, S.K.;Suh, C.S.;Choi, Y.M.;Kim, J.G.;Moon, S.Y.;Lee, J.Y.;Chae, H.D.;Kim, C.H.
    • Clinical and Experimental Reproductive Medicine
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    • v.26 no.1
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    • pp.9-20
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    • 1999
  • The genetic defects in human gametes and embryos can cause adverse effects on overall reproductive events. Biopsy of embryos for preimplantation genetic diagnosis (PGD) offers a new possibility of having children free of the genetic disease. In addition, advanced embryo culture method may enhance the effectiveness of embryo biopsy for the practical application of PGD. This experimental study was undertaken to evaluate the effects of coculture on the development in vitro of biopsied mouse embryos as a preclinical model for PGD of human embryos. Embryos were obtained after in vitro fertilization (IVF) from F1 hybrid mice (C57BLfemale/CBAmale). Using micromanipulation, 1, 2, 3 or 4 blastomeres of 8-cell stage embryos were aspirated through a hole made in the zona pellucida by zona drilling (ZD) with acidic Tyrode's solution (ATS). After biopsy of blastomeres, embryos were cultured in vitro for 110 hours in Ham's F-10 supplemented with 0.4% BSA or cocultured on the monolayer of Vero cells in the same medium. The frequence of blastocyst formation were recorded, and the embryos beyond blastocyst stage were stained with 10% Giemsa to count the total number of nuclei in each embryo. There was no significant difference in the blastocyst formation between the zona intact control group and the zona drilling (ZD) only, or biopsied groups. The hatching rate of all the treatment groups except 4/8 group was significantly higher than that of control group. In all the treatment groups, there was a significant reduction in the mean cell number of embryos beyond blastocyst stage ($50.2{\pm}14.0$ in control group vs. $41.2{\pm}7.9$ in ZD, $39.3{\pm}8.8$ in 7/8, $29.7{\pm}6.4$ in 6/8, $25.1{\pm}5.7$ in 5/8, and $22.1{\pm}4.3$ in 4/8 groups, p<0.05). When the same treatments were followed by coculture with Vero cells, a similar pattern was seen in the blastocyst formation and the hatching rate. However, in all the treatment groups, there was a significant increase in the mean cell number of embryos beyond blastocyst stage with coculture, compared with the parallel groups without coculture. In the cleavage rate of biopsied blastomeres cultured for 110 hours after IVF, there was no significant difference between coculture and non-coculture groups (87.2% vs. 78.7%). However, the mean cell number of embryos developed from the biopsied blastomeres was significantly higher in coculture group ($11.5{\pm}4.7\;vs.\;5.9{\pm}1.9$, p<0.05). In conclusion, biopsy of mouse embryos after ZD with ATS is a safe and highly efficient method for PGD, and coculture with Vero cells showed a positive effect on the development in vitro of biopsied mouse embryos and blastomeres as a preclinical model for PGD of human embryos.

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Conditional PTEN-deficient Mice as a Prostate Cancer Chemoprevention Model

  • Koike, Hiroyuki;Nozawa, Masahiro;De Velasco, Marco A;Kura, Yurie;Ando, Naomi;Fukushima, Emiko;Yamamoto, Yutaka;Hatanaka, Yuji;Yoshikawa, Kazuhiro;Nishio, Kazuto;Uemura, Hirotsugu
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.1827-1831
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    • 2015
  • Background: We generated a mouse model of prostate cancer based on the adult-prostate-specific inactivation of phosphatase and tensin homolog (PTEN) using the Cre-loxP system. The potential of our mice as a useful animal model was examined by evaluating the chemopreventive efficacy of the anti-androgen, chlormadinone acetate (CMA). Materials and Methods: Six-week-old mice were treated subcutaneously with $50{\mu}g/g$ of CMA three times a week for 9 or 14 weeks and sacrificed at weeks 15 and 20. Macroscopic change of the entire genitourinary tract (GUT) and histologically evident prostate gland tumor development were evaluated. Proliferation and apoptosis status in the prostate were examined by immunohistochemistry. Results: CMA triggered significant shrinkage of not only the GUT but also prostate glands at 15 weeks compared to the control (p=0.017 and p=0.010, respectively), and the trend became more marked after a further five-weeks of treatment. The onset of prostate adenocarcinoma was not prevented but the proliferation of cancer cells was inhibited by CMA, which suggested the androgen axis is critical for cancer growth in these mice. Conclusions: Conditional PTEN-deficient mice are useful as a preclinical model for chemoprevention studies and serve as a valuable tool for the future screening of potential chemopreventive agents.

Model Systems in Radiation Biology: Implication for Preclinical Study of Radiotherapy (방사선 생물학을 위한 모델 시스템: 방사선치료의 전임상 연구)

  • Kim, Wanyeon;Seong, Ki Moon;Yang, Hee Jung;Youn, HyeSook;Youn, BuHyun
    • Journal of Life Science
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    • v.22 no.11
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    • pp.1558-1570
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    • 2012
  • In radiation biology, analysis of various mechanisms in response to radiation has been accomplished with the use of model organisms. These model organisms are powerful tools for providing a biologically intact in vivo environment to assess physiological and pathophysiological processes affected by radiation. Accumulated data using these models have been applied to human clinical studies (including the evaluation of radiotherapeutic efficacy) and discovery of radiotherapy reagents. However, there are few studies to provide overall integrated information about these useful model organisms. Thus, this review summarizes the results of radiation biology studies using four well-known model organisms: yeast, Caenorhabditis elegans, Drosophila melanogaster, and mice.

Pre-clinical Screening Methods for Evaluating Anti-wrinkle Effect

  • Cho Moon Kyun
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.29 no.2 s.43
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    • pp.37-65
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    • 2003
  • Nowadays, we find out new anti-wrinkle-care-ingredients by in vitro searching methods using many kind of cell-culture-models for investigation of the effective anti-wrinkle-care-ingredients. But, theses new ingredients don't have effect on the human-model for anti-wrinkle, not likely on in vitro. In other words, there are so many differences between the effects on in vitro models and the clinical human models, practically. But, we actually have difficulty in putting all of the new anti-wrinkle-care-ingredients to the test on human models directly. To solve this problem, we have investigated that by using the artificial skin-culture-model or the animal model, In this lecture I will review the detail of assessment method far evaluation of anti-wrinkle agents in vitro and animal model and discuss the pros and cons of each method. Then I will present the results of Preclinical Screening trials, And especially animal model may be a good candidate for evaluation of anti-wrinkle agents.

Corrosive Stricture Model Induced-Esophageal Burn : Animal Pilot Data (NaOH 용액을 이용한 부식성 식도 협착 동물모델 형성에 관한 연구)

  • Kim, Min-Tae
    • Journal of the Korean Society of Radiology
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    • v.15 no.5
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    • pp.643-647
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    • 2021
  • The purpose of this study was to access the possibility and ideal model for corrosive-induced tissue hyperplasia in the rat esophagus. Twenty rat were divided into two group: a healthy group, corrosive group. corrosive burn in esophagus were produced using 30% NaOH on the distal esophagus. After surgical procedure, behavioral and weight changes were monitored on a weekly. At 3 weeks after surgical procedure, fluoroscopic esophagogram was performed and then all rats sacrificed for histological analysis by administering inhalable pure carbon dioxide. Technical surgery for corrosive stricture were 100%. A total of 2 rats died in corrosive group from a corrosive burn related to dysphagia within 14 days. The esophageal stenosis ratio was significantly higher in the corrosive group than in the healthy group (40.1 ± 9.2 % and 1.4 ± 7.2%, respectively; p = 0.001). The tissue hyperplasia ratio was also significantly higher in the Corrosive group (62.5 ± 9% and 22.08 ± 6%, respectively; p = 0.001). Infusion of 30% NaOH may suggest alternative option to evaluation tool for preclinical study in a rat corrosive model.

Effect of the size of the bony access window and the collagen barrier over the window in sinus floor elevation: a preclinical investigation in a rabbit sinus model

  • Sim, Jeong-Eun;Kim, Sangyup;Hong, Ji-Youn;Shin, Seung-Il;Chung, Jong-Hyuk;Lim, Hyun-Chang
    • Journal of Periodontal and Implant Science
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    • v.52 no.4
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    • pp.325-337
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    • 2022
  • Purpose: The aim of this study was to investigate the effect of (1) the size of the bony access window and (2) collagen membrane coverage over the window in sinus floor elevation in a rabbit sinus model. Methods: Small bony access windows (SW; ø 2.8 mm) were made in 6 rabbits and large windows (LW; ø 6 mm) in 6 other rabbits. Both sinuses in each rabbit were allocated to groups with or without coverage of a collagen membrane (CM) on the window, resulting in 4 groups: SW, LW, SW+CM, and LW+CM. After 4 weeks of healing, micro-computed tomographic, histologic, and histomorphometric analyses were performed. Results: Bony healing in the window area was incomplete in all groups, but most bone graft particles were well confined in the augmented cavity. Histologically, the pattern of new bone formation was similar in all groups. Histomorphometrically, the percentage of newly formed bone was greater in the groups with CM than in the groups without CM, and in the groups with SW than in the groups with LW (12.92%±6.40% in the SW+CM group, 4.21%±7.73% in the SW group, 10.45%±4.81% in the LW+CM group, 11.77%±3.83% in the LW group). The above differences were not statistically significant (P>0.05). Conclusions: The combination of a small bony access window and the use of a collagen membrane over the window favored new bone formation compared to other groups, but this result should be further investigated due to the limitations of the present animal model.