• Title/Summary/Keyword: xenograft mouse model

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Optical Imaging Technology for Real-time Tumor Monitoring

  • Shin, Yoo-kyoung;Eom, Joo Beom
    • Medical Lasers
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    • v.10 no.3
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    • pp.123-131
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    • 2021
  • Optical imaging modalities with properties of real-time, non-invasive, in vivo, and high resolution for image-guided surgery have been widely studied. In this review, we introduce two optical imaging systems, that could be the core of image-guided surgery and introduce the system configuration, implementation, and operation methods. First, we introduce the optical coherence tomography (OCT) system implemented by our research group. This system is implemented based on a swept-source, and the system has an axial resolution of 11 ㎛ and a lateral resolution of 22 ㎛. Second, we introduce a fluorescence imaging system. The fluorescence imaging system was implemented based on the absorption and fluorescence wavelength of indocyanine green (ICG), with a light-emitting diode (LED) light source. To confirm the performance of the two imaging systems, human malignant melanoma cells were injected into BALB/c nude mice to create a xenograft model and using this, OCT images of cancer and pathological slide images were compared. In addition, in a mouse model, an intravenous injection of indocyanine green was used with a fluorescence imaging system to detect real-time images moving along blood vessels and to detect sentinel lymph nodes, which could be very important for cancer staging. Finally, polarization-sensitive OCT to find the boundaries of cancer in real-time and real-time image-guided surgery using a developed contrast agent and fluorescence imaging system were introduced.

Treatment of BG-1 Ovarian Cancer Cells Expressing Estrogen Receptors with Lambda-cyhalothrin and Cypermethrin Caused a Partial Estrogenicity Via an Estrogen Receptor-dependent Pathway

  • Kim, Cho-Won;Go, Ryeo-Eun;Choi, Kyung-Chul
    • Toxicological Research
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    • v.31 no.4
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    • pp.331-337
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    • 2015
  • Synthetic pyrethroids (SPs) are the most common pesticides which are recently used for indoor pest control. The widespread use of SPs has resulted in the increased exposure to wild animals and humans. Recently, some SPs are suspected as endocrine disrupting chemicals (EDCs) and have been assessed for their potential estrogenicity by adopting various analyzing assays. In this study, we examined the estrogenic effects of lambda-cyhalothrin (LC) and cypermethrin (CP), the most commonly used pesticides in Korea, using BG-1 ovarian cancer cells expressing estrogen receptors (ERs). To evaluate the estrogenic activities of two SPs, LC and CP, we employed MTT assay and reverse-transcription polymerase chain reaction (RT-PCR) in LC or CP treated BG-1 ovarian cancer cells. In MTT assay, LC ($10^{-6}M$) and CP ($10^{-5}M$) significantly induced the growth of BG-1 cancer cells. LC or CP-induced cell growth was antagonized by addition of ICI 182,720 ($10^{-8}M$), an ER antagonist, suggesting that this effect appears to be mediated by an ER-dependent manner. Moreover, RT-PCR results showed that transcriptional level of cyclin D1, a cell cycle-regulating gene, was significantly up-regulated by LC and CP, while these effects were reversed by co-treatment of ICI 182,780. However, p21, a cyclin D-ckd-4 inhibitor gene, was not altered by LC or CP. Moreover, $ER{\alpha}$ expression was not significantly changed by LC and CP, while down-regulated by E2. Finally, in xenografted mouse model transplanted with human BG-1 ovarian cancer cells, E2 significantly increased the tumor volume compare to a negative control, but LC did not. Taken together, these results suggest that LC and CP may possess estrogenic potentials by stimulating the growth of BG-1 ovarian cancer cells via partially ER signaling pathway associated with cell cycle as did E2, but this estrogenic effect was not found in in vivo mouse model.

Toll-like Receptor 5 Agonist Inhibition of Growth of A549 Lung Cancer Cells in Vivo in a Myd88 Dependent Manner

  • Zhou, Shi-Xiang;Li, Feng-Sheng;Qiao, Yu-Lei;Zhang, Xue-Qing;Wang, Zhi-Dong
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2807-2812
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    • 2012
  • The purpose of this study was to examine the effect of a Toll-like receptor 5 (TLR5) agonist, CBLB502, on the growth and radiosensitivity of A549 lung cancer cells in vivo. Expression of myeloid differentiation factor 88 (MyD88) or TLR5 was stably knocked down in human lung cancer cells (A549) using lentivirus expressing short hairpin RNA targeting human MyD88 or TLR5. Lack of MyD88 or TLR5 expression enhanced tumor growth in mouse xenografts of A549 lung cancer cells. CBLB502 inhibited the growth of A549 lung cancer cells, not A549-MyD88-KD cells in vivo in the murine xenograft model. Our results showed that the inhibition of A549 by CBLB502 in vivo was realized through regulating the expression of neutrophil recruiting cytokines and neutrophil infiltration. Finally, we found that activation of TLR5 signaling did not affect the radiosensitivity of tumors in vivo.

Antibody-secreting macrophages generated using CpG-free plasmid eliminate tumor cells through antibody-dependent cellular phagocytosis

  • Cha, Eun Bi;Shin, Keun Koo;Seo, Jinho;Oh, Doo-Byoung
    • BMB Reports
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    • v.53 no.8
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    • pp.442-447
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    • 2020
  • The non-viral delivery of genes into macrophages, known as hard-to-transfect cells, is a challenge. In this study, the microporation of a CpG-free and small plasmid (pCGfd-GFP) showed high transfection efficiency, sustainable transgene expression, and good cell viability in the transfections of Raw 264.7 and primary bone marrow-derived macrophages. The non-viral method using the pCGfd vector encoding anti-EGFR single-chain Fv fused with Fc (scFv-Fc) generated the macrophages secreting anti-EGFR scFv-Fc. These macrophages effectively phagocytized tumor cells expressing EGFR through the antibody-dependent mechanism, as was proved by experiments using EGFR-knockout tumor cells. Finally, peri-tumoral injections of anti-EGFR scFv-Fc-secreting macrophages were shown to inhibit tumor growth in the xenograft mouse model.

Insulin Promotes Proliferation and Migration of Breast Cancer Cells through the Extracellular Regulated Kinase Pathway

  • Pan, Feng;Hong, Li-Quan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.15
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    • pp.6349-6352
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    • 2014
  • The present study was undertaken to determine the roles of insulin in the growth of transplanted breast cancer in nude mice, and the proliferation and migration of MCF-7 human breast cancer cells and assess its influence on downstream signaling pathways. In a xenograft mouse model with injection of MCF-7 human breast cancer cells, tumor size was measured every other day. The insulin level and insulin receptor (IR) were increased in the breast cancer patient tissues. Insulin injected subcutaneously around the tumor site in mice caused increase in the size and weight of tumor masses, and promoted proliferation and migration of MCF-7 cells. The effects of insulin on the increase in the proliferation and migration of MCF-7 human breast cancer cells were abolished by pretreatment with the extracellular regulated kinase (ERK) inhibitor PD98059. Insulin increased the phosphorylation of ERK in the MCF-7 cells. These results indicate that insulin promotes the growth of breast cancer in nude mice, and increases the proliferation and migration of MCF-7 human breast cancer cells via the ERK pathway.

A New Cell Counting Method to Evaluate Anti-tumor Compound Activity

  • Wang, Xue-Jian;Zhang, Xiu-Rong;Zhang, Lei;Li, Qing-Hua;Wang, Lin;Shi, Li-Hong;Fang, Chun-Yan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.8
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    • pp.3397-3401
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    • 2014
  • Determining cell quantity is a common problem in cytology research and anti-tumor drug development. A simple and low-cost method was developed to determine monolayer and adherent-growth cell quantities. The cell nucleus is located in the cytoplasm, and is independent. Thus, the nucleus cannot make contact even if the cell density is heavy. This phenomenon is the foundation of accurate cell-nucleus recognition. The cell nucleus is easily recognizable in images after fluorescent staining because it is independent. A one-to-one relationship exists between the nucleus and the cell; therefore, this method can be used to determine the quantity of proliferating cells. Results indicated that the activity of the histone deacetylase inhibitor Z1 was effective after this method was used. The nude-mouse xenograft model also revealed the potent anti-tumor activity of Z1. This research presents a new anti-tumor-drug evaluation method.

The Synergistic Anticancer Effect of Artesunate Combined with Allicin in Osteosarcoma Cell Line in Vitro and in Vivo

  • Jiang, Wei;Huang, Yong;Wang, Jing-Peng;Yu, Xiao-Yun;Zhang, Lin-Yi
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.8
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    • pp.4615-4619
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    • 2013
  • Background: Artesunate, extracted from Artemisia annua, has been proven to have anti-cancer potential. Allicin, diallyl thiosulfinate, the main biologically active compound derived from garlic, is also of interest in cancer treatment research. This object of this report was to document synergistic effects of artesunate combined with allicin on osteosarcoma cell lines in vitro and in vivo. Methods: After treatment with artesunate and allicin at various concentrations, the viability of osteosarcoma cells was analyzed by MTT method, with assessment of invasion and motility, colony formation and apoptosis. Western Blotting was performed to determine the expression of caspase-3/9, and activity was also detected after drug treatment. Moreover, in a nude mouse model established with orthotopic xenograft tumors, tumor weight and volume were monitored after drug administration via the intraperitoneal (i.p.) route. Results: The viability of osteosarcoma cells in the combination group was significantly decreased in a concentration and time dependent manner; moreover, invasion, motility and colony formation ability were significantly suppressed and the apoptotic rate was significantly increased through caspase-3/9 expression and activity enhancement in the combination group. Furthermore, suppression of tumor growth was evident in vivo. Conclusion: Our results indicated that artesunate and allicin in combination exert synergistic effects on osteosarcoma cell proliferation and apoptosis.

Engineering Autogenous Cartilage Using PLA Coated PGA Chondrocyte Complex (자가연골세포와 PLA-coated PGA 복합체를 이용한 연골조직 재생)

  • Kim, Woo Seob
    • Archives of Plastic Surgery
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    • v.32 no.1
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    • pp.1-4
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    • 2005
  • Previous sucessful results of neocartilage formation using tissue engineering technique in immunocompromised nude mouse xenograft model were reported. For clinical application, autogenous cell is preferrable to allogenic or xenogenic cell for circumvention of immune rejection. This study evaluates the feasibility of producing a engineered cartilage using autogenous chondrocytes. Chondrocytes were isolated from the auricular catilage of New Zealand White rabbit and seeded onto PGA polymer coated with polylactic acid in round pattern(diameter 0.7 cm, thickness 0.1 cm) at a concentration $7{\times}10^7$ chondrocytes per $cm^3$. Each Autogenous Cell-polymer constructs were implanted subcutaneously into the left side of dorsum of twelve Rabbits. Polymer templates not containg cells were implanted into the right side as a control. Fifteen rabbits were sacrificed at the following intervals: 5 rabbits at nine weeks, 7 rabbits at twelve weeksNew autogenous cartilage formation which retained the approximate dimensions of origianl round polymer template in 11 of 12 cell seeded implants. Histological examination using hematoxyline and eosin stain revealed vast majority of implants developed into mature cartilage. This study opens up the possibility of autologus cell transplant to construct autogenous cartilge.

The Modulation of Squamous Cell Differentiation by Retinoids in Human Squamous Cell Carcinoma Xenografts (Nude Mouse 에 이종이식한 두경부 편평상피세포암의 분화에 대한 Retinoids의 작용)

  • Kim, Sang-Yoon;Yoo, Seung-Joo;Yoo, Keun-Sik;Joo, Joon-Bum;Choi, Doo-Yung;Nam, Soon-Yuhl
    • Korean Journal of Bronchoesophagology
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    • v.5 no.2
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    • pp.119-126
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    • 1999
  • Objectives : To analyze the effect of retinoids on the differentiation in HNSCC xenografts. Materials and Methods : RA (20mg/kg) or 13-cis-RA (60mg/kg) was orally administered once in a day for 30 days in the xenograft model we prepared using athymic nude mice with AMCHN-4 and -6. We carried out H & E staining and immunohistochemical staining with the monoclonal antibody against involucrin and cytokeratin 10. Results : Both RA and 13-cis-RA were found to suppress the differentiation of AMC-HN-4. Interestingly, RA enhanced the differentiation of AMC-HN-6, although 13-cis RA did not exhibit any effect on the differentiation. These results suggest that in vivo effect of retinoids on the HNSCC growth and differentiation might be various. Retinoids-induced P450 in AMC-HN-6 might be one of the mechanisms to explain the reason why the retinoids exhibit various functions in the HNSCC.

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Eupatilin Inhibits Gastric Cancer Cell Growth by Blocking STAT3-Mediated VEGF Expression

  • Cheong, Jae-Ho;Hong, Sung-Yi;Zheng, Yanjun;Noh, Sung-Hoon
    • Journal of Gastric Cancer
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    • v.11 no.1
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    • pp.16-22
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    • 2011
  • Purpose: Eupatilin is an antioxidative flavone and a phytopharmaceutical derived from Artemisia asiatica. It has been reported to possess anti-tumor activity in some types of cancer including gastric cancer. Eupatilin may modulate the angiogenesis pathway which is part of anti-inflammatory effect demonstrated in gastric mucosal injury models. Here we investigated the anti-tumor effects of eupatilin on gastric cancer cells and elucidated the potential underlying mechanism whereby eupatilin suppresses angiogenesis and tumor growth. Materials and Methods: The impact of eupatilin on the expression of angiogenesis pathway proteins was assessed using western blots in MKN45 cells. Using a chromatin immunoprecipitation assay, we tested whether eupatilin affects the recruitment of signal transducer and activator of transcription 3 (STAT3), aryl hydrocarbon receptor nuclear translocator (ARNT) and hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) to the human VEGF promoter. To investigate the effect of eupatilin on vasculogenesis, tube formation assays were conducted using human umbilical vein endothelial cells (HUVECs). The effect of eupatilin on tumor suppression in mouse xenografts was assessed. Results: Eupatilin significantly reduced VEGF, ARNT and STAT3 expression prominently under hypoxic conditions. The recruitment of STAT3, ARNT and HIF-$1{\alpha}$ to the VEGF promoter was inhibited by eupatilin treatment. HUVECs produced much foreshortened and severely broken tubes with eupatilin treatment. In addition, eupatilin effectively reduced tumor growth in a mouse xenograft model. Conclusions: Our results indicate that eupatilin inhibits angiogenesis in gastric cancer cells by blocking STAT3 and VEGF expression, suggesting its therapeutic potential in the treatment of gastric cancer.