• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5371-5374
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• 2013

Objective: Photodynamic therapy (PDT) is an emerging therapeutic procedure suitable for the treatment of cervical cancer. However, the side effects of PDT are severe, including skin ulceration, so we designed an experiment to examine the effects of multiple low-dose photodynamic therapy of 5, 10, 15, 20-tetrakis(1-methylpyridinium-4-yl) porphyrin (Tmpyp4) on tumour growth by utilizing a model in nude mice implanted with Hela cervical cancer cells. Materials and Methods: Female BALB/c nude mice (aged 5-6 weeks, weighing 18-20 g) were used. Hela cervical cancer cells were injected subcutaneously ($1{\times}10^7cells/200{\mu}L$). Ten days after injection, the mice were divided into three groups (n=6), the A group of controls without any treatment, the B group receiving a single-treatment with Tmpyp4 (10 mg/kg, intratumor injection) and irradiation (blue laser, $108J/cm^2$), and the C group given three-treatments with Tmpyp4 (10 mg/kg, intratumor injection) and irradiation at intervals of two days. After starting treatment, tumours were measured every two days, to assess growth. At 2 weeks after the last treatment of C group, tumour tissue and organs were collected from each mouse to evaluate tumor histology and organ damage. Results: Tumour growth in C group was significantly inhibited compared with A and B groups (P<0.05), without any injury to the skin and internal organs. Conclusion: Our novel findings demonstrated that multiple low-dose photodynamic therapy of Tmpyp4 could inhibit cervical cancer growth significantly with no apparent side effects.

• Archives of Plastic Surgery
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• v.44 no.3
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• pp.194-201
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• 2017

Background Platelet-rich plasma (PRP) contains high concentrations of growth factors involved in wound healing. Hydrogel is a 3-dimensional, hydrophilic, high-molecular, reticular substance generally used as a dressing formulation to accelerate wound healing, and also used as a bio-applicable scaffold or vehicle. This study aimed to investigate the effects of PRP and hydrogel on wound healing, in combination and separately, in an animal wound model. Methods A total of 64 wounds, with 2 wounds on the back of each nude mouse, were classified into 4 groups: a control group, a hydrogel-only group, a PRP-only group, and a combined-treatment group. All mice were assessed for changes in wound size and photographed on scheduled dates. The number of blood vessels was measured in all specimens. Immunohistochemical staining was used for the analysis of vascular endothelial growth factor (VEGF) expression. Results Differences in the decrease and change in wound size in the combined-treatment group were more significant than those in the single-treatment groups on days 3, 5, 7, and 10. Analysis of the number of blood vessels through histological examination showed a pattern of increase over time that occurred in all groups, but the combined-treatment group exhibited the greatest increase on days 7 and 14. Immunohistochemical staining showed that VEGF expression in the combined-treatment group exhibited its highest value on day 7. Conclusions This experiment demonstrated improved wound healing using a PRP-hydrogel combined treatment compared to either treatment individually, resulting in a decrease in wound size and a shortening of the healing period.

• International Journal of Stem Cells
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• v.9 no.2
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• pp.186-191
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• 2016

Background and Objectives: With the global demand for dairy protein for consumption growing annually, there has been increasing activity in the research field of dairy protein synthesis and production. From a manipulation perspective, it is more difficult to use live cattle for laboratory studies on the production of milk as well as of dairy protein such as casein, as compared with using laboratory animals like rodents. Therefore, we aimed to develop a mouse model of bovine mammary alveolar ducts for laboratory-scale studies. We studied the formation of the bovine mammary gland ductal structure by transplanting the MAC-T bovine alveolar cell line into mice. Methods and Results: MAC-T cells ($1{\times}10^7$) were suspended in Matrigel and injected into the dorsal tissue of 8-week-old male BALB/C nude mice. Histological analysis of tissue dissected from the MAC-T cell-transplanted mice after 6 weeks showed the typical morphology of the tubuloalveolar female gland, as well as glands made up of branching ducts that were surrounded by smooth muscle with small alveoli budding off the ducts. In addition, the epithelial markers CK14 and CK18 were expressed within the duct-like structure. Prolactin was detected in the duct interior in these CK14+ and CK18+ cells but not in the non-transplanted MAC-T cells. Conclusions: These results showed that duct-like tissue had been successfully formed after 6 weeks of transplantation of the CK14+ and CK18+ MAC-T cells into mice dorsal tissue. This mouse model will be a useful tool for further research on the bovine mammary gland.

• 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.

• The Journal of the Korean bone and joint tumor society
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• v.11 no.1
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• pp.46-53
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• 2005

Purpose: Bisphosphonates (BPs) are the analogues of endogenous pyrophosphates: they have been used in the treatment of skeletal diseases such as Paget's disease, osteoporosis, and tumorinducing ostelysis, and are used in treatment of osteolytic metastasis of breast cancer recently. They are also used as one of the therapeutic agents for metastasis of prostatic cancer of which metastasis makes the mixed nature of osteolysis and ostegenesis. Although the action mechanism of BPs are well known for diseases with excessive osteoclastic bone resorption, the direct effect of BPs has not been known yet. This study was intended to see the tumor suppression capability of Zoledronic acid(ZOL) using nude mouse with osteosarcoma. Materials and Methods: MG-63 and HOS osteosarcoma cell lines were used and the transforemed MG-63-GFP and HOS-GFP cells, which were made for detection under fluorescent light, were subcutaneously injected to make osteosarcoma. The five 6-week male mice were used for the experiment at each group. After the injection, mice were cultivated until tumor pieces grow up to $3{\times}3{\times}3$ $mm^3$ and ZOL of 120 ug/kg was subcutaneously injected twice a week. Sizes of tumor were measured twice a week and photographed under fluorescent light. Results: In in vivo test with HOS osteosarcoma cell lines, mean size of tumors was 2,520 $mm^3$ in control group and was 131 $mm^3$ in ZOL group, which showed 94% of reduction comparing with the control ; with MG-63 osteosarcoma cell lines, mean size of tumors was 2,866 $mm^3$ in control group and was 209 $mm^3$ in test group with 72% of reduction (p<0.05). Conclusion: In in vivo tests with nude mice, we suggest that ZOL has direct effect on osteosarcoma cells and it would be used as one of the therapeutic agents for osteosarcoma, especially to ZOL-sensitive osteosarcoma cells.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4263-4266
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• 2012

Colorectal cancer has become a major disease threatening human health. To establish animal models that exhibit the characteristics of human colorectal cancer will not only help to study the mechanisms underlying the genesis and development effectively, but also provide ideal carriers for the screening of medicines and examining their therapeutic effects. In this study, we established a stable, colon cancer nude mouse model highly expressing green fluorescent protein (GFP) for spontaneous metastasis after surgical orthotopic implantation (SOI). GFP-labeled colon cancer models for metastasis after SOI were successfully established in all of 15 nude mice and there were no surgery-related complications or deaths. In week 3, primary tumors expressing GFP were observed in all model animals under fluoroscopy and two metastatic tumors were monitored by fluorescent imaging at the same time. The tumor volumes progressively increased with time. Seven out of 15 tumor transplanted mice died and the major causes of death were intestinal obstruction and cachexia resulting from malignant tumor growth. Eight model animals survived at the end of the experiment, 6 of which had metastases (6 cases to mesenteric lymph nodes, 4 hepatic, 2 pancreatic and 1 mediastinal lymph node). Our results indicate that our GFP-labeled colon cancer orthotopic transplantation model is useful with a high success rate; the transplanted tumors exhibit similar biological properties to human colorectal cancer, and can be used for real-time, in vivo, non-invasive and dynamic observation and analysis of the growth and metastasis of tumor cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1502-1506
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• 2006

To investigate the inhibitory effects of Citaowan (CTW) on the growth and angiogenesis of breast cancer in vivo. Orthotopic breast cancer model was established by injection of MDA-MB-231 cells into mammary fat pad of nude mice. Seven weeks after injection, CTW was orally administered at dose of 50, 100 mg/mouse every day for 40 days. Body weight, tumor volume, tumor apoptosis, microvessel density and tumor proliferation were evaluated, after the mice were sacrificed. The body weight and tumor volume were not significantly changed in CTW group compared with the control group. Tumor apoptosis, proliferation and microvessel density were significantly reduced in CTW group (100 mg/mouse) compared with the control group. These data indicate that CTW has anti-angiogenic and proapoptotic effects on breast cancer.

• Journal of Korean Neurosurgical Society
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• v.55 no.3
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• pp.131-135
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• 2014

Objective : With the growing interests of bacteria as a targeting vector for cancer treatment, diverse genetically engineered Salmonella has been reported to be capable of targeting primary or metastatic tumor regions after intravenous injection into mouse tumor models. The purpose of this study was to investigate the capability of the genetically engineered Salmonella typhimurium (S. typhimurium) to access the glioma xenograft, which was monitored in mouse brain tumor models using optical bioluminescence imaging technique. Methods : U87 malignant glioma cells (U87-MG) stably transfected with firefly luciferase (Fluc) were implanted into BALB/cAnN nude mice by stereotactic injection into the striatum. After tumor formation, attenuated S. typhimurium expressing bacterial luciferase (Lux) was injected into the tail vein. Bioluminescence signals from transfected cells or bacteria were monitored using a cooled charge-coupled device camera to identify the tumor location or to trace the bacterial migration. Immunofluorescence staining was also performed in frozen sections of mouse glioma xenograft. Results : The injected S. typhimurium exclusively localized in the glioma xenograft region of U87-MG-bearing mouse. Immunofluorescence staining also demonstrated the accumulation of S. typhimurium in the brain tumors. Conclusion : The present study demonstrated that S. typhimurium can target glioma xenograft, and may provide a potentially therapeutic probe for glioma.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.1067-1072
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• 2013

Hiwi, a human homologue of the Piwi family, plays an important role in stem cell self-renewal and is overexpressed in various human tumors. This study aimed to determine whether an RNA interference-based strategy to suppress Hiwi expression could inhibit tumor growth in a xenograft mouse model. A rare population of $SSC^{lo}\;Alde^{br}$ cells was isolated and identified as lung cancer stem cells in our previous study. Plasmids containing U6 promoter-driven shRNAs against Hiwi or control plasmids were successfully established. The xenograft tumor model was generated by subcutaneously inoculating with lung cancer stem cell $SSC^{lo}\;Alde^{br}$ cells. After the tumor size reached about 8 mm in diameter, shRNA plasmids were injected into the mice via the tail vein three times a week for two weeks, then xenograft tumor growth was assessed. In nude mice, intravenously delivery of Hiwi shRNA plasmids significantly inhibited tumor growth compared to treatment with control scrambled shRNA plasmids or the vehicle PBS. No mice died during the experiment and no adverse events were observed in mice administered the plasmids. Moreover, delivery of Hiwi shRNA plasmids resulted in a significant suppressed expression of Hiwi and ALDH-1 in xenograft tumor samples, based on immunohistochemical analysis. Thus, shRNA-mediated Hiwi gene silencing in lung cancer stem cells by an effective in vivo gene delivery strategy appeared to be an effective therapeutic approach for lung cancer, and may provide some useful clues for RNAi gene therapy in solid cancers.

• Journal of the Optical Society of Korea
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• v.17 no.1
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• pp.91-96
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• 2013

We report a method for optical monitoring of tumors in an animal model using optical coherence tomography (OCT). In a spectral domain OCT system, a superluminescent diode light source with a full width of 66 nm at half maximum and peak wavelength of 950 nm was used to take images having an axial resolution of 6.8 ${\mu}m$. Cancer cells of PC-3 were cultured and inoculated into the hypodermis of auricle tissues in BALB/c nude mice. We observed tumor formation and growth at the injection region of cancer cells in vivo and obtained the images of tumor mass center and sparse circumferences. On the $5^{th}$ day from an inoculation of cancer cells, histological images of the tumor region using cross-sectional slicing and dye staining of specimens were taken in order to confirm the correlation with the high resolution OCT images. The OCT image of tumor mass compared with normal tissues was analyzed using its A-scan data so as to obtain a tissue attenuation rate which increases according to tumor growth.