• Title, Summary, Keyword: subcutaneous xenograft

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Establishment of and Comparison between Orthotopic Xenograft and Subcutaneous Xenograft Models of Gallbladder Carcinoma

  • Du, Qiang;Jiang, Lei;Wang, Xiao-Qian;Pan, Wei;She, Fei-Fei;Chen, Yan-Ling
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.8
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    • pp.3747-3752
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    • 2014
  • Background: Gallbladder carcinoma (GBC) is the most common carcinoma of the biliary system. Among its research models, orthotopic xenograft models, important research tools, have been rarely reported in the literature however. Aim: To explore establishment of an orthotopic xenograft model and to evaluate the advantage and disadvantage as compared with other models. Materials and Methods: Subcutaneous xenograft and orthotopic xenograft models of gallbladder carcinoma in nude mice were established and compared with human gallbladder carcinomas. Results: For the orthotopic xenograft model and clinical gallbladder carcinomas, the lymph node metastatic rates were 69.2% and 53.3% (p>0.05); ascites generation rates, 38.5% and 11.7%(p<0.05); liver invasive rates, 100% and 61.7%(p<0.05); and lymphatic vessel densities (LVD), $10.4{\pm}3.02$ and $8.77{\pm}2.92$ (p>0.05), respectively. In the subcutaneous xenograft model, no evidence of ascites generation, lymph node metastasis and liver metastasis were found, and its LVD was lower ($4.56{\pm}1.53$, p<0.05). Conclusions: Compared with the subcutaneous xenograft model, the orthotopic xenograft model better simulates clinical gallbladder carcinoma in terms of metastasis and invasion, which may be attributed to the difference in microenvironment and LVD.

Establishment of Highly Tumorigenic Human Gastric Carcinoma Cell Lines from Xenograft Tumors in Mice

  • Song, Kyung-A;Park, Jihyun;Kim, Ha-Jung;Kang, Myung Soo;Kim, Sun Young
    • Biomedical Science Letters
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    • v.23 no.3
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    • pp.238-250
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    • 2017
  • Patient's primary tumor-derived tumor cell lines likely represent ideal tools for human tumor biology in vitro and in vivo. Here, we describe eight human gastric carcinoma cell lines derived from established tumors in vivo upon subcutaneous transplantation of primary gastric carcinoma specimens in BALB/c nude mice. These xenografted gastric tumor cell lines (GTX) displayed close similarity with primary gastric tumor tissues in their in vivo growth pattern and genomic alterations. GTX-085 cells were resistant to cisplatin, while GTX-087 was the most sensitive cell line. GTX-085 was the only cell line showing a metastatic potential. Epithelial cell adhesion molecule (EPCAM) expression was especially strong in all tissue samples, as well as in cell cultures. GTX-139, the largest tumor graft obtained after injection, displayed distinct expression of CD44v6, fibroblast growth factor receptor 2 (FGFR2), and prominin 1 (PROM1, also known as CD133). In summary, we established eight xenograft gastric cancer cell lines from gastric cancer patient tissues, with their histological and molecular features consistent with those of the primary tumors. The established GTX cell lines will enable future studies of their responses to various treatments for gastric cancer.

New Model of In-situ Xenograft Lymphangiogenesis by a Human Colonic Adenocarcinoma Cell Line in Nude Mice

  • Sun, Jian-Jun;Jing, Wei;Ni, Yan-Yan;Yuan, Xiao-Jian;Zhou, Hai-Hua;Fan, Yue-Zu
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2823-2828
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    • 2012
  • Objective: To explore a new model of in-situ xenograft lymphangiogenesis of human colonic adenocarcinomas in nude mice. Method: On the basis of establishing subcutaneous xenograft lymphangiogenesis model of human colonic adenocarcinoms, in-situ xenografts were established through the in situ growth of the HT-29 human colonic adenocarcinoma cell line in nude mice. The numbers of lymphangiogenic microvessels, the expression of lymphatic endothelial cell markers lymphatic vessel endothelial hyaloronic acid receptor-1 (LYVE-1), D2-40 and the lymphatic endothelial growth factors vascular endothelial growth factor-C (VEGF-C), -D (VEGF-D) and receptor-3 (VEGFR-3) were compared by immunohistochemical staining, Western bolt and quantitative RT-PCR in xenograft in-situ models. Results: Some microlymphatics with thin walls, large and irregular or collapsed cavities and increased LMVD, with strong positive of LYVE-1, D2-40 in immunohistochemistry, were observed, identical with the morphological characteristics of lymphatic vessels and capillaries. Expression of LYVE-1 and D2-40 proteins and mRNAs were significantly higher in xenograpfts in-situ than in the negative control group(both P<0.01). Moreover, the expression of VEGF-C, VEGF-D and VEGFR-3 proteins and mRNAs were significantly higher in xenografts in-situ (both P<0.01), in conformity with the signal regulation of the VEGF-C,-D/VEGFR-3 axis of tumor lymphangiogenesis. Conclusions: In-situ xenografts of a human colonic adenocarcinoma cell line demonstrate tumor lymphangiogenesis. This novel in-situ animal model should be useful for further studying mechanisms of lymph node metastasis, drug intervention and anti-metastasis therapy in colorectal cancer.

Therapeutic Effect of 18β-Glycyrrhetinic Acid on HT-29 Cancer Cell in a Murine Xenograft Model (HT-29 암세포 이종이식으로 유발된 종양에 대한18β-Glycyrrhetinic Acid의 치료효과)

  • Han, Yongmoon;Kim, Jeonghyeon
    • YAKHAK HOEJI
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    • v.59 no.4
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    • pp.164-169
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    • 2015
  • In the present study, we determined the effect of $18{\beta}$-glycyrrhetinic acid ($18{\beta}$-GA) in the mice model bearing xenografts of HT-29 human colon cancer cell line. Data from the cytotoxicity assay displayed that $18{\beta}$-GA induced cell death in HT-29. The cytotoxicity was enhanced as the $18{\beta}$-GA treatment was prolonged. In case of 72 hrs treatment, $LD_{50}$ of $18{\beta}$-GA was approximately $90{\mu}M$, and the efficacy at $100{\mu}M$ of $18{\beta}$-GA appeared to be equivalent to that of doxorubicin at $1{\mu}M$. Based on the in vitro data, we tested the anti-tumor effect of $18{\beta}$-GA in thymic mice (Balb/c strain). Xenograft tumors were generated by subcutaneous injection of HT-29 ($3{\times}10^6cells/mouse$) to mice and the mice were treated intraperitoneally with $18{\beta}$-GA ($50{\mu}g/time/mouse$) every other day for 4 times. The tumor volumes were measured for a period of 14 days. Data displayed that the $18{\beta}$-GA treatment reduced the tumor volumes (P < 0.05) as compared to control mice. However, this activity was demolished when athymic mice (Balb/c nu/nu) were used instead of thymic mice. This observation appeared that T lymphocyte played an important role in the anti-tumor activity. In conclusion, our results indicate that $18{\beta}$-GA has anti-tumor activity in HT-29 tumor-bearing mice, which may be associated with T cells.

Biosynthesized Platinum Nanoparticles Inhibit the Proliferation of Human Lung-Cancer Cells in vitro and Delay the Growth of a Human Lung-Tumor Xenograft in vivo -In vitro and in vivo Anticancer Activity of bio-Pt NPs-

  • Bendale, Yogesh;Bendale, Vineeta;Natu, Rammesh;Paul, Saili
    • Journal of Pharmacopuncture
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    • v.19 no.2
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    • pp.114-121
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    • 2016
  • Objectives: Lung cancer remains a deadly disease with unsatisfactory overall survival. Cisplatin, a standard platinum (Pt)-based chemotherapeutic agent, has the potential to inhibit the growth of lung cancer. Its use, however, is occasionally limited by severe organ toxicity. However, until now, no systematic study has been conducted to verify its efficacy with proper experimental support in vivo. Therefore, we examined whether biosynthesized Pt nanoparticles (NPs) inhibited human lung cancer in vitro and in vivo to validate their use in alternative and complementary medicine. Methods: We evaluated the in vitro and the in vivo anticancer efficiencies of biosynthesized Pt NPs in a subcutaneous xenograft model with A549 cells. Severe combined immune deficient mice (SCID) were divided into four groups: group 1 being the vehicle control group and groups 2, 3 and 4 being the experimental groups. Once the tumor volume had reached $70-75mm^3$, the progression profile of the tumor growth kinetics and the body weights of the mice were measured every week for 6 weeks after oral administration of Pt NPs. Doses of Pt NPs of 500, 1,000 and 2,000 mg/kg of body weight were administered to the experimental groups and a dose of honey was administered to the vehicle control group. The efficacy was quantified by using the delay in tumor growth following the administration of Pt NPs of A549 human-lung-cancer xenografts growing in SCID mice. Results: The in vitro cytotoxicity evaluation indicated that Pt NPs, in a dose-dependent manner, inhibited the growth of A549 cells, and the in vivo evaluation showed that Pt NPs at the mid and high doses effectively inhibited and delayed the growth of lung cancer in SCID mice. Conclusion: These findings confirm the antitumor properties of biosynthesized Pt NPs and suggest that they may be a cost-effective alternative for the treatment of patients with lung cancer.

Loquat (Eriobotrya japonica) leaf extract inhibits the growth of MDA-MB-231 tumors in nude mouse xenografts and invasion of MDA-MB-231 cells

  • You, Mi-Kyoung;Kim, Min-Sook;Jeong, Kyu-Shik;Kim, Eun;Kim, Yong-Jae;Kim, Hyeon-A
    • Nutrition Research and Practice
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    • v.10 no.2
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    • pp.139-147
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    • 2016
  • BACKGROUND/OBJECFTIVES: The present study was conducted to examine the inhibitory effect of loquat leaves on MDA-MB-231 cell proliferation and invasion. MATERIALS/METHODS: Female athymic nude mice were given a subcutaneous (s.c.) inoculation of MDA-MB-231 cells and randomly grouped to receive a s.c. injection of either 500 mg/kg ethanol, water extract or vehicle five times a week. Tumor growth, mitotic rate and necrosis were examined. MDA-MB-231 cells were cultured with DMSO or with various concentrations of loquat water or ethanol extract. Proliferation, adhesion, migration, invasion and matrix metalloproteinase (MMP) activity were examined. RESULTS: Tumor growth of xenograft nude mouse was significantly reduced by loquat extracts. The results of mitotic examination revealed that loquat extracts reduced tumor cell division. Both ethanol and water extracts significantly inhibited MDA-MB-231 cell proliferation. The protein expression of ErbB3 was significantly down-regulated by loquat leaf extracts. Loquat leaf extracts increased apoptosis of MDA-MB-231 cells following 24 hour incubation and the ethanol extract was more potent in inducing apoptosis than the water extract. Furthermore, loquat extracts inhibited adhesion, migration and invasion of MDA-MB-231 cells. MMP activity was significantly inhibited by loquat extracts. CONCLUSION: Our results show that extracts of loquat inhibit the growth of tumor in MDA-MB-231 xenograft nude mice and the invasion of human breast cancer cells, indicating the inhibition of tumor cell proliferation and invasion.

A New Bioluminescent Rat Prostate Cancer Cell Line: Rapid and Accurate Monitoring of Tumor Growth (효과적인 항암효능측정을 위한 발광 전립선 세포의 개발 및 평가)

  • Lee, Mi-Sook;Jung, Jae-In;Kwon, Seung-Hae;Shim, In-Sop;Hahm, Dae-Hyun;Han, Jeong-Jun;Han, Dae-Seok;Yoonpark, Jung-Han;Her, Song
    • Journal of Life Science
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    • v.20 no.11
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    • pp.1738-1741
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    • 2010
  • Caliper measurements of tumor volume have been widely used in the assessment of tumors in animal models. However, experiments based on caliper data have resulted in unreliable estimates of tumor growth, due to necrotic areas of tumor mass. To overcome this systematic bias, we engineered a new luciferase-expressing rat prostate cancer cell line (MLL-Luc) that produces bioluminescence from viable cancer cells. MLL-Luc cells showed a strong correlation between bioluminescence intensity and cell number ($R^2$=0.99) and also accurately quantified tumor growth, with reduced bioluminescence signals caused by necrotic cells in a subcutaneous MLL-Luc xenograft model. The accurate quantification of tumor growth with bioluminescence imaging (BLI) was confirmed by a better antitumor effect of combination chemotherapy, compared to that based on caliper measurements with a correlation between the bioluminescence signal and tumor volume ($R^2$=0.84). These data suggest that bioluminescent MLL xenografts are a powerful and quantitative tool for monitoring tumor growth and are useful in evaluating the efficacy of anticancer drugs, with less systematic bias.

The Anti-calcification Effect of Dithiobispropionimidate, Carbodiimide and Ultraviolet Irradiation Cross-linking Compared to Glutaraldehyde in Rabbit Implantation Models

  • Park, Samina;Kim, Soo Hwan;Lim, Hong-Gook;Lim, Cheong;Kim, Yong Jin
    • The Korean Journal of Thoracic and Cardiovascular Surgery
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    • v.46 no.1
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    • pp.1-13
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    • 2013
  • Background: Glutaraldehyde (GA) is a widely used cross-linking agent for improving mechanical properties and resistance to enzymatic degradation of collagenous tissue, but it has several drawbacks such as calcification and cytotoxicity. The aim of this study was to find the alternative effective cross-linking methods to GA. Materials and Methods: Bovine pericardium was processed with GA with ethanol+octanol and glycine detoxification, and polyethylene glycol (PG) space filler, dimethyl 3,3'-dithiobispropionimidate (DTBP), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) treatment, and the physical fixation of ultraviolet irradiation were done. The biologic material properties of variously treated pericardial tissues were assessed by biochemical, mechanical and histological tests. Treated pericardial tissues were also implanted subcutaneously or intramuscularly into the rabbit for 10 weeks to assess the xenoreactive antibody response of immunoglobulin G and M, their anti-calcification effect. Results: The biochemical and mechanical properties of EDC fixed pericardial tissues were comparable to the GA fixed tissue. The cytotoxicity was lowest in space filler treated GA fixed group. In rabbit subcutaneous or intramuscular implantation models, decellularization, space filler, EDC treatment group showed significantly lower calcium content than GA only and DTBP treatment group (p<0.05, analysis of variance). The titer of anti $Gal{\alpha}1-3Gal{\beta}1$-4GlcNAc-R antibodies did not change in the postimplantation serial enzyme-linked immunosorbent assay. Hematoxylin and eosin and von Kossa staining showed that decellularization, space filler, EDC, and ultraviolet treatment had less inflammatory cell infiltration and calcium deposits. Conclusion: The decellularization process, PG filler, and EDC treatments are good alternative cross-linking methods compared to GA only fixation and primary amine of DTBP treatment for cardiovascular xenograft preservation in terms of the collagen cross-linking stability and in vivo anti-calcification effects.

Autophagy Involvement in Olanzapine-Mediated Cytotoxic Effects in Human Glioma Cells

  • Wang, Yi-Xuan;Xu, Shu-Qing;Chen, Xiang-Hui;Liu, Rui-Si;Liang, Zhong-Qin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.19
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    • pp.8107-8113
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    • 2014
  • The aim of this study was to investigate the effects of olanzapine on growth inhibition as well as autophagy in glioma cells in vitro and in vivo. The proliferation of both LN229 and T98 glioma cells, measured by MTT assay, was suppressed in a concentration-dependent and time-dependent manner. Moreover, apoptosis of both cells was significantly increased with the treatment of olanzapine as evidenced by increased Bcl-2 expression, Hoechst 33258 staining and annexinV-FITC/PI staining. Olanzapine treatment also enhanced activation of autophagy with increased expression of LC3-II, expression of protein p62, a substrate of autophagy, being decreased. The growth inhibition by olanzapine in both glioma cell lines could be blocked by co-treatment with 3-MA, an autophagy inhibitor. Furthermore, olanzapine effectively blocked the growth of subcutaneous xenografts of LN229 glioma cells in vivo. The increased level of protein LC3-II and decreased level of p62 followed by a decreased level of Bcl-2, suggesting that autophagy may contribute to apoptosis. In addition, reduced proliferation of glioma cells was shown by a decrease of Ki-67 staining and increased caspase-3 staining indicative of apoptosis in mouse xenografts. These results indicated that olanzapine inhibited the growth of glioma cells accompanied by induction of autophagy and apoptosis both in vitro and in vivo. Olanzapine-induced autophagy plays a tumor-suppressing role in glioma cells.