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Sample records for athymic nude mice

  1. Study of camelpox virus pathogenesis in athymic nude mice.

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    Sophie Duraffour

    Full Text Available Camelpox virus (CMLV is the closest known orthopoxvirus genetically related to variola virus. So far, CMLV was restricted to camelids but, recently, three human cases of camelpox have been described in India, highlighting the need to pursue research on its pathogenesis, which has been hampered by the lack of small animal models. Here, we confirm that NMRI immunocompetent mice are resistant to intranasal (i.n. CMLV infection. However, we demonstrate that CMLV induced a severe disease following i.n. challenge of athymic nude mice, which was accompanied with a failure in gaining weight, leading to euthanasia of the animals. On the other hand, intracutaneous (i.c. infection resulted in disease development without impacting the body weight evolution. CMLV replication in tissues and body fluids was confirmed in the two models. We further analyzed innate immune and B cell responses induced in the spleen and draining lymph nodes after exposure to CMLV. In both models, strong increases in CD11b(+F4/80(+ macrophages were seen in the spleen, while neutrophils, NK and B cell responses varied between the routes of infection. In the lymph nodes, the magnitude of CD11c(+CD8α(+ lymphoid and CD11c(+CD11b(+ myeloid dendritic cell responses increased in i.n. challenged animals. Analysis of cytokine profiles revealed significant increases of interleukin (IL-6 and IL-18 in the sera of infected animals, while those of other cytokines were similar to uninfected controls. The efficacy of two antivirals (cidofovir or HPMPC, and its 2, 6-diaminopurine analog was evaluated in both models. HPMPC was the most effective molecule affording 100% protection from morbidity. It appeared that both treatments did not affect immune cell responses or cytokine expression. In conclusion, we demonstrated that immunodeficient mice are permissive for CMLV propagation. These results provide a basis for studying the pathogenesis of CMLV, as well as for evaluating potential antiviral

  2. Thymus dependency of induced immune responses against Hymenolepis nana (cestode) using congenitally athymic nude mice.

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    Ito, A

    1985-04-01

    Anti-parasite antibody responses were compared among several strains of mice experimentally infected with the dwarf tapeworm, Hymenolepis nana. The antibody titres were highly variable among the mouse strains in addition to variation in worm fecundity and longevity. The influence of the thymus on both infection and anti-parasite antibody production (especially of IgE isotype) was studied by the use of congenitally athymic (nu/nu) nude and their phenotypically normal (nu/+) CD-1(ICR) mice infected with H. nana. All nude (nu/nu) mice harboured fully mature 70 day old adult tapeworms of the first generation derived from eggs initially given on day 0. In addition, they contained (a) younger second generation adults derived from autoinfection and present in the intestinal lumen, (b) a number of abnormally large (about 1-2 mm in diameter) balloon like, fluid filled cysticercoids in not only the intestinal tissue but also parenteral tissues such as the mesenteric lymph nodes, liver and lung, and (c) normal cysticercoids derived from challenging eggs in the intestinal tissue. Infected nude mice produced no antibodies detectable by PCA (IgE) and double diffusion (IgG) tests. In contrast, normal (nu/+) mice and nude mice reconstituted with thymocytes expelled almost all luminal adults of the primary infection by day 70 and produced antibodies to extracts of adult H. nana. Neither autoinfection nor reinfection following egg challenge occurred in any of these normal (nu/+) and reconstituted nude mice. Therefore, acquired immune responses against H. nana (as assessed by resistance not only to the tissue phase measured by the failure of tissue cysticercoid recovery from egg challenge, but also to the lumen phase assessed by the failure of autoinfection adult recovery and 'worm expulsion' of the initially established adults) are all thymus-dependent in mice. The antibody responses examined are also thymus-dependent.

  3. Thymus dependency of induced immune responses against Hymenolepis nana (cestode) using congenitally athymic nude mice.

    Science.gov (United States)

    Ito, A

    1985-01-01

    Anti-parasite antibody responses were compared among several strains of mice experimentally infected with the dwarf tapeworm, Hymenolepis nana. The antibody titres were highly variable among the mouse strains in addition to variation in worm fecundity and longevity. The influence of the thymus on both infection and anti-parasite antibody production (especially of IgE isotype) was studied by the use of congenitally athymic (nu/nu) nude and their phenotypically normal (nu/+) CD-1(ICR) mice infected with H. nana. All nude (nu/nu) mice harboured fully mature 70 day old adult tapeworms of the first generation derived from eggs initially given on day 0. In addition, they contained (a) younger second generation adults derived from autoinfection and present in the intestinal lumen, (b) a number of abnormally large (about 1-2 mm in diameter) balloon like, fluid filled cysticercoids in not only the intestinal tissue but also parenteral tissues such as the mesenteric lymph nodes, liver and lung, and (c) normal cysticercoids derived from challenging eggs in the intestinal tissue. Infected nude mice produced no antibodies detectable by PCA (IgE) and double diffusion (IgG) tests. In contrast, normal (nu/+) mice and nude mice reconstituted with thymocytes expelled almost all luminal adults of the primary infection by day 70 and produced antibodies to extracts of adult H. nana. Neither autoinfection nor reinfection following egg challenge occurred in any of these normal (nu/+) and reconstituted nude mice. Therefore, acquired immune responses against H. nana (as assessed by resistance not only to the tissue phase measured by the failure of tissue cysticercoid recovery from egg challenge, but also to the lumen phase assessed by the failure of autoinfection adult recovery and 'worm expulsion' of the initially established adults) are all thymus-dependent in mice. The antibody responses examined are also thymus-dependent. PMID:4006301

  4. Metastatic potential of human renal cell carcinoma: experimental model using subrenal capsule implantation in athymic nude mice

    NARCIS (Netherlands)

    F.S. Grossi (F.); X. Zhao (X.); J.C. Romijn (Johannes); F.J.W. ten Kate; F.H. Schröder (Fritz)

    1992-01-01

    textabstractThe aim of this study was to determine whether subrenal capsule (SRC) implantation is a suitable model for the study of the metastatic potential of our human renal cell carcinoma (HRCC) lines and to establish new sublines with enhanced metastatic ability. NMRI athymic nude mice 7-11 week

  5. Membrane cell grafts, fresh and frozen to cover full thickness wounds in athymic nude mice

    Institute of Scientific and Technical Information of China (English)

    1998-01-01

    objective: To find a new way to cover full-thickness wounds. Methods: Biobrane(r), an adherent, flexible temporary wound dressing was incubated with cultured human keratinocytes. The cells adhered quickly forming "membrane-celgrafts" (MCG). Some of the grafts were frozen and after thawing viability was verified with a XTT colorimetric assay.MCGs, fresh and cryopreserved, were transplanted on full thickness wounds created on athymic nude mice. Conventional cultured epidermal grafts (CEG) and wounds without cell grafts served as control. Results: MCGs resulted in a differentiated epithelium of human phenotype and immunohistochemistry, immunofluorescence and electronmicroscopy were performed.Compared with CEG-grafted sites a reduced wound contraction was noticed and complete remodelling of the basement membrane zone was found. Conclusion: The efficiency of the easy, uncomplicated production, cryopreservation and use as well as the short culture period could lead to a new approach in the treatment of burn and chronic wounds.

  6. Optimized protocols for Mycobacterium leprae strain management: frozen stock preservation and maintenance in athymic nude mice.

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    Trombone, Ana Paula Fávaro; Pedrini, Sílvia Cristina Barbosa; Diório, Suzana Madeira; Belone, Andréa de Faria Fernandes; Fachin, Luciana Raquel Vicenzi; do Nascimento, Dejair Caitano; Rosa, Patricia Sammarco

    2014-03-23

    Leprosy, caused by Mycobacterium leprae, is an important infectious disease that is still endemic in many countries around the world, including Brazil. There are currently no known methods for growing M. leprae in vitro, presenting a major obstacle in the study of this pathogen in the laboratory. Therefore, the maintenance and growth of M. leprae strains are preferably performed in athymic nude mice (NU-Foxn1(nu)). The laboratory conditions for using mice are readily available, easy to perform, and allow standardization and development of protocols for achieving reproducible results. In the present report, we describe a simple protocol for purification of bacilli from nude mouse footpads using trypsin, which yields a suspension with minimum cell debris and with high bacterial viability index, as determined by fluorescent microscopy. A modification to the standard method for bacillary counting by Ziehl-Neelsen staining and light microscopy is also demonstrated. Additionally, we describe a protocol for freezing and thawing bacillary stocks as an alternative protocol for maintenance and storage of M. leprae strains.

  7. Hymenolepis nana: worm recovery from congenitally athymic nude and phenotypically normal rats and mice.

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    Ito, A; Kamiyama, T

    1984-10-01

    When eggs or mouse-derived cysticercoids of Hymenolepis nana were inoculated into previously uninfected congenitally athymic nude (rnu/rnu) rats of an outbred Rowett strain, they failed to mature in the intestinal lumen. They also failed to mature in phenotypically normal (rnu/+) littermates, except when these hosts were treated with cortisone acetate from the beginning of the lumen phase. The Rowett rat, either thymus-deficient or not, was susceptible to tissue cysticercoids but resistant to luminal adults. It is therefore considered to be an unnatural host, at least for mouse-derived H. nana. There was little or no difference in susceptibility to initial tissue cysticercoids between these nude rats and phenotypically normal ones. The normal rats became completely resistant to reinfection with eggs and no secondary cysticercoids developed in their intestinal tissue, whereas the nude rats showed unaltered susceptibility to secondary tissue cysticercoids. Thus, acquired resistance to egg challenge, assessed by the failure of tissue cysticercoid recovery, was thymus-dependent. However, innate resistance to both a primary egg dose, assessed by the low recovery rates of tissue cysticercoids, and to a primary cysticercoid dose, assessed by the failure of luminal adult recovery, were thymus-independent. The effect of cortisone acetate to initiate maturation of H. nana appeared to be unrelated to thymus function. In contrast, all mice, either thymus-deficient or not, were highly susceptible to both phases. The number of worms recovered was more than 10 times greater than that of cysticercoids established in the rat's intestinal tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Dietary stearic acid leads to a reduction of visceral adipose tissue in athymic nude mice.

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    Ming-Che Shen

    Full Text Available Stearic acid (C18:0 is a long chain dietary saturated fatty acid that has been shown to reduce metastatic tumor burden. Based on preliminary observations and the growing evidence that visceral fat is related to metastasis and decreased survival, we hypothesized that dietary stearic acid may reduce visceral fat. Athymic nude mice, which are used in models of human breast cancer metastasis, were fed a stearic acid, linoleic acid (safflower oil, or oleic acid (corn oil enriched diet or a low fat diet ad libitum. Total body weight did not differ significantly between dietary groups over the course of the experiment. However visceral fat was reduced by ∼70% in the stearic acid fed group compared to other diets. In contrast total body fat was only slightly reduced in the stearic acid diet fed mice when measured by dual-energy x-ray absorptiometry and quantitative magnetic resonance. Lean body mass was increased in the stearic acid fed group compared to all other groups by dual-energy x-ray absorptiometry. Dietary stearic acid significantly reduced serum glucose compared to all other diets and increased monocyte chemotactic protein-1 (MCP-1 compared to the low fat control. The low fat control diet had increased serum leptin compared to all other diets. To investigate possible mechanisms whereby stearic acid reduced visceral fat we used 3T3L1 fibroblasts/preadipocytes. Stearic acid had no direct effects on the process of differentiation or on the viability of mature adipocytes. However, unlike oleic acid and linoleic acid, stearic acid caused increased apoptosis (programmed cell death and cytotoxicity in preadipocytes. The apoptosis was, at least in part, due to increased caspase-3 activity and was associated with decreased cellular inhibitor of apoptosis protein-2 (cIAP2 and increased Bax gene expression. In conclusion, dietary stearic acid leads to dramatically reduced visceral fat likely by causing the apoptosis of preadipocytes.

  9. Phellinus linteus extract sensitizes advanced prostate cancer cells to apoptosis in athymic nude mice.

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    Tsuji, Takanori; Du, Wei; Nishioka, Takashi; Chen, Lihua; Yamamoto, Daisuke; Chen, Chang Yan

    2010-03-31

    Phellinus linteus (PL) mushroom possesses anti-tumor property. We previously reported that the treatment with PL caused cultured human prostate cancer cells to undergo apoptosis. To further studying the mechanisms of PL-mediated apoptosis, we performed xenograft assay, together with in vitro assays, to evaluate the effect of PL on the genesis and progression of the tumors formed from the inoculation of prostate cancer PC3 or DU145 cells. After the inoculation, nude mice were injected with PL every two days for 12 days. Although PL treatment did not prevent the formation of the inoculated tumors, the growth rate of the tumors after PL treatment was dramatically attenuated. We then tested the effect of PL on the tumors 12 days after the inoculation. After inoculated tumors reached a certain size, PL was administrated to the mice by subcutaneous injection. The histochemistry or immunochemistry analysis showed that apoptosis occurred with the activation of caspase 3 in the tumors formed by inoculating prostate cancer DU145 or PC3 cells. The data was in a good agreement with that from cultured cells. Thus, our in vivo study suggests that PL not only is able to attenuate tumor growth, but also to cause tumor regression by inducing apoptosis.

  10. Phellinus linteus extract sensitizes advanced prostate cancer cells to apoptosis in athymic nude mice.

    Directory of Open Access Journals (Sweden)

    Takanori Tsuji

    Full Text Available Phellinus linteus (PL mushroom possesses anti-tumor property. We previously reported that the treatment with PL caused cultured human prostate cancer cells to undergo apoptosis. To further studying the mechanisms of PL-mediated apoptosis, we performed xenograft assay, together with in vitro assays, to evaluate the effect of PL on the genesis and progression of the tumors formed from the inoculation of prostate cancer PC3 or DU145 cells. After the inoculation, nude mice were injected with PL every two days for 12 days. Although PL treatment did not prevent the formation of the inoculated tumors, the growth rate of the tumors after PL treatment was dramatically attenuated. We then tested the effect of PL on the tumors 12 days after the inoculation. After inoculated tumors reached a certain size, PL was administrated to the mice by subcutaneous injection. The histochemistry or immunochemistry analysis showed that apoptosis occurred with the activation of caspase 3 in the tumors formed by inoculating prostate cancer DU145 or PC3 cells. The data was in a good agreement with that from cultured cells. Thus, our in vivo study suggests that PL not only is able to attenuate tumor growth, but also to cause tumor regression by inducing apoptosis.

  11. Antitumoral effects of vasoactive intestinal peptide in human renal cell carcinoma xenografts in athymic nude mice.

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    Vacas, Eva; Arenas, M Isabel; Muñoz-Moreno, Laura; Bajo, Ana M; Sánchez-Chapado, Manuel; Prieto, Juan C; Carmena, María J

    2013-08-01

    We studied antitumor effect of VIP in human renal cell carcinoma (RCC) (A498 cells xenografted in immunosuppressed mice). VIP-treated cells gave resulted in p53 upregulation and decreased nuclear β-catenin translocation and NFκB expression, MMP-2 and MMP-9 activities, VEGF levels and CD-34 expression. VIP led to a more differentiated tubular organization in tumours and less metastatic areas. Thus, VIP inhibits growth of A498-cell tumours acting on the major issues involved in RCC progression such as cell proliferation, microenvironment remodelling, tumour invasion, angiogenesis and metastatic ability. These antitumoral effects of VIP offer new therapeutical possibilities in RCC treatment.

  12. THE ESTABLISHMENT OF A NEW ANIMAL MODEL FOR GASTRIC CANCER STUDY BY ORTHOTO PIC IMPLANTATION OF GASTRIC CANCER CELLS INTO ATHYMIC NUDE MICE

    Institute of Scientific and Technical Information of China (English)

    曾知真; 施尧; 萧树东; 江绍基; 张素胤; 殳裕华

    1992-01-01

    An animal model mimicking human gastric cancer by gastric wall implantation technique in athymic nude mice was reported. Two human gastric cancer cell lines. MKN-45 and MKN-28, were used in this study. All animals with gastric wall implantation of cancer cells of these two cell lines developed grossly visible gastric tumors after 3-4 weeks of implantation. Histopathological examination showed that tumors prirnarily grew at serosal side of stomach, and progressively invaded the gastric mucosa, but none showed metastasis in this study. All tumor-bearing animals died within 5-8 weeks after implantation. These results indicated that gastric wall of nude mice provided a good soil for growth and propagation of human gastric cancer cells. The model was useful for in vivo study on biological behavior of various types of human gastric cancers.

  13. Cidofovir treatment improves the pathology caused by the growth of human papillomavirus-positive cervical carcinoma xenografts in athymic nude mice.

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    De Schutter, Tim; Andrei, Graciela; Topalis, Dimitri; Duraffour, Sophie; Mitera, Tania; Naesens, Lieve; van den Oord, Joost; Matthys, Patrick; Snoeck, Robert

    2013-02-28

    Cidofovir has shown antiproliferative effects against human papillomavirus (HPV)-positive cells and successfully suppressed the growth of HPV-positive xenografts in athymic nude mice. The present study evaluated the effect of cidofovir on several disease parameters in this animal model. Intratumoral administration of cidofovir resulted in a beneficial effect on body weight gain, a reduction in splenomegaly, a partial restoration of tryptophan catabolism, and diminished the inflammatory state induced by the xenografts. Administration of cidofovir to tumor-free animals did not have a direct effect on these parameters. Beyond suppressing tumor growth, intratumoral treatment with cidofovir ameliorated the pathology associated with HPV-tumor growth.

  14. Vascularization and innervation of slits within polydimethylsiloxane sheets in the subcutaneous space of athymic nude mice.

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    Gurlin, Rachel E; Keating, Mark T; Li, Shiri; Lakey, Jonathan Rt; de Feraudy, Sébastien; Shergill, Bhupinder S; Botvinick, Elliot L

    2017-01-01

    Success of cell therapy in avascular sites will depend on providing sufficient blood supply to transplanted tissues. A popular strategy of providing blood supply is to embed cells within a functionalized hydrogel implanted within the host to stimulate neovascularization. However, hydrogel systems are not always amenable for removal post-transplantation; thus, it may be advantageous to implant a device that contains cells while also providing access to the circulation so retrieval is possible. Here we investigate one instance of providing access to a vessel network, a thin sheet with through-cut slits, and determine if it can be vascularized from autologous materials. We compared the effect of slit width on vascularization of a thin sheet following subcutaneous implantation into an animal model. Polydimethylsiloxane sheets with varying slit widths (approximately 150, 300, 500, or 1500 µm) were fabricated from three-dimensional printed molds. Subcutaneous implantation of sheets in immunodeficient mice revealed that smaller slit widths have evidence of angiogenesis and new tissue growth, while larger slit widths contain native mature tissue squeezing into the space. Our results show that engineered slit sheets may provide a simple approach to cell transplantation by providing a prevascularized and innervated environment.

  15. Qualitative and semi quantitative analysis in the healing area of athymic nude mice skin engrafted with human skin sterilized with gamma radiation

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    Miranda, Jurandir Tomaz de; Bringel, Fabiana; Alves, Nelson Mendes; Antebi, Uri; Funari, Ana Paula; Mathor, Monica B., E-mail: tomaz_ju@hotmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2015-07-01

    In recent decades there has been a great interest in the radio-sterilized grafts for human skin grafts. This tissue is taken from a cadaver or multi-organ donor and samples are processed and stored in glycerol at concentrations above 85%. Although this procedure is carried out under aseptic conditions, after the final packaging one can sterilize the tissues with ionizing radiation in order to increase the safety level of sterility. The purpose of this study was to evaluate the behavior of the healing repair process that occurs between the graft and the skin of athymic NUDE mice. The samples of human skin treated with glycerol were divided into three groups: the control group 1 (non-irradiated), irradiated group 2 at 25 kGy and irradiated group 3, at 50 kGy. These tissues were grafted onto athymic NUDE mice which were sacrificed after 3, 7 and 21 days. After the sacrifice, part of the back fur of the animals containing human skin graft was removed with hematoxylin and eosin (H/E). The histological sections were analyzed for the integrity of tissue, presence and location of keratinocytes, fibroblasts, defense cells and blood vessels. Thus it was examined whether over time the graft was incorporated into the body or if there was a process of healing by secondary intention. (author)

  16. Mitotic activity and delay in fixation of tumour tissue. The influence of delay in fixation on mitotic activity of a human osteogenic sarcoma grown in athymic nude mice.

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    Graem, N; Helweg-Larsen, K

    1979-09-01

    The purpose of the present investigation was to study the effect of delay in fixation on the mitotic activity in tumour tissue. A human osteogenic sarcoma, especially suitable for counting of mitoses, grown in athymic nude mice, was fixed with varying delay and the mitotic, prophase, metaphase and ana-telophase indices were determined. An almost exponential decline of the mitotic index was observed with a reduction to 49.4% and 15.0% after respectively 60 and 180 minutes. The proportional incidence of prophases, metaphases and ana-telophases changed so that a relative accummulation of advanced phases occured during the 180 minutes of observation. It is concluded that delay in fixation of a magnitude, which is not uncommon in routine surgical pathology, may allow the majority of mitoses to terminate, resulting in unreliable assessments of mitotic activity.

  17. Antrodia camphorata induces G(1) cell-cycle arrest in human premyelocytic leukemia (HL-60) cells and suppresses tumor growth in athymic nude mice.

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    Yang, Hsin-Ling; Kumar, K J Senthil; Kuo, Ya-Ting; Chang, Hebron C; Liao, Jiunn-Wang; Hsu, Li-Sung; Hseu, You-Cheng

    2014-09-01

    Antrodia camphorata is a well-known medicinal mushroom in Taiwan. The broth from a fermented culture of Antrodia camphorata (AC) has been shown to induce apoptosis in cultured human premyelocytic leukemia (HL-60) cells. In the present study, we examined the effects of AC on cell cycle arrest in vitro in HL-60 cells and on tumor regression in vivo using an athymic nude mouse model. We found that AC (20-80 μg mL(-1)) treatment significantly induced G1 cell-cycle arrest in HL-60 cells by reducing the levels of cyclin D1, CDK4, cyclin E, CDK2, cyclin A, and phosphorylation of retinoblastoma protein (p-Rb). Moreover, AC treatment led to significantly increased protein expression levels of CDK inhibitors, including p21(WAF1) and p15(NIK4B). Additionally, AC treatment markedly induced intracellular ROS generation and mitochondrial dysfunction in HL-60 cells. Furthermore, the in vivo study results revealed that AC treatment was effective in terms of delaying the tumor incidence in nude mice that had been inoculated with HL-60 cells as well as in reducing the tumor burden. Histological analysis confirmed that AC treatment significantly modulated the xenografted tumor progression as demonstrated by a reduction in mitotic cells. Our data strongly suggest that Antrodia camphorata could be an anti-cancer agent for human leukemia.

  18. Modulation of total IgE levels in serum of normal and athymic nude BALB/c mice by cells and exogenous antigenic stimulation

    NARCIS (Netherlands)

    Savelkoul, H.F.J.; Akker, van den T.W.; Soeting, P.W.C.; Oudenaren, van A.; Benner, R.

    1989-01-01

    Several different grades of T-system impairment were studied for their effects on the total serum IgE concentration in BALB/c mice. Homozygous athymic nu/nu mice and their heterozygous nu/ littermates were compared for serum IgE levels while kept under either barrier-maintained or conventional condi

  19. Fisetin, a phytochemical, potentiates sorafenib-induced apoptosis and abrogates tumor growth in athymic nude mice implanted with BRAF-mutated melanoma cells.

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    Pal, Harish Chandra; Baxter, Ronald D; Hunt, Katherine M; Agarwal, Jyoti; Elmets, Craig A; Athar, Mohammad; Afaq, Farrukh

    2015-09-29

    Melanoma is the most deadly form of cutaneous malignancy, and its incidence rates are rising worldwide. In melanoma, constitutive activation of the BRAF/MEK/ERK (MAPK) and PI3K/AKT/mTOR (PI3K) signaling pathways plays a pivotal role in cell proliferation, survival and tumorigenesis. A combination of compounds that lead to an optimal blockade of these critical signaling pathways may provide an effective strategy for prevention and treatment of melanoma. The phytochemical fisetin is known to possess anti-proliferative and pro-apoptotic activities. We found that fisetin treatment inhibited PI3K signaling pathway in melanoma cells. Therefore, we investigated the effect of fisetin and sorafenib (an RAF inhibitor) alone and in combination on cell proliferation, apoptosis and tumor growth. Combination treatment (fisetin + sorafenib) more effectively reduced the growth of BRAF-mutated human melanoma cells at lower doses when compared to individual agents. In addition, combination treatment resulted in enhanced (i) apoptosis, (ii) cleavage of caspase-3 and PARP, (iii) expression of Bax and Bak, (iv) inhibition of Bcl2 and Mcl-1, and (v) inhibition of expression of PI3K, phosphorylation of MEK1/2, ERK1/2, AKT and mTOR. In athymic nude mice subcutaneously implanted with melanoma cells (A375 and SK-MEL-28), we found that combination therapy resulted in greater reduction of tumor growth when compared to individual agents. Furthermore, combination therapy was more effective than monotherapy in: (i) inhibition of proliferation and angiogenesis, (ii) induction of apoptosis, and (iii) inhibition of the MAPK and PI3K pathways in xenograft tumors. These data suggest that simultaneous inhibition of both these signaling pathways using combination of fisetin and sorafenib may serve as a therapeutic option for the management of melanoma.

  20. Diffuse scaling dermatitis in an athymic nude mouse.

    Science.gov (United States)

    Russo, M; Invernizzi, A; Gobbi, A; Radaelli, E

    2013-07-01

    This report describes the clinicopathological features of a case of diffuse scaling dermatitis that occurred in a 16-week-old female athymic nude (CrTac:NCr-Foxn1(nu)) mouse. Gross presentation was suggestive of Corynebacterium bovis infection (scaly skin disease). However, C. bovis was not isolated from the skin of the affected animal or from the skin of unaffected CrTac:NCr-Foxn1(nu) mice housed in the same cage or room. Staphylococcus xylosus was instead isolated in high numbers from the skin lesion, whereas only a few colonies were recovered from the skin of unaffected mice. Microscopically, the affected skin was characterized by chronic hyperplastic and hyperkeratotic dermatitis with focal ulcerations, extensive serocellular crusts, and intralesional clusters of Gram-positive coccoid bacteria. Although gross presentation of the reported case was suggestive of C. bovis infection, epidemiological, histopathological, and bacteriological findings definitively ruled out an outbreak of scaly skin disease. A diagnostic hypothesis of hyperplastic and hyperkeratotic dermatitis associated with opportunistic S. xylosus infection was formulated based on increased bacterial burden and presence of intralesional Gram-positive coccoid bacteria.

  1. Dissemination in athymic nude mice of lacZ transfected small cell lung cancer cells identified by X-gal staining

    DEFF Research Database (Denmark)

    Rømer, M U; Christiansen, J; Brünner, N;

    1995-01-01

    with the chromogenic substrate X-gal. lacZ expressing cells were investigated after subcutaneous (s.c.) inoculation and intravenous (i.v.) injection. The X-gal detection of beta-D-galactosidase activity proved to be a rapid and easy means for specific and highly sensitive identification of metastases. All primary s.......c. tumors stained by X-gal. The primary tumors of GLC-2 regularly demonstrated local invasive growth and produced multiple metastases in several organs. In contrast, primary DMS 456 tumors only occasionally demonstrated local invasion and very rarely generated secondary foci. No experimental metastases were......The small cell lung cancer cell lines GLC-2 and DMS 456 were genetically labeled with the lacZ gene and examined for invasive and metastatic potential in META/Bom nude mice. The lacZ gene encodes the enzyme beta-D- galactosidase, and cells expressing this enzyme were identified by staining...

  2. Solitary Lung Tumors and Their Spontaneous Metastasis in Athymic Nude Mice Orthotopically Implanted with Human Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Takeshi Yamaura

    2000-07-01

    Full Text Available We examined the tumorigenic and metastatic potentials of three human non-small cell lung cancer (NSCLC cell lines. PC-14, A549 or Lu-99 cell lines suspended in Matrigel-containing phosphate-buffered saline were orthotopically implanted into the lungs of nude mice. The formation of a solitary tumor nodule in the lung was observed after the implantation of all cell lines. Intrapulmonary implantation of PC-14 or Lu-99 cells resulted in spontaneous distant metastases. In contrast, A549 cells caused multiple intrapulmonary metastases to the right and left lobes of the lung without producing visible lymphatic metastasis. We also investigated the expression of matrix metal loproteinases (MMPs, urokinase-type plasminogen activator (u-PA, u-PA receptor (u-PAR and c-MET in these cell lines in vitro and in vivo. Reverse transcription polymerase chain reaction (RT-PCR analysis showed that the expression of MMP-2 and membrane-type 1 MMP (MT1-MMP was elevated in PC-14 as compared with the other two cell lines. In contrast, stronger expression of c-METwas observed in A549 than in PC-14 or Lu-99. These results indicate that differential patterns of metastasis of lung cancer might be associated with differential expression of metastasis-associated molecules. Our orthotopic implantation models display clinical features resembling those of NSCLC, may provide a useful basis for lung cancer research.

  3. Protection of athymic (Nu/Nu BALB/c mice against Plasmodium berghei by splenocytes from normal (Nu/ + BALB/c mice

    Directory of Open Access Journals (Sweden)

    José J. Ferraroni

    1985-12-01

    Full Text Available Athymic BALB/c (Nu/Nu mice died at 7-13 days after inoculation (DAI of Plasmodium berghei NK65, whereas their heterozygous (Nu/+ littermates died at 7-8 DAI. Nude (Nu/Nu mice, reconstituted with 2 x 10(7 splenocytes from uninfected heterozygous (Nu/+ littermates at 20 days before parasite inoculation (DBI, died about 2 days earlier than control nude mice; nude mice reconstituted at 10 or 2 DBI lived 2 to 4 days longer than control nudes; and nude mice reconstituted 2 DAI lived even longer and some survived. These findings indicate that P. berghei NK65 induces at least two T-cell dependent immune phenomena, one suppressive and the other stimulatory. Reconstitution of nude mice with T-cells from BALB/c (Nu/+ mice appeared to reduce or bypass suppressive T-cell activities which allowed the formation of a protective immune response by some of the nude mice.

  4. Endocrine therapy of human breast cancer grown in nude mice

    DEFF Research Database (Denmark)

    Brünner, N; Osborne, C K; Spang-Thomsen, M

    1987-01-01

    Although there have been extensive studies of rodent breast tumor models, and of human breast cancer cell lines in culture, there is still need for a human tumor model which can be manipulated experimentally but also provides a valid expression of the tumor cells in a host environment. Athymic nude...... mice bearing transplanted human breast tumors have been proposed as such a model. This review therefore discusses the use of the athymic nude mouse model of the study of human breast cancer biology, and focuses on four subjects: 1. biological characteristics of heterotransplanted breast tumors; 2....... endocrinology and pharmacology of hormonal agents in the nude mouse; 3. endocrine sensitivity of heterotransplanted tumors; and 4. applicability and limitations of this model for the study of human breast cancer....

  5. Cortisone-sensitive, innate resistance to Hymenolepis nana infection in congenitally athymic nude rats.

    Science.gov (United States)

    Ito, A; Kamiyama, T

    1987-06-01

    The innate resistance of the unnatural rat host to the mouse tapeworm Hymenolepis nana is cortisone sensitive but thymus independent. When congenitally athymic nude rats were orally given eggs, cysticercoids, or adult worms of H. nana, no lumenal adults were established except when they were treated with cortisone acetate during the expected lumenal development. The effect of cortisone to promote adult maturation in the rats was compared in nude and normal rats given eggs of H. nana. The fecundity of the worms (assessed by the fresh worm biomass and the number of infective eggs produced) was much higher in cortisone-treated nude rats than in cortisone-treated normal rats. When the nude rats reconstituted with thymocytes were given eggs and treated with cortisone, the fecundity of H. nana dropped to the same level as in cortisone-treated normal rats. It is strongly suggested that the unnatural rat host has thymus-independent cortisone sensitive resistance to an initial infection (which is the main component of the innate resistance and blocks the lumenal establishment of this parasite) and thymus-dependent resistance (which suppresses the established worms' fecundity and may be ascribed to acquired resistance to the ongoing infection).

  6. Kinetics of small lymphocytes in normal and nude mice after splenectomy

    DEFF Research Database (Denmark)

    Hougen, H P; Hansen, F; Jensen, E K

    1977-01-01

    Autoradiography and various quantitations on lymphoid tissues have been used to evaluate the kinetics of small lymphocytes in normal (+/nu or +/+) and congenitally athymic nude (nu/nu) NMRI mice 1 month after splenectomy or sham-splenectomy. The results indicate that splenectomy causes depressed...

  7. Cystic metacestodes of a rat-adapted Taenia taeniaeformis established in the peritoneal cavity of scid and nude mice.

    Science.gov (United States)

    Ito, A; Ma, L; Sato, Y

    1997-08-01

    In vitro-hatched (but not activated) oncospheres of a rat-adapted strain of Taenia taeniaeformis intraperitoneally inoculated into severe combined immunodeficiency (scid), congenitally athymic (nude) and immunocompetent (normal) female BALB/c mice developed into cystic metacestodes in the peritoneal cavity (but not in the liver) of scid and nude mice exclusively. This suggests that cystic metacestodes of this parasite, usually harboured in the liver only, can establish in scid and nude mice provided that the oncospheres are inoculated into the peritoneal cavity. Immunodeficient mice, especially scid mice, may be a good experimental animal model for the intermediate host of any taeniid species, of human, domestic- or wild-animal origin.

  8. Kinetics of small lymphocytes in normal and nude mice after splenectomy

    DEFF Research Database (Denmark)

    Hougen, H P; Hansen, F; Jensen, E K;

    1977-01-01

    Autoradiography and various quantitations on lymphoid tissues have been used to evaluate the kinetics of small lymphocytes in normal (+/nu or +/+) and congenitally athymic nude (nu/nu) NMRI mice 1 month after splenectomy or sham-splenectomy. The results indicate that splenectomy causes depressed ......, are released from the lympho-myeloid organs in compensation for the loss of long-lived, thymus-derived cells....

  9. Inconsistent formation and nonfunction of insulin-positive cells from pancreatic endoderm derived from human embryonic stem cells in athymic nude rats.

    Science.gov (United States)

    Matveyenko, Aleksey V; Georgia, Senta; Bhushan, Anil; Butler, Peter C

    2010-11-01

    Embryonic stem cell therapy has been proposed as a therapeutic strategy to restore β-cell mass and function in T1DM. Recently, a group from Novocell (now ViaCyte) reported successful development of glucose-responsive islet-like structures after implantation of pancreatic endoderm (PE) derived from human embryonic stem cells (hESC) into immune-deficient mice. Our objective was to determine whether implantation of hESC-derived pancreatic endoderm from Novocell into athymic nude rats results in development of viable glucose-responsive pancreatic endocrine tissue. Athymic nude rats were implanted with PE derived from hESC either via implantation into the epididymal fat pads or by subcutaneous implantation into TheraCyte encapsulation devices for 20 wk. Blood glucose, weight, and human insulin/C-peptide secretion were monitored by weekly blood draws. Graft β-cell function was assessed by a glucose tolerance test, and graft morphology was assessed by immunohistochemistry and immunofluorescence. At 20 wk postimplantation, epididymal fat-implanted PE progressed to develop islet-like structures in 50% of implants, with a mean β-cell fractional area of 0.8 ± 0.3%. Human C-peptide and insulin were detectable, but at very low levels (C-peptide = 50 ± 26 pmol/l and insulin = 15 ± 7 pmol/l); however, there was no increase in human C-peptide/insulin levels after glucose challenge. There was no development of viable pancreatic tissue or meaningful secretory function when human PE was implanted in the TheraCyte encapsulation devices. These data confirm that islet-like structures develop from hESC differentiated to PE by the protocol developed by NovoCell. However, the extent of endocrine cell formation and secretory function is not yet sufficient to be clinically relevant.

  10. Identification of the mononuclear cell infiltrate in the superior cervical ganglion of athymic nude and euthymic rats after guanethidine-induced sympathectomy

    DEFF Research Database (Denmark)

    Thygesen, P; Hougen, H P; Christensen, H B;

    1990-01-01

    Guanethidine sulphate 40 mg/kg intraperitoneally for 14 days induced chromatolysis and nerve cell death in the superior cervical ganglia of athymic nude (rnu/rnu) LEW/Mol rats and their euthymic (+/rnu) LEW/Mol heterozygous littermates. Histologically the sympathetic ganglia were dominated by an ...

  11. Postnatal and postpartal morphology of the mammary gland in nude mice.

    Science.gov (United States)

    Militzer, K; Schwalenstöcker, H

    1996-08-01

    The object of this work was to compare the postnatal and postpartal morphology of the mammary gland of nu/nu with that of nu/(+)-mice. All studies were carried out on groups of female (athymic) nude mice with NMRI genetic background, their nu/(+)-siblings and dams. The various age groups (3, 21, 40, 55, 70 and 120 days) each consisted of 6 nu/nu- and 6 heterozygous nu/(+)-mice respectively. The morphological examination of the mammary gland tissue were made on histological sections and whole mounts. Body weights, total areas of the mammary glands and the number of the terminal end buds were compared. The mammary gland of the athymic nude mouse exhibited no essential morphological differences from the normal developing mammary gland of the hairy euthymic nu/(+)-animal. The area of the mammary gland increased with increasing body weight. Both collectives of mice differed only in their rate of mammary gland development. As a result, the terminal end buds appeared numerously as growth points of mammary gland in nu/(+)-animals as early as the 21st day of life. The athymic nude mice showed a maximum only on the 40th day of life and a lower degree of density and differentiation of specific mammary gland structures (lateral buds, lobulo-alveolar glandular endings) until the 70th day of life. The mammary gland of 120-day-old animals and dams of both animal groups reached the same state of maturity. Thus it is not the rate of development of the dam, but other, yet unidentified factors, which determine, if successful breeding of nude mice with homozygous parents is possible.

  12. Hardware, software, and scanning issues encountered during small animal imaging of photodynamic therapy in the athymic nude rat

    Science.gov (United States)

    Cross, Nathan; Sharma, Rahul; Varghai, Davood; Spring-Robinson, Chandra; Oleinick, Nancy L.; Muzic, Raymond F., Jr.; Dean, David

    2007-02-01

    Small animal imaging devices are now commonly used to study gene activation and model the effects of potential therapies. We are attempting to develop a protocol that non-invasively tracks the affect of Pc 4-mediated photodynamic therapy (PDT) in a human glioma model using structural image data from micro-CT and/or micro-MR scanning and functional data from 18F-fluorodeoxy-glucose (18F-FDG) micro-PET imaging. Methods: Athymic nude rat U87-derived glioma was imaged by micro-PET and either micro-CT or micro-MR prior to Pc 4-PDT. Difficulty insuring animal anesthesia and anatomic position during the micro-PET, micro-CT, and micro-MR scans required adaptation of the scanning bed hardware. Following Pc 4-PDT the animals were again 18F-FDG micro-PET scanned, euthanized one day later, and their brains were explanted and prepared for H&E histology. Histology provided the gold standard for tumor location and necrosis. The tumor and surrounding brain functional and structural image data were then isolated and coregistered. Results: Surprisingly, both the non-PDT and PDT groups showed an increase in tumor functional activity when we expected this signal to disappear in the group receiving PDT. Co-registration of the functional and structural image data was done manually. Discussion: As expected, micro-MR imaging provided better structural discrimination of the brain tumor than micro-CT. Contrary to expectations, in our preliminary analysis 18F-FDG micro-PET imaging does not readily discriminate the U87 tumors that received Pc 4-PDT. We continue to investigate the utility of micro-PET and other methods of functional imaging to remotely detect the specificity and sensitivity of Pc 4-PDT in deeply placed tumors.

  13. Development and characterization of multidrug resistant human hepatocarcinoma cell line in nude mice

    Institute of Scientific and Technical Information of China (English)

    Bao-Jin Zhai; Ze-Yong Shao; Chun-Liang Zhao; Kai Hu; Feng Wu

    2006-01-01

    AIM: To establish a multidrug resistant (MDR) cell subline from the human hepatocarcinoma cell line (HepG2)in nude mice.METHODS: HepG2 cell cultures were incubated with increasing concentrations of adriamycin (ADM) to develop an ADM-resistant cell subline (HepG2/ADM) with crossresistance to other chemotherapeutic agents. Twenty male athymic BALB/c-nu/nu mice were randomized into HepG2/nude and HepG2/ADM/nude groups (10 in each group). A cell suspension (either HepG2 or HepG2/ADM)was injected subcutaneously into mice in each group.Tumor growth was recorded, and animals were sacrificed 4-5 wk after cell implantation. Tumors were prepared for histology, and viable tumor was dispersed into a single-cell suspension. The IC50 values for a number of chemotherapeutic agents were determined by 2, 3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt (MTT) assay. Rhodamine-123retention/efflux and the level of resistance-associated proteins were determined by flow cytometry. The mRNA expression of mdr1, mrp and Irp genes was detected using reverse transcriptase polymerase chain reaction (RT-PCR) in HepG2/nude and HepG2/ADM/nude groups.RESULTS: The appearances of HepG2/nude cells were slightly different from those of HepG2/ADM/nude cells.Similar tumor growth curves were determined in both groups. A cross-resistance to ADM, vincristine, cisplatin and 5-fiuorouracil was seen in HepG2/ADM/nude group.The levels of P-glycoprotein and multidrug resistanceassociated proteins were significantly increased. The mRNA expression levels of mdr1, mrp and Irp were higher in HepG2/ADM/nude cells.CONCLUSION: ADM-resistant HepG2 subline in nude mice has a cross resistance to chemotherapeutic drugs.Tt may be used as an in vivo model to investigate the mechanisms of MDR, and explore the targeted approaches to overcoming MDR.

  14. The athymic nude rat. Immunobiological characteristics with special reference to establishment of non-antigen-specific T-cell reactivity and induction of antigen-specific immunity

    DEFF Research Database (Denmark)

    Hougen, H P

    1991-01-01

    and function of the thymus are briefly described. The thymus has two main functions: production of T lymphocytes and production of thymic hormones. The intrathymic T-cell ontogeny is described along with the two thymocyte selection mechanisms, positive and negative selection. Different thymic hormones...... cells. Little research has been performed on bone marrow of athymic nude rats but morphologically there seems to be no difference from findings in normal animals. The thymus-dependent areas of peripheral lymphoid organs, i.e. the paracortical area of lymph nodes, the periarteriolar sheet of the splenic...

  15. FOXN1 homozygous mutation associated with anencephaly and severe neural tube defect in human athymic Nude/SCID fetus.

    Science.gov (United States)

    Amorosi, S; D'Armiento, M; Calcagno, G; Russo, I; Adriani, M; Christiano, A M; Weiner, L; Brissette, J L; Pignata, C

    2008-04-01

    The forkhead, Fox, gene family comprises a diverse group of 'winged-helix' transcription factors that play important roles in development, metabolism, cancer and aging. Recently, several forkhead genes have been demonstrated to play critical roles in lymphocyte development and effector functions. Alterations of the FOXN1 gene in both mice and humans result in a severe combined immunodeficiency caused by an intrinsic defect of the thymus associated with congenital alopecia (Nude/severe combined immunodeficiency phenotype). FOXN1 is a member of the class of proteins involved in the development and differentiation of the central nervous system. We identified a human fetus homozygous for a mutation in FOXN1 gene who lacked the thymus and also had abnormal skin, anencephaly and spina bifida. Moreover, we found that FOXN1 gene is expressed in mouse developing choroid plexus. These observations suggest that FOXN1 may be involved in neurulation in humans.

  16. Deficiency of Mouse CD4+CD25+Foxp3+Regulatory T Cells in Xenogeneic Pig Thymus-Grafted Nude Mice Suffering from Autoimmune Diseases

    Institute of Scientific and Technical Information of China (English)

    Baojun Zhang; Chenming Sun; Yanyan Qu; Aijun Zhang; Jun Liu; Lianjun Zhang; Zeqing Niu; Yong Zhao

    2008-01-01

    Xenogeneic thymus transplantation can efficiently induce specific immune tolerance to donor antigens in athymic recipients.However,many nude mice snffer from autoimmune diseases(AID) for over 10 weeks after xenogeneic thymus transplantation.CD4+CD25+Foxp3+ regulatory T (Treg)cells were recently determined to play a pivotal role in keeping immune tolerance in humans and mice.Thus,we investigated this subpopulation of Treg cells in the periphery of pig thymus-grafted nude mice suffering from AID.Our results showed that the expression of Foxp3, CTLA-4 and GITR on mouse CD4+CD25+T cells and the ratio of CD4+CD25+Foxp3+Treg cells to CD4+T cells were significantly decreased in the periphery of pig thymus-grafted nude mice snfiering from AID,compared with healthy pig or mouse thymus-grafted nude mice.Furthermore,mouse CD4+CD25+T cells in pig thymus-grafted nude mice Sufiering from AID showed more severe deficiency in immunosuppressive function compared with the counterpart in xenogeneic pig or syngeneic thymus-grafted nude mice without AID.Thus,the decreased frequency, altered phenotype and functional deficiency of mouse CD4+CD25+Treg cells in pig thymus-grafted nude mice may contribute to the development of AID in this model.

  17. Growth of human bronchial carcinomas in nude mice.

    OpenAIRE

    1985-01-01

    Two hundred and thirteen lung tumours of primary site and 42 metastases were heterotransplanted into nude mice with an overall success rate of 44%. There were differences in success between the histological types. Squamous cell and adenocarcinoma had the highest success rate (51% and 43%, respectively) whereas large cell and small cell carcinoma had a lower success rate (38% for both). The average volume doubling times in the first passage in nude mice ranged from 8.2 in large cell carcinomas...

  18. Monitoring Pc 4-mediated photodynamic therapy of U87 tumors with 18F- fluorodeoxy-glucose PET imaging in the Athymic Nude Rat

    Science.gov (United States)

    Varghai, Davood; Cross, Nathan; Spring-Robinson, Chandra; Sharma, Rahul; Feyes, Denise K.; Ahmad, Yusra; Oleinick, Nancy L.; Muzic, Raymond F., Jr.; Dean, David

    2007-02-01

    Introduction: We have previously demonstrated the use of phthalocyanine Pc 4 for the photodynamic therapy (PDT) of ectopic human glial tumors in the athymic nude rat brain. We wish to determine whether 18F-fluorodeoxy-glucose ( 18F-FDG) Positron Emission Tomography (PET) imaging can detect the reduction in tumor metabolism that must occur after Pc 4-PDT-induced necrosis. Methods: 2.5 x 10 5 U87 cells were injected into the brains of 12 athymic nude rats. After 7 days of tumor growth, all 12 animals were imaged functionally by 18F-FDG micro-PET (μPET) and structurally by micro-CT and/or micro-MR. These animals received 0.5 mg/kg b.w. Pc 4 via tail-vein injection. One day later the scalp was re-incised and the tumor illuminated with 30 J/cm2 of 672-nm light from a diode laser. The next day these animals were again 18F-FDG μPET imaged. Next, the animals were euthanized and their brains were explanted for H&E histology. Results: Histology showed that tumors in the 6 Pc 4-PDT-treated animals demonstrated necrosis ranging from full to frank (severe). Preliminary analysis showed that 18F-FDG μPET activity in 3 of the 6 non-PDT group (i.e., no tumor necrosis observed) animals was seen to increase 2.28 times following tumor photoirradiation, whereas 18F-FDG μPET activity in 5 of the 6 PDT group (i.e., tumor necrosis observed) animals was seen to increase 1.15 times following tumor photoirradiation. Discussion: The increased 18F-FDG μPET activity in the PDT group was unexpected. We had expected this activity to decrease and are presently investigating the cause of this observation.

  19. Intravesical Instillation in Pure Line LEW Rats and Nude Mice

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jie; XIE Shusheng; GUO Xiaoyun; MO Zengnan

    2007-01-01

    In order to study bladder intravesical instillation methods in pure line LEW rats and nude mice, female LEW rats and nude mice aged 2 to 4 weeks were sacrificed. Their urethra and bladder were observed under anatomical microscopy. A trochar was prepared according to the outline and angle of the urethra. Ink was poured into female rats and nude mice bladder though urethra. Filling and staining of bladder were observed and evaluated under anatomical microscopy. Status and urethral injury of rats and mice were observed. The results showed that urethra anatomic structure of rats and nude mice was different from that of human urethra. When bladder was filled with ink and became blue, liquid was not seen to leak out. The success rate of intubation was high (100%). Living activities of animals weren't influenced by intravesical instillation. It was concluded that bladder irrigation might be a kind of valid and utilizable method in pure line rat and nude mouse empirical study. The model may be a more effective tool for study of bladder tumor.

  20. Cell surface phenotype of cytolytic T lymphocyte precursors in aged nude mice.

    Science.gov (United States)

    Maryanski, J L; MacDonald, H R; Sordat, B; Cerottini, J C

    1981-12-01

    The cell surface phenotype of cytolytic T lymphocyte precursors (CTL-P) in congenitally athymic C57BL/6 nu/nu mice has been investigated. CTL-P were detected and quantitated in a limited dilution mixed leukocyte microculture assay system supplemented with interleukin 2. Minimal estimates of the frequency of CTL-P among nylon wool passed (NWP) nude spleen cells were obtained following elimination of Thy-1-bearing or Lyt-2-bearing cells with monoclonal antibodies plus complement. Alternatively, NWP spleen cells bearing Thy-1 or Lyt-2 were positively selected on a cell sorter and assayed for CTL-P frequency. Both positive and negative selection techniques demonstrated that essentially all (greater than 98%) CTL-P in NWP nude spleen expressed Thy-1 and that the majority (80-90%) expressed Lyt-2. In control NWP spleen cells from normal C57BL/6 mice, greater than 98% of CTL-P were positive for both Thy-1 and Lyt-2. These data demonstrate that most functional alloreactive CTL-P developing in the apparent absence of thymic influence already express both Thy-1 and Lyt-2 prior to exposure to antigen.

  1. Incubation and application of transgenic green fluorescent nude mice in visualization studies on glioma tissue remodeling

    Institute of Scientific and Technical Information of China (English)

    DONG Jun; LAN Qing; HUANG Qiang; DAI Xing-liang; LU Zhao-hui; FEI Xi-feng; CHEN Hua; ZHANG Quan-bin; ZHAO Yao-dong; WANG Zhi-min; WANG Ai-dong

    2012-01-01

    Background The primary reasons for local recurrence and therapeutic failure in the treatment of malignant gliomas are the invasion and interactions of tumor cells with surrounding normal brain cells.However,these tumor cells are hard to be visualized directly in histopathological preparations,or in experimental glioma models.Therefore,we developed an experimental human dual-color in vivo glioma model,which made tracking solitary invasive glioma cells possible,for the purpose of visualizing the interactions between red fluorescence labeled human glioma cells and host brain cells.This may offer references for further studying the roles of tumor microenvironment during glioma tissue remodeling.Methods Transgenic female C57BL/6 mice expressing enhanced green fluorescent protein (EGFP) were crossed with male Balb/c nude mice.Then sib mating was allowed to occur continuously in order to establish an inbred nude mice strain with 50% of their offspring that are EGFP positive.Human glioma cell lines U87-MG and SU3 were transfected with red fluorescent protein (RFP) gene,and a rat C6 glioma cell line was stained directly with CM-Dil,to establish three glioma cell lines emitting red fluorescence (SU3-RFP,U87-RFP,and C6-CM-Dil).Red fluorescence tumor cells were inoculated via intra-cerebral injection into caudate nucleus of the EGFP nude mice.Tumor-bearing mice were sacrificed when their clinical symptoms appeared,and the whole brain was harvested and snap frozen for further analysis.Confocal laser scanning microscopy was performed to monitor the mutual interactions between tumor cells and host brain cells.Results Almost all the essential tissues of the established EGFP athymic Balb/c nude mice,except hair and erythrocytes,fluoresced green under excitation using a blue light-emitting flashlight with a central peak of 470 nm,approximately 50% of the offsprings were nu/nu EGFP+.SU3-RFP,U87-RFP,and C6-CM-Dil almost 100% expressed red fluorescence under the fluorescence

  2. Characterization of oral ulcer and pathological scar in nude mice model.

    Science.gov (United States)

    Sukhitashvili, N; Imnadze, I; Tabaghua, G; Gogilashvili, Q; Amiranashvili, I

    2012-04-01

    Ulceration of mouth mucosa is frequently occurs after injuries in oral cavity. Oral ulcers are relatively common and these lesions cause strong pain and discomfort. Frequently, injury of the oral tissues results in abnormal fibroblast activation and keloid formation. This pathological scar formation is often associates with pain and malfunction of the organ. To understand these phenomena and develop effective treatment, reproducible animal models have to be introduced. Athymic nude mice where used to create animal models. 1% HCl acid solution was used for chemical damage of the mucosa tissue. Surgical operation was performed to create traumatic injury in the mouse oral cavity. Tissues were analyzed using immunohistochemistry methods. All of the HCl treated animals developed ulcers on the skin and mucosa of the oral cavity. Most of the mice on the place of surgical wound developed keloid tissue. Mice in which we induced pathological processes of the oral tissue, did not gain body weight. Moreover their mass had tendency to decrease. Hematoxilyn-eosin staining of the ulcerated mice tissues revealed extended coagulation necrosis - covering all tissue layers of the oral cavity. Strong local inflammatory cell infiltration and absence of proliferative cells has been demonstrated in these ulcerated and adjusted oral tissues. Morphological analysis of scar tissue revealed fibrotic hypertrophy of the injured oral tissues in these animals with the expressed infiltration of inflammatory cells. Our animal models reflect morphology of the specific injury and functionally imitate the disease.

  3. Karyotypic evolution during neoplastic progression in nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Kraemer, P.M.; Campbell, E.W.; Cooper, J.L.; Stallings, R.; Wharton, W.

    1985-01-01

    When tumorigenic cultured cell populations are inoculated into nude mice, the tumorigenic process generally requires further progression and selection in vivo. This in vivo progression should be reflected in the altered properties of the tumor cells, as compared to the cells implanted. Karyotypic instability was studied during this process. 6 refs., 5 figs.

  4. Monitoring Pc 4-mediated photodynamic therapy of U87 tumors with dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) in the athymic nude rat

    Science.gov (United States)

    Varghai, Davood; Covey, Kelly; Sharma, Rahul; Cross, Nathan; Feyes, Denise K.; Oleinick, Nancy L.; Flask, Chris A.; Dean, David

    2008-02-01

    Post-operative verification of the specificity and sensitivity of photodynamic therapy (PDT) is most pressing for deeply placed lesions such as brain tumors. We wish to determine whether Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) can provide a non-invasive and unambiguous quantitative measure of the specificity and sensitivity of brain tumor PDT. Methods: 2.5 x 10 5 U87 cells were injected into the brains of six athymic nude rats. After 5-6 days, the animals received 0.5 mg/kg b.w. of the phthalocyanine photosensitizer Pc 4 via tail-vein injection. On day 7 peri-tumor DCE-MRI images were acquired on a 7T microMRI scanner before and after tail-vein administration of 100 μL gadolinium and 400 μL saline. After this scan the animals received a 30 J/cm2 dose of 672-nm light from a diode laser (i.e., PDT). The DCE-MRI scan protocol was repeated on day 13. Next, the animals were euthanized and their brains were explanted for Hematoxylin and Eosin (H&E) histology. Results: No tumor was found in one animal. The DCE-MRI images of the other five animals demonstrated significant tumor enhancement increase (p tumor necrosis. Discussion: The change in signal detected by DCE-MRI appears to be due to PDT-induced tumor necrosis. This DCE-MRI signal appears to provide a quantitative, non-invasive measure of the outcome of PDT in this animal model and may be useful for determining the safety and effectiveness of PDT in deeply placed tumors (e.g., glioma).

  5. Analysis of 18F-fluorodeoxy-glucose PET imaging data captured before and after Pc 4-mediated photodynamic therapy of U87 tumors in the athymic nude rat

    Science.gov (United States)

    Cross, Nathan; Varghai, Davood; Spring-Robinson, Chandra; Sharma, Rahul; Muzic, Raymond F., Jr.; Oleinick, Nancy L.; Dean, D.

    2007-02-01

    Introduction: Several workers have proposed the use of PET (Positron Emission Tomography) imaging for the outcome assessment of photodynamic therapy (PDT), especially for deep-seated tumors. We report on our study of 18Ffluorodeoxy- glucose (18F-FDG) PET imaging following brain tumor Pc4-PDT. Our working hypothesis was that the tumor's metabolic activity would decline dramatically following Pc 4-PDT owing to tumor necrosis. Methods: Seven days after intraparenchymal implantation of U87 cells, the brains of 12 athymic nude rats were imaged by micro-CT and/or micro-MR. These animals were also 18F-FDG micro-PET (μPET) scanned before and after Pc 4-PDT. 18F-FDG was used to trace metabolic activity that was monitored via μPET. Occurrence of PDT was confirmed on histology. The analysis of 18F-FDG dose and animal weight normalized μPET activity was studied over the 90 minute µPET scan. Results: Currently, μPET data have been studied for: (1) three of the animals that did not indicate tumor necrosis on histology and were assigned to a "Non-PDT" group, and (2) six animals that exhibited tumor necrosis on histology and were assigned to a "PDT" group. The μPET-detected 18F-FDG uptake activity in the tumor region before and after photoirradiation increased in the Non-PDT group an average of 2.28 times, and in the PDT group it increased an average of 1.15 times. Discussion: We are investigating the cause of the increase in 18F-FDG μPET activity that we observed in the PDT group. The methodology used in this study should be useful in determining whether this or other PET, SPECT, or MR functional imaging protocols will detect both the specificity and sensitivity of brain tumor necrosis following Pc 4-PDT.

  6. Human Islet Oxygen Consumption Rate and DNA Measurements Predict Diabetes Reversal in Nude Mice

    OpenAIRE

    Papas, K.K.; Colton, C. K.; Nelson, R. A.; Rozak, P.R.; Avgoustiniatos, E.S.; Scott, W. E.; Wildey, G. M.; Pisania, A.; Weir, G. C.; Hering, B. J.

    2007-01-01

    There is a need for simple, quantitative and prospective assays for islet quality assessment that are predictive of islet transplantation outcome. The current state-of-the-art athymic nude mouse bioassay is costly, technically challenging and retrospective. In this study, we report on the ability of 2 parameters characterizing human islet quality: (1) oxygen consumption rate (OCR), a measure of viable volume; and (2) OCR/DNA, a measure of fractional viability, to predict diabetes reversal in ...

  7. Spontaneous Hymenolepis nana infection in a breeding colony of nude mice.

    Science.gov (United States)

    Hauff, P; Arnold, W

    1990-01-01

    The spontaneous occurrence of a parasitic infection with the dwarf tapeworm Hymenolepis nana is nude mice was observed under conventional conditions. Clinical, pathological and histological observations are described.

  8. Photodynamic therapy with the phthalocyanine photosensitizer Pc 4 of SW480 human colon cancer xenografts in athymic mice.

    Science.gov (United States)

    Whitacre, C M; Feyes, D K; Satoh, T; Grossmann, J; Mulvihill, J W; Mukhtar, H; Oleinick, N L

    2000-05-01

    Photodynamic therapy (PDT) using the silicon phthalocyanine photosensitizer Pc 4 [HOSiPcOSi(CH3)2(CH2)3N-(CH3)2] is an oxidative stress associated with induction of apoptosis in various cell types. We assessed the effectiveness of Pc 4-PDT on SW480 colon cancer xenografts grown in athymic nude mice. Animals bearing xenografts were treated with 1 mg/kg body weight Pc 4 and 48 h later were irradiated with 150 J/cm2 672-nm light from a diode laser delivered at 150 mW/cm2. Biochemical studies were performed in xenografts resected at various time points up to 26 h after Pc 4-PDT treatment, whereas tumor size was evaluated over a 4-week period in parallel experiments. In the tumors resected for biochemical studies, apoptosis was visualized by activation of caspase-9 and caspase-3 and a gradual increase in the cleavage of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) to a maximum of approximately 60% of the total PARP present at approximately 26 h. At that time all Pc 4-PDT-treated tumors had regressed significantly. Two signaling responses that have previously been shown to be associated with Pc 4-PDT-induced apoptosis in cultured cells, p38 mitogen-activated protein kinase and p21/WAF1/Cip1, were examined. A marked increase in phosphorylation of p38 was observed within 1 h after Pc 4-PDT without changes in levels of the p38 protein. Levels of p21 were not altered in the xenografts in correspondence with the presence of mutant p53 in SW480 cells. Evaluation of tumor size showed that tumor growth resumed after a delay of 9-15 days. Our results suggest that: (a) Pc 4-PDT is effective in the treatment of SW480 human colon cancer xenografts independent of p53 status; (b) PARP cleavage may be mediated by caspase-9 and caspase-3 activation in the Pc 4-PDT-treated tumors; and (c) p38 phosphorylation may be a trigger of apoptosis in response to PDT in vivo in this tumor model.

  9. Photodynamic therapy of human squamous cell carcinoma in vitro and in xenografts in nude mice.

    Science.gov (United States)

    Megerian, C A; Zaidi, S I; Sprecher, R C; Setrakian, S; Stepnick, D W; Oleinick, N L; Mukhtar, H

    1993-09-01

    Photodynamic therapy (PDT) of cancer is an experimental tumor therapy which is based on the combined use of a systematically administered photosensitizer to a tumor-bearing host and local illumination of the lesion by a high-intensity visible light source, typically a tunable argon dye laser. Human squamous cell carcinoma (HSCC) is the most frequently encountered malignancy of the head and neck. In this study, responses of HSCC cells to PDT were examined in in vitro and in vivo systems. In in vitro studies, the HSCC cells showed a positive photodynamic response with Photofrin-II (Pf-II), chloroaluminum phthalocyanine tetrasulfonate (AlPcTS), and a newly synthesized silicon phthalocyanine (SiPc IV). Single cell suspension of HSCC injected subcutaneously on the back of athymic nude mice resulted in a well-circumscribed tumor mass. The animals required a low tumor dose for the successful establishment of a tumor. The tumor was minimally immunogenic and showed neither macroscopic signs of early metastasis to lung, kidney, liver, or spleen nor evidence of surrounding erythema, fluctuation, or tenderness until the late stages of necrosis. Intraperitoneal administration of AlPcTS or SiPc IV to tumor-bearing mice resulted in rapid uptake of the photosensitizers in liver, skin, and tumor tissue. Twenty-four hours following the intraperitoneal administration of AlPcTS or SiPc IV to tumor-bearing animals, the tumor to normal skin ratio of the photosensitizer was 1.6 or 1.5, respectively. Administration of Pf-II (5 mg/kg) to tumor-bearing animals followed 24 hours later by irradiation of the tumor (135 J/cm2, 630 nm light from an argon pumped-dye laser) resulted in greater than 80% ablation in tumor volume 24 hours post-PDT. These characteristics make this tumor model system suitable for PDT studies of human tumor cells in vitro as well as in vivo.

  10. Targeted radiotherapy with {sup 177} Lu-DOTA-TATE in athymic mice with induced pancreatic malignant tumours

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez C, J.; Murphy, C.A. de; Pedraza L, M. [Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, 14000 Mexico D.F. (Mexico); Ferro F, G. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico); Murphy S, E. [Hospital Santelena, 06000 Mexico D.F. (Mexico)

    2006-07-01

    Malignant pancreas tumours induced in athymic mice are a good model for peptide receptor targeted radiotherapy. The objective of this research was to estimate pancreatic tumour absorbed radiation doses after administration of {sup 177}Lu-DOTA-TATE in mice as a therapeutic radiopharmaceutical that could be used in humans. AR42J murine pancreas cancer cells expressing somatostatin receptors, were implanted in athymic mice (n=18) to obtain the {sup 177}Lu-DOTA-TATE biokinetics and dosimetry. To estimate its therapeutic efficacy 87 MBq were injected in a tail vein of 3 mice and 19 days p.i. there were a partial relapse. There was an epithelial and sarcoma mixed tumour in the kidneys of mouse III. The absorbed dose to tumour, kidney and pancreas was 50.5 {+-} 7.2 Gy, 17.5 {+-} 2.5 Gy and 12.6 {+-} 2.3 Gy respectively. These studies justify further therapeutic and dosimetry estimations to ensure that {sup 177}Lu-DOTA-TATE will act as expected in man considering its kidney radiotoxicity. (Author)

  11. Survivin ASODN targeted therapy in XWLC-05 cell transplanted nude mice

    Institute of Scientific and Technical Information of China (English)

    Weiwei Wang; Shaojia Wang; Gaofeng Li; Lei Li; Ruibing Cheng

    2012-01-01

    Objective: The aim of this study was to study the inhibiting effect of survivin mRNA on transplanted XWLC-05 tumor on nude mice. Methods: We established XWLC-05 transplanted nude mice model. 44 mice would be divided randomly into 4 groups: control group (blank), Lip group (simple liposome), survivin SODN group (transfected by sense oligonudeotide) and survivin ASODN group (transfected by antisense oligonudeotide). We would study general activities of nude mice in these 4 groups, measure the size of tumor and calculate the tumor inhabiting rate also. Pathological methods were applied in the analysis of the effect of different treatment on heart, kidney and liver of nude mice in these 4 groups. Results: Tumor grew slowly and size, weight of tumor was lower in survivin ASODN group when compared with that of others. Nude mice of survivin ASODN group showed lower growth index and tumor inhabiting rate was significantly higher than that of other groups (P 0.05). We found a great deal of tumor cell necrosis in survivin ASODN group. No death of nude mice was observed in all 4 groups and we did not found obvious lesion in vital organs. Conclusion: Survivin ASDON could be used for the inhibition of subcutaneously transplanted tumor in nude mice without obvious lesion in vital organs.

  12. Targeted radiotherapy with {sup 177} Lu-DOTA-TATE in athymic mice with induced pancreatic malignant tumours

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, M. A de; Pedraza L, M. [Department of Nuclear Medicine, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico D.F. (Mexico); Rodriguez C, J. [Faculty of Medicine, UAEM, Toluca, Estado de Mexico (Mexico); Ferro F, G. [ININ, 52045 Estado de Mexico (Mexico); Murphy S, E. [Hospital Santelena, Mexico D.F. (Mexico)

    2006-07-01

    Malignant pancreas tumours induced in athymic mice are a good model for targeted radiotherapy. The objective of this research was to estimate pancreatic tumour absorbed radiation doses and to evaluate {sup 177}Lu-DOTA-TATE as a therapeutic radiopharmaceutical that could be used in humans. AR42J murine pancreas cancer cells, which over-express somatostatin receptors, were injected in athymic mice and 20 days later the mean tumour size was 3.08 square cm (n=3). A mean of 86.3 MBq {sup 177}Lu-DOTA-TATE, was injected in a tail vein and 19 days after therapy the size of the tumours was 0.81 square cm. There was a partial relapse and after 16 days, when sacrificed, the mean tumour size was 8.28 cubic cm. An epithelial and sarcoma mixed tumour in the kidney of one treated mouse was found. The tumour of the control mouse was 8.61 cubic cm when sacrificed 14 days after tumour induction. Radiotherapy estimates to the tumours was 35.9-39.7 Gy and the tumours might have been completely reduced with a second therapy dose. These preliminary studies justify further therapeutic and dosimetry estimations to ensure that Lu-{sup 177}-DOTA-TATE will act as expected in man, considering kidney radiation. (Author)

  13. Methylseleninic acid restricts tumor growth in nude mice model of metastatic breast cancer probably via inhibiting angiopoietin-2

    Directory of Open Access Journals (Sweden)

    Wu Xiaojing

    2012-05-01

    Full Text Available Abstract Background Angiopoietin-2 (Ang-2 plays critical roles in vascular morphogenesis and its upregulation is frequently associated with various tumors. Previous studies showed that certain selenium compounds possess anti-tumor effects. However, the underlining mechanism has not been elucidated in detail. Plus, results of research on the anti-tumor effects of selenium compounds remain controversial. Methods We investigated levels of Ang-2 and vascular endothelial growth factor (VEGF on the estrogen-independent bone metastatic mammary cancer (MDA-MB-231 cells in response to treatment by methylseleninic acid (MSeA, and further examined the effects of MSeA oral administration on xenograft mammary tumors of athymic nude mice by RT-PCR, Western, radioimmuno assay, and Immunohistochemistry. Results Treatment of MDA-MB-231 cells with MSeA caused significant reduction of Ang-2 mRNA transcripts and secretion of Ang-2 proteins by the cells. Level of VEGF protein was accordingly decreased following the treatment. Compared with the controls, oral administration of MSeA (3 mg/kg/day for 18 days to the nude mice carrying MDA-MB-231 induced tumors resulted in significant reduction in xenograft tumor volume and weights, significant decrease in microvascular density, and promotion of vascular normalization by increasing pericytes coverage. As expected, level of VEGF was also decreased in MSeA treated tumors. Conclusions Our results point out that MSeA exerts its anti-tumor effects, at least in part, by inhibiting the Ang-2/Tie2 pathway, probably via inhibiting VEGF.

  14. Experimental infection of Balb/c nude mice with Hepatitis E virus

    Directory of Open Access Journals (Sweden)

    Zhu Jianguo

    2009-06-01

    Full Text Available Abstract Background Several animal species can reportedly act as reservoirs for Hepatitis E virus (HEV, a zoonotic pathogen. HEV and antibody to the virus have been detected in a variety of animals including rodents. Pig and rat models for HEV have been established for HEV, but a nude mouse has not yet been developed. Methods Balb/c nude mice were inoculated with swine HEV, both orally and via intravenous injection to insure infection. Negative control and experimental contact-exposed groups of mice were also included in the study. The liver, spleen, kidney, jejunum, ileum, cecum and colon of each mouse from all three groups were collected for reverse transcription nested polymerase chain reaction (RT-nPCR detection, indirect immunofluorescence observation and histopathologic examination. The sera from nude mice were tested for anti-HEV IgG by enzyme linked immunosorbent assay (ELISA. Activities of liver enzymes, including alanine aminotransferase (ALT, aspartate aminotransferase (AST and alkaline phosphatase (ALP, as well as total bilirubin (TBIL were also measured in the sera of the nude mice. Results HEV antigens and HEV RNA were detected in liver, spleen, kidney, jejunum, ileum and colon both by indirect immunofluorescence and by RT-nPCR in all of the inoculated and in one of the contact-exposed nude mice. Histopathological changes were observed in the liver and spleen of these mice. Infected mice showed increased levels of AST, ALP, and anti-HEV IgG in sera. The livers of contact-exposed mice showed obvious histopathological damage. Conclusion Nude mice could be readily infected by HEV isolated from pigs. The nude mouse may therefore be a useful animal model for studying the pathogenesis of HEV.

  15. Fractionated irradiation combined with carbogen breathing and nicotinamide of two human glioblastomas grafted in nude mice

    OpenAIRE

    Sun, Lin-Quan; Buchegger, Franz; Coucke, Philippe; MIRIMANOFF

    2001-01-01

    This study addressed the potential radiosensitizing effect of nicotinamide and/or carbogen on human glioblastoma xenografts in nude mice. U-87MG and LN-Z308 tumors were irradiated with either 20 fractions over 12 days or 5 fractions over 5 days in air-breathing mice, mice injected with nicotinamide, mice breathing carbogen, or mice receiving nicotinamide plus carbogen. The responses to treatment were assessed using local control and moist desquamation. In U-87MG tumors, the enhancement ratios...

  16. [Effects of baicalin on HL-60 cell xenografts in nude mice and its mechanism].

    Science.gov (United States)

    Zheng, Jing; Hu, Jian-Da; Huang, Yi; Chen, Ying-Yu; Li, Jing; Chen, Bu-Yuan

    2012-10-01

    This study was aimed to investigate the effects of baicalin on HL-60 cell xenografts in nude mice in vivo and explore its mechanism. Xenograft tumor model of HL-60 cells in nude mice was established, which was divided randomly into 6 groups: negative control group (injection of 5% NaHCO(3)), 25, 50 and 100 mg/kg baicalin groups, combination group (50 mg/kg baicalin + 2 mg/kg VP16) and positive control group (VP16 4 mg/kg). The nude mice with HL-60 cell xenografts were treated with drugs via intraperitoneal injection daily. After treatment for 14 days average weigh and inhibitory rate of transplanted tumor stripped from 5 nude mice in each group were calculated, and the ultrastructure change of xenografts cells were tested by transmission electron microscopy. Histopathologic examination was used to observed the change of main organs in nude mice. The expression of signaling molecular PI3K/Akt proteins extracted from xenografts was detected by Western blot. The effects of baicalin on overall survival time in nude mice with HL-60 cell xenografts were evaluated. The results showed that baicalin could inhibit the growth of transplanted tumors in dose-dependent manner. There were more necrotic and apoptotic cells in mice of baicalin-treated groups and combination group than that in mice of negative control group. Baicalin could inhibit the proliferation of HL-60 cells in vivo by down-regulating the PI3K/Akt/mTOR signal pathway, where the expressions of p-Akt, mTOR and p-mTOR proteins decreased compared with negative control group, and no significant difference of Akt expression was found between different groups. Compared with negative control group, the median survival time of mice in combination group was more prolongated (P HL-60 cell xenografts in nude mice, and prolong median survival time of nude mice. The possible mechanisms may be related to inhibition of Akt activity and down-regulation of the PI3K/Akt/mTOR signal pathway. The combination of baicalin and VP16

  17. Anti-tumorigenic and Pro-apoptotic effects of CKBM on gastric cancer growth in nude mice

    Directory of Open Access Journals (Sweden)

    2004-08-01

    Full Text Available Natural botanical products can be integrated with western medicine to optimize the treatment outcome, increase immune function and minimize the side effects from western drug treatment. CKBM is a combination of herbs and yeasts formulated based on traditional Chinese medicinal principles. Previous study has demonstrated that CKBM is capable of improving immune responsiveness through the induction of cytokine mediators, such as TNF-α and IL-6. In this study, we aimed to investigate the effect of this immunomodulatory drug on gastric cancer growth using a human xenograft model. Gastric cancer tissues were implanted subcutaneously into athymic nude mice followed by a 14-day or 28-day of CKBM treatment. Results showed that higher doses of CKBM (0.4 or 0.8 ml/mouse/day produced a dose-dependent inhibitory effect on gastric tumor growth after 28-day drug treatment. This was associated with a decrease of cellular proliferation by 30% with concomitant increase in apoptosis by 97% in gastric tumor cells when compared with the control group. In contrast, CKBM showed no effect on angiogenesis in gastric tumors. This study demonstrates the anti-tumorigenic action of CKBM on gastric cancer probably via inhibition of cell proliferation and induction of apoptosis, and provides future potential targets of this drug candidate on cancer therapy.

  18. Reduction of burn scar formation by halofuginone-eluting silicone gel sheets: a controlled study on nude mice.

    Science.gov (United States)

    Zeplin, Philip H

    2012-03-01

    Burn scar formations can cause disfiguration and loss of dermal function. The purpose of this study was to examine whether application of modified silicone gel sheets with an antifibrotic drug halofuginone-eluting hybrid surface produce an effect on scar development. There were a total of 2 animal groups. The athymic nude mice (nu/nu) of both groups underwent transplantation of full-thickness human skin grafts onto their backs and setting of partial thickness burn injury. The status of local scar development was observed over a period of 3 months after the application of silicone gel sheets and also after application of surface-modified halofuginone-eluting silicone gel sheets. Subsequently, via real-time polymerase chain reaction, the cDNA levels from key mediators of scar formation (transforming growth factor beta, COL1A1, connective tissue growth factor, fibroblast growth factor 2, matrix metalloproteinase 2, matrix metalloproteinase 9) were established and statistically evaluated. In comparison with uncoated silicone gel sheets, the application of halofuginone-eluting silicone gel sheets lead to a significant difference in gene expression activity in scar tissue. Halofuginone-eluting hybrid surface silicone gel sheets significantly increase the antiscarring effect of adhesive silicone gel sheets by deceleration and downregulation of scar development by normalization of the expression activity.

  19. LACK OF HETEROTRANSPLANTATION OF MAREK'S DISEASE LYMPHOMA-DERIVED CELL LINES AND MD LYMPHOMA CELLS TO NUDE MICE

    OpenAIRE

    1980-01-01

    Nude mice of BALB/c background were used for the heterotransplantation of Marek's Disease (MD) lymphoma-derived cell lines (MDCC-MSB 1,MDCC-RP 1 and MDCC-JP 2) or MD lymphoma developed in a Marek's disease virus-inoculated chicken. None out of the 57 nude mice developed tumors at the site of inoculation. These nude mice formed cytotoxic antibody against MD lymphoma-derived line cells 6-14 weeks after inoculation. The lack of heterotransplantation of cells from avian origin into nude mice is d...

  20. Alpinia pricei Rhizome Extracts Induce Cell Cycle Arrest in Human Squamous Carcinoma KB Cells and Suppress Tumor Growth in Nude Mice

    Directory of Open Access Journals (Sweden)

    You-Cheng Hseu

    2011-01-01

    Full Text Available Alpinia pricei has been shown to induce apoptosis in human squamous carcinoma (KB cells. In this study, we report the effectiveness of the ethanol (70% extracts of A. pricei rhizome (AP extracts in terms of tumor regression as determined using both in vitro cell culture and in vivo athymic nude mice models of KB cells. We found that the AP extract (25–200 μg/mL treatment decreased the proliferation of KB cells by arresting progression through the G2/M phase of the cell cycle. This cell cycle blockade was associated with reductions in cyclin A and B1, Cdc2, and Cdc25C, and increased p21/WAF1, Wee1, p53 and phospho-p53 (p-p53 in a dose- and time-dependent manner. Moreover, we found that AP extract treatment decreased metalloproteinase-9 (MMP-9 and urokinase plasminogen activator (u-PA expression, while expression of their endogenous inhibitors, tissue inhibitor of MMP-1 (TIMP-1 and plasminogen activator inhibitor-1 (PAI-1, were increased in KB cells. Furthermore, AP extract treatment effectively delayed tumor incidence in nude mice inoculated with KB cells and reduced the tumor burden. AP extract treatment also induced apoptotic DNA fragmentation, as detected by in situ TUNEL staining. Thus, A. pricei may possess antitumor activity in human squamous carcinoma (KB cells.

  1. LY293111 Improves Efficacy of Gemcitabine Therapy on Pancreatic Cancer in a Fluorescent Orthotopic Model in Athymic Mice

    Directory of Open Access Journals (Sweden)

    Rene Hennig

    2005-04-01

    Full Text Available Pancreatic cancer has an abysmal prognosis because of late diagnosis and lack of effective therapeutics. New drugs are desperately needed. The present study determined the effect of the LTB4 receptor antagonist, LY293111, on tumor growth and metastases in a fluorescent orthotopic model of pancreatic cancer. Pancreatic cancer cells (S2-013 with stable expression of enhanced green fluorescent protein were implanted into the duodenal pancreatic lobe of athymic mice. Animals were allocated to four groups (eight mice per group: control (no treatment; LY293111; gemcitabine; and LY293111 + gemcitabine. Monitoring of the surgical procedure and follow-up examinations at 2, 3, and 4 weeks after implantation to monitor tumor growth and metastases were performed using a fluorescence microscope and the reversible skin-flap technique. A staging and scoring system was developed to evaluate tumor progression, based on the TNM classification. Control animals developed end-stage disease with invasive cancer, metastases, and cachexia. Tumor growth and incidence of metastases were significantly reduced in all treated mice. However, combined treatment with LY293111 and gemcitabine was most effective. LY293111 is a novel therapeutic agent for pancreatic cancer, which improves the efficacy of gemcitabine. It is well tolerated and can be administered orally and, therefore, provides a new hope for patients suffering from pancreatic adenocarcinoma.

  2. Cytolytic T lymphocyte precursor cells in congenitally athymic C57BL/6 nu/nu mice: quantitation, enrichment, and specificity.

    Science.gov (United States)

    Maryanski, J L; MacDonald, H R; Sordat, B; Cerottini, J C

    1981-03-01

    A sensitive limiting dilution microculture system was used to obtain minimal estimates of the frequency of CTL precursor cells (CTL-P) in spleens from 5- to 14-mo-old C57BL/6 nu/nu mice. Frequency determinations of CTL-P directed against H-2d alloantigens ranged from 1/159,000 to 1/12,400. The relatively low frequency of CTL-P was enriched nearly 10-fold (to 1/2300) by passage of nude spleen cells over a column of nylon wool. After priming nude spleen cells for 7 days in conventional MLC, 1 to 3% of the MLC cells could be operationally identified as CTL-P. Furthermore, the progeny of MLC-primed nude CTL-P were specifically cytolytic for target cells of the strain used for priming. Such a system may be useful for analyzing the specificity repertoires of cells of the T cell lineage that have not undergone thymic influence.

  3. Regulation of Leishmania (L.) amazonensis protein expression by host T cell dependent responses: differential expression of oligopeptidase B, tryparedoxin peroxidase and HSP70 isoforms in amastigotes isolated from BALB/c and BALB/c nude mice.

    Science.gov (United States)

    Teixeira, Priscila Camillo; Velasquez, Leonardo Garcia; Lepique, Ana Paula; de Rezende, Eloiza; Bonatto, José Matheus Camargo; Barcinski, Marcello Andre; Cunha-Neto, Edecio; Stolf, Beatriz Simonsen

    2015-02-01

    Leishmaniasis is an important disease that affects 12 million people in 88 countries, with 2 million new cases every year. Leishmania amazonensis is an important agent in Brazil, leading to clinical forms varying from localized (LCL) to diffuse cutaneous leishmaniasis (DCL). One interesting issue rarely analyzed is how host immune response affects Leishmania phenotype and virulence. Aiming to study the effect of host immune system on Leishmania proteins we compared proteomes of amastigotes isolated from BALB/c and BALB/c nude mice. The athymic nude mice may resemble patients with diffuse cutaneous leishmaniasis, considered T-cell hyposensitive or anergic to Leishmania's antigens. This work is the first to compare modifications in amastigotes' proteomes driven by host immune response. Among the 44 differentially expressed spots, there were proteins related to oxidative/nitrosative stress and proteases. Some correspond to known Leishmania virulence factors such as OPB and tryparedoxin peroxidase. Specific isoforms of these two proteins were increased in parasites from nude mice, suggesting that T cells probably restrain their posttranslational modifications in BALB/c mice. On the other hand, an isoform of HSP70 was increased in amastigotes from BALB/c mice. We believe our study may allow identification of potential virulence factors and ways of regulating their expression.

  4. Detection of PIVKA II produced by human hepatoma cells in nude mice.

    Science.gov (United States)

    Kohda, H; Ono, M; Sekiya, C; Ohta, H; Ohhira, M; Ohhira, M; Yoshida, Y; Ikeda, N; Namiki, M

    1991-03-01

    A novel experimental nude mouse model, which is useful for investigation of the mechanisms of PIVKA II synthesis, was established by inoculation with PIVKA II-producing human hepatoma cells (huH-1). We have found markedly elevated levels of PIVKA II in the plasma of nude mice transplanted with huH-1 cells and increased PIVKA II content in huH-1 tumor tissues. Whereas we have not found detectable level of PIVKA II neither in the plasma nor in tumor tissues of nude mice transplanted different human hepatoma cells (HLF) which is not producing PIVKA II. Histology of the tumor tissues produced by huH-1 cells revealed a thick trabecular pattern with blood spaces.

  5. STUDY ON NUDE MICE INOCULATED WITH MYCOBACTERIUM LEPRAE BY MULTIPLE ROUTES

    Institute of Scientific and Technical Information of China (English)

    王荷英; 张伟云; 喻林冲; 施美琴; 刘季和

    1995-01-01

    Immune-defieient nude mice were inoculated with nude mouse derived Mycobacterium leprae by multiple routes (intravenously, subcutaneously at the foot pads and ears). The results showed that these inoculated animals were capable of producing a great number of Mycohecteritma leprae to a level 1011-12 per gram of tissue, and were detected histopathologically to have heavy lepromatous lesions. The dissemination of the infeetion was found particulerly in sites with lower body temperature. The ccgaulsms have a partiality to striated muscles and peripheral nerves. The authors suggest that experimental lepeosy in nude mice is a very useful tool for leprosy resarch, especially Jn cotmtries without armadillos. Compared with the single-route inoculation reported previously, multiple-route inoculation is more available.

  6. Comparative Hair Restorer Efficacy of Medicinal Herb on Nude (Foxn1nu Mice

    Directory of Open Access Journals (Sweden)

    Shahnaz Begum

    2014-01-01

    Full Text Available Eclipta alba (L. Hassk, Asiasarum sieboldii (Miq. F. Maek (Asiasari radix, and Panax ginseng C. A. Mey (red ginseng are traditionally acclaimed for therapeutic properties of various human ailments. Synergistic effect of each standardized plant extract was investigated for hair growth potential on nude mice, as these mutant mice genetically lack hair due to abnormal keratinization. Dried plant samples were ground and extracted by methanol. Topical application was performed on the back of nude mice daily up to completion of two hair growth generations. The hair density and length of Eclipta alba treated mice were increased significantly P>0.001 than control mice. Hair growth area was also distinctly visible in Eclipta alba treated mice. On the other hand, Asiasari radix and Panax ginseng treated mice developing hair loss were recognized from the abortive boundaries of hair coverage. Histomorphometric observation of nude mice skin samples revealed an increase in number of hair follicles (HFs. The presence of follicular keratinocytes was confirmed by BrdU labeling, S-phase cells in HFs. Therefore, Eclipta alba extract and/or phytochemicals strongly displayed incomparability of hair growth promotion activity than others. Thus, the standardized Eclipta alba extract can be used as an effective, alternative, and complementary treatment against hair loss.

  7. TRIP-Br2 promotes oncogenesis in nude mice and is frequently overexpressed in multiple human tumors

    Directory of Open Access Journals (Sweden)

    Peh Bee

    2009-01-01

    Full Text Available Abstract Background Members of the TRIP-Br/SERTAD family of mammalian transcriptional coregulators have recently been implicated in E2F-mediated cell cycle progression and tumorigenesis. We, herein, focus on the detailed functional characterization of the least understood member of the TRIP-Br/SERTAD protein family, TRIP-Br2 (SERTAD2. Methods Oncogenic potential of TRIP-Br2 was demonstrated by (1 inoculation of NIH3T3 fibroblasts, which were engineered to stably overexpress ectopic TRIP-Br2, into athymic nude mice for tumor induction and (2 comprehensive immunohistochemical high-throughput screening of TRIP-Br2 protein expression in multiple human tumor cell lines and human tumor tissue microarrays (TMAs. Clinicopathologic analysis was conducted to assess the potential of TRIP-Br2 as a novel prognostic marker of human cancer. RNA interference of TRIP-Br2 expression in HCT-116 colorectal carcinoma cells was performed to determine the potential of TRIP-Br2 as a novel chemotherapeutic drug target. Results Overexpression of TRIP-Br2 is sufficient to transform murine fibroblasts and promotes tumorigenesis in nude mice. The transformed phenotype is characterized by deregulation of the E2F/DP-transcriptional pathway through upregulation of the key E2F-responsive genes CYCLIN E, CYCLIN A2, CDC6 and DHFR. TRIP-Br2 is frequently overexpressed in both cancer cell lines and multiple human tumors. Clinicopathologic correlation indicates that overexpression of TRIP-Br2 in hepatocellular carcinoma is associated with a worse clinical outcome by Kaplan-Meier survival analysis. Small interfering RNA-mediated (siRNA knockdown of TRIP-Br2 was sufficient to inhibit cell-autonomous growth of HCT-116 cells in vitro. Conclusion This study identifies TRIP-Br2 as a bona-fide protooncogene and supports the potential for TRIP-Br2 as a novel prognostic marker and a chemotherapeutic drug target in human cancer.

  8. Pluripotent Embryonic Stem Cells Developed into Medulloepithelioma in Nude Mice Eyes

    Institute of Scientific and Technical Information of China (English)

    Yongping Li; Xiufeng Zhong; Jianhua Yan; Jianxian Lin; Song Tang; Xuan Wu; Shulong Li; Guanguang Feng; Yuzhen Yi

    2002-01-01

    Purpose: The pluripotent embryonic stem cells can differentiate into various kinds offormal tissues. There is no previous report on the differentiation of embryonic stem cellin the intraocular environment. In this paper, the authors tried to investigate theintraocular growth character of mice embryonic stem cells in nude mice.Methods: Murine embryonic stem cells were cultured and maintained in anundifferentiated state in vitro. They were transplanted into the right eyes of 20 nude miceby microinjection under operating microscope. Animal eye observation, light microscopeand immunohistochemical examinations were implemented.Results: Two to three days after transplantation, small pieces of gray-white materialcould be viewed in the vitreous cavity. Between the 15th and 20th day, the gray-whitemass grew into the anterior chamber in 4 nude mice eyes. Then, the mass at the anteriorchamber extended extraocularly. On the 30th day, a remarkable proptosis was observedin two of the four nude mice. In 6 to 45 days, the mice were executed for morphologicalexamination which showed the following typical structures: (1) Undifferentiated cellswith prominent nucleolius. (2) Flexner-Wintersteiner-like rosettes. (3) Medulloepithe-lioma-like structure: the cells were arranged in sheets, cords, tubes, and cysts. (4) Large,spindle-or astrocyte-like cells. (5) Cartilage-like structure. Immunohistochemically, mostof the cells were highly positive in NSE staining and a few cells were moderately positivein GFAP staining.Conclusions: Both animal eye findings and morphologic examinations certificated thatthe transplanted embryonic stem cells could grow in the eyes of nude mice anddifferentiate into intraocular medulloepithelioma.

  9. Establishment and characterization of human uveal malignant melanoma xenografts in nude mice

    DEFF Research Database (Denmark)

    Heegaard, S; Spang-Thomsen, M; Prause, J U

    2003-01-01

    and electron microscopy. Only one of the eight transplanted primary tumours (13%) was established as a xenograft in nude mice. Furthermore, the take rate of the transplantable tumour was low (13%). The growth of the tumour fitted a Gompertz function, and the calculated tumour volume doubling time was 54 days...

  10. Investigations on hormone dependency of human mammary carcinomas transplanted into nude mice

    DEFF Research Database (Denmark)

    Brünner, N; Spang-Thomsen, M

    1981-01-01

    Since human mammary cancer can be transplanted into nude mice, this makes possible the in vivo study of relations between hormone dependency and the steroid hormone receptor content of the tumors. The macroscopic growth curve of the transplanted tumors during endocrine therapy will reflect the ho...

  11. ATP-ase positive cells in human oral mucosa transplanted to nude mice

    DEFF Research Database (Denmark)

    Dabelsteen, E; Kirkeby, S

    1981-01-01

    A model to study the differentiation of human oral epithelium in vivo utilizing transplantation of human tissue to nude mice has been described. Previous studies have described the epithelial cells in this model. In this study we demonstrate that 8 d after transplantation, Langerhans cells, ident...

  12. The PDZ protein TIP-1 facilitates cell migration and pulmonary metastasis of human invasive breast cancer cells in athymic mice

    Energy Technology Data Exchange (ETDEWEB)

    Han, Miaojun [Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Yunnan (China); Graduate School, Chinese Academy of Sciences, Beijing (China); Department of Radiation Oncology, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States); Wang, Hailun [Department of Radiation Oncology, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States); Zhang, Hua-Tang [Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Yunnan (China); Han, Zhaozhong, E-mail: zhaozhong.han@vanderbilt.edu [Department of Radiation Oncology, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States); Department of Cancer Biology, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States); Vanderbilt-Ingram Cancer Center, School of Medicine, Vanderbilt University, Nashville, TN 37232 (United States)

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer This study has revealed novel oncogenic functions of TIP-1 in human invasive breast cancer. Black-Right-Pointing-Pointer Elevated TIP-1 expression levels in human breast cancers correlate to the disease prognosis. Black-Right-Pointing-Pointer TIP-1 knockdown suppressed the cell migration and pulmonary metastasis of human breast cancer cells. Black-Right-Pointing-Pointer TIP-1 knockdown suppressed the expression and functionality of motility-related genes. -- Abstract: Tax-interacting protein 1 (TIP-1, also known as Tax1bp3) inhibited proliferation of colon cancer cells through antagonizing the transcriptional activity of beta-catenin. However, in this study, elevated TIP-1 expression levels were detected in human invasive breast cancers. Studies with two human invasive breast cancer cell lines indicated that RNAi-mediated TIP-1 knockdown suppressed the cell adhesion, proliferation, migration and invasion in vitro, and inhibited tumor growth in mammary fat pads and pulmonary metastasis in athymic mice. Biochemical studies showed that TIP-1 knockdown had moderate and differential effects on the beta-catenin-regulated gene expression, but remarkably down regulated the genes for cell adhesion and motility in breast cancer cells. The decreased expression of integrins and paxillin was accompanied with reduced cell adhesion and focal adhesion formation on fibronectin-coated surface. In conclusion, this study revealed a novel oncogenic function of TIP-1 suggesting that TIP-1 holds potential as a prognostic biomarker and a therapeutic target in the treatment of human invasive breast cancers.

  13. Expression of phosphatase and tensin homolog deleted on chromosome ten in liver of athymic mice with hepatocellular carcinoma and the effect of Fuzheng Jiedu Decoction

    Institute of Scientific and Technical Information of China (English)

    Li-Rong Yin; Ze-Xiong Chen; Shi-Jun Zhang; Bao-Guo Sun; Yong-Dong Liu; Hong-Zhong Huang

    2008-01-01

    AIM:To explore the expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in liver of athymic mice with hepatocellular carcinoma (HCC) and the effect of Fuzheng Jiedu Decoction (FJD). METHODS: Forty eight male BALB/c athymic mice models were built by Bel-7402 with an indirect method. After 24 h of postoperation, the 48 athymic mice were distributed randomly into 4 groups: A, B, C, D, each group had 12 athymic mice. Group A were were treated by intragastric administration with FT207 (Tegafur) for 4 wk. Group B, C and D were treated by intragastric administration with FJD (complex prescription of Chinese crude drug) that had been delegated into 3 kinds of density as the low, middle, and high for 4 wk. At last,athymic mice were put to death, live time, volume of tumors, exponent of tumors and the tumor metastasis in livers were observed; and PTEN was detected in hepatic tissue, latero-cancer tissue and cancer tissue by immunohistochemistry.RESULTS: Four weeks later, the total survival rate in treatment group (A + B + C) was 50% and higher than the control group (0%) treated by FT207, (P 0.05). Tumor metastasis in livers of the treatment group was less than the controls (Fisher's Exact Test, P = 0.021). Thee result of immunohistochemistry showed that the intensity of PTEN in latero-cancer tissue was the highest, and then the hepatic tissue, the lowest was cancer tissue (Kruskal- Wallis test, .67, P = 0.000). It also showed that the intensity of PTEN in treatment groups (A, B, C) was higher than the control group (D) (F = 5.90,P = 0.002 in hepatic tissue and F = 15.99, P = 0.000 in latero-cancer tissue and .08, P = 0.000 in cancer tissue), and group B is the highest in the treatment groups (P 0.05).CONCLUSION: FJD can prolong the survival time and decrease tumor metastasis in livers of these experimental mice. Mechanisms of FJD healing HCC may partially be explained by enhancing the expression of PTEN in liver.

  14. Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) of photodynamic therapy (PDT) outcome and associated changes in the blood-brain barrier following Pc 4-PDT of glioma in an athymic nude rat model

    Science.gov (United States)

    Belle, Vaijayantee; Anka, Ali; Cross, Nathan; Thompson, Paul; Mott, Eric; Sharma, Rahul; Gray, Kayla; Zhang, Ruozhen; Xu, Yueshuo; Sun, Jiayang; Flask, Chris A.; Oleinick, Nancy L.; Dean, David

    2012-02-01

    Introduction: Dynamic Contrast-Enhanced-Magnetic Resonance Imaging (DCE-MRI) appears to provide an unambiguous means of tracking the outcome of photodynamic therapy (PDT) of brain tumors with the photosensitizer Pc 4. The increase in Gd enhancement observed after Pc 4-PDT may be due to a temporary opening of the blood-brain-barrier which, as noted by others, may offer a therapeutic window. Methods: We injected 2.5 x 105 U87 cells into the brains of 9 athymic nude rats. After 8-9 days peri-tumor DCE-MRI images were acquired on a 7.0 T microMRI scanner before and after the administration of 150 μL Gd. DCE-MRI scans were repeated three times following Pc 4-PDT. Results: The average, normalized peak enhancement in the tumor region, approximately 30-90 seconds after Gd administration, was 1.31 times greater than baseline (0.03 Standard Error [SE]) prior to PDT and was 1.44 (0.02 SE) times baseline in the first Post-PDT scans (Day 11), a statistically significant (p ~ 0.014, N=8) increase over the Pre- PDT scans, and was 1.38 (0.02 SE) times baseline in the second scans (Day 12), also a statistically significant (p ~ 0.008, N=7) increase. Observations were mixed in the third Post-PDT scans (Day 13), averaging 1.29 (0.03 SE) times baseline (p ~ 0.66, N=7). Overall a downward trend in enhancement was observed from the first to the third Post-PDT scans. Discussion: DCE-MRI may provide an unambiguous indication of brain tumor PDT outcome. The initial increase in DCE-MRI signal may correlate with a temporary, PDT-induced opening of the blood-brain-barrier, creating a potential therapeutic window.

  15. Study of primary leiomyosarcoma induced by MNNG in BALB/C nude mice

    Institute of Scientific and Technical Information of China (English)

    Jian Si Zhu; Qi Su; Jian Guo Zhou; Ping Lin Hu; Jin Hua Xu

    2000-01-01

    @@ INTRODUCTION It has been well known that MNNG is one of the strong and multipotential carcinogens that have been frequently reported inducing malignant peptic tumors. We have successfully induced rat and dog gastric adenocarcinomas, squamous cell carcinomas of rat forestomach and gastric leiomyosarcoma of rats since 1979. In order to replicate the model of human gastric carcinoma in rats, large doses of MNNG was administered to BALB/C nude mice, to which human embryonic mucosa had been transplanted. During the experiment, the primary leiomyosarcoma (PLS) of the nude mouse was unexpectedly obtained.

  16. Lidamycin Induces Apoptosis of B-Cell Lymphoma Cells and Inhibits Xenograft Growth in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    Hong Fang; Shenghua Zhang; Qingfang Miao; Dongsheng Xiong; Yongsu Zhen

    2009-01-01

    OBJECTIVE To study the cytotoxicity of Lidamycin (LDM) and its induction of apoptosis in Raji and Daudi cells of B-cell lymphoma, and the inhibition of growth of the lymphoma Raji xenograft in nude mice.METHODS MTT assay was used to observe the inhibition by LDM on the proliferation of the Raji and Daudi cells. Annexin V-FITC/PI double-stain, in combination with flow cytometry (FCM), was used to determine the induction of apoptosis by LDM in Raji cells. The B-cell lymphoma Raji xenograft model in nude mice was set up to detect the in vivo antitumor activity of LDM.RESULTS LDM markedly inhibited the proliferation of the Raji and Daudi cells in vitro, with IC50 values of 7.13×10-11 mol/L and 2.91×10-10 mol/L, respectively. The apoptotic rates of Raji cells were respectively 77.98% and 67.63% at 0.5 nmol/L and 0.25 nmol/L of LDM, indicating an obvious induction of apoptosis in Raji cells. LDM inhibited the formation and growth of human B-cell lymphoma Raji xenograft in nude mice. The inhibition rates of tumor growth were respectively 74.9% and 65.2% in LDM at dosage group of 0.05 mg/kg and 0.025 mg/kg, suggesting an apparent prolongation of survival time in the nude mouse bearing lymphoma.CONCLUSION LDM can effectively induce apoptosis of the B-cell lymphoma cells and inhibit the xenograft growth in nude mice.

  17. Differentiation of Embryonic Stem Cells into Neurons and Retina—like Structure in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    LiYP; GeJ

    1999-01-01

    Purpose:To investigate the intraocular growth and biological characteristics of mice embryonic stem cells in nude mice.Methods:Murine embryonic stem cells(D3 cell line)were cultured and maintained in an undifferentiated state in vitro,then transplanted into the anterior chamber of nude mice.Mophological and immunohistochemical examinations were implemented.Results:Two to three days after transplantation,yellow-white floating granules,sheets and masses were seen inside the anterior chamber and vitreous cavity,and enlarged gradually,14-20days later,the mice were executed.Morphological examination showed that there were undifferentiated cells and some round or polygonal differentiated cells in anterior chamber and vitreous cavity.The morphology of these differentiated cells were similar to that of the retina.The cells were highly positive in NSE staining.Conclusion:The tranplanted embryonic stem cells cold grow in the eyes of nude mice with tendency to differentiate into neurons and retina-like structure.

  18. Serum steroid levels in intact and endocrine ablated BALB/c nude mice and their intact littermates

    DEFF Research Database (Denmark)

    Brünner, N; Svenstrup, B; Spang-Thomsen, M;

    1986-01-01

    An investigation was made of the serum steroid levels found in intact and endocrine ablated nude mice of both sexes and in their intact homozygous littermates. The results showed that nude mice have a normal steroidogenesis, but with decreased levels of circulating steroids compared to those...... of the littermates. The efficacy of the endocrine ablations was confirmed by the reduction in serum oestrone following oophorectomy, and by the reduction in serum testosterone and progesterone following orchiectomy. The normal steroidogenesis in nude mice, and the similarities between mouse and man with regard...

  19. Tumorigenicity, Motility and Liver Metastasis of Human Gastric Carcinoma Lines with High Metastatic Potential in the Liver of Nude Mice

    OpenAIRE

    1995-01-01

    To analyze the human gastric carcinoma metastasis to the liver, a human gastric carcinoma line, AZ521 was injected into the spleens of nude mice. Cells from the few liver metastatic foci of injected AZ521 were expanded in vitro and subsequently injected into the spleens of nude mice. By repeating these proce-dures five times, we were able to obtain a cell line, designated AZ-H5c, with high metastatic potential in nude mice. It was observed that animals had liver metastasis in 10 of 12 (83%) c...

  20. Radionecrosis skin model induced an athymic mouse nude (Nu/Nu) for development of dermal-epidermal human substitute based regenerative therapy; Modelo de radionecrose cutanea induzida em camundongos Nude (Nu/Nu) para desenvolvimento de terapias regenerativas baseadas em substitutos dermo-epidermicos humanos

    Energy Technology Data Exchange (ETDEWEB)

    Mosca, Rodrigo Crespo

    2014-07-01

    The neoplasms incidence has increased significantly in recent years and continued population growth and aging will increase the statistics of this illness in the world's diseases. The cancer treatment usually consists in individual or combined use of chemotherapy, surgery and radiotherapy depending on the etiology of the tumor. In cases where radiotherapy is used in addition to the therapeutic effects of radiation, specific complications can occur, and in the skin, these complications can be present with a clinical expression ranging from erythema to radionecrosis, and this latter being the adverse effect with greater severity. The radionecrosis treatment consists in debridement necrotic areas and covering the surgical wounds. Autologous grafts are most commonly used for this covering, however when large areas are affected, allografts can be used for occlusive treatment and the keratinocytes and adipose derived stem cells (ADSC) addition becomes an alternative, due to the knowing for immunomodulatory and regenerative response. For that reason, aiming to simulate the radionecrosis adverse effects, an animal model of induced cutaneous radionecrosis was created, in athymic mouse Nude (Nu/Nu), for developing regenerative therapies based on human dermal-epidermal substitutes containing keratinocytes and ADSC, which proved occlusive as an efficient treatment, furthermore, having this radionecrosis animal model established, new possibilities for treatment of diseases involving dermal regeneration, can be tested. (author)

  1. Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential

    Institute of Scientific and Technical Information of China (English)

    Zhao-You Tang; Lun-Xiu Qin; Hui-Chuan Sun; Lu Wang; Jian Zhou; Yah Li; Zeng-Chen Ma; Xin-Da Zhou; Zhi-Quan Wu; Zhi-Ying Lin; Bing-Hui Yang; Fan-Xian Sun; Jian Tian; Sheng-Long Ye; Yin-Kun Liu; Kang-Da Liu; Qiong Xue; Jie Chen; Jing-Lin Xia

    2001-01-01

    Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient like metastatic model of human HCC in nude mice (LCI-D20)and a Iow metastatic model of human HCC in nude mice LCI-D35 ) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metastasis to liver, lungs, lymph nodes and peritoneal seeding.Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-Iincreased gradually following tumor progression in LCID20 model, and correlated with tumor size and AFP level,Phasic expression of tissue intercellular adhesion molecule-I in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including antiangiogenesis, antisense approach, metalloproteinase inhibitor, differentiation inducer, etc. It is concluded that the establishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vivo and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence.``

  2. ATRA inhibits experimental liver metastasis of gastric cancer cells in nude mice

    Institute of Scientific and Technical Information of China (English)

    Yu Qiang Chen; Qiao Wu; Zheng Ming Chen; Fu Chen; Wen Jin Su

    2000-01-01

    AIM To study the effects of ATRA on experimental liver metastasis of gastric cancer cells.METHODS MGc80-3 and SGC-7901 cells were injectied into spleen subcapsule of nude mice, who weresubsequently administrated with ATRA every other day. Food-intake and body weight of mice were measuredweekly. After six weeks, the nude mice were executed, tumors in spleen and liver were examinedpathologically, microtumor vessel density (MVD) was accounted by immunohistochemical method and serumCEA was measured by radioimmunoassay.RESULTS Nude mice administrated with ATRA, the growth of spleen tumor and its metastatic ability toliver were inhibited, the metastatic rate was decreased by 33.3% (MGc80-3) and 50.0% (SGC-7901). SpleenMVD and liver MVD were reduced by 28.6% and 22.9% (MGc80-3), 23.7% and 37.6% (SGC-7901),respectively. The serum CEA was lowered by 43.4% (MGc80-3).CONCLUSION ATRA can effectively inhibit the experimental liver metastasis of gastric cancer cells,which is relavant with the decrease of MVD and CEA.

  3. Antitumor activity and biodistribution of cisplatin nanocapsules in nude mice bearing human ovarian carcinoma xenografts

    OpenAIRE

    Staffhorst, R.W.H.M.; Born, K.; Erkelens, C.A.M.; Hamelers, I.H.L.; Peters, G J; Boven, E.; de Kroon, A.I.P.M.

    2008-01-01

    Cisplatin nanocapsules represent a novel lipid formulation of the anticancer drug cis-diamminedichloridoplatinum(II) (cisplatin), characterized by an unprecedented cisplatin-tolipid molar ratio, and exhibiting strongly increased in-vitro cytotoxicity compared with the free drug. In this study, antitumor efficacy and biodistribution of PEGylated cisplatin nanocapsules were compared with those of the free drug in a mouse tumor model. Nude mice bearing human ovarian carcinoma OVCAR-3 xenografts ...

  4. Establishment of a mdrl Multidrug Resistant Model of Orthotopic Transplantation of Liver Carcinoma on Nude Mice

    Institute of Scientific and Technical Information of China (English)

    HANYu; CHENXiaoping

    2005-01-01

    Objective: To develop a new method of inducing mdrl multidrug resistance by establishing a nude mice model of orthotopic transplantation of liver carcinoma by sporadic abdominal chemotherapy at intervals. Methods: Hepatocellular carcinoma HepG2 cell was cultured and injected subcutaneously to form the tumor-supplying mice. The tumor bits from the tumor-supplying mice were implanted under the envelope of the mice liver and induced by abdominal chemotherapy with Pharmorubicin. Physical examination, ultrasonography, spiral CT and operative inspection were used to examine tumor progression. RT-PCR and immunohistochemistry were adopted to detect the expression of mdrl-mRNA and its encoded protein P-gp protein (P-gp). Results: There was no operative dead, the rate of implanting tumor successfully was 88% (22/25), the rate of implanting secondly successfully was 100% (3/3), and the rate of inducing successfully was 80% (16/20). The expression of mdrl-mRNA and the P-gp in the inducing group was 23 folds and 13 folds in the control group respectively. Conclusion: We have established an in vivo model of mdr using nude mice transplanted with orthotopic liver neoplasm coupled to chemotherapy.

  5. Reversal of multidrug resistance by magnetic Fe3O4 nanoparticle copolymerizating daunorubicin and 5-bromotetrandrine in xenograft nude-mice

    Directory of Open Access Journals (Sweden)

    Baoan Chen

    2009-03-01

    Full Text Available Baoan Chen1,* Jian Cheng1,* Yanan Wu1, Feng Gao1, Wenlin Xu2, et al 1Department of Hematology;2Department of Hematology, The Affiliated People’s Hospital, Jiangsu University, Zhenjiang, PR China *These authors have contributed equally to this workAbstract: In this paper we establish the xenograft leukemia model with stable multidrug resistance in nude mice and to investigate the reversal effect of 5-bromotetrandrine (5-BrTet and magnetic nanoparticle of Fe3O4 (MNP-Fe3O4 combined with daunorubicin (DNR in vivo. Two subclones of K562 and K562/A02 cells were inoculated subcutaneously into the back of athymic nude mice (1 × 107 cells/each respectively to establish leukemia xenograft models. Drug-resistant and sensitive tumor-bearing nude mice were assigned randomly into five groups which were treated with normal saline; DNR; NP-Fe3O4 combined with DNR; 5-BrTet combined with DNR; 5-BrTet and MNP-Fe3O4 combined with DNR, respectively. The incidence of formation, growth characteristics, weight, and volume of tumors were observed. The histopathologic examination of tumors and organs were detected. For resistant tumors, the protein levels of Bcl-2, and BAX were detected by Western blot. Bcl-2, BAX, and caspase-3 genes were also detected. For K562/A02 cells xenograft tumors, 5-BrTet and MNP-Fe3O4 combined with DNR significantly suppressed growth of tumor. A histopathologic examination of tumors clearly showed necrosis of the tumors. Application of 5-BrTet and MNP-Fe3O4 inhibited the expression of Bcl-2 protein and upregulated the expression of BAX and caspase-3 proteins in K562/A02 cells xenograft tumor. It is concluded that 5-BrTet and MNP-Fe3O4 combined with DNR had a significant tumor-suppressing effect on a MDR leukemia cells xenograft model.Keywords: 5-bromotetrandrine, magnetic nanoparticle of Fe3O4, multidrug-resistance, xenograft model

  6. Influence of MSA on Cell Growth and Spontaneousn Metastasis of L9981-Luc Lung Cancer Transplanted Model in Nude Mice by Bioluminescence Imaging

    OpenAIRE

    Yuanrong REN; Wang, Yuli; Liu, Hongyu; YAN, HUIQIN; Chen, Jun; Hou, Mei; Li, Weimin; Yaguang FAN; Zhou, Qinghua

    2013-01-01

    Background and objective Methylseleninic acid (MSA) is an artificially developed selenium compound. It has been proven that MSA could inhibit growth and metastasis on many tumor cells. This study investigated whether MSA has an impact on the growth and metastasis of L9981-Luc lung cancer transplanted model in nude mice or not. Methods A transplantated tumor model was established in nude mice. Fifteen nude mice were randomly divided into three groups: the control group treated with normal sali...

  7. Effects of a fraction from Naja naja atra venom on transplanted hepatic carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    XuT; LiuZT

    2002-01-01

    The effects of a fraction from Naja naja atra venom(FNNAV) on inhibiting the growing of hepatic carcinoma and inducing the apoptosis of hepatic carcinoma were studied.It showed that the weight of transplants of hepatic carcinoma was lower both in middle and high concentration FNNAV groups compared with the control group after ten days treatment with FNNAV,and the nude mice of high concentration FNNAV group lived longer than those of the control group.It has been found that the expression of bcl-2 gene in transplants of hepatic carcinoma in FNNAV groups was decreased by using SABC method.By counting the peripheral blood WBC and bone marrow cells it proved that FNNAV did not affect the function of bone marrow in a short period.These results suggest that FNNAV has the anti-tumor effects on transkplanted hepatic carcinoma in nude mice and could prolong the life of mice bearing the tumor.No inhibitory effect of FNNAV on bone marrow was observed.

  8. 3-Bromopyruvate inhibits human gastric cancer tumor growth in nude mice via the inhibition of glycolysis.

    Science.gov (United States)

    Xian, Shu-Lin; Cao, Wei; Zhang, Xiao-Dong; Lu, Yun-Fei

    2015-02-01

    Tumor cells primarily depend upon glycolysis in order to gain energy. Therefore, the inhibition of glycolysis may inhibit tumor growth. Our previous study demonstrated that 3-bromopyruvate (3-BrPA) inhibited gastric cancer cell proliferation in vitro. However, the ability of 3-BrPA to suppress tumor growth in vivo, and its underlying mechanism, have yet to be elucidated. The aim of the present study was to investigate the inhibitory effect of 3-BrPA in an animal model of gastric cancer. It was identified that 3-BrPA exhibited strong inhibitory effects upon xenograft tumor growth in nude mice. In addition, the antitumor function of 3-BrPA exhibited a dose-effect association, which was similar to that of the chemotherapeutic agent, 5-fluorouracil. Furthermore, 3-BrPA exhibited low toxicity in the blood, liver and kidneys of the nude mice. The present study hypothesized that the inhibitory effect of 3-BrPA is achieved through the inhibition of hexokinase activity, which leads to the downregulation of B-cell lymphoma 2 (Bcl-2) expression, the upregulation of Bcl-2-associated X protein expression and the subsequent activation of caspase-3. These data suggest that 3-BrPA may be a novel therapy for the treatment of gastric cancer.

  9. Screening of the residual normal ovarian tissue adjacent to orthotopic epithelial ovarian carcinomas in nude mice.

    Science.gov (United States)

    Zhu, G H; Wang, S T; Yao, M Z; Cai, J H; Chen, C Y; Yang, Z X; Hong, L; Yang, S Y

    2014-04-16

    The objective of this study was to explore the feasibility and methods of screening the residual normal ovarian tissue adjacent to orthotopic ovarian carcinomas in nude mice. Human epithelial ovarian cancer cells (OVCAR3) were subcutaneously implanted for a tumor source and ovarian orthotopic transplantation. The cancer tissue, proximal paraneoplastic tissue, middle paraneoplastic tissue, remote paraneoplastic tissue, and normal ovarian tissue were removed. CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was detected by reverse transcription polymerase chain reaction. We obtained 35 paraneoplastic residual ovarian tissues with normal biopsies from 40 cases of an orthotopic epithelial ovarian carcinoma model (87.5%). CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was lower in proximal paraneoplastic tissue than in cancer tissue (P tissue (P tissue as well as among residual normal ovarian tissues with different severity (P > 0.05). In ovarian tissues of 20 normal nude mice, the expression of CK- 7, CA125, p53, survivin, MMP-2, and TIMP-2 was negative. Overall, the expression levels of CK-7, CA125, p53, survivin, MMP-2, TIMP-2, and other molecular markers showed a decreasing trend in the non-cancer tissue direction. The expression levels can be used as standards to screen residual normal ovarian tissue. We can obtain relatively safe normal ovarian tissues adjacent to epithelial ovarian cancer.

  10. Growth curves of three human malignant tumors transplanted to nude mice

    DEFF Research Database (Denmark)

    Spang-Thomsen, M; Nielsen, A; Visfeldt, J

    1980-01-01

    Experimental growth data for three human malignant tumors transplanted to nude mice of BALB/c origin are analyzed statistically in order to investigate whether they can be described according to the Gompertz function. The aim is to set up unequivocal standards for planned therapeutic experiments...... and to develop an essential part of the determination of proliferation parameters for the tumors. The results indicate that the course of tumor growth can be described with good approximation by the Gompertz function. A transformation of this function depicts the growth rectilinearly and appears to be suitable...... mice. For tumors whose growth is described according to the Gompertz function, recording of the growth of the tumor size in two dimensions is sufficient for calculating other relevant growth parameters, if the three linear tumor measurements are proportional throughout the growth period. The initial...

  11. Antitumor and Antiangiogenic Activities of Curcumin in Cervical Cancer Xenografts in Nude Mice

    Directory of Open Access Journals (Sweden)

    Pornphrom Yoysungnoen-Chintana

    2014-01-01

    Full Text Available To evaluate the effects of curcumin (CUR on tumor progression and angiogenesis in cervical cancer- (CaSki- implanted nude mice and on the angiogenic biomarkers: vascular endothelial growth factor (VEGF, cyclooxygenase-2 (COX-2, and epidermal growth factor receptor (EGFR. CaSki cells were subcutaneously injected in nude mice to establish subcutaneous tumors. One month after injection, mice were orally administered vehicle or 500, 1,000, and 1,500 mg/kg of CUR daily × 30 consecutive days. Tumor volume was measured every 3-4 days. At the end of the study, tumor microvasculature was observed under confocal microscope, and immunohistochemical analyses were performed to detect CD31, VEGF, COX-2, and EGFR. CUR at the doses of 1,000 and 1,500 mg/kg showed significant tumor growth retardation (21.03% and 35.57% versus CaSki + vehicle group. The microvascular density (MVD in CaSki + vehicle group was significantly increased versus Control + vehicle group and significantly reduced by CUR (1,000 and 1,500 mg/kg. VEGF, COX-2, and EGFR expressions were upregulated in CaSki + vehicle group and attenuated significantly by CUR (1,000 and 1,500 mg/kg. In conclusion, high dose CUR inhibited tumor growth and angiogenesis in CaSki-implanted mice probably mediated by the downregulation of VEGF, COX-2 and EGFR. CUR may have a role in treating human cervical cancer and should be explored further.

  12. Inhibitory effect of soluble platelet-derived growth factor receptor β on intraosseous growth of breast cancer cells in nude mice.

    Science.gov (United States)

    Shan, Hongchao; Takahashi, Tetsuyuki; Bando, Yoshimi; Izumi, Keisuke; Uehara, Hisanori

    2011-10-01

    Bone metastasis is a frequent complication of advanced breast cancer. On the basis of functional and molecular evidence, signaling mediated by the binding of platelet-derived growth factor (PDGF)-BB and -DD to PDGF receptor β (PDGFRβ) is critical for the survival and growth of metastatic breast cancer cells within the bone microenvironment. In this study, we propose a new approach to blocking PDGFRβ signaling using soluble PDGFRβ (sPDGFRβ) as a decoy receptor for PDGF-BB and -DD secreted from tumor cells and bone marrow stromal cells. A bone-seeking TNBCT/Bo cell line was established by in vivo selection from TNBCT human breast cancer cells, which are negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 protein expression. The TNBCT/Bo cells were transfected with a mammalian expression vector encoding the extracellular domain of PDGFRβ. A stable transfectant (TNBCT/Bo-sPDGFRβ) grew at a similar rate to that of control cells under normal culture conditions, although growth stimulation of human fibroblasts with PDGF-BB was neutralized by the culture medium from TNBCT/Bo-sPDGFRβ cells. Intratibial injection of TNBCT/Bo-sPDGFRβ cells into athymic nude mice resulted in a significant decrease in tumor incidence compared with control mice (P growth correlated with decreased cancer cell proliferation, angiogenesis, and recruitment of stromal cells, and with an increase in the number of apoptotic cells. These findings suggest that sPDGFRβ is useful for the treatment of breast cancer bone metastasis.

  13. Anti-tumor effect of thalidomide and paclitaxel on hepatocellular carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhong-lin; LIU Zhi-su; SUN Quan

    2005-01-01

    Background Thalidomide is reviving for its antiangiogenic effect on corneal neovascularization models. Recently, it has been employed in tumor research in several types of solid carcinomas. However, its effect on hepatocellular carcinoma (HCC) has not yet been clarified. Methods A total of 48 nude mice bearing human HCC with a high metastatic potential were randomly divided into 4 groups. Thalidomide (200 mg/kg), paclitaxel (13 mg/kg), or their combination, which was dissolved in 0.5% sodium carboxyl methyl cellulose (CMC) suspension, was intraperitoneally injected in each group since the second day of the establishment of animal model. The group simply administered with 0.5% CMC was set as placebo-control. The mice were sacrificed on the 30th day, for the measurement of tumor size, weight and metastasis in the lungs. The levels of CD34 and endothelial growth factor (VEGF) mRNA in tumor tissues were detected by immunohistochemistry and semiquantitative RT-PCR, respectively, and microvessel density (MVD) was evaluated. Results No statistical difference was found in tumor weight and volume between the thalidomide group and control (P>0.05). Paclitaxel showed a growth-inhibiting effect on tumors (P<0.05). The value of MVD and VEGF mRNA and metastases to the lungs in each group were lower than those in the placebo-control group (P<0.05); such difference in the combination group was statistically significant (P<0.05). Conclusions Paclitaxel, but not thalidomide, has significant growth inhibitory effect on tumors, but both significantly inhibit angiogenesis and metastasis of human HCC in nude mice, such effects of paclitaxel can be amplified by thalidomide.

  14. Detection of esophageal squamous cell carcinoma by cathepsin B activity in nude mice.

    Directory of Open Access Journals (Sweden)

    Wei Ma

    Full Text Available BACKGROUND AND OBJECTIVE: Despite great progress in treatment, the prognosis for patients with esophageal squamous cell carcinoma (ESCC remains poor, highlighting the importance of early detection. Although upper endoscopy can be used for the screening of esophagus, it has limited sensitivity for early stage disease. Thus, development of new diagnosis approach to improve diagnostic capabilities for early detection of ESCC is an important need. The aim of this study was to assess the feasibility of using cathepsin B (CB as a novel imaging target for the detection of human ESCC by near-infrared optical imaging in nude mice. METHODS: Initially, we examined specimens from normal human esophageal tissue, intraepithelial neoplasia lesions, tumor in situ, ESCC and two cell lines including one human ESCC cell line (Eca-109 and one normal human esophageal epithelial cell line (HET-1A for CB expression by immunohistochemistry and western blot, respectively. Next, the ability of a novel CB activatable near-infrared fluorescence (NIRF probe detecting CB activity presented in Eca-109 cells was confirmed by immunocytochemistry. We also performed in vivo imaging of tumor bearing mice injected with the CB probe and ex vivo imaging of resected tumor xenografts and visceral organs using a living imaging system. Finally, the sources of fluorescence signals in tumor tissue and CB expression in visceral organs were identified by histology. RESULTS: CB was absent in normal human esophageal mucosa, but it was overexpressed in ESCC and its precursor lesions. The novel probe for CB activity specifically detected ESCC xenografts in vivo and in vitro. CONCLUSIONS: CB was highly upregulated in human ESCC and its precursor lesions. The elevated CB expression in ESCC allowed in vivo and in vitro detection of ESCC xenografts in nude mice. Our results support the usefulness of CB activity as a potential imaging target for the detection of human ESCC.

  15. Genital-tract infection and disease in nude and immunologically competent mice after inoculation of a human strain of Chlamydia trachomatis.

    OpenAIRE

    1982-01-01

    A fast, human strain of Chlamydia trachomatis was introduced into the uterus of progesterone-treated CBA mice and congenic CBA nude mice through the uterine wall or via the cervical canal. The numbers of inclusions produced by samples taken from the vagina of the nude mice were significantly greater (P less than 0.05) than those produced by samples from immunologically competent normal mice. However, the infection was self-limited, lasting about 60 days, and there was no statistical differenc...

  16. CD8+ T cells are crucial for the ability of congenic normal mice to reject highly immunogenic sarcomas induced in nude mice with 3-methylcholanthrene

    DEFF Research Database (Denmark)

    Boesen, M; Svane, I M; Engel, A M;

    2000-01-01

    An attempt was made to identify the selection pressures put upon a growing tumour by CD8+ T cells. To this end tumours induced with 3-methylcholanthrene in T cell-deficient nude mice and in congenic T cell-competent nu/+ mice were transplanted to nu/+ recipients. The rejection rate of the sarcomas...

  17. Characterization of human glioblastoma cell lines in vitro and their xenografts in nude mice by DNA fingerprinting

    DEFF Research Database (Denmark)

    Türeci, O; Fischer, H; Lagoda, P;

    1990-01-01

    Human gliomas were grown as permanent tissue cultures and xenografts in nude mice. DNA fingerprint patterns from two human gliomas were established using two different hypervariable multilocus probes [( GTG]5 and 33.15). In general the cell lines investigated showed an overall stability in the DNA...

  18. Clonal evolution demonstrated by flow cytometric DNA analysis of a human colonic carcinoma grown in nude mice

    DEFF Research Database (Denmark)

    Vindeløv, L L; Spang-Thomsen, M; Visfeldt, J

    1982-01-01

    A spontaneous change in DNA content of a human colonic carcinoma grown in nude mice was observed fortuitously. The tumor initially had a G1 cell DNA content of 1.3 times that of normal cells. Flow cytometric DNA analysis showed in transplant generation 56 the appearance of a new subpopulation which...

  19. Changes of proliferation kinetics after X-irradiation of a human malignant melanoma grown in nude mice

    DEFF Research Database (Denmark)

    Spang-Thomsen, M; Vindeløv, L L

    1984-01-01

    A human malignant melanoma grown in nude mice was exposed to single-dose X-irradiation and the effect on the proliferation kinetics was investigated by two methods. Flow cytometric DNA analysis was performed on tumour tissue obtained by sequential fine-needle aspirations after the treatment to mo......-related increasing proportion of radiation-inactivated tumour cells....

  20. Endocrine sensitivity of the receptor-positive T61 human breast carcinoma serially grown in nude mice

    DEFF Research Database (Denmark)

    Brünner, N; Spang-Thomsen, M; Skovgaard Poulsen, H;

    1985-01-01

    A study was made on the effect of ovariectomy, 17 beta-oestradiol, and tamoxifen on the oestrogen and progesterone receptor-positive T61 human breast carcinoma grown in nude mice. The effect of the treatment was evaluated by the specific growth delay calculated on the basis of Gompertz growth...

  1. Associations between the uptake of {sup 111}In-DTPA-trastuzumab, HER2 density and response to trastuzumab (Herceptin) in athymic mice bearing subcutaneous human tumour xenografts

    Energy Technology Data Exchange (ETDEWEB)

    McLarty, Kristin; Cornelissen, Bart; Scollard, Deborah A. [University of Toronto, Department of Pharmaceutical Sciences, Toronto, ON (Canada); Done, Susan J. [University of Toronto, Department of Medical Biophysics, Toronto, ON (Canada)]|[University of Toronto, Department of Laboratory Medicine and Pathobiology, Toronto, ON (Canada)]|[University Health Network, Department of Pathology, Toronto, ON (Canada); Chun, Kathy [North York General Hospital, Genetics Program, Toronto, ON (Canada); Reilly, Raymond M. [University of Toronto, Department of Pharmaceutical Sciences, Toronto, ON (Canada)]|[University of Toronto, Department of Medical Imaging, Toronto, ON (Canada)]|[University Health Network, Toronto General Research Institute, Toronto, ON (Canada)]|[University of Toronto, Leslie Dan Faculty of Pharmacy, Toronto, ON (Canada)

    2009-01-15

    The purpose of the study was to investigate the associations between uptake of {sup 111}In-DTPA-trastuzumab, tumour HER2 density and response to trastuzumab (Herceptin) of human breast cancer (BC) xenografts in athymic mice. The tumour uptake of {sup 111}In-DTPA-trastuzumab in athymic mice bearing BC xenografts with increasing HER2 density (0 to 3+) was evaluated. Specific uptake ratios were established in biodistribution (SUR) and imaging studies (ROI-SUR) using {sup 111}In-labeled mouse IgG ({sup 111}In-DTPA-mIgG). Further corrections were made for circulating radioactivity using tumour-to-blood ratios defined as a localization index (LI) and region-of-interest localization index (ROI-LI), respectively. Mice were treated with trastuzumab (Herceptin). A tumour growth inhibition index (TGI) was calculated and relative TGIs calculated by dividing the TGI of control by that of trastuzumab-treated mice. Strong, nonlinear associations with HER2 density were obtained if the uptake of {sup 111}In-DTPA-trastuzumab was corrected for nonspecific IgG localization (i.e., SUR; r{sup 2}=0.99) and circulating radioactivity (i.e., LI; r{sup 2} =0.87), but without these corrections, the association between HER2 density and tumour uptake was poor (r{sup 2}=0.22). There was a strong association between ROI-SUR and ROI-LI values and HER2 expression (r{sup 2}=0.90 and r{sup 2}=0.95), respectively. All tumours were imaged. Relative TGI values were associated with increasing uncorrected tumour uptake of {sup 111}In-DTPA-trastuzumab but not always with HER2 density (i.e., MCF-HER2-18 cells with trastuzumab-resistance). HER2 expression (0 to 3+) can be differentiated using {sup 111}In-DTPA-trastuzumab, but requires correction of tumour uptake for nonspecific IgG localization and circulating radioactivity. The uncorrected uptake of {sup 111}In-DTPA-trastuzumab was associated with tumour response to trastuzumab. (orig.)

  2. Angiostatin inhibits pancreatic cancer cell proliferation and growth in nude mice

    Institute of Scientific and Technical Information of China (English)

    Ding-Zhong Yang; Jing He; Ji-Cheng Zhang; Zhuo-Ren Wang

    2005-01-01

    AIM: To observe the biologic behavior of pancreatic cancer cells in vitro and in vivo, and to explore the potential value of angiostatin gene therapy for pancreatic cancer.METHODS: The recombinant vector pcDNA3.1(+)-angiostatin was transfected into human pancreatic cancer cells PC-3 with Lipofectamine 2000, and paralleled with the vector and mock control. Angiostatin transcription and protein expression were determined by immunofluorescence and Western blot. The stable cell line was selected by G418. The supernatant was collected to treat endothelial cells. Cell proliferation and growth in vitro were observed under microscope. Cell growth curves were plotted.The troms-fected or untroms-fected cells overexpressing angiostatin vector were implanted subcutaneously into nude mice. The size of tumors was measured, and microvessel density count (MVD) in tumor tissues was assessed by immunohistochemistry with primary anti-CD34antibody.RESULTS: After transfected into PC-3 with Lipofectamine 2000 and selected by G418, macroscopic resistant cell clones were formed in the experimental group transfected with pcDNA 3.1(+)-angiostatin and vector control. But untreated cells died in the mock control. Angiostatin protein expression was detected in the experimental group by immunofluorescence and Western-blot. Cell proliferation and growth in vitro in the three groups were observed respectively under microscope. After treatment with supernatant, significant differences were observed in endothelial cell (ECV-304) growth in vitro. The cell proliferation and growth were inhibited. In nude mice model, markedly inhibited tumorigenesis and slowed tumor expansion were observed in the experimental group as compared to controls, which was parallel to the decreased microvessel density in and around tumor tissue.CONCLUSION: Angiostatin does not directly inhibit human pancreatic cancer cell proliferation and growth in vitro,but it inhibits endothelial cell growthin vitro. It exerts the anti

  3. Experimental study of the antitumor effect of phosphorus-32 glassmicrospheres on the tumor loaded nude mice

    Institute of Scientific and Technical Information of China (English)

    Lu Liu; Pei Lin Huang; Guan Sheng Tong

    2000-01-01

    AIM To evaluate the pharmacological effect of phosphorus-32 glass microspheres (32p-GMS) injected intothe implanted human liver cancer cell mass in nude mice.METHODS Fifty-two Balb/c tumor loaded nude mice were allocated into treatment group (n =38) andcontrol group (n = 14), in the former group different doses of 32p-GMS were injected into the tumor mass,while in the latter group 31 P-GMS or no treatment were given instead of 32 P-GMS. After dynamicallyobserving the growth of tumor for d 3 - d 28, the experimental animals were killed in batches, the tumor andits nearby tissues were examined by light and electronic microscopy.RESULTS In comparing with the control group, the treatment group showed the tumor inhibiting rates of59.7% -93.6% (Variance analysis of the mean weight of different doses and control group after square rootcorrection, F= 579.62, P<0.01). As the tumor mass attained the absorbed dose of 7320Gy, the tumor cellswere completely destroyed and at this maximal dose in one case, the epithelial tissue neighboring to this massshowed the signs of metaplasia. When the absorbed doses ranged from 1830Gy to 3660Gy, most of the tumorcells showed the evidences of injury or necrosis, and some well differentiated tumor cells appeared. As theabsorbed dose being 366Gy or less, some tumor cells remained in active proliferative stage with a lot offibroblasts and lymphocytes presented in the neighboring interstitial tissues.CONCLUSION When the experimental model of implanted human liver cancer cells received 32p-GMS of1830Gy-3660Gy, it produces excellent anticancer action without any injury to the normal neighboringtissues and the prominent anticancer effect is found within d 3 after intratumor injection.

  4. Radioimmunoimaging of osteogenic sarcoma xenografts in nude mice using monoclonal antibodies to osteogenic sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Sakahara, H.; Endo, K.; Nakashima, T.; Koizumi, M.; Ohta, H.; Kunimatsu, M.; Torizuka, K.; Nakamura, T.; Tanaka, H.; Kotoura, Y.

    1985-05-01

    The authors have developed several monoclonal antibodies against human osteogenic sarcoma, one of which; OST7 (IgGl) selectively localized in osteogenic sarcoma xenografts in nude mice. In the present study, F(ab')/sub 2/ fragment was compared with whole IgG and those labeled with In-111 as well as I-131 were used as a radiotracer for the scintigraphic imaging of tumors. IgC and F(ab')/sub 2/ were labeled with I-131 using chloramine-T method and injected into nude mice bearing human osteogenic sarcoma. Scintigrams at day 2 clearly delineated the site of tumors with almost no radioactivity in other organs with F(ab')/sub 2/, which yielded much better images than whole IgG. Tumor-to-blood ratio of 6.09-27.87 was obtained at day 2 using F(ab')/sub 2/, whereas it was 0.76-1.12 at day 2 and 2.05-3.27 at day 7 with IgG. I-131 labeled nonspecific F(ab')/sub 2/ or IgG resulted in no or very low tumor uptake with tumor-to-blood ratio of 0.94-1.18 at day 2 for F(ab')/sub 2/ and 0.67-0.76 at day 7 for IgG, respectively. In-111 labeled F(ab')/sub 2/ fragment of OST7, which was prepared using DTPA as a bifunctional chelate, also showed a high tumor accumulation with tumor-to-blood ratio of 11.67-17.54 at day 2, but higher background activity in the liver and kidney was observed than I-131 labeled one. These results indicate that F(ab')/sub 2/ fragment of OST7 labeled with either I-131 or In-111, has a great potential for the radioimmunoimaging of osteogenic sarcoma.

  5. Experimental iodine-125 seed irradiation of intracerebral brain tumors in nude mice

    Directory of Open Access Journals (Sweden)

    Haveman Jaap

    2007-09-01

    Full Text Available Abstract Background High-dose radiotherapy is standard treatment for patients with brain cancer. However, in preclinical research external beam radiotherapy is limited to heterotopic murine models– high-dose radiotherapy to the murine head is fatal due to radiation toxicity. Therefore, we developed a stereotactic brachytherapy mouse model for high-dose focal irradiation of experimental intracerebral (orthotopic brain tumors. Methods Twenty-one nude mice received a hollow guide-screw implanted in the skull. After three weeks, 5 × 105 U251-NG2 human glioblastoma cells were injected. Five days later, a 2 mCi iodine-125 brachytherapy seed was inserted through the guide-screw in 11 randomly selected mice; 10 mice received a sham seed. Mice were euthanized when severe neurological or physical symptoms occurred. The cumulative irradiation dose 5 mm below the active iodine-125 seeds was 23.0 Gy after 13 weeks (BEDtumor = 30.6 Gy. Results In the sham group, 9/10 animals (90% showed signs of lethal tumor progression within 6 weeks. In the experimental group, 2/11 mice (18% died of tumor progression within 13 weeks. Acute side effects in terms of weight loss or neurological symptoms were not observed in the irradiated animals. Conclusion The intracerebral implantation of an iodine-125 brachytherapy seed through a stereotactic guide-screw in the skull of mice with implanted brain tumors resulted in a significantly prolonged survival, caused by high-dose irradiation of the brain tumor that is biologically comparable to high-dose fractionated radiotherapy– without fatal irradiation toxicity. This is an excellent mouse model for testing orthotopic brain tumor therapies in combination with radiation therapy.

  6. SNCG shRNA suppressed breast cancer cell xenograft formation and growth in nude mice

    Institute of Scientific and Technical Information of China (English)

    SHEN Pei-hong; FAN Qing-xia; LI Yan-wei; ZHANG Wei; HE Xiao-kai; WANG Zhen; ZHANG Yun-han

    2011-01-01

    Background Overexpression of breast cancer-specific gene 1 (SNCG) is associated with poor prognosis in advanced breast cancer patients. This study aimed to determine the effects of SNCG knockdown in breast cancer cells by using small hairpin RNA (shRNA).Methods Four different SNCG shRNA oligonucleotides were designed and chemically synthesized to construct mammalian expression vectors. These vectors were then stably transfected into a breast cancer MCF-7 cell line to knockdown SNCG expression. After SNCG knockdown was confirmed, the stable cell lines were inoculated into nude mice. SNCG mRNA and protein expressions were analyzed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively in both the stable cell lines and xenografts.Results All four SNCG shRNA constructs significantly reduced SNCG mRNA and protein levels in MCF-7 cells, as compared to the unrelated sequence control shRNA and the liposome control mice (P<0.05). SNCG-knockdown MCF-7cells formed significantly smaller tumor masses than cells expressing the unrelated sequence control or the liposome control mice (P<0.05).Conclusion SNCG shRNA effectively suppressed breast cancer cell formation in vivo and may be a useful clinical strategy to control breast cancer.

  7. Avidin chase reduces side effects of radioimmunotherapy in nude mice bearing human colon carcinoma

    Institute of Scientific and Technical Information of China (English)

    Gui-Ping Li; Yong-Xian Wang; Kai Huang; Hui Zhang; Chun-Fu Zhang

    2005-01-01

    AIM: To evaluate the influence of avidin chase on the side effects of radioimmunotherapy (RIT) in nude mice bearing human colon carcinoma and therapeutic outcome.METHODS: Purified anti-CEA monoclonal antibody (McAb)was biotinylated with NHS-biotin, and then radiolabeled with 188Re by the direct method. 188Re-labeledbiotinylated anti-CEA McAb (188Re-CEA McAb-Bt) was intravenously injected followed by intravenous injection of avidin after 24 h. SPECT imaging and biodistribution study were performed at 28-48 h after the injection of 188Re-CEA McAb-Bt. Three groups of nude mice subcutaneously grafted with human colon carcinoma were treated 7 d after the graft. Mice in the avidin chase group received intravenous injection of 188Re-CEA McAb-Bt (11.1 MBq/20 μg) followed by intravenous injection of cold avidin (80 μg) after 24 h. Mice in the control group (treated group without avidin chase) only received the injection of 188Re-CEA McAb-Bt (11.1 MBq/20 μg), another control group (non-treated group) only received 0.1 mL normal saline solution. Toxicity was evaluated on the basis of change of body weight and peripheral WBC counts, and therapy effects were determined by variation in tumor volume. Histological analysis of tumors was also performed.RESULTS: Avidin chase markedly accelerated the clearance of 188Re-CEA McAb-Bt from the blood and normal tissues. The tumor uptakes of 188Re-CEA Mc Ab-Bt at 28 h were 5.90 and 6.42% ID/g, respectively, in chase group and in non-chase group, while the tumor-to-background (T/NT) ratios were 3.19 and 0.56, respectively. The tumor uptake was slightly decreased by avidin chase, but the T/NT ratios were increased. In treated groups the growth rate of body weight and the number of WBC decreased after injection of 188Re-CEA McAb-Bt, and the WBC counts recovered earlier in the group with avidin chase than in the group without avidin chase. Compared to the nontreated group, treated groups with and without avidin chase showed significant anti

  8. In Vivo Imaging of Human Malignant Mesothelioma Grown Orthotopically in the Peritoneal Cavity of Nude Mice

    Directory of Open Access Journals (Sweden)

    Mingqian Feng, Jingli Zhang, Miriam Anver, Raffit Hassan, Mitchell Ho

    2011-01-01

    Full Text Available Malignant mesothelioma (MM causes significant morbidity and mortality in patients. With increasing efforts devoted to developing therapeutics targeting mesothelioma, a xenograft mouse model with in vivo tumor imaging is especially desired for evaluating anti-tumor therapies. In the present study, we fluorescently labeled the NCI-H226 human mesothelioma cell line by a lentiviral vector harboring a luciferase-GFP (Luc/GFP fusion gene driven by the RNA polymerase II promoter. After single-cell cloning by flow cytometry, a clone (named LMB-H226-GL that stably expresses high levels of Luc/GFP was obtained. The in vivo tumorigenicity of Luc/GFP-labeled LMB-H226-GL was determined by using intraperitoneal injections of the cells in nude mice. LMB-H226-GL was found to be able to consistently form solid tumors in the peritoneum of mice. Tumor growth and aggressive progression could be quantitated via in vivo bioluminescence imaging. The model exhibited the pathological hallmarks consistent with the clinical progression of MM in terms of tumor growth and spread inside the peritoneal cavity. To evaluate the in vivo efficacy of drugs targeting mesothelioma, we treated mice with SS1P, a recombinant immunotoxin currently evaluated in Phase II clinical trials for treatment of mesothelioma. All the tumor-bearing mice had a significant response to SS1P treatment. Our results showed that this is a well-suited model for mesothelioma, and may be useful for evaluating other novel agents for mesothelioma treatment in vivo.

  9. Aminoguanidine impedes human pancreatic tumor growth and metastasis development in nude mice

    Institute of Scientific and Technical Information of China (English)

    Nora A Mohamad; Graciela P Cricco; Lorena A Sambuco; Máximo Croci; Vanina A Medina; Alicia S Gutiérrez; Rosa M Bergoc; Elena S Rivera; Gabriela A Martín

    2009-01-01

    AIM: To study the action of aminoguanidine on pancreatic cancer xenografts in relation to cell proliferation, apoptosis, redox status and vascularization.METHODS: Xenografts of PANC-1 cells were developed in nude mice. The animals were separated into two groups: control and aminoguanidine treated. Tumor growth, survival and appearance of metastases were determined in v/vo in both groups. Tumors were excised and ex v/vo histochemical studies were performed. Cell growth was assessed by Ki-67 expression. Apoptosis was studied by intratumoral expression of B cell lymphoma-2 protein (Bcl-2) family proteins and Terminal deoxynucleotidyl transferase biotin-dUTP Nick End Labeling (Tunel). Redox status was evaluated by the expression of endothelial nitric oxide synthase (eNOS),catalase, copper-zinc superoxide dismutase (CuZnSOD),manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPx). Finally, vascularization was determined by Massons trichromic staining, and by VEGF and CD34 expression.RESULTS: Tumor volumes after 32 d of treatment by aminoguanidine (AG) were significantly lower than in control mice (P < 0.01). Median survival of AG mice was significantly greater than control animals (P < 0.01). The appearance of both homolateral and contralateral palpable metastases was significantly delayed in AG group. Apoptotic cells, intratumoral vascularization (trichromic stain) and the expression of Ki-67, Bax, eNOS, CD34, VEGF, catalase, CuZnSOD and MnSOD were diminished in AG treated mice (P < 0.01),while the expression of Bcl-2 and GPx did not change.CONCLUSION: The antitumoral action of aminoguanidine is associated with decreased cell proliferation, reduced angiogenesis, and reduced expression of antioxidant enzymes.

  10. Growth-inhibiting effects of taxol on human liver cancer in vitro and in nude mice

    Institute of Scientific and Technical Information of China (English)

    Jin Hui Yuan; Ru Ping Zhang; Ru Gang Zhang; Li Xia Guo; Xing Wang Wang; Hong Xie; Dan Luo; Yong Xie

    2000-01-01

    AIM To investigate the effects of taxol on SMMC-7721 human hepatoma and its mechanisms. MLETHODS In vitro cell growth was assessed by trypan blue exclusion method. Experimental hepatoma model was established by seeding SMMC-7721 cells subcutaneously into Balb/c (nu/nu) nude mice. In vivo tumor growth was determined by measurement of tumor diameter with Vernier calipers. The syntheses of DNA,RNA and protein were analyzed by incorporation of 3H-thymidine, 3H-uridine and 3H-leucine respectively. Using light and electron microscopes to observe the morphological changes of cells including mitosis and apoptosis. RESULTS Taxol was effective against SMMC 7721 human hepetoma cell growth in the ranges of 2.5 nmol/L - 10 nmol/L with mitotic arrest and apoptosis in vitro. DNA, RNA and protein syntheses in cells were also obviously suppressed by in vitro treatment of taxol for 72 h. Taxol at 2.5 nmol/L reduced 3H-thymidine uptake to about 34% of the control value (P<0.05). Increasing the dose of taxol to 20 nmol/L resulted in a greater decrease in 3Hthymidine incorporation to 60% of the control value (P<0.01). At a concentration of 20 nmol/L, the 3H-uridine and 3H-leucine uptakes were reduced to 52% (P<0.05) and 63%(P<0.01), respectively. In vivo, taxol significantly inhibited SMMC-7721 tumor growth at 10 mg/kg, i.p., once daily for 10 d. A more than 90% decrease in tumor volume was observed by day 11 (P<0.01) similarly with mitotic arrest and cell apoptosis. CONCLUSION Taxol has a marked anticancer activity in SMMC-7721 human hepatoma both in vitro and in nude mice. Its mechanisms might be associated with mitotic arrest, subsequently,apoptosis of the hepatoma cells. No obvious toxicity was observed with in vivo administration of taxol.

  11. Changing in lipid profile induced by the mutation of Foxn1 gene: A lipidomic analysis of Nude mice skin.

    Science.gov (United States)

    Lanzini, Justine; Dargère, Delphine; Regazzetti, Anne; Tebani, Abdellah; Laprévote, Olivier; Auzeil, Nicolas

    2015-11-01

    Nude mice carry a spontaneous mutation affecting the gene Foxn1 mainly expressed in the epidermis. This gene is involved in several skin functions, especially in the proliferation and the differentiation of keratinocytes which are key cells of epithelial barrier. The skin, a protective barrier for the body, is essentially composed of lipids. Taking into account these factors, we conducted a lipidomic study to search for any changes in lipid composition of skin possibly related to Foxn1 mutation. Lipids were extracted from skin biopsies of Nude and BALB/c mice to be analyzed by liquid chromatography coupled to a high resolution mass spectrometer (HRMS). Multivariate and univariate data analyses were carried out to compare lipid extracts. Identification was performed using HRMS data, retention time and mass spectrometry fragmentation study. These results indicate that mutation of Foxn1 leads to significant modifications in the lipidome in Nude mice skin. An increase in cholesterol sulfate, phospholipids, sphingolipids and fatty acids associated with a decrease in glycerolipids suggest that the lipidome in mice skin is regulated by the Foxn1 gene.

  12. Imaging of HER2/neu-positive BT-474 human breast cancer xenografts in athymic mice using {sup 111}In-trastuzumab (Herceptin) Fab fragments

    Energy Technology Data Exchange (ETDEWEB)

    Tang Ying [Division of Nuclear Medicine, University Health Network, Toronto, Ontario, M5G 2C4 (Canada); Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, M5S 2S2 (Canada); Wang, Judy [Division of Nuclear Medicine, University Health Network, Toronto, Ontario, M5G 2C4 (Canada); Scollard, Deborah A. [Division of Nuclear Medicine, University Health Network, Toronto, Ontario, M5G 2C4 (Canada); Mondal, Hridya [Division of Nuclear Medicine, University Health Network, Toronto, Ontario, M5G 2C4 (Canada); Holloway, Claire [Sunnybrook and Women' s College Health Sciences Center, Toronto, Ontario, M4N 3M5 (Canada); Kahn, Harriette J. [Sunnybrook and Women' s College Health Sciences Center, Toronto, Ontario, M4N 3M5 (Canada); Reilly, Raymond M. [Division of Nuclear Medicine, University Health Network, Toronto, Ontario, M5G 2C4 (Canada) and Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, M5S 2S2 (Canada) and Department of Medical Imaging, University of Toronto, Toronto, Ontario, M5S 3E2 (Canada)]. E-mail: raymond.reilly@utoronto.ca

    2005-01-01

    Trastuzumab (Herceptin) Fab were prepared by digestion of intact IgG with immobilized papain, derivatized with diethylenetriaminepentaacetic acid (DTPA) and radiolabeled with {sup 111}In. The dissociation constant (K{sub d}) for binding of Fab to HER2/neu-positive SK-BR-3 human breast cancer cells was two- to threefold higher than for intact IgG (14-36 vs. 8-14 nM). The binding affinity was not significantly decreased after DTPA derivatization (K{sub d}=47 nM). {sup 111}In-trastuzumab Fab localized specifically in HER2/neu-positive BT-474 human breast cancer xenografts in athymic mice with tumor uptake of 7.8{+-}0.7% injected dose (ID)/g and tumor/blood ratio of 25.2{+-}1.6 at 72 h postinjection compared with 2.7{+-}0.7% ID/g and 7.0{+-}0.9 for {sup 111}In-HuM195 anti-CD33 Fab (significantly different, P<.001). Small (3-5 mm in diameter) BT-474 tumors were imaged with {sup 111}In-trastuzumab Fab as early as 24 h postinjection.

  13. The soluble EP2 receptor FuEP2/Ex2 suppresses endometrial cancer cell growth in an orthotopic xenograft model in nude mice.

    Science.gov (United States)

    Takahashi, Tetsuyuki; Ogawa, Hirohisa; Izumi, Keisuke; Uehara, Hisanori

    2011-07-01

    Endometrial cancer is one of the most common gynecologic malignancies and many factors influence in its growth and development. As in many other types of cancer, prostaglandin E(2) (PGE(2)) is thought to be an accelerator of cell proliferation and endometrial cancer progression. In this study, we examined the effect of FuEP2/Ex2, a soluble decoy receptor for PGE(2) on growth of endometrial cancer cells. A stable transfectant expressing FuEP2/Ex2 was established from human endometrial cancer Ishikawa cells (Ish-FuEP2/Ex2). Ish-FuEP2/Ex2 cells expressed FuEP2/Ex2 mRNA and protein. Expression levels of E-prostanoid receptor 1 (EP1), EP2, EP3, EP4, and F-prostanoid receptor (FP) were almost the same in Ish-FuEP2/Ex2 and vector control cells. Growth rates of Ish-FuEP2/Ex2 under normal culture conditions were also similar to vector control cells, although PGE(2)-induced growth stimulation was completely inhibited in Ish-FuEP2/Ex2 or by Ish-FuEP2/Ex2 culture medium. Moreover, phosphorylation of extracellular signal-regulated kinase (ERK) and induction of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), cyclin D1, and c-fos mRNA by PGE(2) were not observed in Ish-FuEP2/Ex2 and Ish-FuEP2/Ex2 culture medium-treated vector control cells, although they were found when treated with prostaglandin F(2α). An orthotopic xenograft model in athymic nude mice revealed that Ish-FuEP2/Ex2-injected mice had significantly decreased mean tumor area. The proportion of Ki-67-positive cells in the tumor lesion was also significantly lower in Ish-FuEP2/Ex2-injected mice. These findings suggest that an EP-targeting strategy using FuEP2/Ex2 may be of use in the treatment of endometrial cancer.

  14. Thymidine Kinase-Negative Herpes Simplex Virus 1 Can Efficiently Establish Persistent Infection in Neural Tissues of Nude Mice.

    Science.gov (United States)

    Huang, Chih-Yu; Yao, Hui-Wen; Wang, Li-Chiu; Shen, Fang-Hsiu; Hsu, Sheng-Min; Chen, Shun-Hua

    2017-02-15

    Herpes simplex virus 1 (HSV-1) establishes latency in neural tissues of immunocompetent mice but persists in both peripheral and neural tissues of lymphocyte-deficient mice. Thymidine kinase (TK) is believed to be essential for HSV-1 to persist in neural tissues of immunocompromised mice, because infectious virus of a mutant with defects in both TK and UL24 is detected only in peripheral tissues, but not in neural tissues, of severe combined immunodeficiency mice (T. Valyi-Nagy, R. M. Gesser, B. Raengsakulrach, S. L. Deshmane, B. P. Randazzo, A. J. Dillner, and N. W. Fraser, Virology 199:484-490, 1994, https://doi.org/10.1006/viro.1994.1150). Here we find infiltration of CD4 and CD8 T cells in peripheral and neural tissues of mice infected with a TK-negative mutant. We therefore investigated the significance of viral TK and host T cells for HSV-1 to persist in neural tissues using three genetically engineered mutants with defects in only TK or in both TK and UL24 and two strains of nude mice. Surprisingly, all three mutants establish persistent infection in up to 100% of brain stems and 93% of trigeminal ganglia of adult nude mice at 28 days postinfection, as measured by the recovery of infectious virus. Thus, in mouse neural tissues, host T cells block persistent HSV-1 infection, and viral TK is dispensable for the virus to establish persistent infection. Furthermore, we found 30- to 200-fold more virus in neural tissues than in the eye and detected glycoprotein C, a true late viral antigen, in brainstem neurons of nude mice persistently infected with the TK-negative mutant, suggesting that adult mouse neurons can support the replication of TK-negative HSV-1.

  15. Study of angiogenesis induced by metastatic and non-metastatic liver cancer by corneal micropocket model in nude mice

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    AIM To study the angiogenesis induced by liver cancer with different metastatic potentials using corneal micropocket model in nude mice.METHODS Corneal micropockets were created in nude mice. Tumor tissues and liver tissues were implanted into the corneal micropockets. Angiogenesis was observed using a digital camera under slit-lamp biomicroscope, and compared among different grafts and incision alone. Vascular responses were recorded in regard to the range, number and length of new blood vessels toward the grafts or incisions.RESULTS Vascular responses induced by tumor tissues were greater than those by incision alone and liver tissue grafts. LCI-D20 induced more intensive angiogenesis than LCI-D35.CONCLUSION Highly metastatic liver cancer LCI D20 was more angiogenic than low metastatic cancer LCI D35 and liver tissue. Micropocket was a useful model to study dynamic process of angiogenesis in vivo.

  16. SCARLESS SKIN WOUND HEALING IN FOXN1 DEFICIENT (NUDE) MICE IS ASSOCIATED WITH DISTINCTIVE MATRIX METALLOPROTEINASE EXPRESSION

    OpenAIRE

    2011-01-01

    Similar to mammalian fetuses FOXN1 deficient (nude) mice are able to restore the structure and integrity of injured skin in a scarless healing process by mechanisms independent of the genetic background. Matrix metalloproteinases (MMPs) are required for regular skin wound healing and the distinctive pattern of their expression has been implicated to promote scarless healing. In this study, we analyzed the temporal and spatial expression patterns of these molecules during the incisional skin w...

  17. Tanapoxvirus lacking a neuregulin-like gene regresses human melanoma tumors in nude mice.

    Science.gov (United States)

    Zhang, Tiantian; Suryawanshi, Yogesh R; Kordish, Dennis H; Woyczesczyk, Helene M; Jeng, David; Essani, Karim

    2017-02-01

    Neuregulin (NRG), an epidermal growth factor is known to promote the growth of various cell types, including human melanoma cells through ErbB family of tyrosine kinases receptors. Tanapoxvirus (TPV)-encoded protein TPV-15L, a functional mimic of NRG, also acts through ErbB receptors. Here, we show that the TPV-15L protein promotes melanoma proliferation. TPV recombinant generated by deleting the 15L gene (TPVΔ15L) showed replication ability similar to that of wild-type TPV (wtTPV) in owl monkey kidney cells, human lung fibroblast (WI-38) cells, and human melanoma (SK-MEL-3) cells. However, a TPV recombinant with both 15L and the thymidine kinase (TK) gene 66R ablated (TPVΔ15LΔ66R) replicated less efficiently compared to TPVΔ15L and the parental virus. TPVΔ15L exhibited more robust tumor regression in the melanoma-bearing nude mice compared to other TPV recombinants. Our results indicate that deletion of TPV-15L gene product which facilitates the growth of human melanoma cells can be an effective strategy to enhance the oncolytic potential of TPV for the treatment of melanoma.

  18. Preliminary research on dendritic cells loaded with resistant breast cancer antigens in breast cancer-bearing nude mice

    Institute of Scientific and Technical Information of China (English)

    Wei Zhuang; Limin Lun

    2015-01-01

    Objective The aim of the study was to investigate the inhibitory ef ects of dendritic cel s (DCs) loaded with resistant breast cancer antigens on breast cancer in nude mice. Methods A single-cel suspension was prepared from a primary breast cancer and chemotherapeutic drugs were screened using the ATP-PCA susceptibility testing system. Cancer cel s were treated with 1/10 × IC50, 1/5 × IC50, 1/2 × IC50, 1 × IC50, and 2 × IC50 medium until their growth became steady in the 2 × IC50 medium. Peripheral blood mononuclear cel s (PBMCs) were obtained from the peripheral blood of patients with leukapheresis. The obtained adherent cel s were induced by granulocyte-macrophage colony-stimu-lating factor (GM-CSF) and interleukin-4 (IL-4) to generate DCs, which carried resistant strain cel lysis compounds or non-treated cancer cel lysis compounds. The former mature DCs carried resistant breast tumor antigens. A breast tumor-bearing nude mouse model was established with these resistant strains and the mice were randomly divided in three groups. The mice in the treatment group were injected with DCs loaded with resistant breast cancer antigens. The control group consisted of mice injected with DCs loaded with primary tumor cel antigens and the blank group consisted of mice injected with the same volume of normal saline. Changes in the cancers were observed. Results After treatment with the ef ector cel s, the cancer volume and weight were significantly dif erent to those before treatment in every group of mice (P Conclusion DCs loaded with resistant breast cancer antigens demonstrated a significant inhibition ef ect on the cancers of breast tumor-bearing nude mice.

  19. Alphastatin downregulates vascular endothelial cells sphingosine kinase activity and suppresses tumor growth in nude mice bearing human gastric cancer xenografts

    Institute of Scientific and Technical Information of China (English)

    Lin Chen; Tao Li; Rong Li; Bo Wei; Zheng Peng

    2006-01-01

    AIM: To investigate whether alphastatin could inhibit human gastric cancer growth and furthermore whether sphingosine kinase (SPK) activity is involved in this process.METHODS: Using migration assay, MTT assay and Matrigel assay, the effect of alphastatin on vascular endothelial cells (ECs) was evaluated in vitro. SPK and endothelial differentiation gene (EDG)-1, -3, -5 mRNAs were detected by reverse transcription-polymerase chain reaction (RT-PCR). SPK activity assay was used to evaluate the effect of alphastatin on ECs. Matrigel plug assay in nude mice was used to investigate the effect of alphastatin on angiogenesis in vivo. Female nude mice were subcutaneously implanted with human gastric cancer cells (BGC823) for the tumor xenografts studies.Micro vessel density was analyzed in Factor Ⅷ-stained tumor sections by the immunohistochemical SP method.RESULTS: In vitro, alphastatin inhibited the migration and tube formation of ECs, but had no effect on proliferation of ECs. RT-PCR analysis demonstrated that ECs expressed SPK and EDG-1, -3, -5 mRNAs. In vivo,alphastatin sufficiently suppressed neovascularization of the tumor in the nude mice. Daily administration of alphastatin produced significant tumor growth suppression. Immunohistochemical studies of tumor tissues revealed decreased micro vessel density in alphastatin-treated animals as compared with controls.CONCLUSION: Downregulating ECs SPK activity may be one of the mechanisms that alphastatin inhibits gastric cancer angiogenesis. Alphastatin might be a useful and relatively nontoxic adjuvant therapy in the treatment of gastric cancer.

  20. Scaffold-Free Coculture Spheroids of Human Colonic Adenocarcinoma Cells and Normal Colonic Fibroblasts Promote Tumorigenicity in Nude Mice

    Directory of Open Access Journals (Sweden)

    Jong-il Park

    2016-02-01

    Full Text Available The aim of this study was to form a scaffold-free coculture spheroid model of colonic adenocarcinoma cells (CACs and normal colonic fibroblasts (NCFs and to use the spheroids to investigate the role of NCFs in the tumorigenicity of CACs in nude mice. We analysed three-dimensional (3D scaffold-free coculture spheroids of CACs and NCFs. CAC Matrigel invasion assays and tumorigenicity assays in nude mice were performed to examine the effect of NCFs on CAC invasive behaviour and tumorigenicity in 3D spheroids. We investigated the expression pattern of fibroblast activation protein-α (FAP-α by immunohistochemical staining. CAC monocultures did not form densely-packed 3D spheroids, whereas cocultured CACs and NCFs formed 3D spheroids. The 3D coculture spheroids seeded on a Matrigel extracellular matrix showed higher CAC invasiveness compared to CACs alone or CACs and NCFs in suspension. 3D spheroids injected into nude mice generated more and faster-growing tumors compared to CACs alone or mixed suspensions consisting of CACs and NCFs. FAP-α was expressed in NCFs-CACs cocultures and xenograft tumors, whereas monocultures of NCFs or CACs were negative for FAP-α expression. Our findings provide evidence that the interaction between CACs and NCFs is essential for the tumorigenicity of cancer cells as well as for tumor propagation.

  1. Multimodality imaging assessments of response to metformin therapy for breast cancer in nude mice

    Institute of Scientific and Technical Information of China (English)

    MAO Yi; XIA Rui; WANG Lei; WANG Yu-qing; GAO Fa-bao

    2013-01-01

    Background Metformin is the most widely used anti-diabetic drug in the world.An increasing body of evidence shows metformin also blocks cell cycle progression and selectively induces apoptosis via caspase activation in some breast tumor cells.Diffusion-weighted imaging (DWl) and bioluminescence imaging (BLI) have great potential in the evaluation of the early response to cancer therapies.We used DWl and BLI in evaluating the response of breast cancer to metformin.Methods The luciferase-engineered human breast cancer cell line MDA-MB-231 was inoculated into the mammary fat pad of nude mice.Twelve female nude mice bearing tumors were divided into two groups.The mice in the treatment group received metformin (2 mg/ml in drinking water daily) after tumor inoculation,and the mice in the control group were offered drinking water without any drug added.We performed 7T magnetic resonance imaging and optical imaging every week.Imaging included T1-and T2-weighted imaging,DWl,and BLI.After imaging.The tumors were collected and subjected to histological analysis.Results The mean photons/second of tumors in the treatment group was (3.00±0.43)×106 at day one,(1.01±0.14)×107 at 2 weeks,(5.79±1.42)×107 at 4 weeks,and (2.33±0.70)×107 at 8 weeks.The mean photons/second of tumors in the control group was (3.29±0.59)×106 at day one,(3.59±0.63)×107 at 2 weeks,(3.87±0.56)×108 at 4 weeks,and (4.12±1.72)x108 at 8 weeks.Compared to the control group,the treatment group showed an obvious decrease in the mean bioluminescence (photons/s) of the tumors and fewer metastases.Histological examination confirmed the presence of fewer metastases.DWI showed the apparent diffusion coefficient (ADC) value of the tumors; the mean ADC value was (0.9287±0.04346)x10-3 mm2/s in the treated tumors and (0.7553±0.01804)x103 mm2/s in the untreated tumors.The ADC value of tumors in the treatment group was significantly higher than the control tumors (P=0.0013).Conclusions The growth and

  2. Experimental evaluation of boron neutron capture therapy of human breast carcinoma implanted on nude mice

    Science.gov (United States)

    Bose, Satya Ranjan

    2000-06-01

    An in-pool small animal irradiation neutron tube (SAINT) facility was designed, constructed and installed at the University of Virginia Nuclear Research Reactor (UVAR). Thermal neutron flux profiles were measured by foil activation analysis (gold) and verified with DORT and MCNP computer code models. The gamma-ray absorbed dose in the neutron-gamma mixed field was determined from TLD measurements. The SAINT thermal neutron flux was used to investigate the well characterized human breast cancer cell line MCF-7B on both in-vitro samples and in- vivo animal subjects. Boronophenylalanine (BPA enriched in 95% 10B) was used as a neutron capturing agent. The in-vitro response of MCF-7B human breast carcinoma cells to BPA in a mixed field of neutron-gamma radiation or pure 60Co gamma radiation was investigated. The best result (lowest surviving fraction) was observed in cell cultures pre-incubated with BPA and given the neutron irradiation. The least effective treatment consisted of 60Co irradiation only. Immunologically deficient nude mice were inoculated subcutaneously with human breast cancer MCF-7B cells and estradiol pellets (to support tumor growth). The tumor volume in the mouse control group increased over time, as expected. The group of mice exposed only to neutron treatment exhibited initial tumor volume reduction lasting until 35 days following the treatment, followed by renewed tumor growth. Both groups given BPA plus neutron treatment showed continuous reduction in tumor volume over the 55-day observation period. The group given the higher BPA concentration showed the best tumor reduction response. The results on both in-vitro and in-vivo studies showed increased cell killing with BPA, substantiating the incorporation of BPA into the tumor or cell line. Therefore, BNCT may be a possible choice for the treatment of human breast carcinoma. However, prior to the initiation of any clinical studies, it is necessary to determine the therapeutic efficacy in a large

  3. Inhibition of gastric cancer cell adhesion in nude mice by inraperitoneal phospholipids.

    Science.gov (United States)

    Jansen, Marc; Treutner, Karl-Heinz; Jansen, Petra Lynen; Zuber, Sebastian; Otto, Jens; Tietze, Lothar; Schumpelick, Volker

    2005-06-01

    Adhesion of tumor cells to mesothelial cells or extracellular matrix components is a pivotal step in developing peritoneal dissemination after gastric cancer. As phospholipids were found to reduce adhesion formation, especially at sites of peritoneal lesions, we assessed the inhibition of attachment of NUGC-4 gastric cancer cells by local treatment with phospholipids to the peritoneum in nude mice. Gastric cancer cells (1xl0(6)) suspended in either normal saline (controls) or phospholipid suspension 75 mg/kg body weight (PL75) or 150 mg/kg (PL150) were injected intraperitoneally into 90 female BALB/c nu/nu mice. The treatment groups were subdivided into animals with defined peritoneal lesions and animals without lesions. After 30 days the extent of peritoneal carcinosis and the Peritoneal Cancer Index were evaluated. Statistical analysis was performed with two factorial ANOVAs. The level of significance was adjusted according to Bonferrorni (alpha = 0.00278). During a 90-day observation period the survival rate was determined using the log rank test. After 30 days the intraperitoneal tumor volume was reduced by PL150 up to 0.6 ml (SEM 0.16) and 0.48 ml (SEM 0.09) in mice with peritoneal lesions compared to 0.9 ml (SEM 0.2) and 0.9 ml (SEM 0.1) in the control group (P = 0.04). The mean area of tumor adhesion amounted to 145 mm(2) (SEM 17) (P = 0.08) and 164 mm(2) (SEM 32.8) (P = 0.049) with peritoneal lesions after treatment with PL150 [controls: 216 mm(2) (SEM 28.5) and 245 mm(2) (SEM 29.3)]. The peritoneal cancer index was 16.4 (SEM 1.7) in the control group and 9 (SEM 1.68) with PL150 (P = 0.0002). In the subgroup with peritoneal lesions, the respective values were as follows: controls: 20.8 (SEM 0.85); PL 150:14.3 (SEM 1.07) (P = 0.0001). We found a prolonged survival rate after treatment with PL150. However, this effect was not significantly different to that seen in the control group. Treatment with PL75 had no significant influence. Phospholipids may be an

  4. Anticancer activity of resveratrol on implanted human primary gastric carcinoma cells in nude mice

    Institute of Scientific and Technical Information of China (English)

    Hai-Bo Zhou; Juan-Juan Chen; Wen-Xia Wang; Jian-Ting Cai; Qin Du

    2005-01-01

    AIM: To investigate the apoptosis of implanted primary gastric cancer cells in nude mice induced by resveratrol and the relation between this apoptosis and expression of bcl-2and bax.METHODS: A transplanted tumor model was established by injecting human primary gastric cancer cells into subcutaneous tissue of nude mice. Resveratrol (500 mg/kg, 1000 mg/kg and 1500 mg/kg) was directly injected beside tumor body 6 times at an interval of 2 d. Then changes of tumor volume were measured continuously and tumor inhibition rate of each group was calculated. We observed the morphologic alterations by electron microscope, measured the apoptotic rate by TUNEL staining method, detected the expression of apoptosis-regulated genes bcl-2and bax by immunohistochemical staining and PT-PCR.RESULTS: Resveratrol could significantly inhibit carcinoma growth when it was injected near the carcinoma. An inhibitory effect was observed in all therapeutic groups and the inhibition rate of resveratrol at the dose of 500 mg/kg,1 000 mg/kg and 1 500 mg/kg was 10.58%, 29.68% and 39.14%, respectively. Resveratrol induced implanted tumor cells to undergo apoptosis with apoptotic characteristics,including morphological changes of chromatin condensation,chromatin crescent formation, nucleus fragmentation. The inhibition rate of 0.2 mL of normal saline solution, 1 500 mg/kg DMSO, 500 mg/kg resveratrol, 1 000 mg/kg resveratrol, and 1 500 mg/kg resveratrol was L3.68±0.37%, 13.8±0.43%,48.7±1.07%, 56.44±1.39% and 67±0.96%, respectively. The positive rate of bcl-2 protein of each group was 29.48±0.51%,27.56±1.40%, 11.86±0.97%, 5.7±0.84% and 3.92±0.85%,respectively by immunohistochemical staining. The positive rate of bax protein of each group was 19.34±0.35%,20.88±0.91%, 40.02±1.20%, 45.72±0.88% and 52.3±1.54%,respectively by immunohistochemical staining. The density of bcl-2 mRNA in 0.2 mL normal saline solution, 1 500 mg/kg DMSO, 500 mg/kg resveratrol, 1 000 mg/kg resveratrol,and 1 500 mg

  5. Synergistic effect of cisplatin and synchrotron irradiation on F98 gliomas growing in nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Ricard, Clement; Fernandez, Manuel [Grenoble Institut des Neurosciences, Grenoble (France); Université Joseph Fourier, Grenoble (France); Requardt, Herwig [European Synchrotron Radiation Facility, Grenoble (France); Wion, Didier [Grenoble Institut des Neurosciences, Grenoble (France); Université Joseph Fourier, Grenoble (France); Vial, Jean-Claude [Université Joseph Fourier, Grenoble (France); Laboratoire Interdisciplinaire de Physique, St Martin d’Hères (France); Segebarth, Christoph; Sanden, Boudewijn van der, E-mail: boudewijn.vandersanden@ujf-grenoble.fr [Grenoble Institut des Neurosciences, Grenoble (France); Université Joseph Fourier, Grenoble (France)

    2013-09-01

    Synchrotron photoactivation therapy of cisplatin relies on a synergistic effect of synchrotron X-rays and platinum and leads to tumor-cell-killing effects and reduction of the tumor blood perfusion. Among brain tumors, glioblastoma multiforme appears as one of the most aggressive forms of cancer with poor prognosis and no curative treatment available. Recently, a new kind of radio-chemotherapy has been developed using synchrotron irradiation for the photoactivation of molecules with high-Z elements such as cisplatin (PAT-Plat). This protocol showed a cure of 33% of rats bearing the F98 glioma but the efficiency of the treatment was only measured in terms of overall survival. Here, characterization of the effects of the PAT-Plat on tumor volume and tumor blood perfusion are proposed. Changes in these parameters may predict the overall survival. Firstly, changes in tumor growth of the F98 glioma implanted in the hindlimb of nude mice after the PAT-Plat treatment and its different modalities have been characterized. Secondly, the effects of the treatment on tumor blood perfusion have been observed by intravital two-photon microscopy. Cisplatin alone had no detectable effect on the tumor volume. A reduction of tumor growth was measured after a 15 Gy synchrotron irradiation, but the whole therapy (15 Gy irradiation + cisplatin) showed the largest decrease in tumor growth, indicating a synergistic effect of both synchrotron irradiation and cisplatin treatment. A high number of unperfused vessels (52%) were observed in the peritumoral area in comparison with untreated controls. In the PAT-Plat protocol the transient tumor growth reduction may be due to synergistic interactions of tumor-cell-killing effects and reduction of the tumor blood perfusion.

  6. Effects and possible anti-tumor immunity of electrochemotherapy with bleomycin on human colon cancer xenografts in nude mice

    Institute of Scientific and Technical Information of China (English)

    Min-Hua Zheng; Bao-Ming Yu; Bo Feng; Jian-Wen Li; Ai-Guo Lu; Ming-Liang Wang; Wei-Guo Hu; Ji-Yuan Sun; Yan-Yan Hu; Jun-Jun Ma

    2005-01-01

    AIM: To evaluate the anti-tumor effects and possible involvement of anti-tumor immunity of electrochemotherapy (ECT) employing electroporation and bleomycin in human colon cancer xenografts in nude mice, and to establish the experimental basis for clinical application of ECT.METHODS: Forty nude mice, inoculated subcutaneously human colon cancer cell line LoVo for 3 wk, were allocated randomly into four groups: B+E+ (ECT), B+E- (administration of bleomycin alone), B-E+ (administration of electric pulses alone), and B-E- (no treatment). Tumor volumes were measured daily. The animals were killed on the 7th d, the weights of xenografts were measured, and histologies of tumors were evaluated. Cytotoxicity of spleen natural killer (NK) and lymphokine-activated killer (LAK) cells was then assessed by lactic dehydrogenase release assay.RESULTS: The mean tumor volume of group B+E+ was statistically different from the other three groups after the treatment (F= 36.80, P<0.01). There was one case of complete response, seven cases of partial response (PR) in group B+E+, one case of PR in group B+E- and group B-E+ respectively, and no response was observed in group B-E-. The difference of response between group B+E+ and the other three groups was statistically significant (χ2 = 25.67, P<0.01). Histologically, extensive necrosis of tumor cells with considerable vascular damage and inflammatory cells infiltration were observed in group B+E+. There was no statistical difference between the cytotoxicity of NK and LAK cells in the four treatment groups.CONCLUSION: ECT significantly enhances the chemosensitivity and effects of chemotherapy in human colon cancer xenografts in nude mice, and could be a kind of novel treatment modality for human colon cancer.The generation of T-cell-dependent, tumor-specific immunity might be involved in the process of ECT.

  7. Preliminary research on the pathological role of cathepsin-B in subcutaneous heteroplastic pancreatic carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    ZHANG Chong; SUN Jia-bang; LIU Da-chuan; CUI Ye-qing; LIU Shuang; SUN Hai-chen

    2009-01-01

    Background Cathespin-B (cath-B) is an important proteolytic enzyme involved in the disease course of invasion in many types of cancer. Cath-B expression in subcutaneous heteroplastic pancreatic carcinoma in nude mice has not been studied. We investigated the role of cath-B in a model of heteroplastic pancreatic carcinoma in BALB/c nude mice.Methods Thirty-two six-week-old female BALB/c nude mice were equally divided into four groups. PANC-1 cells were inoculated subcutaneously in the left axillary region. Besides volume, weight of subcutaneous tumor, and change in body weight, cath-B expression in each group was measured by immunohistochemical staining, PCR and Western blotting. Its relationship to microvessel density (MVD), CD44v6, and placenta growth factor (PLGF) was also examined. CA-074Me,a specific inhibitor of cath-B, was injected intraperitoneally (i.p.) at different stages of tumor growth in group B and C.Gemcitabine (GEM), was also injected (i.p.) in group D to compare anti-tumor efficacy with CA-074Me.Results Expression of cath-B at different levels was related to tumor growth, MVD, and PLGF expression. In group A (control group), cath-B expression was enhanced more than that seen in other groups. CA-074Me clearly inhibited cath-B expression and tumor growth in group B. There was no difference between group C and D with respect to anti-tumor effect.Conclusions Cath-B correlates with the growth and angiogenesis of tumors, but not with the adhesion induced by CD44v6. CA-074Me clearly inhibited cath-B expression and demonstrated an anti-neoplastic and anti-angiogenesis effect.

  8. Systemic delivery of full-length C/EBPβ /liposome complex suppresses growth of human colon cancer in nude mice

    Institute of Scientific and Technical Information of China (English)

    Li SUN; Bei Bei FU; Ding Gan LIU

    2005-01-01

    C/EBPβ(CCAAT/enhancer-binding protein β) is an important transcription factor involved in cellular proliferation and differentiation. Overexpression of the full-length C/EBPβ protein results in cellular growth arrest and apoptosis.Using a nonviral liposome as carrier, we delivered the full-length C/EBPβ expression plasmid, Pcn, into nude mice bearing CW-2 human colon cancer tumors via tail vein. Southern blots revealed that the major organs and tumors were transfected. Experimental gene therapy showed that a strong suppression of tumor growth was observed in the pCNtreated mice, and such suppression was due to the overexpression of C/EBPβ, leading to the increased apoptosis in tumors of Pcn-treated mice. No apparent toxic effects of Pcn/liposome complex were observed in the animals. Thus, C/EBPβ has tumor suppression effect in vivo and may be used in gene therapy for cancers.

  9. In vivo tracking of human placenta derived mesenchymal stem cells in nude mice via 14C-TdR labeling

    OpenAIRE

    2015-01-01

    Background In order to shed light on the regenerative mechanism of mesenchymal stem cells (MSCs) in vivo, the bio-distribution profile of implanted cells using a stable and long-term tracking method is needed. We herein investigated the bio-distribution of human placental deciduas basalis derived MSCs (termed as PDB-MSCs) in nude mice after intravenous injection by carbon radioisotope labeling thymidine (14C-TdR), which is able to incorporate into new DNA strands during cell replication. Resu...

  10. Interaction between three subpopulations of Ehrlich carcinoma in mixed solid tumours in nude mice: evidence of contact domination

    DEFF Research Database (Denmark)

    Aabo, K; Vindeløv, L L; Spang-Thomsen, M

    1994-01-01

    Clonal interaction between three subpopulations of Ehrlich carcinoma were studied during growth as mixed solid tumours and as ascites tumours in immune-incompetent nude NMRI mice. The tumour cell lines differed in DNA content as determined by DNA flow cytometry (FCM). Tumour growth was evaluated...... by tumour growth curves including calculation of tumour volume doubling times, tumour weight on day 14, cell cycle times (per cent labelled mitoses) and cell cycle distributions (FCM). Two subpopulations (E1.15 and E1.95) showed nearly identical growth characteristics during both solid and ascites tumour...

  11. Comparison of characteristics of human small cell carcinoma of the lung in patients, in vitro and transplanted into nude mice

    DEFF Research Database (Denmark)

    Engelholm, S A; Spang-Thomsen, M; Vindeløv, L L;

    1986-01-01

    % of the cases. Fifty-four % of the tumours could be established as serially transplantable tumours in nude mice. The tumours were characterized by histology, electron microscopy, DNA index, and cell cycle distribution. The in vitro cell lines were furthermore characterized by the plating efficiency...... and by doubling time. The macroscopic growth of the heterotransplanted tumours was ascribed to a transformed Gompertz function. The tumour cells preserved their light microscopic constitution of small cell carcinoma of the lung in the model systems. The heterogeneity of the original tumours was reflected in vitro...

  12. Characterization of casein kinase II in human colonic carcinomas after heterotransplantation into nude mice

    DEFF Research Database (Denmark)

    Seitz, G; Münstermann, U; Schneider, H R

    1989-01-01

    they were derived. Immunoblots using a polyclonal CKII-specific antibody showed that the increase of activity was due to a higher expression of the enzyme. Immunohistochemical studies on cross sections of nude mouse tumours showed that most of the CKII molecules were located at the peripheral part...

  13. Growth kinetics of four human breast carcinomas grown in nude mice

    DEFF Research Database (Denmark)

    Spang-Thomsen, M; Rygaard, K; Hansen, L;

    1989-01-01

    The immune-deficient nude mouse with human tumor xenografts is an appropriate model system for performing detailed growth kinetic examinations. In the present study one estrogen and progesterone receptor-negative (T60) and three receptor-positive (Br-10, MCF-7, T61) human breast cancer xenografts...

  14. Skin graft influence in human tissue radiated in nude mice regeneration; Influencia do enxerto de pele humana irradiada na regeneracao tecidual de camundongos nude

    Energy Technology Data Exchange (ETDEWEB)

    Miranda, Jurandir Tomaz de

    2016-07-01

    Over the last few years it has increased the interest in the human skin grafts radio sterilized for application mainly in extensive and deep burns. Because these grafts quickly grip and present antigenic lower potential, compared with other treatments used. The purpose of this study was to evaluate the histoarchitecture of human skin grafts irradiated with doses 25 kGy, 50 kGy and non-irradiated during the repair tissue process in nude mice submitted by skin grafting in the dorsal region. Three groups of animals received irradiated human skin grafts (25 kGy and 50 kGy) and non-irradiated and were euthanized on the 3{sup rd}, 7{sup th} and 21{sup th} day after the surgery. Indeed, routine histologic procedures, tissue samples were stained with hematoxylin and eosin (HE) for quantification of keratinocytes, fibroblasts, immune cells and blood vessels and immunofluorescence (IF) was performed to determine the expression human collagen type I and collagen type I and III mouse. Therefore, quantification of both the cells and the collagen types was performed by image analysis using Image-Pro Plus 6.0 software. Histologic results demonstrated at a dose of 25 kGy that human skin irradiation when grafted influences the increase in the number of cells in wound site over time and it provides better dispersion of these cells. In addition, on the 21{sup st} day, three groups of animals with human skin graft were embedded part of the graft in the healing process. On the other hand, the group not irradiated showed greater incorporation of the graft (43 %), but less production of collagen type III mouse (22 %). Since the groups irradiated skin graft showed lower graft incorporation (6 and 15%), but with greater production of collagen type III mice (35 % and 28 % to 25 kGy and 50 kGy, respectively). In conclusion, this study presented that the group irradiated to 25 kGy and it has a higher cell proliferation and vessel formation, and better remodeling of the healing area. (author)

  15. Receptor FGFRL1 acts as a tumor suppressor in nude mice when overexpressed in HEK 293 Tet-On cells

    Science.gov (United States)

    Zhuang, Lei; Steinberg, Florian; Trueb, Beat

    2016-01-01

    Fibroblast growth factor receptor-like 1 (FGFRL1) is a transmembrane receptor that interacts with heparin and FGF ligands. In contrast to the classical FGF receptors, FGFR1 to FGFR4, it does not appear to affect cell growth and proliferation. In the present study, an inducible gene expression system was utilized in combination with a xenograft tumor model to investigate the effects of FGFRL1 on cell adhesion and tumor formation. It was determined that recombinant FGFRL1 promotes the adhesion of HEK 293 Tet-On® cells in vitro. Moreover, when such cells are induced to express FGFRL1ΔC they aggregate into huge clusters. If injected into nude mice, the cells form large tumors. Notably, this tumor growth is completely inhibited when the expression of FGFRL1 is induced. The forced expression of FGFRL1 in the tumor tissue may restore contact inhibition, thereby preventing growth of the cells in nude mice. The results of the present study demonstrate that FGFRL1 acts as a tumor suppressor similar to numerous other cell adhesion proteins. It is therefore likely that FGFRL1 functions as a regular cell-cell adhesion protein. PMID:28101211

  16. Uptake of the {sup 188}Re(V)-DMSA complex by cervical carcinoma cells in nude mice: pharmacokinetics and dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Salinas, Laura; Ferro-Flores, Guillermina E-mail: gff@nuclear.inin.mxtendilla@acnet.net; Arteaga-Murphy, Consuelo; Pedraza-Lopez, Martha; Hernandez-Gutierrez, Salomon; Azorin-Nieto, Juan

    2001-03-01

    The uptake of the rhenium-188 ({sup 188}Re(V)-DMSA) complex of dimercaptosuccinic acid by cervical carcinoma cells in nude mice was evaluated. The pharmacokinetics and dosimetry calculations in normal rats were also evaluated. The images obtained in mice did not show significant accumulation in metabolic organs and the biodistribution studies showed that 3.52{+-}0.76% of the injected activity per gram (n=4) was taken up by the tumor. This percentage produces a cumulated activity of 35.63{+-}8.40 MBq h and an equivalent dose per injected activity of 260{+-}8.91 mSv/MBq. Pharmacokinetics and dosimetry of the {sup 188}Re(V)-DMSA complex indicate that this radiopharmaceutical could be evaluated in patients with soft tissue tumors, since the risk of radiation damage to the kidney or red bone marrow could not be an obstacle for its application in therapeutic nuclear medicine.

  17. Effects of thalidomide on angiogenesis and tumor growth and metastasis of human hepatocellular carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    Zhong-Lin Zhang; Zhi-Su Liu; Quan Sun

    2005-01-01

    AIM: To investigate the effects of thalidomide on angiogenesis, tumor growth and metastasis of hepatocellular carcinoma in nude mice.METHODS: Twenty-four nude mice were randomly divided into therapy group and control group, 12 mice in each group. Thalidomide dissolved in 0.5% sodium carboxyl methyl cellulose (CMC) suspension was administered intraperitoneally once a day at the dose of 200 mg/kg in therapy group, and an equivalent volume of 0.5% CMC in control group. Mice were sacrificed on the 30th d, tumor size and weight and metastases in liver and lungs were measured. CD34 and VEGF mRNA in tumor tissue were detected by immunohistochemistry and semi-quantitative RT-PCR respectively and microvessel density (MVD) was counted. Serum concentrations of TNF-α and ALT and AFP were also tested.RESULTS: MVD and VEGF mRNA in therapy group were less than those in control group (31.08±16.23 vessels/HP vs 80.00±26.27 vessels/HP, 0.0538±0.0165 vs 0.7373±0.1297,respectively, P<0.05). No statistical difference was observed in tumor size and weight and metastases in liver and lungs.TNF-α was significantly lower in therapy group than in control group (28.64±4.64 ng/L vs42.69±6.99 ng/L, P<0.05). No statistical difference in ALT and AFP was observed between groups.CONCLUSION: Thalidomide can significantly inhibitangiogenesis and metastasis of hepatocellular carcinoma.Italso has inhibitory effects on circulating TNF-α.

  18. Effect of antidepressants on body weight, ethology and tumor growth of human pancreatic carcinoma xenografts in nude mice

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To investigate the effects of mirtazapine and fluoxetine, representatives of the noradrenergic and specific serotonergic antidepressant (NaSSA) and se- lective serotonin reuptake inhibitor (SSRI) antidepres- sant respectively, on body weight, ingestive behavior, locomotor activity and tumor growth of human pancre- atic carcinoma xenografts in nude mice. METHODS: A subcutaneous xenograft model of hu- man pancreatic cancer cell line SW1990 was estab- lished in nude mice. The tumor-bearing mice were ran- domly divided into mirtazapine group [10 mg/(kg'd)], (an equivalent normal saline solution) (7 mice in each group). Doses of all drugs were administered orally, once a day for 42 d. Tumor volume and body weight were measured biweekly. Food intake was recorded once a week. Locomotor activity was detected weekly using an open field test (OFT). RESULTS: Compared to the fluoxetine, mirtazapine significantly increased food intake from d 14 to 42 and attenuated the rate of weight loss from d 28 to 42 (t = 4.38, P = 10.89, P < 0.01). These effects disappeared in the mirtazapine and fluoxetine groups during 2-6 wk. The grooming activity was higher in the mirtazapine group than in the fluoxetine group (10.1 ± 2.1 vs 7.1 ± 1.9 ) (t = 2.40, P < 0.05) in the second week. There was no significant difference in tumor vol- ume and tumor weight of the three groups. CONCLUSION: Mirtazapine and fluoxetine have no effect on the growth of pancreatic tumor. However, mirtazapine can significantly increase food intake and improve nutrition compared with fluoxetine in a pan- creatic cancer mouse model.

  19. Alendronate decreases orthotopic PC-3 prostate tumor growth and metastasis to prostate-draining lymph nodes in nude mice

    Directory of Open Access Journals (Sweden)

    Väänänen Kalervo

    2008-03-01

    Full Text Available Abstract Background Metastatic prostate cancer is associated with a high morbidity and mortality but the spreading mechanisms are still poorly understood. The aminobisphosphonate alendronate, used to reduce bone loss, has also been shown to inhibit the invasion and migration of prostate cancer cells in vitro. We used a modified orthotopic PC-3 nude mouse tumor model of human prostate cancer to study whether alendronate affects prostate tumor growth and metastasis. Methods PC-3 cells (5 × 105 were implanted in the prostates of nude mice and the mice were treated with alendronate (0.5 mg/kg/day in PBS, s.c. or vehicle for 4 weeks. After sacrifice, the sizes of tumor-bearing prostates were measured and the tumors and prostate-draining regional iliac and sacral lymph nodes were excised for studies on markers of proliferation, apoptosis, angiogenesis and lymphangiogenesis, using histomorphometry and immunohistochemistry. Results Tumor occurrence in the prostate was 73% in the alendronate-treated group and 81% in the control group. Mean tumor size (218 mm3, range: 96–485 mm3, n = 11 in the alendronate-treated mice was 41% of that in the control mice (513 mm3, range: 209–1350 mm3, n = 13 (p p p p Conclusion Our results demonstrate that alendronate treatment opposes growth of orthotopic PC-3 tumors and decreases tumor metastasis to prostate-draining lymph nodes. This effect could be at least partly explained by decreased angiogenesis and increased apoptosis. The results suggest that bisphosphonates have anti-tumoral and anti-invasive effects on primary prostate cancer.

  20. Insulin-producing cells from adult human bone marrow mesenchymal stem cells control streptozotocin-induced diabetes in nude mice.

    Science.gov (United States)

    Gabr, Mahmoud M; Zakaria, Mahmoud M; Refaie, Ayman F; Ismail, Amani M; Abou-El-Mahasen, Mona A; Ashamallah, Sylvia A; Khater, Sherry M; El-Halawani, Sawsan M; Ibrahim, Rana Y; Uin, Gan Shu; Kloc, Malgorzata; Calne, Roy Y; Ghoneim, Mohamed A

    2013-01-01

    Harvesting, expansion, and directed differentiation of human bone marrow-derived mesenchymal stem cells (BM-MSCs) could provide an autologous source of surrogate β-cells that would alleviate the limitations of availability and/or allogenic rejection following pancreatic or islet transplantation. Bone marrow cells were obtained from three adult type 2 diabetic volunteers and three nondiabetic donors. After 3 days in culture, adherent MSCs were expanded for two passages. At passage 3, differentiation was carried out in a three-staged procedure. Cells were cultured in a glucose-rich medium containing several activation and growth factors. Cells were evaluated in vitro by flow cytometry, immunolabeling, RT-PCR, and human insulin and c-peptide release in responses to increasing glucose concentrations. One thousand cell clusters were inserted under the renal capsule of diabetic nude mice followed by monitoring of their diabetic status. At the end of differentiation, ∼5-10% of cells were immunofluorescent for insulin, c-peptide or glucagon; insulin, and c-peptide were coexpressed. Nanogold immunolabeling for electron microscopy demonstrated the presence of c-peptide in the rough endoplasmic reticulum. Insulin-producing cells (IPCs) expressed transcription factors and genes of pancreatic hormones similar to those expressed by pancreatic islets. There was a stepwise increase in human insulin and c-peptide release by IPCs in response to increasing glucose concentrations. Transplantation of IPCs into nude diabetic mice resulted in control of their diabetic status for 3 months. The sera of IPC-transplanted mice contained human insulin and c-peptide but negligible levels of mouse insulin. When the IPC-bearing kidneys were removed, rapid return of diabetic state was noted. BM-MSCs from diabetic and nondiabetic human subjects could be differentiated without genetic manipulation to form IPCs that, when transplanted, could maintain euglycemia in diabetic mice for 3 months

  1. Change in expression of apoptosis genes after hyperthermia, chemotherapy and radiotherapy in human colon cancer transplanted into nude mice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the change in expression of p53, Bcl-2, and Bax genes in human colon cancer cells transplanted into nude mice after hyperthermia,chemotherapy, radiotherapy, thermochemotherapy,thermoradiotherapy and thermochemoradiotherapy.METHODS: Human colon cancer cell line (HT29)was transplanted into the hind limbs of nude mice.Under laboratory simulated conditions of hyperthermia (43℃, 60 min), the actual radiation doses and doses of mitomycin C (MMC) were calculated in reference to the clinical radiotherapy for human rectal cancer and chemotherapy prescription for colon cancer. The mice were divided into 6 groups according to the treatment approaches: hyperthermia, chemotherapy,radiotherapy, thermochemotherapy, thermoradiotherapy,and thermochemoradiotherapy. The mice were sacrificed at different time points and the tumor tissue was taken for further procedures. The morphologic changes in membrane, cytoplasm and nuclei of tumor cells of p53, Bcl-2, and Bax after treatment, were observed by immunohistochemistry staining.RESULTS: All of the six treatment modalities downregulated the expression of p53, Bcl-2 and up-regulated the expression of Bax at different levels. The combined therapy of hyperthermia, with chemotherapy, and/or irradiation showed a greater effect on down-regulating the expression of p53 (0.208 ± 0.009 vs 0.155 ± 0.0115,P < 0.01) and Bcl-2 (0.086 ± 0.010 vs 0.026 ± 0.0170,P < 0.01) and up-regulating Bax expression (0.091 ±0.0013 vs 0.207 ±0.027, P < 0.01) compared with any single therapy.CONCLUSION: Hyperthermia enhances the effect of radio- and chemotherapy on tumors by changing the expression of apoptosis genes, such as p53, Bcl-2 and Bax.

  2. Detection and assessment of human tumours producing granulocyte-macrophage colony-stimulating factor (GM-CSF) by heterotransplantation into nude mice.

    OpenAIRE

    1980-01-01

    Production of granulocyte-macrophage colony-stimulating factor(s) (GM-CSF) by human tumours was investigated using heterotransplantation of a number of different tumours in nude mice. An increase in granulocyte numbers (> 20,000/mm3) in the peripheral blood of nude mice accompanied the growth of 9 of the 25 transplanted tumours. GM-CSF activity tested against normal human marrow cells was relatively high in 6 of these 9 tumours. Moreover there was either weak activity or none at all in 14 of ...

  3. Combined therapeutic effect and molecular mechanisms of metformin and cisplatin in human lung cancer xenografts in nude mice

    Directory of Open Access Journals (Sweden)

    Yu-Qin Chen

    2015-01-01

    Full Text Available Objective: This work was aimed at studying the inhibitory activity of metformin combined with the commonly used chemotherapy drug cisplatin in human lung cancer xenografts in nude mice. We also examined the combined effects of these drugs on the molecular expression of survivin, matrix metalloproteinase-2 (MMP-2, vascular endothelial growth factor-C (VEGF-C, and vascular endothelial growth factorreceptor-3 (VEGFR-3 to determine the mechanism of action and to explore the potential applications of the new effective drug therapy in lung cancer. Materials and Methods: The nude mice model of lung cancer xenografts was established, and mice were randomly divided into the metformin group, the cisplatin group, the metformin + cisplatin group, and the control group. The animals were killed 42 days after drug administration, and the tumor tissues were then sampled to detect the messenger ribonucleic acid (mRNA and protein expression levels of survivin, MMP-2, VEGF-C, and VEGFR-3 by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR. Results: The protein and mRNA expression levels of survivin, MMP-2, VEGF-C, and VEGFR-3 in the cisplatin group and the combined treatment group were lower than that in the control group (P < 0.05. In the metformin group, the expression of MMP-2 protein and mRNA was lower than that in the control group (P < 0.05. The protein and mRNA expression levels of survivin, MMP-2, VEGF-C, and VEGFR-3 in the combined treatment group were lower than that in the cisplatin group and the metformin group (P < 0.05. Conclusions: Metformin inhibited the expression of MMP-2, cisplatin and the combined treatment inhibited the expression of survivin, MMP-2, VEGF-C, and VEGFR-3, and the combined treatment of metformin with cisplatin resulted in enhanced anti-tumor efficacy.

  4. Experimental study on ultrasound-guided intratumoral injection of "Star-99" in treatment of hepatocellular carcinoma of nude mice

    Institute of Scientific and Technical Information of China (English)

    Li-Wu Lin; Xiao-Dong Lin; Yi-Mi He; Shang-Da Gao; En-Sheng Xue

    2003-01-01

    AIM: To investigate the anti-cancer effect and the immunological mechanism of ultrasound-guided intratumoral injection of Chinese medicine "Star-99" in hepatocellular carcinoma (HCC) of nude mice.METHODS: Twenty-eight human hepatocellular carcinoma SMMC-7721 transplanted nude mice, 14 of hypodermically implanted and 14 of orthotopic liver transplanted, were randomly divided into three groups of which 14 mice with Star-99, and 7 with ethanol and saline respectively. Ten days after the transplantation the medicines were injected into the tumors of all the nude mice once every 5 days.After 4 injections the nude mice were killed. The diameters of three dimension of the tumors were measured by high frequency ultrasound before and after the treatment and the tumor growth indexes* (TGI) were calculated.Radioimmunoassay was used to detect the serum levels of interleukin-2 (IL-2) and tumor necrosis factor (TNF)-alpha.The tumor tissues were sent for flow cytometry (FCM) DNA analysis. Apoptotic cells were visualized by TUNEL assay.All the experiments were carried out by double blind method. zRESULTS: The TGI of Star-99 group (0.076±0.024) was markedly lower than that of the saline group (4.654±1.283)(P<0.01). It also seemed to be lower than that of the ethanol group (0.082±0.028), but not significantly different (P>0.05).Serum levels of IL-2 and TNF-α were markedly higher than those of ethanol group and saline groups (P<0.05). The mean apoptotic index (AI: percentage of TUNEL signal positive cells)in Star-99 group (48.98±5.09 %) was significantly higher than that of the ethanol group (11.95±2.24 %) and the saline group (10.48±3.85 %) (P<0.01). FCM DNA analysis showed that the appearance rate of the apoptosis peak in Srar-99group was 92.9 %, markedly higher than that of the ethanol group (14.3 %) and the saline group (0.0 %) (P<0.01).Correlation (r=0.499, P<0.05) was found between AI and serum level of TNF-α.CONCLUSION: Star-99 has an effect on the

  5. Effect of 17 beta-oestradiol on growth curves and flow cytometric DNA distribution of two human breast carcinomas grown in nude mice

    DEFF Research Database (Denmark)

    Brünner, N; Spang-Thomsen, M; Vindeløv, L

    1983-01-01

    The effect of 17 beta-oestradiol on a "receptor positive" and on a "receptor negative" human breast carcinoma grown in nude mice was studied. Experimental growth data were used to determine the effect on tumour growth. Flow cytometric DNA analysis (FCM) performed on tumour tissue obtained...

  6. An approach to automatic blood vessel image registration of microcirculation for blood flow analysis on nude mice.

    Science.gov (United States)

    Lin, Wen-Chen; Wu, Chih-Chieh; Zhang, Geoffrey; Wu, Tung-Hsin; Lin, Yang-Hsien; Huang, Tzung-Chi; Liu, Ren-Shyan; Lin, Kang-Ping

    2011-04-01

    Image registration is often a required and a time-consuming step in blood flow analysis of large microscopic video sequences in vivo. In order to obtain stable images for blood flow analysis, frame-to-frame image matching as a preprocessing step is a solution to the problem of movement during image acquisition. In this paper, microscopic system analysis without fluorescent labelling is performed to provide precise and continuous quantitative data of blood flow rate in individual microvessels of nude mice. The performance properties of several matching metrics are evaluated through simulated image registrations. An automatic image registration programme based on Powell's optimisation search method with low calculation redundancy was implemented. The matching method by variance of ratio is computationally efficient and improves the registration robustness and accuracy in practical application of microcirculation registration. The presented registration method shows acceptable results in close requisition to analyse red blood cell velocities, confirming the scientific potential of the system in blood flow analysis.

  7. Adeno-associated virus-mediated doxycycline-regulatable TRAIL expression suppresses growth of human breast carcinoma in nude mice

    Directory of Open Access Journals (Sweden)

    Zheng Liu

    2012-04-01

    Full Text Available Abstract Background Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL functions as a cytokine to selectively kill various cancer cells without toxicity to most normal cells. Numerous studies have demonstrated the potential use of recombinant soluble TRAIL as a cancer therapeutic agent. We have showed previous administration of a recombinant adeno-associated virus (rAAV vector expressing soluble TRAIL results in an efficient suppression of human tumor growth in nude mice. In the present study, we introduced Tet-On gene expression system into the rAAV vector to control the soluble TRAIL expression and evaluate the efficiency of the system in cancer gene therapy. Methods Controllability of the Tet-On system was determined by luciferase activity assay, and Western blotting and enzyme-linked immunoabsorbent assay. Cell viability was determined by MTT assay. The breast cancer xenograft animal model was established and recombinant virus was administrated through tail vein injection to evaluate the tumoricidal activity. Results The expression of soluble TRAIL could be strictly controlled by the Tet-On system in both normal and cancer cells. Transduction of human cancer cell lines with rAAV-TRE-TRAIL&rAAV-Tet-On under the presence of inducer doxycycline resulted in a considerable cell death by apoptosis. Intravenous injection of the recombinant virus efficiently suppressed the growth of human breast carcinoma in nude mice when activated by doxycycline. Conclusion These data suggest that rAAV-mediated soluble TRAIL expression under the control of the Tet-On system is a promising strategy for breast cancer therapy.

  8. Effects of Acanthus ebracteatus Vahl on tumor angiogenesis and on tumor growth in nude mice implanted with cervical cancer

    Directory of Open Access Journals (Sweden)

    Mahasiripanth T

    2012-08-01

    Full Text Available Taksanee Mahasiripanth,1 Sanya Hokputsa,2 Somchai Niruthisard,3 Parvapan Bhattarakosol,4 Suthiluk Patumraj51Inter-Department of Physiology, Chulalongkorn University, Bangkok, Thailand; 2Research and Development Institute, Government Pharmaceutical Organization, Bangkok, Thailand; 3Obstetrics and Gynecology Department, 4Department of Microbiology, 5Center of Excellence for Microcirculation, Faculty of Medicine, Chulalongkorn University, Bangkok, ThailandPurpose: The aim of this study was to examine the effects of the crude extract of Acanthus ebracteatus Vahl (AE on tumor growth and angiogenesis by utilizing a tumor model in which nude mice were implanted with cervical cancer cells containing human papillomavirus 16 DNA (HPV-16 DNA.Materials and methods: The growth-inhibitory effect of AE was investigated in four different cell types: CaSki (HPV-16 positive, HeLa (HPV-18 positive, hepatocellular carcinoma cells (HepG2, and human dermal fibroblast cells (HDFs. The cell viabilities and IC50 values of AE were determined in cells incubated with AE for different lengths of time. To conduct studies in vivo, female BALB/c nude mice (aged 6–7 weeks, weighing 20–25 g were used. A cervical cancer-derived cell line (CaSki with integrated HPV-16 DNA was injected subcutaneously (1 × 107 cells/200 µL in the middle dorsum of each animal (HPV group. One week after injection, mice were fed orally with AE crude extract at either 300 or 3000 mg/kg body weight/day for 14 or 28 days (HPV-AE groups. Tumor microvasculature and capillary vascularity were determined using laser scanning confocal microscopy. Tumor tissue was collected from each mouse to evaluate tumor histology and vascular endothelial growth factor (VEGF immunostaining.Results: The time-response curves of AE and the dose-dependent effect of AE on growth inhibition were determined. After a 48-hour incubation period, the IC50 of AE in CaSki was discovered to be significantly different from that of

  9. Pleiotrophin Transforms NIH 3T3 Cells and Induces Tumors in Nude Mice

    Science.gov (United States)

    Chauhan, Anil K.; Li, Yue-Sheng; Deuel, Thomas F.

    1993-01-01

    The pleiotrophin (PTN) gene (Ptn) encodes an 18-kDa protein that is highly conserved among mammalian species and that functions as a weak mitogen and promotes neurite-outgrowth activity in vitro. To further investigate the role PTN plays in regulating cell growth, we overexpressed the bovine PTN cDNA and now show that PTN phenotypically transforms NIH 3T3 cells, as evidence by increased cell number at confluence, focus formation, anchorage-independent growth, and tumor formation in the nude muse. The results demonstrate that the Ptn gene has the potential to regulate NIH 3T3 cell growth and suggest that PTN may influence abnormal cell growth in vivo.

  10. Antitumor Activities and Apoptosis-regulated Mechanisms of Fermented Wheat Germ Extract in the Transplantation Tumor Model of Human HT-29 Cells in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jia Yan; XIAO Xiang; DONG Ying; WU Jing; ZHOU Xing Hua

    2015-01-01

    Objective A subcutaneous transplantation tumor model of human HT-29 cells in nude mice was established to evaluate anticarcinogenic activities, and the apoptosis-regulated mechanism effect of aqueous extract of fermented wheat germ with Lactobacillus plantarum dy-1 (LFWGE). Methods The HT-29 cells were transplanted via subcutaneous injection of 1×107 cells into the right flank of each nude mouse. Then, nude mice were treated for 30 d with LFWGE (high-dose 2 g/kg/d;low-dose 1 g/kg/d) and for 7 d with 5-fluorouracil (5-FU, 25 mg/kg/d) by gavage and intraperitoneal injection, respectively. An inhibition of tumor growth was observed. Results Tumor volume and weights decreased significantly in both groups of nude mice treated with LFWGE. In addition, the cell apoptosis rate of the LFWGE group (2 g/kg/d, 60.1%±4.4%; 1 g/kg/d, 58.6%±6.9%) was significantly higher than that of the control group (11.5%±1.6%) and 5-FU group (32.1%±3.5%) as measured by the TUNEL assay. Moreover, the real-time fluorescent quantitative PCR and Western blot method further confirmed these enhancing apoptosis and growth inhibition effects. The involvement of LFWGE in inducing apoptosis was confirmed by the expression of Bax, Bcl-2, Caspase-3, and CyclinD1. Conclusion The results showed that LFWGE could induce subcutaneous transplantation tumor apoptosis in nude mice and could be as a natural nutrient supplements or chemopreventive agent in the treatment of human colon cancer.

  11. A nude mice model of human rhabdomyosarcoma lung metastases for evaluating the role of polysialic acids in the metastatic process.

    Science.gov (United States)

    Daniel, L; Durbec, P; Gautherot, E; Rouvier, E; Rougon, G; Figarella-Branger, D

    2001-02-22

    PSA is an oncodevelopmental antigen usually expressed in human tumors with high metastatic potential. Here we set up a metastatic model in nude mice by using TE671 cells, which strongly express PSA-NCAM. We observed the formation of lung metastases when TE671 cells were injected intravenously, intramuscularly, and intraperitoneally, but not subcutaneously. Intraperitoneal injections also induced peritoneal carcinosis, ascites, and liver metastases. To evaluate the putative role of PSA in the metastatic process we used a specific cleavage of PSA on NCAM by endoneuraminidase-N on intraperitoneal primary tumors. Mice with primary intramuscular tumors were taken as control. Repeated injections of endoneuraminidase-N led to a decrease in PSA expression in primary intraperitoneal nodules and ascites but not in intramuscular primary tumors. Endoneuraminidase-N also increased the delay in ascitic formation and decreased the number of lung or liver metastases in the case of intraperitoneal tumors but not in the case of intramuscular tumors. When metastases occurred in endoneuraminidase-N injected animals, they strongly expressed PSA-NCAM. Therefore, we established a relationship between PSA expression on the surface of primary tumor cells and the metastatic process.

  12. Transplantability of human lymphoid cell line, lymphoma, and leukemia in splenectomized and/or irradiated nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, S.; Shimosato, Y.; Kuroki, M.; Sato, Y.; Nakajima, T.

    1980-07-01

    The effects of splenectomy and/or whole-body irradiation of nude mice before xenotransplantation of lymphoid cell lines, lymphoma, and leukemia were studied. Transplantation after whole-body irradiation resulted in the increased ''take'' rate of three cultured cell lines (two of T-cell-derived acute lymphocytic leukemia and one of B-cell derived acute lymphocytic leukemia) and in the tumorous growth of Burkitt-derived Raji and spontaneously transformed lymphoblastoid cell lines. With splenectomy plus irradiation as a pretreatment, tumorous growth occurred in four other cell lines which were not transplantable after irradiation only (two cell lines of Epstein-Barr virus-transformed cord blood cells and one each of null acute lymphocytic leukemia and nodular lymphoma-derived cell lines). Direct transplantation of leukemia and lymphoma cells into the pretreated mice was successful in 7 of 24 cases (29%). B-cell-derived diffuse large lymphoid lymphoma was transplantable in three of seven cases (43%). However, lymphoma and leukemia of peripheral T-cell origin was difficult to transplant even with pretreatment, and only one pleomorphic T-cell lymphoma grew to a significant size (2 cm). One tumor each of B-cell-derived diffuse large lymphoid and T-cell diffuse lymphoblastic lymphoma became transplantable.

  13. Arsenic Trioxide Induced Differentiation and Apoptosis in Human Nasopharyngeal Carcinoma Xenografts in BALB/C Nude Mice

    Institute of Scientific and Technical Information of China (English)

    ZHENGYuwu; DUCaiwen; LIDerui; LINYingcheng; WUMingyao

    2004-01-01

    To study the effect of arsenic trioxide (As2O3) on human poorly differentiated nasopharyngeal cancer cell line, CSNE-1, in vivo and its possible mechanism of action. Methods: CSNE-1 cells were established as xenografts in BALB/C nude mice. The tumor-bearing mice were treated with As2O3 at the dose of 5 mg/kg every day. The tumor growth was observed by tumor-growth curve. Morphologic changes were studied under light microscopy and electron microscopy. TUNEL was used to detect apoptosis. The expression of PCNA, p53, Bcl-2 and Bax were determined by immunohistochemistry. Results: The cell growth and proliferate activity were significantly inhibited by As203 at the dose of 5 mg/kg every day. Morphologic changes such as the formation of keratinization of tumor cells, decreased ratio of nuclear/cytoplasm, increased organelle and plasmic fibril in cytoplasm were identified. Cytodesma, desmosomes and micro-process were seen under light microscopy and transmission electron microscopy, which revealed that the cancer cells underwent differentiation. In addition, remarkable cell apoptosis were observed by TUNEL assay. Over expression of p53 and Bax was detected in the As203 treatment group when compared with control group. Conclusion: As203 inhibited proliferation of human poorly differentiated nasopharyngeal cancer cell CSNE-1 by inducing differentiation and apoptosis, which may be related to the up-regulation of p53 and Bax expression.

  14. Visualization of in Vivo Hydrogen Sulfide Production by a Bioluminescence Probe in Cancer Cells and Nude Mice.

    Science.gov (United States)

    Tian, Xiaodong; Li, Zhiyan; Lau, Choiwan; Lu, Jianzhong

    2015-11-17

    Hydrogen sulfide (H2S) has emerged as an exciting endogenous gasotransmitter in addition to nitric oxide and carbon monoxide. However, its precise measurement in living cells and animals remains a challenge. In this study, a novel bioluminescence H2S probe was designed and synthesized by modifying the 6'-amino group of d-aminoluciferin into a 6'-azido group, which was highly selective against other reactive sulfur, nitrogen, and oxygen species. Our H2S probe azidoluciferin sensitively reacted with H2S to release d-aminoluciferin with a strong bioluminescence signal. On the basis of its high selectivity and sensitivity, the H2S probe was used to detect H2S production in live cancer cells and nude mice. The bioluminescence signal decreased in mice treated with propargylglycine, an inhibitor of H2S, suggesting that our H2S probe can detect endogenous H2S in real time, in vivo. Overall, the excellent sensing properties of the probe combined with its bioimaging capability make it a useful tool to study H2S biological roles.

  15. Intervention of Mirtazapine on gemcitabine-induced mild cachexia in nude mice with pancreatic carcinoma xenografts

    Institute of Scientific and Technical Information of China (English)

    Shu-Man Jiang; Jian-Hua Wu; Lin Jia

    2012-01-01

    AIM:To investigate the effect of Mirtazapine on tumor growth,food intake,body weight,and nutritional status in gemcitabine-induced mild cachexia.METHODS:Fourteen mice with subcutaneous xenografts of a pancreatic cancer cell line (SW1990) were randomly divided into Mirtazapine and control groups.Either Mirtazapine (10 mg/kg) or saline solution was orally fed to the mice every day after tumor implantation.A model of mild cachexia was then established in both groups by intraperitoneal injection of Gemcitabine (50 mg/kg) 10 d,13 d,and 16 d after tumor implantation.Tumor size,food intake,body weight,and nutritional status were measured during the experiment.All mice were sacrificed at day 28.RESULTS:(1) After 7 d of gemcitabine administration,body-weight losses of 5%-7% which suggested mild cachexia were measured; (2) No significant difference in tumor size was detected between the Mirtazapine and control groups (P > 0.05); and (3) During the entire experimental period,food intake and body weight were slightly greater for the Mirtazapine group compared with controls (although these differences were not statistically significant).After 21 d,mice in the Mirtazapine group consumed significantly more food than control mice (3.95 ± 0.14 g vs 3.54 ± 0.10 g,P =0.004).After 25 d,mice in the Mirtazapine group were also significantly heavier than control mice (17.24 ± 0.53 g vs 18.05 ± 0.68 g,P =0.014).CONCLUSION:Mild cachexia model was successfully established by gemcitabine in pancreatic tumor-bearing mice.Mirtazapine can improve gemcitabine-induced mild cachexia in pancreatic tumor-bearing mice.It was believed to provide a potential therapeutic perspective for further studies on cachexia.

  16. Effects of endogenous nitric oxide induced by 5-fluorouracil and L-Arg on liver carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To study the effects of endogeous nitric oxide induced by 5-fluorouracil (5-FU) and L-arginine (L-Arg)on the human liver carcinoma model in nude mice.METHODS: The human liver carcinoma model in nude mice was established with BEL-7402 cells and normal saline (NS), 5-FU and 5-FU + L-Arg injected intraperitoneally. The tumor size was measured. The necrotic degree and range were observed under microscope. The apoptosis of cancer cell was detected by turmina deoxynucleotidyl transferanse mediated dUTP nick end labeling (TUNEL) method. Immunohistochemical method was performed to determine the expression of iNOS, P16, BAX. The chemical colorimetry was used to test the activity and nitrate reductase method was adopted to test the concentration of nitric oxide (NO) in the tumor tissue. The BI2000 pathological image analyzer was used to analyze the result of immunohistochemistry.RESULTS: 5-FU combined with L-Arg could inhibit the tumor growth apparently. In NS, 5-FU and 5-FU+L-Arg groups, the changes of tumor volumes were 257.978 ± 59.0, 172.232 ± 66.0 and 91.523 ± 26.7 mm3,respectively (P < 0.05 5-FU vs 5-FU + L-Arg group;P < 0.05 NS vs 5-FU + L-Arg group; P < 0.05, NS vs 5-FU group).The necrotic range and apoptosis index were significantly increased after the drug injection. The necrotic range was biggest in 5-FU + L-Arg group (x2 = 15.963, P < 0.05).The apoptosis indexes were as follows: NS, 17.4% ± 6.19%; 5-FU, 31.3% ± 12.3%; and 5-FU + L-Arg, 46% ± 15.24% (P < 0.05, 5-FU vs 5-FU + L-Arg; P < 0.05, NS vs 5-FU + L-Arg; P < 0.05, NS vs 5-FU). The expression and activity of iNOS were increased in the tumor tissue.The concentration of NO was also increased. F of optical density of iNOS, iNOS activity and NO concentration are 31.693, 21.949, and 33.909, respectively, P < 0.05. The concentration of NO was related to the expression of P16 and BAX. The correlation coefficient was 0.764 and 0.554.CONCLUSION: 5-FU combined with L-Arg can inhibit the

  17. General gambogic acids inhibited growth of human hepatoma SMMC-7721 cells in vitro and in nude mice

    Institute of Scientific and Technical Information of China (English)

    Qing-long GUO; Qi-dong YOU; Zhao-qiu WU; Sheng-tao YUAN; Li ZHAO

    2004-01-01

    AIM: To study the inhibitory effect of general gambogic acids (GGA) on transplantation tumor SMMC-7721 in experimental animal model and SMMC-7721 cells in vitro. METHODS: Anti-tumor activity of GGA in the experimental transplantation tumor SMMC-7721 was evaluated by relative tumor growth ratio. Cell morphology was observed with inverted microscope and electron microscope. Cell proliferation was measured by MTT assay and the telomerase activity was determined by PCR. RESULTS: In vivo study indicated that GGA (2, 4, and 8 mg/kg,iv, 3 times per week for 3 weeks) displayed an inhibitory effect on the growth of transplantation tumor SMMC7721 in nude mice compared with the normal saline group (P<0.01). At the concentrations of 0.625-5.0 mg/L,GGA remarkably inhibited the proliferation of SMMC-7721 cells in vitro. GGA 2 mg/L dramatically changed morphology of SMMC-7721 cells and inhibited the telomerase activity in SMMC-7721 cells. CONCLUSION:GGA had inhibitory effect on the growth of SMMC-7721, which might be related to its inhibition of telomerase activity.

  18. Combining metformin and nelfinavir exhibits synergistic effects against the growth of human cervical cancer cells and xenograft in nude mice

    Science.gov (United States)

    Xia, Chenglai; Chen, Ruihong; Chen, Jinman; Qi, Qianqian; Pan, Yanbin; Du, Lanying; Xiao, Guohong; Jiang, Shibo

    2017-01-01

    Human cervical cancer is the fourth most common carcinoma in women worldwide. However, the emergence of drug resistance calls for continuously developing new anticancer drugs and combination chemotherapy regimens. The present study aimed to investigate the anti-cervical cancer effects of metformin, a first-line therapeutic drug for type 2 diabetes mellitus, and nelfinavir, an HIV protease inhibitor, when used alone or in combination. We found that both metformin and nelfinavir, when used alone, were moderately effective in inhibiting proliferation, inducing apoptosis and suppressing migration and invasion of human cervical cell lines HeLa, SiHa and CaSki. When used in combination, these two drugs acted synergistically to inhibit the growth of human cervical cancer cells in vitro and cervical cancer cell xenograft in vivo in nude mice, and suppress cervical cancer cell migration and invasion. The protein expression of phosphoinositide 3-kinase catalytic subunit PI3K(p110α), which can promote tumor growth, was remarkably downregulated, while the tumor suppressor proteins p53 and p21 were substantially upregulated following the combinational treatment in vitro and in vivo. These results suggest that clinical use of metformin and nelfinavir in combination is expected to have synergistic antitumor efficacy and significant potential for the treatment of human cervical cancer. PMID:28252027

  19. Marked antitumor activity of cat's whiskers tea (Orthosiphon stamineus extract in orthotopic model of human colon tumor in nude mice

    Directory of Open Access Journals (Sweden)

    Foaud Saleih R Al-Suede

    2012-08-01

    Full Text Available Orthosiphon stamineus is used to treat kidney ailments including angiogenesis-dependent diseases. O. stamineus has shown to possess strong anti-angiogenic activity. In present study, an orthotopic nude mouse model of colon cancer was employed to study the factors that influence suppression of tumor by standardized 50% ethanol extract of O. stamineus leaves (EOS. Human colorectal cancer cells (HCT116 were surgically injected into the cecal wall of mice. Two different oral doses (100 and 200 mg/kg/day were given for 5 weeks. EOS suppressed 61.62±3.7% and 82.8±1.5% tumor growth at 100 and 200 mg/kg, respectively. Tumor histology revealed significant reduction in vascularization. Anti-angiogenic efficacy of EOS was investigated in human endothelial cells (HUVEC. In vitro, EOS inhibited migration and tube formation of HUVECs. HPLC data showed high content of rosmarinic acid in EOS. This work supports previous anti-tumor works on the plant in which suppression of VEGFR phosphorylation is thought to be involved.

  20. Models of Human Metastatic Colon Cancer in Nude Mice Orthotopically Constructed by Using Histologically Intact Patient Specimens

    Science.gov (United States)

    Fu, Xinyu; Besterman, Jeffrey M.; Monosov, Ann; Hoffman, Robert M.

    1991-10-01

    There is an important need for clinically relevant animal models for human cancers. Toward this goal, histologically intact human colon-cancer specimens derived surgically from patients were implanted orthotopically to the colon or cecum of nude mice. We have observed extensive orthotopic growth in 13 of 20 cases of implanted patient colon tumors. These showed various growth patterns with subsequent regional, lymph-node, and liver metastasis, as well as general abdominal carcinomatosis. Thus, models for human colon cancer have been developed that show (i) local growth, (ii) abdominal metastasis, (iii) general abdominal carcinomatosis with extensive peritoneal seeding, (iv) lymph-node metastasis, (v) liver metastasis, and (vi) colonic obstruction. These models permit the passage of the tumors to form large cohorts. They will facilitate research into the biology of colon cancer metastatic capability and the development of new drugs active against metastatic cancer. These models may also predict the clinical course and the in vivo response to drugs of the cancer of individual patients.

  1. Undifferentiated Human Adipose-derived Stromal/Stem Cells loaded onto Wet-Spun Starch-polycaprolactone Scaffolds Enhance Bone Regeneration: Nude Mice Calvarial Defect in vivo Study

    Science.gov (United States)

    Carvalho, Pedro P.; Leonor, Isabel B.; Smith, Brenda J.; Dias, Isabel R.; Reis, Rui L.; Gimble, Jeffrey M.; Gomes, Manuela E.

    2014-01-01

    The repair of large bony defects remains challenging in the clinical setting. Human adipose-derived stromal/stem cells (hASCs) have been reported to differentiate along different cell lineages, including the osteogenic. The objective of the present study was to assess the bone regeneration potential of undifferentiated hASCs loaded in starch-polycaprolactone (SPCL) scaffolds, in a critical-sized nude mice calvarial defect. Human ASCs were isolated from lipoaspirate of five female donors, cryopreserved and pooled together. Critical-sized (4 mm) calvarial defects were created in the parietal bone of adult male nude mice. Defects were either left empty, treated with an SPCL scaffold alone, or SPCL scaffold with human ASCs. Histological analysis and Micro-CT imaging of the retrieved implants were performed. Improved new bone deposition and osseointegration was observed in SPCL loaded with hASC engrafted calvarial defects as compared to control groups that showed little healing. Non differentiated human ASCs enhance ossification of non-healing nude mice calvarial defects, and wet-spun SPCL confirmed its suitability for bone tissue engineering. This study supports the potential translation for ASC use in the treatment of human skeletal defects. PMID:24123913

  2. Expression of Bmi-1 and EZH2 in tissues adjacent to human epithelial ovarian cancer cells of orthotopic implantation in nude mice

    Institute of Scientific and Technical Information of China (English)

    Genhai Zhu; Lan Hong; Shengtan Wang; Zhaoxin Yang; Chunying Chen; Shixuan Wang

    2015-01-01

    Objective This study investigated the feasibility of screening residual normal ovarian tissues based on the expression of Bmi-1 and EZH2 in tissues adjacent to orthotopic ovarian carcinomas in nude mice. Methods The human epithelial ovarian cancer cel line OVCAR3 was grown in subcutaneous tissues and the tumor tissues were orthotopical y implanted. The expression levels of Bmi-1 and EZH2 were detected by immunohistochemical staining and RT-PCR in cancer tissues, proximal and remote tissues with respect to the cancer tissues, and normal ovarian tissues of nude mice. Results Thirty-five ovarian tissue samples with normal biopsy results were obtained from 40 cases of human epithelial ovarian cancer in the nude mice in which the tumor tissues were orthotopical y implanted. Bmi-1 and EZH2 expression levels were lower in proximal paraneoplastic tissue samples than in cancer tissue samples (P Conclusion The expression levels of Bmi-1 and EZH2 were reduced with increasing distance from the cancer tissues. Negative expression of these tumor-associated genes can be used as a standard for the screening of normal ovarian tissues adjacent to tumor tissues. Normal ovarian tissues can be obtained from the tissues adjacent to tumors.

  3. Effects of recombinant human growth hormone on growth of human gastric carcinoma xenograft model in nude mice

    Institute of Scientific and Technical Information of China (English)

    Dao-Ming Liang; Jia-Yong Chen; Yi Zhang; Ping Gan; Jie Lin; An-Bao Chen

    2006-01-01

    AIM: To study effects of recombinant human growth hormone (rhGH) on growth of a human gastric carcinoma cell in vivo.METHODS: Experimental mice were divided into control group, rhGH group, oxaliplatin (L-OHP) group and rhGH+L-OHP group. Cultured human gastric carcinoma cells BGC823 were inoculated into right axilla of nude mice and carcinoma xenograft model wasestablished successfully. Inhibitory rate of xenograft tumor growth was estimated by measuring tumor volume; expression of proliferating cell nuclear antigen (PCNA), Bax and Bcl-2 proteins of xenograft tumor was detected using immunohistochemical S-P method.RESULTS: Tumor growth inhibitory rate, the positive expression rate of PCNA, Bax and Bcl-2 were 49.3%,58.2%, 65.2% and 59.2% in rhGH+L-OHP group respectively; 46.6%, 62.5%, 59.7% and 64.7% in L-OHP group; 5.0%, 82.7%, 23.2% and 82.2% in rhGH group and 0, 77.8%, 23.5% and 80.3% in control group. There was significant difference between rhGH+L-OHP group (or L-OHP group ) and control group or rhGH group (P <0.05), whereas there were no significant differences (P >0.05) between L-OHP group and rhGH+L-OHP group and between rhGH group and control group.CONCLUSION: rhGH does not accelerate the proliferation of human gastric cancer cell in vivo.

  4. A novel gain of function mutant in C-kit gene and its tumorigenesis in nude mice

    Institute of Scientific and Technical Information of China (English)

    Chen-Guang Bai; Xiao-Hong Liu; Qiang Xie; Fei Feng; Da-Lie Ma

    2005-01-01

    AIM: To transfect mutant C-kit cDNA at codon 579 into human embryonic kidney cell line to observe its role in the pathogenesis of gastrointestinal stromal tumor (GIST).METHODS: Eukaryotic expression vectors of pcDNA3-Kit-NW and pcDNA3-Kit-W were constructed. Then pcDNA3-Kit-NW and pcDNA3-Kit-W plasmids were transfected into human embryonic kidney cell line by Lipofectamine. The resistant done was screened by G418filtration and identified by sequencing, Western blotting,and immunocytochemical staining. Human embryonic kidney cells were divided into three groups including pcDNA3-Kit-NW, pcDNA3-Kit-W, and vector control groups. Absorbency value with a wavelength of 574 nm was detected by MTT analysis. Mice were injected with three groups of cells. Volume, mass, and histological examinations of the tumors in different groups were measured and compared.RESULTS: The C-kit gene and mutant C-kit gene were successfully cloned into the eukaryotic expression vector pcDNA3. pcDNA3-Kit-NW and pcDNA3-Kit-W were successfully transfected into human embryonic kidney cell line and showed stable expression in this cell line.Cell proliferating activity had significant differences between pcDNA3-Kit-NW and pcDNA3, pcDNA3-KitNW and pcDNA3-Kit-W (P<0.05), respectively. Tumors were only observed in nude mice implanted with cells transfected with pcDNA3-Kit-NW.CONCLUSION: Mutation of C-kit gene increases the proliferation activity of human cells and plays an important role in the malignant transformation of GIST.

  5. Comparison of conventional and novel PET tracers for imaging mesothelioma in nude mice with subcutaneous and intrapleural xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Tsuji, Atsushi B.; Sogawa, Chizuru; Sugyo, Aya [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Sudo, Hitomi [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, 113-8421 (Japan); Toyohara, Jun [Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 206-8670 (Japan); Koizumi, Mitsuru [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Abe, Masaaki; Hino, Okio [Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, 113-8421 (Japan); Harada, Yoshi-nobu; Furukawa, Takako [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Suzuki, Kazutoshi [Molecular Probe Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Saga, Tsuneo [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan)], E-mail: saga@nirs.go.jp

    2009-05-15

    Introduction: Malignant mesothelioma is a highly aggressive tumor originating in the pleura, peritoneum and pericardium, and the prognosis of patients undergoing current treatment remains poor. To develop new therapies, it is important to have a noninvasive imaging system for evaluating the efficacy of such prospective treatments. We have established clinically relevant mouse models and evaluated conventional and novel positron emission tomography (PET) tracers. Methods: Epithelioid and sarcomatoid mesothelioma cells were inoculated subcutaneously and intrapleurally into nude mice. Biodistribution and PET imaging studies were conducted by injecting [{sup 18}F]fluoro-2-deoxy-D-glucose (FDG), 3'-[{sup 18}F]fluoro-3'-doxythymidine (FLT) or 4'-methyl-[{sup 11}C]thiothymidine (S-dThd) into the mouse models. In vitro cellular uptake of [{sup 14}C]FDG and [{sup 3}H]FLT and thymidine kinase 1 (TK{sub 1}) activity in both cell lines were measured. Expression of glucose transporter 1 (GLUT-1) and Ki-67 in xenografted tumors was evaluated by immunohistochemical staining. Results: In epithelioid mesothelioma models, biodistribution experiments showed that tumor uptake of [{sup 11}C]S-dThd was significantly higher than that of [{sup 18}F]FDG. On the other hand, in sarcomatoid models, [{sup 18}F]FDG showed significantly higher accumulation than the other two tracers. These differential uptakes of the three tracers were confirmed by PET imaging. The cellular uptake of [{sup 14}C]FDG and [{sup 3}H]FLT and TK{sub 1} activity in sarcomatoid cells were higher than those of epithelioid cells. GLUT-1 protein was strongly expressed in sarcomatoid but not in epithelioid tumor. We observed a high percentage of Ki-67-positive cells in both epithelioid and sarcomatoid tumors. Conclusions: We established nude mouse models of epithelioid and sarcomatoid subtypes of mesothelioma. PET tracers applicable for the evaluation of epithelioid and sarcomatoid mesothelioma would vary

  6. A novel model of distal colon cancer in athymic mice Novo modelo de câncer de cólon distal em camundongos atímicos

    Directory of Open Access Journals (Sweden)

    Denise Gonçalves Priolli

    2012-06-01

    Full Text Available PURPOSE: The present a novel adenocarcinoma model in athymic mice. METHODS: Seven athymic mice were used. Colon diversion and distal fistula were made. Adenocarcinoma cells were inoculated in the submucosa of fistula. Tumor growth was monitored daily. Scintigraphy with 99mTc-MIBI was performed to identify the tumor. RESULTS: The model of distal colon cancer is feasible. Tumor detection was possible by both, macroscopically and molecular imaging. All resections demonstrated poorly differentiated tumors. Colon obstruction occurred in one case, similarly to evolution in human tumors of distal colon. CONCLUSION: The proposed model of distal colon cancer is feasible, allows for easy monitoring of tumoral growth by both, macroscopically and molecular imaging, and is suitable for studying the evolution of tumor with implementation of cytotoxic therapy in vivo.OBJETIVO: Apresentar novo modelo de adenocarcinoma distal em camundongos atímicos. MÉTODOS: Foram utilizados sete camundongos atímicos. Desvio do cólon distal e fístula foram feitas. Células de adenocarcinoma foram inoculadas na submucosa da fístula. O crescimento do tumor foi monitorado diariamente. Cintilografia com 99mTc-MIBI foi realizada para identificar o tumor. RESULTADOS: O modelo de câncer de cólon distal é viável. Detecção do tumor foi possível macroscopicamente e por imagem molecular. Todas as ressecções demonstraram tumores pouco diferenciados. Obstrução do cólon ocorreu em um caso, de forma semelhante à evolução em tumores humanos do cólon distal. CONCLUSÃO: O modelo de câncer do cólon distal proposto é viável, permite a monitorização fácil do crescimento tumoral macroscopicamente e por imagem molecular, sendo adequado para o estudo da evolução de tumor com aplicação de terapia citotóxica in vivo.

  7. Interim report on intrathoracic radiotherapy of human small-cell lung carcinoma in nude mice with Re-188-RC-160, a radiolabeled somatostatin analogue

    Energy Technology Data Exchange (ETDEWEB)

    Zamora, P.O. [Univ. of Bonn (Germany). Dept. of Nuclear Medicine]|[RhoMed Inc., Albuquerque, NM (United States); Bender, H.; Biersack, H.J. [Univ. of Bonn (Germany). Dept. of Nuclear Medicine; Knapp, F.F. Jr. [Oak Ridge National Lab., TN (United States). Health Sciences Research Div.

    1995-07-01

    The purpose of this study was to evaluate the therapeutic efficacy of Re-188-RC-160 in experimental models of human small cell lung carcinomas which mimic the clinical presentation. In the experimental model, cells from the human small cell lung carcinoma cell line NCI-H69 cells were inoculated into the thoracic cavity of athymic mice and rats. Subsequently, the biodistribution of Re-188-RC-160 after injection into the pleural cavity, a radiolabeled somatostatin analogue, was monitored as was the effect on the subsequent growth of tumors. The results presented here, and which are a part of a larger series of studies, suggest that Re-188-RC-160 can be effectively used in this animal model to restrict the growth of small cell lung carcinoma in the thoracic cavity.

  8. Establishment of orthotopic impact/metastasis model of human ovary cancer in nude mice

    Institute of Scientific and Technical Information of China (English)

    侯向华; 辛晓燕; 杨红; 王德堂; 郭慧玲

    2003-01-01

    Objective:To establish a patient-like human ovary carcinoma/spontaneous metastasis model using orthotopic transplanation of histologically intact tumor tissue.Methods:An highly metastatic ovarian tumor line(HO8910PM:Human serum carcinoma of the ovary)previously grown substaneously was transplanted into the ovicapsule using microsurgery technique .Histologically intact human ovary tumor pieces gained from implantation site were passaged between ovicapsules for four generations.Results:All mice developed ovary tumors and the metastatic rates were about 75%.The tumors only metastasized to liver but no other organs.The earliest appearance of metastasis was 14 d and the average survival period was 20.7 ± 4.89 d.The microscopic appearance of the metastases was similar to the tumor observed in the substaneous xenografts and orthotopically transplanted.Chromosomes analysis exhibited the feature of human carcinoma and retained genetic stability during the processes of passage.Conclusion:Orthotopic implanation provides a suitable micro-enviroment in which ovarian cancer can express its intrinsic clinically-relevant properties.This approach is relevant to the spontaneous development of ovarian cancer and is thought to be a useful model for studies of metastatic mechanism and therapy for ovary cancer.

  9. Effects of Chinese Jianpi herbs on cell apoptosis and related gene expression in human gastric cancer grafted onto nude mice

    Institute of Scientific and Technical Information of China (English)

    Ai-Guang Zhao; Hai-Lei Zhao; Xiao-Jie Jin; Jin-Kun Yang; Lai-Di Tang

    2002-01-01

    AIM: To explore the mechanism of the Sijunzi decoction and another Chinese herbal recipe (SRRS) based mainly on the Sijunzi decoction in treatment of gastric cancer.METHODS: A human gastric adenocarcinoma cell line SGC7901 grafted onto nude mouse was used as the animal model. The mice were divided into 3 groups, one control and the two representative experimental conditions. Ahimals in the two experimental groups received either Sijunzi decoction or SRRS over a 40-day period starting at 1st day after grafting. Control animals received saline on an identical schedule. Animals were killed 41 days after being grafted.The effect of therapy was assessed by two ways: (1)tumor size was periodically measured during the life of the animals; (2) tumor weight was determined by a electron balance immediately after the animals killed. For detection of apoptotic cells, apoptotic indices(AI) were examined by the terminal deoxynucleotidyl transferase-mediated deoxyuddine tdphosphate fluorescence nick end labeling (TUNEL) method.Morphological alterations were observed with electron microscopy. S-P immunohistochemical method was used to detect the expression of Ki-67 in xenografts. Expression of bcl-2 and p53 was semiquantitatively detected using a reverse transcriptase-polymerase chain reaction (RT-PCR)technique.RESULTS: When compared with controls, tumor growth (size and weight) was significantly inhibited by treatment with the Sijunzi decoction (P<0.05) or SRRS (P<0.01). The tumor inhibitory rate in the Sijunzi decoction group was 34.33 % and SRRS group 46.53 %. AI of human gastric cancer xenografts in nude mice was significantly increased to 16.24±3.21% using TUNEL method and 11.38±6.46 % by FACScan in the Sijunzi decoction group compared with the controls (TUNEL: 2.63±1.03 %, P<0.01; FACScan: 7.15± 1.32 %, P<0.05). SRRS group was also found a significantly increased AI by using TUNEL method and flow cytometry analysis compared with the controls (TUNEL: 13.18±3

  10. Anti-cancer and anti-angiogenic effects of curcumin and tetrahydrocurcumin on implanted hepatocellular carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    Pornprom Yoysungnoen; Ponthip Wirachwong; Chatchawan Changtam; Apichart Suksamrarn; Suthiluk Patumraj

    2008-01-01

    AIM: To determine the effect of tetrahydrocurcumin (THC) on tumor angiogenesis compared with curcumin (CUR) by using both in vitro and in vivo models of human hepatocellular carcinoma cell line (HepG2).METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay was used for testing the anti-proliferating activities of CUR and THC. In male BALB/c nude mice, 2 x 106 human HepG2 cells were inoculated onto a dorsal skin-fold chamber. One day after HepG2 inoculation, the experimental groups were fed oral daily with CUR or THC (300 mg/kg or 3000 mg/kg). On d 7, 14 and 21, the tumor microvasculature was observed using fluorescence videomicroscopy and capillary vascularity (CV) was measured.RESULTS: Pathological angiogenic features including microvascular dilatation, tortuosity, and hyper-permeability were observed. CUR and THC could attenuate these pathologic features. In HepG2-groups, the CV were significantly increased on d 7 (52.43%), 14 (69.17%), and 21 (74.08%), as compared to controls (33.04%,P < 0.001). Treatment with CUR and THC resulted in significant decrease in the CV (P < 0.005 and P < 0.001, respectively). In particular, the anti-angiogenic effects of CUR and THC were dose-dependent manner. However, the beneficial effect of THC treatment than CUR was observed, in particular, from the 21 d CV (44.96% and 52.86%, P < 0.05).CONCLUSION: THC expressed its anti-angiogenesis without any cytotoxic activities to HepG2 cells even at the highest doses. It is suggested that anti-angiogenic properties of CUR and THC represent a common potential mechanism for their anti-cancer actions.

  11. Sodium phenylacetate enhances the inhibitory effect of dextran derivative on breast cancer cell growth in vitro and in nude mice.

    Science.gov (United States)

    Di Benedetto, M; Kourbali, Y; Starzec, A; Vassy, R; Jozefonvicz, J; Perret, G; Crepin, M; Kraemer, M

    2001-09-14

    Sodium phenylacetate (NaPa) and carboxymethyl benzylamide dextran derivative (CMDB(LS4)) are able to inhibit growth of breast tumour cells. In this study, we explored whether the combination of NaPa and CMDB(LS4)may enhance their respective inhibitory effects on the MCF-7ras cell growth in vitro and in vivo. NaPa inhibited MCF-7ras cell proliferation by reducing the DNA replication concomitantly with a recruitment of cells in G0/G1 phase and by inducing apoptosis in a dose- and time-dependent manner. The addition of CMDB(LS4)potentiated the NaPa antiproliferative effect in the manner dependent on the ratio of CMDB(LS4)and NaPa concentrations. In nude mice, CMDB(LS4)(150 mg kg(-1)) or NaPa (40 mg kg(-1)) administrated twice a week, for 7 weeks inhibited MCF-7ras xenograft growth by 40% and 60%, respectively. The treatment by both, CMDB(LS4)and NaPa, decreased tumour growth by 83% without any toxicity. To better understand the mechanism of NaPa and CMDB(LS4)action we assessed their effect on mitogenic activity of MCF-7ras conditioned medium (CM) on BALBC/3T3 fibroblasts. CMDB(LS4)added to the CM, inhibited its mitogenic activity whereas NaPa had an anti-mitogenic effect when CM was prepared from MCF-7ras cells pretreated with NaPa. Thus, the antiproliferative effects of NaPa and CMDB(LS4)involve 2 different mechanisms explaining, at least in part, the possible synergism between them. Overall, this study points to the potential use of a combination of dextran derivatives with NaPa to inhibit the breast tumour growth.

  12. Trichosanthin inhibits breast cancer cell proliferation in both cell lines and nude mice by promotion of apoptosis.

    Directory of Open Access Journals (Sweden)

    Evandro Fei Fang

    Full Text Available Breast cancer ranks as a common and severe neoplasia in women with increasing incidence as well as high risk of metastasis and relapse. Translational and laboratory-based clinical investigations of new/novel drugs are in progress. Medicinal plants are rich sources of biologically active natural products for drug development. The 27-kDa trichosanthin (TCS is a ribosome inactivating protein purified from tubers of the Chinese herbal plant Trichosanthes kirilowii Maximowicz (common name Tian Hua Fen. In this study, we extended the potential medicinal applications of TCS from HIV, ferticide, hydatidiform moles, invasive moles, to breast cancer. We found that TCS manifested anti-proliferative and apoptosis-inducing activities in both estrogen-dependent human MCF-7 cells and estrogen-independent MDA-MB-231 cells. Flow cytometric analysis disclosed that TCS induced cell cycle arrest. Further studies revealed that TCS-induced tumor cell apoptosis was attributed to activation of both caspase-8 and caspase-9 regulated pathways. The subsequent events including caspase-3 activation, and increased PARP cleavage. With regard to cell morphology, stereotypical apoptotic features were observed. Moreover, in comparison with control, TCS- treated nude mice bearing MDA-MB-231 xenograft tumors exhibited significantly reduced tumor volume and tumor weight, due to the potent effect of TCS on tumor cell apoptosis as determined by the increase of caspase-3 activation, PARP cleavage, and DNA fragmentation using immunohistochemistry. Considering the clinical efficacy and relative safety of TCS on other human diseases, this work opens up new therapeutic avenues for patients with estrogen-dependent and/or estrogen-independent breast cancers.

  13. Fluorescence-guided surgery of retroperitoneal-implanted human fibrosarcoma in nude mice delays or eliminates tumor recurrence and increases survival compared to bright-light surgery.

    Directory of Open Access Journals (Sweden)

    Fuminari Uehara

    Full Text Available The aim of this study is to determine if fluorescence-guided surgery (FGS can eradicate human fibrosarcoma growing in the retroperitoneum of nude mice. One week after retroperitoneal implantation of human HT1080 fibrosarcoma cells, expressing green fluorescent protein (GFP (HT-1080-GFP, in nude mice, bright-light surgery (BLS was performed on all tumor-bearing mice (n = 22. After BLS, mice were randomized into 2 treatment groups; BLS-only (n = 11 or the combination of BLS + FGS (n = 11. The residual tumors remaining after BLS were resected with FGS using a hand-held portable imaging system under fluorescence navigation. The average residual tumor area after BLS + FGS was significantly smaller than after BLS-only (0.4 ± 0.4 mm(2 and 10.5 ± 2.4 mm(2, respectively; p = 0.006. Five weeks after surgery, the fluorescent-tumor areas of BLS- and BLS + FGS-treated mice were 379 ± 147 mm(2 and 11.7 ± 6.9 mm(2, respectively, indicating that FGS greatly inhibited tumor recurrence compared to BLS. The combination of BLS + FGS significantly decreased fibrosarcoma recurrence compared to BLS-only treated mice (p < 0.001. Mice treated with BLS+FGS had a significantly higher disease-free survival rate than mice treated with BLS-only at five weeks after surgery. These results suggest that combination of BLS + FGS significantly reduced the residual fibrosarcoma volume after BLS and improved disease-free survival.

  14. Comparative study of three methods of establishing pancreatic carcinoma model in nude mice%三种裸鼠胰腺癌建模方法的比较

    Institute of Scientific and Technical Information of China (English)

    刘娜; 杨文彬; 曹罡; 王磊

    2012-01-01

    目的 建立人胰腺癌细胞株BXPC-3裸鼠皮下瘤、腹腔内种植转移瘤以及原位移植瘤模型,探讨模型建立方法及其生物学特性.方法 采用直接皮下瘤细胞注射法建立胰腺癌裸鼠皮下瘤模型,开腹后瘤块包埋法建立腹腔内种植转移瘤模型,瘤细胞悬液置入胰腺包膜下建立原位移植模型,观察三种模型接种阳性率及瘤块生长的速度,对移植瘤做病理检查.结果 3种模型构建的阳性率分别为:皮下瘤模型47%(7/15),腹腔种植转移瘤模型100%(14/14),原位移植模型100% (14/14).后两种模型1月后发生肝转移、腹膜转移、肠系膜转移,3组间肿瘤生长速度比较,原位移植模型最快,腹腔种植转移模型其次,皮下瘤模型最慢,差异具有统计学意义(P<0.01).病理检查符合胰腺低分化腺癌.结论 成功建立了胰腺癌BXPC-3细胞株的皮下移植瘤模型、腹腔种植转移模型及原位移植模型,显示了各种模型的独特优势,为胰腺癌生物学行为的基础研究及治疗提供了实验平台.%To establish models of subcutaneous tumor, intra-abdominal metastasis tumor and in situ xenograft in nude mice with human pancreatic cancer cell line BXPC-3 to discuss the modeling methods and the biological characteristics of human pancreatic cancer model in nude mice. Methods Subcutaneous pancreatic tumor model was established by direct subcutaneous injection of human tumor cells in nude mice. Intra-abdominal metastasis tumor model was established by embedding tumor blocks in nude mice after laparotomy. Tumor orthotopic transplantation model was established by injecting tumor cell suspension into pancreatic capsules in nude mice. We observed all the three models for the positive rate of tumor inoculation and growth rate of tumor size, and then made pathological examination of the tumor. Results The positive rate of construction of the three models is as follows: 47% (7/15) for subcutaneous model, 100% (14

  15. 毛囊细胞移植法诱导毛囊的初步研究%Follicular cell implantation for induce hair follicle growth in nude mice

    Institute of Scientific and Technical Information of China (English)

    谭挺; 胡志奇

    2009-01-01

    目的 构建一个可靠有效的移植毛囊细胞诱导毛发发育的模型,以治疗脱发.方法 取自愿捐献的成人头皮标本,联用显微分离与免疫磁珠法获得人毛囊干细胞;消化法获得毛乳头细胞.培养后混合植入裸鼠皮下,观察毛囊形成情况.结果 在裸鼠的皮肤切片中可以看到较为完整的毛囊结构形成.结论 毛囊细胞移植法可以在体内诱导出毛囊样结构,为将来治疗脱发奠定了基础.%Objective To establish a convenient and reliable method for inducing hair regeneration by follicular cell implantation for the treatment of alopecia. Methods The human hair follicle stem cells were separated and purified by micromanipulation and magnetic cell sorting, and human scalp dermal papilla cells were isolated by enzyme digestion. The two cells were mixed and implanted subcutaneously in nude mice to observe the regeneration of the hair follicles. Results Formation of intact hair follicle-like structures was observed in the skin sections of the recipient nude mice. Conclusion Follicular cell implantation can induce hair follicle-like structures in nude mice, which provides a means for efficient hair regeneration for treatment of hair loss.

  16. Inhibition effects of all trans-retinoic acid on the growth and angiogenesis of esophageal squamous cell carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    LU Tai-ying; LI Wen-cai; CHEN Ren-yin; FAN Qing-xia; WANG Liu-xing; WANG Rui-lin; LU Shi-xin; MENG Hui

    2011-01-01

    Background The potential application of retinoic acid receptor activators,such as all trans-retinoic acid (ATRA),for treating various cancers have been studied both pre-clinically and clinically.Whether ATRA has an anticancer effect on human esophageal squamous cancer cell (ESCC) is still unknown.We have explored the anticancer effect of ATRA in ESCC,and in this study,the effects of ATRA on levels and patterns of expression of the vascular endothelial growth factor (VEGF) signal transduction pathway in transplantable tumor growth of the human ESCC cell line,EC9706,in nude mice.Methods The animal model of the ESCC xenograft was made by subcutaneous implantation of tumor cells into nude mice.Reverse transcription-polymerase chain reaction (RT-PCR),Western blotting and immunohistochemical assays were used to detect the expression of the VEGF signal transduction pathway in ESCC xenograft tissues.Results Compared to the control group,the tumor inhibition rates in the low dose ATRA,high dose ATRA,and 5-FU groups were 83.21%,88.32%,91.02%,respectively.The protein and mRNA levels of VEGF were down-regulated after being treated with ATRA and 5-FU compared to the control group (P <0.05).The study also revealed that ATRA specifically down-regulated VEGF and the component of the VEGF signal transduction pathway of CD31,CD34,and CD105 (component of the TGF-β receptor) in ESCC xenograft tissues (P <0.05).Conclusions ATRA can significantly inhibit tumor growth and has anticancer effects on transplantable tumor growth of human ESCC cell line EC9706 in nude mice.These findings indicate that ATRA specifically down regulated VEGF and the components of VEGF signal transduction,which may be an important mechanism responsible for the neoangiogenesis inhibition of ESCC cells.

  17. Regulation of DNA repair mechanism in human glioma xenograft cells both in vitro and in vivo in nude mice.

    Directory of Open Access Journals (Sweden)

    Shivani Ponnala

    Full Text Available BACKGROUND: Glioblastoma Multiforme (GBM is the most lethal form of brain tumor. Efficient DNA repair and anti-apoptotic mechanisms are making glioma treatment difficult. Proteases such as MMP9, cathepsin B and urokinase plasminogen activator receptor (uPAR are over expressed in gliomas and contribute to enhanced cancer cell proliferation. Non-homologous end joining (NHEJ repair mechanism plays a major role in double strand break (DSB repair in mammalian cells. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that silencing MMP9 in combination with uPAR/cathepsin B effects NHEJ repair machinery. Expression of DNA PKcs and Ku70/80 at both mRNA and protein levels in MMP9-uPAR (pMU and MMP9-cathepsin B (pMC shRNA-treated glioma xenograft cells were reduced. FACS analysis showed an increase in apoptotic peak and proliferation assays revealed a significant reduction in the cell population in pMU- and pMC-treated cells compared to untreated cells. We hypothesized that reduced NHEJ repair led to DSBs accumulation in pMU- and pMC-treated cells, thereby initiating cell death. This hypothesis was confirmed by reduced Ku70/Ku80 protein binding to DSB, increased comet tail length and elevated γH2AX expression in treated cells compared to control. Immunoprecipitation analysis showed that EGFR-mediated lowered DNA PK activity in treated cells compared to controls. Treatment with pMU and pMC shRNA reduced the expression of DNA PKcs and ATM, and elevated γH2AX levels in xenograft implanted nude mice. Glioma cells exposed to hypoxia and irradiation showed DSB accumulation and apoptosis after pMU and pMC treatments compared to respective controls. CONCLUSION/SIGNIFICANCE: Our results suggest that pMU and pMC shRNA reduce glioma proliferation by DSB accumulation and increase apoptosis under normoxia, hypoxia and in combination with irradiation. Considering the radio- and chemo-resistant cancers favored by hypoxia, our study provides important therapeutic potential

  18. Effects of Wei Chang An on expression of multiple genes in human gastric cancer grafted onto nude mice

    Institute of Scientific and Technical Information of China (English)

    Ai-Guang Zhao; Ting Li; Sheng-Fu You; Hai-Lei Zhao; Ying Gu; Lai-Di Tang; Jin-Kun Yang

    2008-01-01

    AIM:To investigate the expression of multiple genes in Chinese jianpi herbal recipe Wei Chang An (WCA) in human gastric cancer cell line SGC-7901.METHODS:A human gastric adenocarcinoma cell line SGC-7901 grafted onto nude mice was used as the animal model.The mice were randomly divided into 3 groups,one control and the two representing experimental conditions.Animals in the two experimental groups received either WCA over a 34-d period or 5-fluorouracil (5-FU) over 6-d period starting at 8th d after grafting.Control animals received saline on an identical schedule.Animals were killed 41 d after being grafted.The expression profiles in paired WCA treated gastric cancer samples and the N.S.control samples were studied by using a cDNA array representing 14181 cDNA clusters.The alterations in gene expression levels were confirmed by Real-time Quantitative polymerase chain reaction (qPCR).RESULTS:When compared with controls,the average tumor inhibitory rate in WCA group was 44.32%±5.67% and 5-FU 47.04% 4±11.33% (P<0.01,respectively).The average labeling index (LI) for PCNA in WCA group and 5-FU group was significantly decreased compared with the control group.Apoptotic index (AI) was significantly increased to 9.72%±4.51% using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method in WCA group compared with the controls 2.45%±1.37%.5-FU group was also found to have a significantly increased AI compared with the controls.The expression of cleaved Caspase-3 in WCA group and 5-FU group was significantly increased compared with the control group respectively.There were 45 different expressed sequence tags (ESTs) among the control sample pool and WCA sample pool.There were 24 ESTs up-regulated in WCA samples and 21 ESTs down-regulated.By using qPCR,the expression level of Stat3,rap2 interacting protein x (RIPX),regulator of differentiation 1 (ROD1) and Bcl-2 was lower in WCA group than that in control

  19. Effects of exogenous human leptin on heat shock protein 70 expression in MCF-7 breast cancer cells and breast carcinoma of nude mice xenograft model

    Institute of Scientific and Technical Information of China (English)

    XUE Rong-quan; GU Jun-chao; YU Wei; WANG Yu; ZHANG Zhong-tao; MA Xue-mei

    2012-01-01

    Background It is important to identify the multiple sites of leptin activity in obese women with breast cancer.In this study,we examined the effect of exogenous human leptin on heat shock protein 70 (HSP70) expression in MCF-7 human breast cancer cells and in a breast carcinoma xenograft model of nude mice.Methods We cultured MCF-7 human breast cancer cells and established nude mice bearing xenograffs of these cells,and randomly divided them into experimental and control groups.The experimental group was treated with human leptin,while the control group was treated with the same volume of normal saline.A real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay was developed to quantify the mRNA expression of HSP70 in the MCF-7 human breast cancer cells and in tumor tissues.Western blotting analysis was applied to quantify the protein expression of HSP70 in the MCF-7 cells.Immunohistochemical staining was done to assess the positive rate of HSP70 expression in the tumor tissues.Results Leptin activated HSP70 in a dose-dependent manner in vitro:leptin upregulated significantly the expression of HSP70 at mRNA and protein levels in MCF-7 human breast cancer cells (P <0.001).There was no significant difference in expression of HSP70 mRNA in the implanted tumors between the leptin-treated group and the control group (P>0.05).Immunohistochemical staining revealed no significant difference in tumor HSP70 expression between the leptin-treated group and the control group (P>0.05).Conclusions A nude mouse xenograft model can be safely and efficiently treated with human leptin by subcutaneous injections around the tumor.HSP70 may be target of leptin in breast cancer.Leptin can significantly upregulate the expression of HSP70 in a dose-dependent manner in vitro.

  20. Inhibitory effect of parvovirus H—1 on the formation of colonies of human hepatoma cell line in vitro and its tumors in nude mice

    Institute of Scientific and Technical Information of China (English)

    YANSHANGJUN; CHENGWUMA; 等

    1994-01-01

    The inhibitory effect of parvovirus H-1 on the colonyforming ability.in vitro of QGY-7703,a cultured human hepatoma cell line,and on the formation and growth of its tumors in nude mice was studied.With higher multiplicity of infection(MOI) of H-1 given,survival of the QGY-7703 cells was found to be decreased.H-1 DNA amplification level at 30h postinfection(p.i.) was detected to be 7.4 times higher than that at 2h by dispersed cells assay,while the cells were delayed to enter into S phase.Plaques were formed in the indicator cells(new-born human kidney cell line,NBK) by progeny H-1 virus particles released from the infected QGY-7703 cells by infectious cell center assay.The formation of tumors in nude mice by QGY-7703 cells which were injected s c at 2h postinfection was observed to by prevented in 2 proups with given MOI 25 and 50.The tumor growth of MOI 10 group occurred at a lower exponential rate than that of control,after a 20d latent period.It was evident that parvovirus H-1 exhibited a direct inhibitory effect on the formation and growth of human hepatoma cells in vivo as well as in vitro.

  1. Biased hypermutation occurred frequently in a gene inserted into the IC323 recombinant measles virus during its persistence in the brains of nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Otani, Sanae [Department of Virology and Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585 (Japan); Department of Pediatrics, Graduate School of Medicine, Osaka City University, Osaka (Japan); Ayata, Minoru, E-mail: maverick@med.osaka-cu.ac.jp [Department of Virology and Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585 (Japan); Takeuchi, Kaoru [Laboratory of Environmental Microbiology, Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Ibaraki (Japan); Takeda, Makoto [Department of Virology 3, National Institute of Infectious Diseases, Tokyo (Japan); Shintaku, Haruo [Department of Pediatrics, Graduate School of Medicine, Osaka City University, Osaka (Japan); Ogura, Hisashi [Department of Virology and Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585 (Japan)

    2014-08-15

    Measles virus (MV) is the causative agent of measles and its neurological complications, subacute sclerosing panencephalitis (SSPE) and measles inclusion body encephalitis (MIBE). Biased hypermutation in the M gene is a characteristic feature of SSPE and MIBE. To determine whether the M gene is the preferred target of hypermutation, an additional transcriptional unit containing a humanized Renilla reniformis green fluorescent protein (hrGFP) gene was introduced into the IC323 MV genome, and nude mice were inoculated intracerebrally with the virus. Biased hypermutation occurred in the M gene and also in the hrGFP gene when it was inserted between the leader and the N gene, but not between the H and L gene. These results indicate that biased hypermutation is usually found in a gene whose function is not essential for viral proliferation in the brain and that the location of a gene in the MV genome can affect its mutational frequency. - Highlights: • Wild-type MV can cause persistent infections in nude mice. • Biased hypermutation occurred in the M gene. • Biased hypermutation occurred in an inessential gene inserted between the leader and the N gene.

  2. Zanthoxylum avicennae extracts induce cell apoptosis through protein phosphatase 2A activation in HA22T human hepatocellular carcinoma cells and block tumor growth in xenografted nude mice.

    Science.gov (United States)

    Dung, Tran Duc; Chang, Hsien-Cheh; Chen, Chung-Yu; Peng, Wen-Huang; Tsai, Chang-Hai; Tsai, Fuu-Jen; Kuo, Wei-Wen; Chen, Li-Mien; Huang, Chih-Yang

    2011-12-01

    The use of herbs as alternative cancer therapies has attracted a great deal of attention owing to their lower toxicity. Whether Zanthoxylum avicennae (Ying Bu Bo, YBB) induces liver cancer cell apoptosis remains unclear. In this study, we investigated the effect of YBB extracts (YBBEs) on HA22T human hepatocellular carcinoma cells in vitro and in an in vivo mouse xenograft model. HA22T cells were treated with different concentrations of YBBEs and analyzed with Western blot analysis, TUNEL, JC-1 staining and siRNA transfection assays. Additionally, the HA22T-implanted xenograft nude mice model was applied to confirm the cellular effects. YBBEs-induced apoptosis, up-regulated death receptor apoptotic pathway markers as well as mitochondrial proteins, and suppressed the survival proteins in a dose-dependent manner. Pro-survival Bcl-2 family proteins were inhibited and the pro-apoptotic ones were increased. Protein phosphatase 2A (PP2A) siRNA or okadaic acid reversed the YBBEs effects, confirming the role of PP2A in YBBEs-induced HA22T apoptosis. All our experimental evidence indicates that YBBEs significantly promote HA22T apoptosis and reduce tumor sizes in xenograft nude mice via PP2A in a dose-dependent manner.

  3. Changes in the spectral index of skin-surface laser Doppler signals of nude mice following the injection of CT26 tumor cells.

    Science.gov (United States)

    Liu, Ju-Chi; Hsiu, Hsin; Hsu, Yi-Ping; Tsai, Hung-Chi; Kuo, Chung-Hsien

    2016-01-01

    This study investigated microcirculatory-blood-flow responses in nude mice following the injection of CT26 tumor cells by analyzing the frequency content of skin blood-flow signals recorded on the skin surface. CT26 cells were injected subcutaneously (10^4/100 μl) into the right back flank of each 7-week-old mouse. Three-minute laser Doppler flowmetry (LDF) signals were measured in 60 nude mice. The data sequences were obtained at 1, 2, and 3 weeks after injecting CT26 cells. Mouse tissue samples were cut into sections and examined microscopically to determine the condition of cancer metastasis. Spectral analysis performed after 1 week revealed a significant decrease in the relative energy contribution of the endothelium-related frequency band, and significant increases in those of the myogenic and respiration-related frequency bands of the LDF signals in the metastasis group (n=12). To the best of our knowledge, this is the first study demonstrating the feasibility of evaluating metastasis in animal subjects based on changes in noninvasively measured LDF parameters. Changes in the LDF spectral indexes can be attributed to differences in the microcirculatory regulatory activities. The present measurements performed on the skin surface provide a noninvasive and real-time method for evaluating the microcirculatory responses induced by implanting CT26 tumor cells.

  4. 肿瘤移植裸鼠粪类圆线虫感染病原和分子诊断%Pathogenic and molecular diagnoses of Strongyloides stercoralis infection in tumor transplanted nude mice

    Institute of Scientific and Technical Information of China (English)

    高正琴; 贺争鸣; 关伟鸿

    2014-01-01

    Objective To diagnosis tumor transplanted nude mice Strongyloidiasis .Methods Postmortem microscopic examination of the tumor transplanted nude mice detected Strongyloides stercoralis for morphological identification and double polymerase chain reaction ( PCR ) assay for molecular diagnosis of Strongyloides stercoralis infection in tumor transplanted nude mice .Results Presence of numerous S .stercoralis in autopsy in tumor transplanted nude mice samples preliminary determined the diagnosis of strongyloidiasis .Confirmed diagnosis of Strongyloides stercoralis infection by double PCR detection of specific DNA in tumor transplanted nude mice samples .Conclusion The most important clue to prevent such serious consequences is early diagnosis .Tumor transplanted recipients and donors should be screened for parasitic infections including strongyloidiasis .To the authors ’ knowledge , this study is the first extensive report on diagnosis tumor transplanted nude mice Strongyloidiasis .%目的:肿瘤移植裸鼠粪类圆虫病诊断。方法肿瘤移植裸鼠的尸体解剖显微镜检查发现类圆线虫作形态学鉴定并采用二重PCR进行分子诊断。结果尸检发现肿瘤移植裸鼠样本中出现大量粪类圆线虫,初步确诊粪类圆线虫病,二重PCR检出样本中粪类圆线虫特定DNA进一步确诊。结论防止这种严重后果是早期诊断。肿瘤移植受体和供体应进行寄生虫感染包括类圆线虫病筛查。本研究第一个广泛报道了肿瘤移植裸鼠粪类圆虫病诊断。

  5. In vivo evidences of nanosecond pulsed electric fields for melanoma malignancy treatment on tumor-bearing BALB/c nude mice.

    Science.gov (United States)

    Guo, F; Yao, C; Li, C; Mi, Y; Peng, Q; Tang, J

    2014-08-01

    In order to get in vivo evidences of nanosecond pulsed electric fields (nsPEF) for skin tumor treatment, tumor models in 10 female BALB/c nude mice were established by inoculating them with human melanoma cells A375. These mice were randomly divided into treated group (exposed to nsPEF with intensity of 20 kV/cm and duration of 300 ns) and control group equally. Five days post-nsPEF treatment, tumor growth in the treated group was effectively inhibited (P growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) were observed by immunohistochemistry (P growth can be effectively inhibited by nsPEF, which activate two targets, apoptosis initiation and angiogenesis inhibition.

  6. Morphofunctional evaluation of human skin preserved in glycerol and exposed to gamma radiation: a study in athymic mice; Avaliacao morfofuncional de pele humana conservada em glicerol e submetida a radiacao gama: estudo em camundongos atimicos

    Energy Technology Data Exchange (ETDEWEB)

    Bringel, Fabiana de Andrade

    2011-07-01

    Extensive skin lesions expose the body to damaging agents, which makes spontaneous regeneration difficult and, in many cases, leads patient to death. In such cases, if there are no donating areas for autograft, allografts can be used. In this type of graft, tissue is processed in tissue banks, where it can be subjected to radiosterilization. According to in vitro studies, gamma radiation, in doses higher than 25 kGy, induces alterations in skin preserved in glycerol at 85%, reducing the tensile strength of irradiated tissue. Clinical observation also suggests faster integration of such graft with the receptors tissue. In order to assess if the alterations observed in vitro, would compromise in vivo use, transplants of human tissue, irradiated or not, were performed in Nude mice. The skin of the mice was subjected to macroscopic analysis, optical coherence tomography imaging, histological and biomechanical assays. It was possible to conclude that grafts irradiated with 25 kGy promoted greater initial contraction, without alteration of the final dimensions of the repair area, also displaying a faster closing of the wound. Moreover, the use of irradiated grafts (25 and 50 kGy) enabled the formation of a more organized healing process without significant effects on biomechanical properties. (author)

  7. Biodistribution and SPECT Imaging Study of 99mTc Labeling NGR Peptide in Nude Mice Bearing Human HepG2 Hepatoma

    Directory of Open Access Journals (Sweden)

    Wenhui Ma

    2014-01-01

    Full Text Available A peptide containing Asn-Gly-Arg(NGR sequence was synthesized and directly labeled with Tc. Its radiochemical characteristics, biodistribution, and SPECT imaging were evaluated in nude mice bearing human HepG2 hepatoma. Nude mice bearing HepG2 were randomly divided into 5 groups with 5 mice in each group and injected with ~7.4 MBq Tc-NGR. The SPECT images were acquired in 1, 4, 8, and 12 h postinjection via caudal vein. The metabolism of tracers was determined in major organs at different time points, which demonstrated rapid, significant tumor uptake and slow tumor washout. The control group mice were blocked by coinjecting unlabelled NGR (20 mg/kg. Tumor uptake was (2.52±0.83% ID/g at 1 h, with the highest uptake of (3.26±0.63% ID/g at 8 h. In comparison, the uptake of the blocked control group was (1.65±0.61% ID/g at 1 h after injection. The SPECT static images and the tumor/muscle (T/NT value were obtained. The highest T/NT value was 7.58±1.92 at 8 h. The xenografted tumor became visible at 1 h and the clearest image of the tumor was observed at 8 h. In conclusion, Tc-NGR can be efficiently prepared and it exhibited good properties for the potential SPECT imaging agent of tumor.

  8. Nude mice multi-drug resistance model of orthotopic transplantation of liver neoplasm and Tc-99m MIBI SPECT on p-glycoprotein

    Institute of Scientific and Technical Information of China (English)

    Yu Han; Xiao-Ping Chen; Zhi-Yong Huang; Hong Zhu

    2005-01-01

    AIM: To establish a model of drug-resistant neoplasms using a nude mice model, orthotopic transplantation of liver neoplasm and sporadic abdominal chemotherapy.METHODS: Hepatocellular carcinoma cells HepG2 were cultured and injected subdermally to form the tumorsupplying mice. The orthotopic drug-resistant tumors were formed by implanting the tumor bits under the envelope of the mice liver and induced by abdominal chemotherapy with Pharmorubicin. Physical examination, ultrasonography, spiral CT and visual inspection were used to examine tumor progression. RT-PCR and immunohistochemistry wereused to detect expression of mdr1 mRNA and its encodedprotein p-glycoprotein (p-gp). Tc-99m sestamibi scintigraphy was performed by obtaining planar abdominal images at 20 min after injection, and the liver/heart ratios werecalculated.RESULTS: Post-implantation mortality was 0% (0/25),tumor implantation success was 90% (22/25), and the rate of implanting successfully for the second time was 100% (3/3). Tumor induction using Pharmorubicin was 80% (16/20). The mdr1 mRNA expression of the induced group was 23 times higher than that of the control group, and p-gp protein expression was 13-fold higher compared to the control group. The liver/heart ratio (as assessed in vivo, using Tc-99m radiography) was decreased significantly in the induced group as compared to the control group. CONCLUSION: We have established an in vivo model of mdr1 in nude mice by orthotopic transplantation of liver neoplasm coupled to chemotherapy. We propose that identification of drug resistance as characterized by decreased 99mTc-ppm radiography due to enhanced clearance by p-gp may be useful in detecting in vivo drug resistance, as well as a useful tool in designing more effective therapies.

  9. Guanethidine-induced sympathectomy in the nude rat

    DEFF Research Database (Denmark)

    Juul, A; Juul, P; Christensen, H B

    1989-01-01

    Guanethidine sulphate 40 mg/kg was administered intraperitoneally daily for 14 days to normal Lewis rats and athymic nude rats of a Lewis background (rnu/rnu). Histological examination of the superior cervical ganglia demonstrated a pronounced chromatolysis of the neurones and a loss of the major...... part of the nerve cells accompanied by an increased number of small mononuclear inflammatory cells. The extent of chromatolysis and nerve cell death induced by guanethidine did not differ between normal and nude rats, whereas the increase of the number of mononuclear cells was lower in the nude rats...... than in the normal rats (163 and 268 per cent respectively of the saline treated controls, P less than 0.01). Since guanethidine induced nerve cell death in the T-cell deficient nude rat to the same extent as in normal rats, it is concluded, that the effect is caused by either a thymus...

  10. The effect of pre-low-dose X-ray radiation on tumor inhibition of HepG2 cells in tumor-bearing nude mice

    Institute of Scientific and Technical Information of China (English)

    Weihua Sun; Hongsheng Yu; Qingjun Shang

    2012-01-01

    Objective: The aim of this study was to discuss the effect of pre-low-dose X-ray radiation on P53, Bcl-2 and apoptosis of HepG2 cells in tumor-bearing nude mouse, and further explore the mechanism of low doses radiation. Methods: HepG2 cells were implanted subcutaneously into nude mice. 14 days after the implanting, these mice were divided into 6 groups randomly, S group (sham-irradiation 0 cGy), D1 group (7.5 cGy, dosage rate = 7.5 cGy/min), D2 group, (200 cGy, dosage rate = 100 cGy/min), D1 + 2 h + D2 group, D1 + 6 h + D2 group and D1 + 12 h + D2 group. Tumor-bearing mice in each experimental group were executed at 24 h after the last irradiation. P53 and Bcl-2 were detected by immunohistochem-ical staining, the tumor tissues apoptosis were detected in site (Tunel). Results: Each combined exposure groups (D1 + 2 h + D2 group, D1 + 6 h + D2 group and D1 + 12 h + D2 group) compared with the D2 group, the percentages of positive P53 and Bcl-2 were decreased obviously, and the apoptotic indexs were increased (P< 0.01). Conclusion: Pre-low-dose radiation combined with the conventional radiation can increase the apoptosis of tumor tissues by decreasing the expression of P53 and Bcl-2, it can enhance the anti-tumor effect of conventional radiation, and it can have actual clinical significance on supporting radiotherapy.

  11. Effect of peritumoral injection of boanmycin hydrochloride within temperature-sensitive in situ gel using Hep-G2 hepatoma nude mice model

    Institute of Scientific and Technical Information of China (English)

    WANG Zhi-hui; DING Wei-ming; HU Xiang-dong; LI Mei; XU Hong-zhang; QIAN Lin-xue

    2012-01-01

    Background Boanmycin hydrochloride,a new antitumor agent,has a short half-life and fast clearance speed in vivo.The aim of this research was to investigate the effectiveness of peritumor injection of boanmycin hydrochloride within temperature-sensitive gel in situ using Hep-G2 hepatoma nude mice model.Methods Nude mice with human Hep-G2 tumor in right flank were randomly divided into four groups: normal saline group,in situ gel only group,boanmycin hydrochloride in situ saline group,and boanmycin hydrochloride in situ gel group,and were treated with injection of corresponding agents into peripheral tissue of the tumor.The volume of the tumor and the body weight of the mice were regularly measured,and tumor growth curve was generated.The size,internal echo,and blood flow of the tumors were observed by color Doppler ultrasonography.Histopathologic changes of the tumor after treatment were observed under both optical and transmission electron microscopy.Results The tumor growth was significantly inhibited by peritumoral therapy in boanmycin hydrochloride in situ gel group with the tumor inhibitory rate of 86.76%,The blood flow of the tumor was still seen in both normal saline group and in situ gel only group on color Doppler ultrasound.Punctate calcification and dotted blood flow were seen in boanmycin hydrochloride group; however,there was massive calcification and no blood flow in the tumor in the boanmycin hydrochloride in situ gel group.Large areas of necrosis and apoptotic cells were shown by microscopic observation in boanmycin hydrochloride in situ gel group.Conclusion Temperature-sensitive boanmycin hydrochloride in situ gel can effectively delay the release of boanmycin hydrochloride and increase its anticancer effects for liver cancer in animal model.

  12. Functional Mechanism of Resveratrol in Inhabiting Growth of Cells ls174t and Its Mechanism in Subcutaneously Transplanted Tumor of Nude Mice

    Institute of Scientific and Technical Information of China (English)

    CHEN Jie; DONG Xin-shu; GUO Xing-gang

    2008-01-01

    To explore the functional mechanism of Resveratrol against colon cancer cells Is174t and the growth of colon cancer tissue of tumor-bearing mice,MTT method was used to observe the functions of resveratrol for inhibition against cells ls174t in vitro.Transmission electron microscope was used to observe the cell apoptosis.FCM assay was performed to measure the change of the cell apoptosis rate and of cell cycle,RT-PCR method was used to detect the expressions of bc1-2 and bax mRNA.Western blot method was used to detect the expressions of bc1-2 and bax protein.Cells isi74t were transplanted subcutaneously to nude mice to observe the effect of resveratrol on the growth of subcutaneously transplanted tumor.RT-PCR method was used to detect the expressions of bc1-2 and bax mRNA in the tumor tissue.Western blot method was used to detect the expressions of bc1-2 and bax protein in the tumor tissue.Resveratrol has an effect of inhibiting proliferation of cells ls174t in vitro(P<0.01).It is able to induce the apoptosis of cells Is174t,causing the decrease in the expression of bc1-2 and the increase in the expression of bax.Resveratrol could inhibit the growth of subcutaneously transplanted tumor of nude mice(P<0.05),causing the decrease in the expression of bc1-2 and the increase in the expression of bax.Resveratrol can inhibit the growth of cells 174t and the growth of subcutaneously transplanted tumor.The mechanism is possibly related to the induction of the cell apoptosis and the regulation of bc1-2/bax expression.

  13. Effects of endostatin on expression of vascular endothelial growth factor and its receptors and neovascularization in colonic carcinoma implanted in nude mice

    Institute of Scientific and Technical Information of China (English)

    Yun-He Jia; Xin-Shu Dong; Xi-Shan Wang

    2004-01-01

    AIM: To investigate the antiangiogenic effects of endostatin on colonic carcinoma cell line implanted in nude mice and its mechanism.METHODS: Nude mice underwent subcutaneous injection with LS-174t colonic carcinoma cell line to generate carcinoma and were randomly separated into two groups. Mice received injection of vehicle or endostatin every day for two weeks.After the tumor was harvested, the tumor volumes were determined, and the expressions of CD34, VEGF and Flk-1were examined by immunohistochemical method.RESULTS: Tumor volume was significantly inhibited in the endostatin group (84.17%) and tumor weight was significantly inhibited in the endostatin group (0.197±0.049)compared to the control group (1.198±0.105) (F= 22.56,P = 0.001), microvessel density (MVD) was significantly decreased in the treated group (31.857±3.515) compared to the control group (100.143±4.290) (F= 151.62, P<0.001).Furthermore, the expression of Flk-1 was significantly inhibited in the treated group (34.29%) compared to the control group (8.57%) (x2= 13.745, P = 0.001). However no significant decrease was observed in the expression of vascular endothelial growth factor (VEGF) between these two groups (x2 = 0.119, P = 0.730).CONCLUSION: Endostatin can inhibit tumor growth and angiogenesis by blocking Vegf/Flk-1 pathway. This experiment provides the theory basis for developing a new anti-carcinoma drug through studying the properties of anti-angiogenesis inhibitors.

  14. An ectopic study of tissue-engineered bone with Nell-1 gene modified rat bone marrow stromal cells in nude mice

    Institute of Scientific and Technical Information of China (English)

    HU Jing-zhou; ZHANG Zhi-yuan; ZHAO Jun; ZHANG Xiu-li; LIU Gen-tao; JIANG Xin-quan

    2009-01-01

    Background Tissue engineering techniques combined with gene therapy have been recently used to improve osteogenesis. NEL-like molecule-1 (Nell-1), a novel growth factor, has been reported to have specificity for osteochondral lineage. The study assessed the osteogenic differentiation of rat bone marrow stromal cells (bMSCs) after Nell-1 gene modification and examined its ectopic bone formation ability in a nude mice model with tissue engineering technique.Methods bMSCs obtained from Fischer 344 rats were transduced with either AdNell-1 (Nell-1 group) or Ad-β-galactosidase (AdLacZ, LacZ group) or left untransduced (untransduced group). The expression of Nell-1 protein was determined by Western blotting and transfer efficiency was assessed, mRNA expressions of osteopontin (OP), bone sialoprotein (BSP) and osteocalcin (OC) were assessed by real-time PCR 0, 3, 7, 14, and 21 days after gene transfer. Alkaline phosphatase (ALP) activity was measured and von Kossa test was also conducted. Finally, with a tissue engineering technique, gene transduced bMSCs, combining with β-tricalcium phosphate (β-TCP) at a concentration of 2×107 cells/ml, were implanted at subcutaneous sites on the back of nude mice. Four weeks after surgery, the implants were evaluated with histological staining and computerized analysis of new bone formation.Results Under current transduction conditions, gene transfer efficiency reached (57.9±6.8)%. Nell-1 protein was detected in Nell-1 group but not in untransduced group and LacZ group. Induced by Nell-1, BSPand OPexpression were increased at intermediate stage and OC expression was increased at later stage. ALP activity and the number of calcium nodules were highest in Nell-1 group. Four weeks after implanted into nude mice subcutaneously, the percentage of new bone area in Nell-1 group was (18.1±5.0)%, significantly higher than those of untransduced group (11.3±3.2)% and LacZ group (12.3±3.1)% (P<0.05).Conclusions This study has demonstrated

  15. Anti-tumor effects of polybutylcyanoacrylate nanoparticles of diallyl trisulfide on orthotopic transplantation tumor model of hepatocellular carcinoma in BALB/c nude mice

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhi-mian; YANG Xiao-yun; DENG Shu-hai; XU Wei; GAO Hai-qing

    2007-01-01

    Background Hepatocellular carcinoma (HCC) ranked the second among the causes of cancer mortality in China since the 1990s. Up to now, medication still plays an important role in the treatment of HCC. The therapies based on the allicin as a potential chemopreventive analog although is in its infancy at the present time, may have a significant role in the future management of HCC. Diallyl trisulfide (DATS) is a natural compound derived from garlic. In this study, we investigated the inhibitory effects of hepatic targeted polybutylcyanoacrylate nanoparticles of diallyl trisulfide(DATS-PBCA-NP) on orthotopic transplanted HepG2 hepatocellular carcinoma in nude mice.Methods DATS-PBCA-NP were detected by transmission electron microscope (TEM) and high-performance liquid chromatography (HPLC). The orthotopic transplantation HCC models were established by implanting HCC HepG2 xenograft bits under the envelope of the mice liver. Successful models (n=29) were divided into 4 groups: normal saline(NS), empty nanoparticles (EN), DATS and DATS-PBCA-NP were intravenously administered to the mice respectively for 2 weeks. In vivo antitumor efficacy was evaluated by the measurement of tumor volume. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay and protein levels of apoptosis and cell proliferation proteins by immunoblotting in tumor tissues were performed to elucidate the possible mechanism.Results DATS-PBCA-NP possessed smooth and round appearance, dispersed well, and released in vitro in accord with double phase kinetics model. DATS-PBCA-NP changed the tissue/organ distribution of DATS in vivo. The successful rate of tumor implantation was 100%. Intravenous administration of DATS-PBCA-NP significantly retarded the growth of orthotopically transplanted hepatoma in BALB/c nude mice (compared with the other three groups, all P<0.05) without causing weight loss (P>0.05). TUNEL staining showed that the tumors from DATS-PBCA-NP treated mice

  16. Biodistribution of [sup 125]I labeled monoclonal antibody against gamma seminoprotein in the nude mice bearing human benign prostatic hyperplasia xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Fujino, Awato (Kitasato Univ., Sagamihara, Kanagawa (Japan). School of Medicine)

    1993-07-01

    The biodistribution of [sup 125]I labeled monoclonal antibody against gamma seminoprotein ([gamma]-Sm) in the nude mice bearing human benign prostatic hyperplasia xenograft was evaluated by whole body autoradiography and by counting of radioactivity in organs. The monoclonal antibody (murine Ig G[sub 1], K) to [gamma]-Sm which was established in this institute and its F(ab')[sub 2] fragment were radioiodinated using Iodogen method. The autoradiograms demonstrated specific uptake of [sup 125]I-intact Ig G as well as [sup 125]I-F(ab')[sub 2] within the prostatic adenoma xenografts 4 days after intravenous administrations. Radioactivity in the xenograft was relatively higher than those in the liver, kidney or lung. These results suggest that radio-labeled monoclonal antibody against [gamma]-Sm might be applicable for radioimmunodetection of prostatic tumors which produce [gamma]-Sm. (author).

  17. Effect of vasoactive intestinal polypeptide on MKN45 xenografts in nude mice%VIP对裸鼠MKN45移植瘤的影响

    Institute of Scientific and Technical Information of China (English)

    孙姚; 万娟; 李媛媛; 李国华

    2013-01-01

    Objective To investigate the effect of vasoactive intestinal polypeptide (VIP) on MKN45 xenografts in nude mice. Methods When MKN45 xenografts had grown to approximately 30 mm3 in volume, 18 nude mice were equally randomized into three groups of A (treated with VIP 10 μg · 100 μl-1 · mouce-1) ,B(treated with VIP receptor antagonist 10 μg · 100 μl-1 · mouce-1) and C (treated with PBS 100 μl/mouce). The drugs were injected subcutaneously daily for 4 weeks. The volume of xenografts and body weight were measured weekly. The expressions of ERK protein and mRNA in xenografts were detected by immunocytochemistry and RT-PCR. Results On the 28th day after administration,body weight of nude mice in group VIP was less than that in group B(P<0. 05). On the 21st day after administration, the size of the xenografts in group A was larger than that in the other two groups(P<0. 01). The expression of ERK in xenografts in group A was lower than that in group B(P<0. 05). Conclusion VIP may potentially inhibit the growth of MKN45 xenografts in nude mice through its inhibitory effect on the ERK pathway.%目的 探讨血管活性肠肽(VIP)对裸鼠MKN45移植瘤的影响.方法 将18只人胃癌MKN45细胞株的移植瘤裸鼠随机均分为三组,分别每天皮下注射VIP 10 μg·100 μl-1·只-1 (VIP组)、VIP受体拮抗剂[D-p-C1-phe6,Leu17]-VIP(V4380) 10 μg·100μl-1·只1(拮抗剂组)和PBS100μl/只(对照组).每周称量裸鼠体重及移植瘤体积,4周后处死裸鼠,称量移植瘤重量及体积.用免疫组化及RT-PCR检测移植瘤组织中胞外信号调节激酶(ERK)蛋白及mRNA表达的变化.结果 给药第28天,VIP组裸鼠体重明显轻于拮抗剂组(P<0.05).给药的第14、21天,VIP组移植瘤体积明显小于其它两组(P<0.01).VIP组ERK蛋白的表达显著低于拮抗剂组(P<0.05).结论 VIP可能通过抑制肿瘤细胞ERK/NF-κB通路对人胃癌细胞MKN45裸鼠移植瘤有潜在抑制作用.

  18. Effect of immunosuppressive agents on the guanethidine-induced sympathectomy in athymic and euthymic rats

    DEFF Research Database (Denmark)

    Hougen, H P; Thygesen, P; Christensen, H B;

    1992-01-01

    Guanethidine sulphate causes destruction of peripheral sympathetic neurons and infiltration of mononuclear inflammatory cells in the sympathetic ganglia of both athymic nude (rnu/rnu) and euthymic LEW/Mol rats. The effect of guanethidine is believed to be an autoimmune reaction. To determine...... the effect of immunosuppressive drugs concurrently with guanethidine treatment both athymic and euthymic rats were treated with guanethidine 40 mg/kg i.p. daily for 14 days, cyclophosphamide 100 mg/kg i.p. on days 1 and 8, methylprednisolone 10 mg/kg and cyclosporin A 10 mg/kg daily from days 1 to 7......, and then every other day from days 8 to 14. The number of neurons in the sympathetic ganglia was counted and four subpopulations of mononuclear inflammatory cells were identified by monoclonal antibodies MHC II, CD8 T-cells/NK-cells, CD5 T-cells, CD4 T-cells/macrophages. Our results show...

  19. Transplantation of human glioma stem cells in nude mice with green fluorescent protein expression%人脑胶质瘤干细胞移植于表达绿色荧光蛋白裸小鼠的研究

    Institute of Scientific and Technical Information of China (English)

    吴自成; 黄强; 邵义祥; 薛智谋; 董军; 刁艺; 王爱东; 兰青

    2008-01-01

    Objectives To investigate the possibility of transplantation of human glioma stem cells (HGSCs) in nude mice stably expressing green fluorescent protein (GFP) so as to clearly identify the incubated HGSCs from the host tissues. Methods Transgenic C57BL/6J mice expressing GFP was crossed with nude mice of the line NC, then hairless male nude mice expressing GFP were crossed with hairy female pubescent mice to obtain nude mice with GFP expression the expression of GFP in the skin and organs of these nude mice were evaluated by naked eyes, and immunohistochemical and immunofluorescence assays. HGSCs were transplanted orthotopically into the caudate nuclei of nude mice expressing GFP. Immunohistochemistry was used to observe the transplanted tumor. Results The structures rich in adipose tissue of the 8th generation nude mice were dark green and the other organs were light green. However, green fluorescence was emitted from all tissues under fluorescence microscopy. Confocal fluorescence microscopy showed that the tumor cells were stained red, distinguished from the host ceils distinctly in the brains bearing tumor transplanted orthotopically. Conclusion Nude mice expressing GFP can be obtained by crossing the trangenic mice bearing naive immunity with nude mice. Orthotopic transplantation of HGSCs may be used in the investigation of tumor tissue reconstitution because of the easy identification between the transplantation tumor and host tissue.%目的 培育表达绿色荧光蛋白(GFP)的裸小鼠,并探讨将其用于人胶质瘤干细胞(HGSC)移植实验研究.方法 将C57BL/6J-GFP转基因小鼠与NC系裸小鼠进行交配,在继代时严格挑选都表达GFP的无毛雄鼠与有毛母鼠交配,通过肉眼、免疫组织化学和荧光显微镜等方法观察GFP在裸小鼠皮肤和脏器中的表达情况,继将HGSC原位移植于表达GFP的裸小鼠,以观察移植瘤的生长情况.结果 传至8代的裸小鼠,包括脑在内的全身主要器官和细胞

  20. The experimental study on the radioimmunotherapy of the nasopharyngeal carcinoma overexpressing HER2/neu in nude mice model with intratumoral injection of {sup 188}Re-herceptin

    Energy Technology Data Exchange (ETDEWEB)

    Li Guiping [Radiopharmaceutical Research Centre, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800 (China) and Department of Nuclear Medicine, Nanfang Hospital, First Military Medical University, Guangzhou, 510515 (China)]. E-mail: ligp@fimmu.com; Wang Yongxian [Radiopharmaceutical Research Centre, Shanghai Institute of Applied Physics, the Chinese Academy of Sciences, Shanghai, 201800 (China)]. E-mail: yongxianw@163.com; Huang Kai [Department of Nuclear Medicine, Nanfang Hospital, First Military Medical University, Guangzhou, 510515 (China); Zhang Hui [Department of Nuclear Medicine, Nanfang Hospital, First Military Medical University, Guangzhou, 510515 (China); Peng Wuhe [Department of Nuclear Medicine, Nanfang Hospital, First Military Medical University, Guangzhou, 510515 (China); Zhang Chunfu [Radiopharmaceutical Research Centre, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800 (China)

    2005-01-01

    The therapeutic efficacy of radioimmunotherapy (RIT) of {sup 188}Re-labeled herceptin, which is a humanized anti-p185-HER2/neu monoclonal antibody (mAb), was studied. The nude mice bearing nasopharyngeal carcinoma (NPC) expressing HER2/neu protooncogene were injected with {sup 188}Re-herceptin intratumorally and intravenously. The biodistribution was observed on day 2 (n=3). The tumor growth inhibition rate (IR) was determined by measurement of tumor volume. In the intratumorally treated mice, tumor uptake of {sup 188}Re-herceptin was significantly greater than in the intravenously treated mice [11.53% injected dose (ID)/g vs. 2.79% ID/g at 48 h], and lower normal organ uptake was also seen. The intratumoral administration of {sup 188}Re-herceptin caused greater inhibition of tumor growth at the fourth week as compared to the intravenous administration. It is concluded that intratumoral administration of {sup 188}Re-herceptin makes high level of radioactivity retained in tumor with significantly lower radioactivity retained in normal tissues, and provides a more effective regional therapy for NPC overexpressing HER2/neu.

  1. [Inhibition Function of Dominant-negative Mutant Gene Survivin-D53A to SPC-A1 Lung Adenocarcinoma Xenograft in Nude Mice Models].

    Science.gov (United States)

    Yu, Min; Peng, Xingchen; Lu, You; Huang, Meijuan

    2015-06-01

    Survivin-D53A (SVV-D53A) is a dominant-negative mutant survivin, which represents a potential promising target for cancer gene therapy. The present study was designed to determine whether SVV-D53A plasmid encapsuled by DOTAP: Chol liposome would have the anti-tumor activity against SPC-A1 lung adenocarcinoma, and to detect the possible mechanisms. In our experiment, SPC-A1 cells were transfected in vitro with SVV-D53A plasmid and examined for protein expression by Western blot, then flow cytometric analysis was used to detect apoptosis. SPC-A1 lung adenocarcinoma xenografts were established in vivo in the nude mice, which received the i. v. administrations of SVV-D53A plasmid/liposome complexes. After mice were sacrificed, the paraffin-embedded tumor tissue sections were used for proliferating cell nuclear antigen (PCNA) expression and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Compared with the control group, the mice treated with SVV-D53A plasmid had an obviously reduced tumor volume, with high level of apoptosis and decreased cell proliferation in tumor tissue. The research results proved that the administration of SVV-D53A plasmid resulted in significant inhibition of SPC-A1 cells both in vitro and in vivo. The functional mechanism is that the anti-tumor response causes and induces tumor cell apoptosis.

  2. Effects of Different High Fat Diets on Fatty Acid Composition of Skeletal Muscle and Liver in Nude Mice Bearing Pancreatic Cancer

    Institute of Scientific and Technical Information of China (English)

    Yi-jie DUAN; Feng WANG; Zhong-wen LIU; Ming YU

    2014-01-01

    Objective To investigate the impacts of different dietary fatty acids on fatty acid composition in skeletal muscle and liver in nude mice bearing pancreatic cancer.MethodsSixty C57BL/6 nude mice were randomly divided into 6 groups: saturated fatty acid-fed group (SFA group), monounsaturated fatty acid-fed group (MUFA group), n-6 polyunsaturated fatty acid-fed group (n-6 PUFA group), n-3 polyunsaturated fatty acid-fed group (n-3 PUFA group), iso-caloric control (ISO-C) and normal control (NC). Four high fat diets containing 15% oils derived from coconut (SFA group), olive (MUFA group), soybean (n-6 PUFA group) andflaxseed (n-3 PUFA group) respectively, were prepared. ISO-C and NC groups were fed diet containing 4%-5% soybean oil. After one week of feeding, HPAF-Ⅱ human pancreatic cancer cells were transplanted orthotopically. The mice were fed corresponding diets in the following 14 weeks and then sacrificed. Skeletal muscle and liver tissues were sampled. Fatty acids in the samples were analyzed by gas chromatography-mass spectrometry.ResultsFatty acid composition of skeletal muscle and liver were similar between ISO-C group and NC group.Compared to ISO-C group, the contents of fatty acids in skeletal muscle were: (1) palmitic acid (C16:0), hepentadecane acid (C17:0), stearic acid (C18:0) and arachidonic acid (C20:0) increased inSFA group (P< 0.05); (2)oleic acid (C18:1) increased in MUFA group (P< 0.05); (3)γ-linolenic acid (γ-C18:3) increased in n-6 PUFA group (P<0.05);(4) linolenic acid (C18:3), eicosapentaenoic acid (C20:5) and clupanodonic acid (C22:5) increased in n-3 PUFA group (P<0.05). In the liver, the contents of fatty acids were: (1) saturated fatty acids not increased in SFA group; (2) eicosenoic acid (C20:1) increased in MUFA group (P< 0.05); (3) eicosadienoic acid (C20:2) and arachidonic acid (C20:4) increased in n-6 PUFA group (P < 0.05); (4) linolenic acid, eicosapentaenoic acid, clupanodonic acid and docosahexaenoic acid increased in n-3 PUFA

  3. Evaluation of a new DTPA-derivative chelator: comparative biodistribution and imaging studies of [sup 111]In-labeled B3 monoclonal antibody in athymic mice bearing human epidermoid carcinoma xenografts. [Diethylenetriaminpentaacetic acid

    Energy Technology Data Exchange (ETDEWEB)

    Camera, L.; Kinuya, S.; Garmestani, K.; Pai, L.H.; Brechbiel, M.W.; Gansow, O.A.; Paik, C.H.; Pastan, I.; Carrasquillo, J.A. (National Cancer Inst., Bethesda, MD (United States))

    1993-11-01

    Biodistribution and imaging characteristics of monoclonal antibody (MAb) B3 conjugated to either the 2-(p-isothiocvanatobenzyl)-cyclohexyl-DTPA (CHX-B) or 2-(p-isothiocyanatobenzyl)-6-methyl-DTPA (1B4M) and labeled with [sup 111]In, were evalulated in nude mice bearing A431 human epidermoid carcinoma xenografts. MAb B3, is a murine IgG1k reacting with a carbohydrate antigen abundantly expressed by most carcinomas. Both [sup 111]In-(CHX-B)-B3 and [sup 111]In-(1B4M)-B3 showed good tumor targeting with peak values observed at 72 h with 27.6 [+-] 7.6 and 25.4 [+-] 1.7% ID/g, respectively (P > 0.05). High tumor-to-organ ratios were also observed and, confirmed by the imaging results. In particular, tumor-to liver ratios increased from 5.0 [+-] 0.9 at 24 h to 9.2 [+-] 2.0 at 168 h for [sup 111]In-(CHX-B)-B3 and from 4.5 [+-] 0.6 to 8.9 [+-] 3.5 for [sup 111]In-(1B4M)-B3. This was mainly the result of low liver accumulation of both [sup 111]In-(CHX-B)-B3 and [sup 111]In-(1B4M)-B3, with only 2.48 [+-] 0.46 and 2.5 [+-] 0.9% ID/g at 168h, respectively (P > 0.05). Our findings indicate that either CHX-B or 1B4M can be successfully used for [sup 111]In-labeling of MAbs and that [sup 111]In-B3 may represent a promising radioimmunoimaging agent. (Author).

  4. miRNA-181b increases the sensitivity of pancreatic ductal adenocarcinoma cells to gemcitabine in vitro and in nude mice by targeting BCL-2.

    Science.gov (United States)

    Cai, Baobao; An, Yong; Lv, Nan; Chen, Jianmin; Tu, Min; Sun, Jie; Wu, Pengfei; Wei, Jishu; Jiang, Kuirong; Miao, Yi

    2013-05-01

    Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease and is usually resistant to chemotherapy. MicroRNA‑181b (miR-181b) has been reported to be associated with chemoresistance in various types of cancer. In this study, we investigated the effects of miR-181b on the chemosensitivity of PDAC cells to gemcitabine and the underlying molecular events. miR-181b mimics and inhibitors were synthesized for transient gene transfection in vitro. Lentivirus carrying miR-181b mimics were used to infect PDAC cells for nude mouse xenograft assays by implanting infected PDAC cells into recipient mice. Cell viability was determined by MTT assays, while gene expression was assessed using qRT-PCR, western blot analysis and enzyme-linked immunosorbent assay (ELISA). miR-181b targeting BCL-2 expression was assessed by a dual-luciferase activity assay. The data showed that miRNA-181b expression sensitized PDAC cells to gemcitabine treatment. Although gemcitabine-resistant PDAC cell sublines (SW1990/GR and CFPAC-1/GR) expressed higher levels of miRNA-181b, gemcitabine induced higher levels of apoptosis in PDAC cells transfected with miRNA-181b mimics. The nude mouse xenograft assay data showed that miR-181b transfection also sensitized the cells to gemcitabine treatment in vivo. Molecularly, bioinformatics data predicted that miR-181b was able to bind to BCL-2 mRNA 3'UTR. The dual luciferase activity assay revealed that miRNA-181b downregulated BCL-2 expression. The results from western blot analysis showed a reduced BCL-2 expression following miR-181b transfection but an enhanced caspase-3 activity in miRNA-181b mimic-transfected PDAC cells. This study demonstrates that miRNA-181b sensitizes PDAC cells to gemcitabine by targeting BCL-2.

  5. Establishment of Two Human Breast Cancer Model in Nude Mice%两种人乳腺癌裸鼠移植模型的建立

    Institute of Scientific and Technical Information of China (English)

    饶子亮; 黄威; 郑佳琳; 孙侠; 黄红坤; 钟志勇; 王刚

    2012-01-01

    Objective To establish proper model of human breast cancer in nude mice and study their biological features. Methods MDA-MB -231 and SK-BR - 3 cells(ER - ) were implanted into the left axilla of 10 nude mice. Tumor growth was observed, and the tumor-bearing mice were killed on day 42. The tumor masses were removed, and pathologically examined by the microscope. Results The MDA-MB -231 tumor tubercles could be formed on day 5. The tumor-take rate was 90% (9/10) ,and average volume and weight of the tumor were (426.6 ±333. 8) mm3 and (0.417± 0.276) g reparatively. The SK-BR-3 tumor tubercles could be formed on day 11. The tumor-take rate was 80% (8/10) , and average volume and weight of the tumor were ( 357. 5 ± 246. 4 ) mm3 and (0. 325 ± 0. 167 ) g reparatively. All of the specimens were infiltrating ductal carcinoma. Conclusion We succeeded in establishing two human breast cancer model in nude mice, which reserved certain biological features of human breast cancer, therefore it may be an available model for further research of breast cancer.%目的 建立简便的人乳腺癌裸鼠移植模型,并探讨其部分生物学特性.方法 采用雌激素受体阴性的MDA-MB-231和SK-BR-3人乳腺癌细胞株,分别接种于10只裸鼠左侧腋窝皮下,移植细胞总数为1 x 107/只.观察肿块生长情况,第42天处死荷瘤鼠,切除肿块作病理切片.结果 MDA-MB-231接种后第5d在接种部位可见结节,成瘤率为90% (9/10),接种42 d肿瘤体积426.6±333.8,瘤重0.417±0.276,病理学检查为浸润性导管癌;SK-BR -3接种后第11天在接种部位可见结节,成瘤率为80%(8/10),接种42 d肿瘤体积357.5±246,瘤重0.325±0.167,病理学检查为浸润性导管癌.结论 该方法建立的人乳腺癌裸鼠移植模型,皮下移植方法简单,易于操作,成功率较高,肿瘤可部分保持人乳腺癌生物学特性,为研究人乳腺癌提供了重要工具.

  6. 177Lu-DOTA-HH1, a Novel Anti-CD37 Radio-Immunoconjugate: A Study of Toxicity in Nude Mice

    Science.gov (United States)

    Repetto-Llamazares, Ada H. V.; Larsen, Roy H.; Giusti, Anna Maria; Riccardi, Elena; Bruland, Øyvind S.; Selbo, Pål Kristian; Dahle, Jostein

    2014-01-01

    Background CD37 is an internalizing B-cell antigen expressed on Non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia cells (CLL). The anti-CD37 monoclonal antibody HH1 was conjugated to the bifunctional chelator p-SCN-Bn-DOTA and labelled with the beta-particle emitting radionuclide 177Lu creating the radio-immunoconjugate (RIC) 177Lu-DOTA-HH1 (177Lu-HH1, trade name Betalutin). The present toxicity study was performed prior to initiation of clinical studieswith 177Lu-HH1. Methodology/Principal Findings Nude mice with or without tumor xenografts were treated with 50 to 1000 MBq/kg 177Lu- HH1 and followed for clinical signs of toxicity up to ten months. Acute, life threatening bone marrow toxicity was observed in animals receiving 800 and 1000 MBq/kg 177Lu-HH1. Significant changes in serum concentrations of liver enzymes were evident for treatment with 1000 MBq/kg 177Lu-HH1. Lymphoid depletion, liver necrosis and atrophy, and interstitial cell hyperplasia of the ovaries were also observed for mice in this dose group. Conclusions/Significance 177Lu-DOTA-HH1 was well tolerated at dosages about 10 times above those considered relevant for radioimmunotherapy in patients with B-cell derived malignancies.The toxicity profile was as expected for RICs. Our experimental results have paved the way for clinical evaluation of 177Lu-HH1 in NHL patients. PMID:25068508

  7. 177Lu-DOTA-HH1, a novel anti-CD37 radio-immunoconjugate: a study of toxicity in nude mice.

    Directory of Open Access Journals (Sweden)

    Ada H V Repetto-Llamazares

    Full Text Available CD37 is an internalizing B-cell antigen expressed on Non-Hodgkin lymphoma (NHL and chronic lymphocytic leukemia cells (CLL. The anti-CD37 monoclonal antibody HH1 was conjugated to the bifunctional chelator p-SCN-Bn-DOTA and labelled with the beta-particle emitting radionuclide 177Lu creating the radio-immunoconjugate (RIC 177Lu-DOTA-HH1 (177Lu-HH1, trade name Betalutin. The present toxicity study was performed prior to initiation of clinical studies with 177Lu-HH1.Nude mice with or without tumor xenografts were treated with 50 to 1000 MBq/kg 177Lu- HH1 and followed for clinical signs of toxicity up to ten months. Acute, life threatening bone marrow toxicity was observed in animals receiving 800 and 1000 MBq/kg 177Lu-HH1. Significant changes in serum concentrations of liver enzymes were evident for treatment with 1000 MBq/kg 177Lu-HH1. Lymphoid depletion, liver necrosis and atrophy, and interstitial cell hyperplasia of the ovaries were also observed for mice in this dose group.177Lu-DOTA-HH1 was well tolerated at dosages about 10 times above those considered relevant for radioimmunotherapy in patients with B-cell derived malignancies.The toxicity profile was as expected for RICs. Our experimental results have paved the way for clinical evaluation of 177Lu-HH1 in NHL patients.

  8. Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ming-Fa Hsieh

    2010-12-01

    Full Text Available The triblock copolymer is composed of two identical hydrophilic segments: Monomethoxy poly(ethylene glycol (mPEG and one hydrophobic segment poly(ε‑caprolactone (PCL; which is synthesized by coupling of mPEG-PCL-OH and mPEG‑COOH in a mild condition using dicyclohexylcarbodiimide and 4-dimethylamino pyridine. The amphiphilic block copolymer can self-assemble into nanoscopic micelles to accommodate doxorubixin (DOX in the hydrophobic core. The physicochemical properties and in vitro tests, including cytotoxicity of the micelles, have been characterized in our previous study. In this study, DOX was encapsulated into micelles with a drug loading content of 8.5%. Confocal microscopy indicated that DOX was internalized into the cytoplasm via endocystosis. A dose-finding scheme of the polymeric micelle (placebo showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice. Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats. A biodistribution study displayed that plasma extravasation of DOX in liver and spleen occurred in the first four hours. Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14 of DOX-loaded micelles as compared to multiple administrations of free DOX.

  9. Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cuong, Nguyen-Van [Department of Biomedical Engineering, Chung Yuan Christian University, 200, Chung Pei Rd., Chung Li, Taiwan (China); Department of Chemical Engineering, Ho Chi Minh City University of Industry, 12 Nguyen Van Bao St, Ho Chi Minh (Viet Nam); Jiang, Jian-Lin; Li, Yu-Lun [Department of Biomedical Engineering, Chung Yuan Christian University, 200, Chung Pei Rd., Chung Li, Taiwan (China); Chen, Jim-Ray [Department of Pathology, Chang Gung Memorial Hospital at Keelung, Taiwan and Chang Gung University, College of Medicine, Taoyuan, Taiwan (China); Jwo, Shyh-Chuan [Division of General Surgery, Chang Gung Memorial Hospital at Keelung, Taiwan and Chang Gung University, College of Medicine, Taoyuan, Taiwan (China); Hsieh, Ming-Fa, E-mail: mfhsieh@cycu.edu.tw [Department of Biomedical Engineering, Chung Yuan Christian University, 200, Chung Pei Rd., Chung Li, Taiwan (China)

    2010-12-28

    The triblock copolymer is composed of two identical hydrophilic segments Monomethoxy poly(ethylene glycol) (mPEG) and one hydrophobic segment poly(ε-caprolactone) (PCL); which is synthesized by coupling of mPEG-PCL-OH and mPEG-COOH in a mild condition using dicyclohexylcarbodiimide and 4-dimethylamino pyridine. The amphiphilic block copolymer can self-assemble into nanoscopic micelles to accommodate doxorubixin (DOX) in the hydrophobic core. The physicochemical properties and in vitro tests, including cytotoxicity of the micelles, have been characterized in our previous study. In this study, DOX was encapsulated into micelles with a drug loading content of 8.5%. Confocal microscopy indicated that DOX was internalized into the cytoplasm via endocystosis. A dose-finding scheme of the polymeric micelle (placebo) showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice. Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats. A biodistribution study displayed that plasma extravasation of DOX in liver and spleen occurred in the first four hours. Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14) of DOX-loaded micelles as compared to multiple administrations of free DOX.

  10. Pigment epithelium derived factor inhibits the growth of human endometrial implants in nude mice and of ovarian endometriotic stromal cells in vitro.

    Directory of Open Access Journals (Sweden)

    Yanmei Sun

    Full Text Available Angiogenesis is a prerequisite for the formation and development of endometriosis. Pigment epithelium derived factor (PEDF is a natural inhibitor of angiogenesis. We previously demonstrated a reduction of PEDF in the peritoneal fluid, serum and endometriotic lesions from women with endometriosis compared with women without endometriosis. Here, we aim to investigate the inhibitory effect of PEDF on human endometriotic cells in vivo and in vitro. We found that PEDF markedly inhibited the growth of human endometrial implants in nude mice and of ovarian endometriotic stromal cells in vitro by up-regulating PEDF expression and down-regulating vascular endothelial growth factor (VEGF expression. Moreover, apoptotic index was significantly increased in endometriotic lesions in vivo and endometriotic stromal cells in vitro when treated with PEDF. In mice treated with PEDF, decreased microvessel density labeled by Von Willebrand factor but not by α-Smooth Muscle Actin was observed in endometriotic lesions. And it showed no increase in PEDF expression of the ovary and uterus tissues. These findings suggest that PEDF gene therapy may be a new treatment for endometriosis.

  11. 脉血康对荷MHCC97H人肝癌裸鼠皮下移植瘤VEGF表达的影响%The Effect of Hirudin on the Expression of the Subcutaneous Implanted Tumor VEGF from Hepatocelluar Carcinoma MHCC97H in Athymic Mice

    Institute of Scientific and Technical Information of China (English)

    陈小敏; 李山平; 陈晓亮; 陈升有; 黄桢; 李豪侠

    2011-01-01

    Objective;To study the effect of hirudin on the expression of the subcutaneous implanted tumor VEGF from hepatocelluar carcinoma MHCC97H in athymic mice. Methods; Sixty athymic mice which bore high metastatic MHCC97 hepatocelluar carcinoma were randomized into six groups. Each group consists of ten mice. (1) Positive Control Group: 2mg/kg cisplatin was injected into the mice's abdominal cavity every alternate day; (2) Model Control Group .-mice were lavaged daily with distilled water, 0. 2mL/10g; (3) Low Dose Hirudin Group: mice were lavaged daily with hirudin 0. 5g/ kg; (4) Medium Dose Hirudin Group: mice were lavaged daily with hirudin l.Og/kg; (5) High Dose Hirudin Group; mice were lavaged daily with hirudin 2.0g/kg; (6)Joint Group:mice were lavaged daily with hirudin l.0g/kg and 2mg/ kg cisplatin was injected into their abdominal cavity every alternate day. The experiments lasted twenty - one days. After medication was applied, the athymic mice from each group were weighted every three days. In addition, the maximal diameter A and the minor diameter B of the tubercle of the implanted tumor in each athymic mouse were measured by vernier caliper every three days. Therefore, the volume of the tumor and the relative rate of tumor reproduction (T/C % ) were calculated and used as an indicator for the effectiveness of the treatment. Twenty - four hours after the last medication was applied, the tested animals were put down, weighted and photos were taken. Meanwhile, the tumor was separated from the body of each mouse. The separated tumor was weighed and was made rigid with methanol. The immunised technology was applied in order to measure the change of expression of the tumor VEGF. Results;Compared with the Control Group, the weight of the subcutaneous implanted tumor in athymic mice of the Hirudin Group、 the Cisplatin Injection group、the Joint Group had clearly reduced. The results show strong statistic differences (P 0. 05). Conclusion: The hirudin has

  12. A controlled study of the effects of RU58841, a non-steroidal antiandrogen, on human hair production by balding scalp grafts maintained on testosterone-conditioned nude mice.

    Science.gov (United States)

    De Brouwer, B; Tételin, C; Leroy, T; Bonfils, A; Van Neste, D

    1997-11-01

    Human hair growth can be monitored for several months after the transplantation of scalp samples from men with androgen-dependent alopecia on to female nude mice. Hair production from balding sites has been shown to be inhibited in testosterone-conditioned nude mice. We used this recently reported model to study the effect of a new non-steroidal antiandrogen-RU58841-on human hair growth. Twenty productive scalp grafts from balding men were maintained for 8 months after grafting on to nude mice, and hair production was monitored monthly for 6 months. All mice were conditioned by the topical application of testosterone (testosterone propionate, 300 micrograms in 10 microL; 5 days/week) on the non-grafted flank. The scalp samples were divided equally according to the estimated hair production potential, which was based on the amount of hair present on the scalp samples before grafting. Each of the two equal groups of grafts was further allocated at random to be treated topically (5 days/week) with blinded solutions of either RU58841 1% in ethanol, or ethanol as a control. Twenty-eight active follicles appeared on the 10 control grafts. Among them only two follicles (7%) initiated a second hair cycle. However, the 10 RU58841-treated grafts bore a total of 29 active follicles, and eight of them (28%) showed a second cycle. The values for the linear hair growth rates (LHGR) were significantly (P Recycling and increased LHGR indicate a positive action for RU58841 on human hair growth from balding samples grafted on to testosterone-conditioned nude mice, and encourage a clinical trial to evaluate its potential in the treatment of androgen-dependent alopecia.

  13. The Discussion of Establishing Human Endometrial Carcinoma Xenografts in Ovariectomized Nude Mice%建立去势雌性裸小鼠人子宫内膜癌皮下移植瘤动物模型的探讨

    Institute of Scientific and Technical Information of China (English)

    李玲; 廖秦平

    2012-01-01

    Objective:To discuss the influence of total irradiation on the human endometrial carcinoma xenografts in the ovariectomized nude mice. Methods:One week after the ovariectomy,the female nude mice were randomly distributed into two groups:non-irradiated group and irradiated group. Trie endometrial cells,which had been cultured in vitro,was subcutaneously transplanted into the nude mice one week after the surgery, in the irradiated group the mice were exposed to 4 Gy of total body irradiation 3 h pior to injection with endometrial cells,in the non-irradiated group the mice were injected with endometrial cells in the same time.the mice weight,survival rate and tumor growth of both groups were observed,the diameters of tumors was measured and the volume of tumors was calculated. Results:The both groups have 100% tumor growth; the difference in tumor sizes is not significant (P<0.05). Conclusions:Total body irradiation did not affect the tumor-take rate on human endometrial carcinoma xenografts in ovariectomized nude mice, but increased the death rate of nude mices.%目的:探讨全身外照射对建立切除卵巢后雌性裸小鼠子宫内膜癌皮下移植瘤模型成瘤率的影响.方法:将切除卵巢后1周的裸小鼠随机分为两组,一组全身外照射(4 Gy)3 h后皮下注射子宫内膜癌细胞悬液,另一组未予照射同时间皮下注射子宫内膜癌细胞悬液,观察裸小鼠体质量变化、存活情况和肿瘤的生长情况,测量肿瘤径线并计算体积.结果:2组成瘤率100%;各组肿瘤体积差异无统计学意义(P>0.05),但存活率差异有统计学意义(P<0.05).结论:全身外照射不影响切除卵巢的裸小鼠的成瘤率,但增加裸小鼠的死亡率.

  14. Mendelian analysis of a metastasis-prone substrain of BALB/c nude mice using a subcutaneously inoculated human tumour

    DEFF Research Database (Denmark)

    Schou, M; Brünner, N; Spang-Thomsen, M;

    2006-01-01

    BL/6J +/+ mice we found that the ability to allow a human tumour (MDA-MB-435 BAG) to express its metastatic phenotype is determined by a recessively inheritable trait in the mouse host. We are presently working to identify the genetics responsible for development of metastases. The study also...

  15. Effect of arsenic trioxide on vascular endothelial cell proliferation and expression of vascular endothelial growth factor receptors Flt-1 and KDR in gastric cancer in nude mice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the effect of arsenic trioxide (As2O3) on expression of vascular endothelial growth factor receptor-1 (VEGFR-1, Flt-1) and VEGFR-2 (KDR) in human gastric tumor cells and proliferation of vascular endothelial cells.METHODS: The solid tumor model was formed in nude mice with the gastric cancer cell line SGC-7901. The animals were treated with As2O3. Microvessel density (MVD) and expression of Flt-1 and KDR were detected by immunofluorescence laser confocal microscopy.SGC-7901 cells were treated respectively by exogenous recombinant human VEGF165 or VEGF165 + As2O3. Cell viability was measured by MTT assay. Cell viability of ECV304 cells was measured by MTT assay, and cell cycle and apoptosis were analyzed using flow cytometry.RESULTS: The tumor growth inhibition was 30.33% and 50.85%, respectively, in mice treated with As2O3 2.5 and 5 mg/kg. MVD was significantly lower in arsenic-treated mice than in the control group. The fluorescence intensity levels of Flt-1 and KDR were significantly less in the arsenic-treated mice than in the control group. VEGF165 may accelerate growth of SGC7901 cells, but As2O3 may disturb the stimulating effect of VEGF165. ECV304 cell growth was suppressed by 76.51%, 71.09% and 61.49% after 48 h treatment with As2O3 at 0.5, 2.5 and 5 μmol/L, respectively. Early apoptosis in the As2O3-treated mice was 2.88-5.1 times higher than that in the controls, and late apoptosis was 1.17-1.67 times higher than that in the controls.CONCLUSION: Our results showed that As2O3 delays tumor growth, inhibits MVD, down-regulates Flt-1 and KDR expression, and disturbs the stimulating effect of VEGF165 on the growth of SGC7901 cells. These results suggest that As2O3 might delay growth of gastric tumors through inhibiting the paracrine and autocrine pathways of VEGF/VEGFRs.

  16. Macroporous gelatine spheres as culture substrate, transplantation vehicle, and biodegradable scaffold for guided regeneration of soft tissues. In vivo study in nude mice.

    Science.gov (United States)

    Huss, Fredrik R M; Junker, Johan P E; Johnson, Hans; Kratz, Gunnar

    2007-01-01

    In the course of development of a new type of filler for the correction of small defects in soft tissues we studied macroporous gelatine spheres as culture substrate, transplantation vehicle, and biodegradable scaffold for guided regeneration of soft tissues in vivo. We injected intradermally in nude mice gelatine spheres that had either been preseeded with human fibroblasts or preadipocytes, or left unseeded. We compared the extent of regenerated tissue with that found after injections of saline or single-cell suspensions of human fibroblasts or preadipocytes. Routine histological examinations and immunohistochemical staining for von Willebrand factor (indicating neoangiogenesis) were made after 7, 21, and 56 days. Injected saline or single-cell suspensions had no effect. However, a quick and thorough tissue regeneration with developing neoangiogenesis was elicited by the gelatine spheres and the effect of spheres preseeded with preadipocytes surpassed the effect of spheres preseeded with fibroblasts, which in turn surpassed the effect of unseeded gelatine spheres. We suggest that minor soft tissue defects such as wrinkles or creases can be corrected by injection of naked macroporous gelatine spheres, whereas larger defects are best corrected by injection of macroporous gelatine spheres preseeded with fibroblasts, or preadipocytes, or both.

  17. Intracellular expression of a single-chain antibody directed against type IV collagenase inhibits the growth of lung cancer xenografts in nude mice

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    It was documented that type IV collagenase with two subtypes of 72 ku/MMP-2 and 92 ku/MMP-9 plays an important role in tumor invasion and metastasis. The endoplasmic reticulum (ER)- retained, single chain Fv antibody fragment (scFv) was used to inhibit the function of type IV collagenase. For expression in mammalian cells, the assembled scFv M97 gene with ER retention signal encoding 6 additional amino acids (SEKDEL) was reamplified by PCR. The amplified fragments were cloned into the pcDNA3.1 vector. The resulting plasmid was sequenced and then introduced into PG cells, a highly metastatic human lung cancer cell line, by lipofectAMINE method. The result of intrabody gene therapy showed that type IV collegenase expression was down regulated significantly as measured by ELISA. The biological behavior of PG cell, such as the ability of in vitro invasion through Matrigel, colony formation on soft agar, was also inhibited by scFv M97 transfection. Animal experiments in a xenograft model of human lung cancer showed that scFv M97 transfection significantly prolonged the survival time of nude mice. The results indicate that intracellular antibody technology represents a novel and efficient way to abrogate selectively the activity of type IV collagenase.

  18. Early Effects of Combretastatin A4 Phosphate Assessed by Anatomic and Carbogen-Based Functional Magnetic Resonance Imaging on Rat Bladder Tumors Implanted in Nude Mice

    Directory of Open Access Journals (Sweden)

    Carole D. Thomas

    2006-07-01

    Full Text Available Combretastatin A4 phosphate (CA4P causes rapid disruption of the tumor vasculature and is currently being evaluated for antivascular therapy. We describe the initial results obtained with a noninvasive multiparametric magnetic resonance imaging (MRI approach to assess the early effects of CA4P on rat bladder tumors implanted on nude mice. MRI (4.7 T comprised a fast spin-echo sequence for growth curve assessment; a multislice multiecho sequence for T2 measurement before, 15 minutes after, 24 hours after CA4P (100 mg/kg; and a fast T2W* gradient-echo sequence to assess MR signal modification under carbogen breathing before, 35 minutes after, 24 hours after CA4P. The tumor fraction with increased T2W* signal intensity under carbogen (T+ was used to quantify CA4P effect on functional vasculature. CA4P slowed tumor growth over 24 hours and accelerated necrosis development. T+ decrease was observed already at 35 minutes post-CA4P. Early T2 increase was observed in regions becoming necrotic at 24 hours post-CA4P, as confirmed by high T2 and histology. These regions exhibited, under carbogen, a switch from T2W* signal increase before CA4P to a decrease postCA4P. The combination of carbogen-based functional MRI and T2 measurement may be useful for the early follow-up of antivascular therapy without the administration of contrast agents.

  19. Glomerular filtration rate after alpha-radioimmunotherapy with 211At-MX35-F(ab')2: a long-term study of renal function in nude mice

    DEFF Research Database (Denmark)

    Back, T.; Haraldsson, B.; Hultborn, R;

    2009-01-01

    and animals bearing subcutaneous xenografts of the human ovarian cancer cell line, OVCAR-3, were used. The animals received approximately 0.4, 0.8, or 1.2 MBq in one, two, or three fractions. The mean absorbed doses to the kidneys ranged from 1.5 to 15 Gy. The renal function was studied by serial GFR...... of the glomerular filtration rate (GFR). The renal toxicity was evaluated at levels close to the dose limit for the bone marrow and well within the range for therapeutic efficacy on tumors. Astatinated MX35-F(ab')(2) monoclonal antibodies were administered intravenously to nude mice. Both non-tumor-bearing animals...... manifested late. Examination of the kidney sections showed histologic changes that were overall subdued. Following alpha-RIT with (211)At-MX35-F(ab')(2) at levels close to the dose limit of severe myelotoxicity, the effects found on renal function were relatively small, with only minor to moderate reductions...

  20. 人胃癌组织块裸鼠原位移植/转移模型的建立%Establishment of Orthotopic Implant/Metastatic Model of Human Stomach Cancer using Intact Tumor Tissue in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    刘平; 赵志泉; 张小勇; 潘世扬; 杨国平; 丁小健

    2001-01-01

    目的 用肿瘤组织块原位移植,建立人胃癌裸小鼠原位移植/转移模型。方法 以人胃低分化腺癌细胞系接种于裸小鼠皮下,形成稳定传代的皮下移植瘤,再取该肿瘤组织块原位移植于裸鼠胃壁,观察移植肿瘤的生长状况、移植成功率和自发转移的发生率。结果 原位移植成功率(成瘤率)为100%、局部淋巴结转移率100%、远处淋巴结转移率90%、肝转移发生率为75%。荷瘤鼠的中位生存期为14周,晚期出现消瘦和全身衰竭。结论 该裸小鼠原位移植/转移模型的生物学行为与人胃癌自然生长和转移过程相似,可作为一种有价值的工具用于胃癌转移机理和抗转移实验治疗的研究。%Objective To develop nude mouse orthotopic implant/metastaticmodel of human gastric cancer using intact tumor tissue.Methods Tumor cell line of human gastric adenocarcinoma was inoculated subcutaneously into nude mice to develop implant-tumor.Intact tumor tissue was then collected and implanted orthotopically into the nude mouse stomach.The local tumor growth characteristics,tumor-take rates and metastasis rates were examined.Results A 100% tumor-take rate was obtained in the model.The metastases of local and distant lymph nodes were observed in 100% and 90% of the nude mice respectivcely.The liver metastases were found in 75% of the nimals.The median survival time of the tumor-bearing nude mice was 14 weeks.Emacication and exhaustion of the nude mice were presented in late stage of the experiment.ConclusionThe growth and metastasis characteristics of human stomach cancer were exhibited in the orthotopic implant/metastatic model.This tumor model might be a useful tool in the researches on metastatic mechanisms and antimetastasis treatment of human stomach cancer.

  1. Effects of xenogeneic, allogeneic and isogeneic thymus grafts on lymphocyte populations in peripheral lymphoid organs of the nude rat

    DEFF Research Database (Denmark)

    Hougen, H P; Klausen, B; Stenvang, J P

    1987-01-01

    In order to gain information about the effect of xenografted, allografted and isografted thymic tissue on peripheral lymphoid organs of immune-deficient rats, athymic nude LEW rats of ninth backcross-intercross were grafted with fetal calf and neonatal BDIX and LEW thymus. Adrenalectomy was also...

  2. Gelatin-based Hydrogel Degradation and Tissue Interaction in vivo: Insights from Multimodal Preclinical Imaging in Immunocompetent Nude Mice

    Science.gov (United States)

    Tondera, Christoph; Hauser, Sandra; Krüger-Genge, Anne; Jung, Friedrich; Neffe, Axel T.; Lendlein, Andreas; Klopfleisch, Robert; Steinbach, Jörg; Neuber, Christin; Pietzsch, Jens

    2016-01-01

    Hydrogels based on gelatin have evolved as promising multifunctional biomaterials. Gelatin is crosslinked with lysine diisocyanate ethyl ester (LDI) and the molar ratio of gelatin and LDI in the starting material mixture determines elastic properties of the resulting hydrogel. In order to investigate the clinical potential of these biopolymers, hydrogels with different ratios of gelatin and diisocyanate (3-fold (G10_LNCO3) and 8-fold (G10_LNCO8) molar excess of isocyanate groups) were subcutaneously implanted in mice (uni- or bilateral implantation). Degradation and biomaterial-tissue-interaction were investigated in vivo (MRI, optical imaging, PET) and ex vivo (autoradiography, histology, serum analysis). Multimodal imaging revealed that the number of covalent net points correlates well with degradation time, which allows for targeted modification of hydrogels based on properties of the tissue to be replaced. Importantly, the degradation time was also dependent on the number of implants per animal. Despite local mechanisms of tissue remodeling no adverse tissue responses could be observed neither locally nor systemically. Finally, this preclinical investigation in immunocompetent mice clearly demonstrated a complete restoration of the original healthy tissue. PMID:27698944

  3. Sensing vascularization of ex-vivo produced oral mucosal equivalent (EVPOME) skin grafts in nude mice using optical spectroscopy

    Science.gov (United States)

    Vishwanath, Karthik; Gurjar, Rajan; Kuo, Shiuhyang; Fasi, Anthony; Kim, Roderick; Riccardi, Suzannah; Feinberg, Stephen E.; Wolf, David E.

    2014-03-01

    Repair of soft tissue defects of the lips as seen in complex maxillofacial injuries, requires pre-vascularized multi-tissue composite grafts. Protocols for fabrication of human ex-vivo produced oral mucosal equivalents (EVPOME) composed of epithelial cells and a dermal equivalent are available to create prelaminated flaps for grafting in patients. However, invivo assessment of neovascularization of the buried prelaminated flaps remains clinically challenging. Here, we use diffuse reflectance spectroscopy (DRS) and diffuse correlation spectroscopy (DCS) to non-invasively quantify longitudinal changes in the vessel density and blood-flow within EVPOME grafts implanted in the backs of SCID mice and subsequently to determine the utility of these optical techniques for assessing vascularization of implanted grafts. 20 animals were implanted with EVPOME grafts (1x1x0.05 cm3) in their backs. DRS and DCS measurements were obtained from each animal both atop the graft site and far away from the graft site, at one week post-implantation, each week, for four consecutive weeks. DRS spectra were analyzed using an inverse Monte Carlo model to extract tissue absorption and scattering coefficients, which were then used to extract blood flow information by fitting the experimental DCS traces. There were clear differences in the mean optical parameters (averaged across all mice) at the graft site vs. the off-site measurements. Both the total hemoglobin concentration (from DRS) and the relative blood flow (from DCS) peaked at week 3 at the graft site and declined to the off-site values by week 4. The optical parameters remained relatively constant throughout 4 weeks for the off-site measurements.

  4. Effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and its analogues (EB1089 and analog V) on canine adenocarcinoma (CAC-8) in nude mice.

    Science.gov (United States)

    Kunakornsawat, Sunee; Rosol, Thomas John; Capen, Charles Chabert; Reddy, Gudimetla Satyanarayana; Binderup, Lise; Inpanbutr, Nongnuch

    2002-05-01

    The aim of this study is to determine the effects of 1,25(OH)2D3 and its analogues on tumor growth and body weight, changes in plasma ionized calcium, parathyroid hormone-related protein (PTHrP) production, bone resorption, and the distribution of the 1,25(OH)2D3 receptor (VDR) on tumors in nude mice-bearing the canine adenocarcinoma (CAC-8). Thirty-seven nude mice were implanted subcutaneously with CAC-8. Two weeks after implantation, the mice were divided into 5 groups and injected intraperitoneally 3 times/week for 4 weeks with 5 different substrates. Group I (nontumor-bearing mice) were injected with vehicle. Groups II through V were CAC-8-bearing mice injected with the following: Grp. II, vehicle; Grp. III, analog V; Grp. IV, 1,25(OH)2D3; and Grp. V, EB1089. Our results showed that mice body weight (% change) of CAC-8-bearing mice was significantly lower than those of nontumor-bearing mice (pCAC-8-bearing mice treated with analog V maintained their body weight better than CAC-8-bearing mice treated with either vehicle, 1,25(OH)2D3, or EB1089. A reduction of tumor growth was observed in CAC-8-bearing mice treated with 1,25(OH)2D3 and its analogues; however, the reduction was not statistically significant compared to the vehicle-treated CAC-8-bearing mice. All CAC-8-bearing mice increased osteoclastic bone resorption and hypercalcemia. Immunohistochemical staining of CAC-8 with VDR antibody demonstrated a positive reaction in nuclei of tumor cells. In conclusion, CAC-8-bearing mice treated with analog V were more active and maintained their body weight better than other CAC-8-bearing groups. Analog V-treated mice also showed no toxic side effects of hypercalcemia despite an increase in plasmaionized calcium comparable to nontumor-bearing mice. Tumor volumes of CAC-8-bearing mice treated with 1,25(OH)2D3 and its analogues were smaller than vehicle-treated CAC-8-bearing mice. This finding suggested an inhibitory effect on tumor cell growth.

  5. Long circulating half-life and high tumor selectivity of the photosensitizer meta-tetrahydroxyphenylchlorin conjugated to polyethylene glycol in nude mice grafted with a human colon carcinoma.

    Science.gov (United States)

    Westerman, P; Glanzmann, T; Andrejevic, S; Braichotte, D R; Forrer, M; Wagnieres, G A; Monnier, P; van den Bergh, H; Mach, J P; Folli, S

    1998-06-10

    In a mode of nude mice bearing a human colon carcinoma xenograft, the biodistribution and tumor localization of metatetrahydroxyphenylchlorin (m-THPC) coupled to polyethylene glycol (PEG) were compared with those of the free form of this photosensitizer used in photodynamic therapy (PDT). At different times after i.v. injection of both forms of 125I-labeled photosensitizer, m-THPC-PEG gave on average a 2-fold higher tumor uptake than free m-THPC. In addition, at early times after injection, m-THPC-PEG showed a 2-fold longer blood circulating half-life and a 4-fold lower liver uptake than free m-THPC. The tumor to normal tissue ratios of radioactivity concentrations were always higher for m-THPC-PEG than for free m-THPC at any time point studied from 2 to 96 hr post-injection. Significant coefficients of correlation between direct fluorescence measurements and radioactivity counting were obtained within each organ tested. Fluorescence microscopy studies showed that m-THPC-PEG was preferentially localized near the tumor vessels, whereas m-THPC was more diffusely distributed inside the tumor tissue. To verify whether m-THPC-PEG conjugate remained phototoxic in vivo, PDT experiments were performed 72 hr after injection and showed that m-THPC-PEG was as potent as free m-THPC in the induction of tumor regression provided that the irradiation does for m-THPC-PEG conjugate was adapted to a well-tolerated 2-fold higher level. The overall results demonstrate first the possibility of improving the in vivo tumor localization of a hydrophobic dye used for PDT by coupling it to PEG and second that a photosensitizer conjugated to a macromolecule can remain phototoxic in vivo.

  6. Conversion of adipose-derived stem cells into natural killer-like cells with anti-tumor activities in nude mice.

    Directory of Open Access Journals (Sweden)

    Hongxiu Ning

    Full Text Available Efforts to develop peripheral blood-derived nature killer (NK cells into therapeutic products have been hampered by these cells' low abundance and histoincompatibility. On the other hand, derivation of NK-like cells from more abundant cell sources such as embryonic stem cells (ESCs and umbilical cord blood (UCB requires the selection of rare CD34+ cells. Thus, we sought to convert adipose-derived stem cells (ADSCs, which are abundant and natively CD34+, into NK-like cells. When grown in hematopoietic induction medium, ADSCs formed sphere clusters and expressed hematopoietic markers CD34, CD45, and KDR. Further induction in NK cell-specific medium resulted in a population of cells that expressed NK cell marker CD56, and thus termed ADSC-NK. Alternatively, the hematopoietically induced ADSCs were transduced with NK cell-specific transcription factor E4BP4 prior to induction in NK cell-specific medium. This latter population of cells, termed ADSC-NKE, expressed CD56 and additional NK cell markers such as CD16, CD94, CD158, CD314, FasL, and NKp46. ADSC-NKE was as potent as NK leukemia cell NKL in killing breast cancer cell MCF7 and prostate cancer cells DU145, PC3, LnCap, DuPro, C4-2 and CWR22, but exhibited no killing activity toward normal endothelial and smooth muscle cells. In nude mice test ADSC-NKE was able to significantly delay the progression of tumors formed by MCF7 and PC3. When injected into immunocompetent rats, ADSC-NKE was detectable in bone marrow and spleen for at least 5 weeks. Together, these results suggest that ADSCs can be converted into NK-like cells with anti-tumor activities.

  7. TRAIL-secreting mesenchymal stem cells promote apoptosis in heat-shock-treated liver cancer cells and inhibit tumor growth in nude mice.

    Science.gov (United States)

    Deng, Q; Zhang, Z; Feng, X; Li, T; Liu, N; Lai, J; Shuai, L; Xiong, Q; Fu, C; Zou, H; Wang, Y; Li, X; Ma, K; Bie, P

    2014-03-01

    Liver cancer is one of the top six leading causes of cancer-related death. Radiofrequency ablation (RFA) is an important means of treating liver cancer. Residual cancer after RFA is the most frequent cause of recurrence in cases of liver cancer. The main difference between residual cancer cells and ordinary liver cancer cells is that residual cancer cells experience heat shock. The secretable form of trimeric human tumor necrosis factor-related apoptosis-inducing ligand (stTRAIL) induces apoptosis in a variety of human cancers but not in normal tissues. It has shown potent cancer-selective killing activity and has drawn considerable attention as a possible cancer therapy. In the present work, the therapeutic potential of this stTRAIL-based gene therapy was evaluated in hepatocellular carcinoma subjected to RFA. Rat bone marrow mesenchymal stem cells (BM-MSCs) were isolated and transduced with a lentiviral vector encoding stTRAIL (stTRAIL-MSCs, T-MSCs). Cells treated with heat treatment at 43 °C for 45 min served as simulated residual cancer cells. After treatment with T-MSCs, apoptosis in heat-shock-treated liver cancer cells increased significantly, and caspase-3 was upregulated. When T-MSCs were subcutaneously injected into nude mice, they localized to the tumors and inhibited tumor growth, significantly increasing survival. Collectively, the results of the present study indicate that BM-MSC can provide a steady source of stTRAIL and may be suitable for use in the prevention of the recurrence of hepatocellular carcinoma after RFA with secretable trimeric TRAIL.

  8. Radio-labeling of T7 Peptide with 99mTc and Its Biodistribution 
in Nude Mice Bearing Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yumei HAO

    2014-03-01

    Full Text Available Background and objective Lung cancer is a malignant tumor with high mortality rates. This study aims to develop potential candidates of integrin αvβ3 imaging agents, which can facilitate the diagnosis and treatment of lung cancer. Methods The T7 peptide was labeled with carbonyl technetium. The thin layer chromatography with acetone as the development system was performed to investigate the purity and stability of 99mTc-T7. The binding affinity of 99mTc-T7 with NCI-H157 tumor cells was determined. The biodistribution of 99mTc-T7 in nude mice bearing non-small cell lung carcinoma was observed after injection of 99mTc-T7 at 0.5 h, 1 h, 2 h, 4 h, and 8 h, and the radioactive ratio of tumor (T and non-tumor tissues (NT was calculated. Results 99mTc labeled T7 had high radiochemical purity of more than 90%, which does not require further purification, with good stability in vitro. The association and dissociation constant (KD of 99mTc-T7 with NCI-H157 tumor cells was 196.1 nM. 99mTc-T7 was mainly metabolism through the internal organs with rapid blood removal. Moreover, the uptake in tumor tissue was significantly higher than the muscle with tumor/muscle ratio of 5.8. In addition, the 99mTc-T7 exhibited a transient accumulation in the lungs. Conclusion The 99mTc-T7 could be prepared using a simple method, had high labeling rate and good stability, and could be accumulated at tumor site. Thus, 99mTc-T7 is a potential lung cancer SPECT/CT imaging agent.

  9. Inhibition of tumor growth in xenografted nude mice with adenovirus-mediated endostatin gene comparison with recombinant endostatin protein

    Institute of Scientific and Technical Information of China (English)

    梁志慧; 吴沛宏; 李立; 薛刚; 曾益新; 黄文林

    2004-01-01

    Background Inhibition of tumor growth by endostatin has been shown to be an effective strategy in cancer therapy in mice. However, its widespread application has been hampered by difficulties in a large-scale production of the recombinant endostatin protein, rapid loss bioactivity of the protein, and the cumbersome daily administration. These limitations could be resolved by in vivo delivery and expression of the endostatin gene. In this study, we observed the effect and advantage of endostatin gene therapy mediated by a recombinant adenoviral vector (Ad/hEndo) on the growth of hepatocellular carcinoma BEL-7402 xenografted tumors, comparison with recombinant endostatin protein.Results After 4 courses of treatment, the tumor growth rates of high-dose treated group with 1×109 pfu of Ad/hEndo were inhibited by 42.26% compared with the Ad/LacZ control group (P=0.001) and by 46.26% compared with the NIH buffer control group (P=0.003), respectively. However, in this study, Ad/hEndo at low dose of 5×108 pfu failed to demonstrate significant inhibition of tumor growth, compared with control groups. After daily administration of recombinant human endostatin protein (rhEndo) for 9 days, the ratio of T/C (rhEndo group versus PBS group) was less than 47%. However, two days after rhEndo treatment ceased, the ratio of T/C was more than 50%. The peak of expression of endostatin mRNA in tumor tissue was at 2 or 3 days after administration intratumorally with Ad/hEndo of 1×109 pfu and gradually dropped undetectable by day 7. Dynamic analysis of endostatin concentration in tumor tissue showed that the highest level of mRNA is up at the third day after injection, and dropped to basal level three weeks later.Conclusions Endostatin gene therapy mediated by a recombinant adenoviral vector had significantly inhibited the growth of hepatocellular carcinoma BEL-7402 xenografted tumors at a high dose of 1×109 pfu compared with other groups. The analysis of dynamic expression of

  10. Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides

    Directory of Open Access Journals (Sweden)

    Voelker Hans

    2008-04-01

    Full Text Available Abstract Background Among the most prominent metabolic alterations in cancer cells are the increase in glucose consumption and the conversion of glucose to lactic acid via the reduction of pyruvate even in the presence of oxygen. This phenomenon, known as aerobic glycolysis or the Warburg effect, may provide a rationale for therapeutic strategies that inhibit tumour growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat enriched with omega-3 fatty acids and medium-chain triglycerides (MCT. Methods Twenty-four female NMRI nude mice were injected subcutaneously with tumour cells of the gastric adenocarcinoma cell line 23132/87. The animals were then randomly split into two feeding groups and fed either a ketogenic diet (KD group; n = 12 or a standard diet (SD group; n = 12 ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The two diets were compared based on tumour growth and survival time (interval between tumour cell injection and attainment of target tumour volume. Results The ketogenic diet was well accepted by the KD mice. The tumour growth in the KD group was significantly delayed compared to that in the SD group. Tumours in the KD group reached the target tumour volume at 34.2 ± 8.5 days versus only 23.3 ± 3.9 days in the SD group. After day 20, tumours in the KD group grew faster although the differences in mean tumour growth continued significantly. Importantly, they revealed significantly larger necrotic areas than tumours of the SD group and the areas with vital tumour cells appear to have had fewer vessels than tumours of the SD group. Viable tumour cells in the border zone surrounding the necrotic areas of tumours of both groups exhibited a glycolytic phenotype with expression of glucose transporter-1 and transketolase-like 1 enzyme. Conclusion Application of an unrestricted ketogenic diet enriched with omega-3 fatty acids and MCT

  11. 糖尿病裸鼠胰腺癌神经浸润模型建立及其评价%Establishment and evaluation of in vivo model of sciatic neural invasion by PanCa cells in diabetic nude mice

    Institute of Scientific and Technical Information of China (English)

    李军辉; 马双余; 刘晗; 马清涌

    2013-01-01

    Objective To establish the in vivo model of sciatic neural invasion by PanCa cells in diabetic nude mice for exploring the effects of hyperglycemia on the sciatic neural invasion in pancreatic cancer. Methods The 3 - 5 - week-old male athymic nu/nu mice were randomized into diabetic group and normal glucose group. The streptozotocin and normal saline were intravenously administrated to establish the diabetic model in two groups,respectively. BXPC-3 was injected via the sciatic nerve of the right hind limb to induce sciatic nerve paralysis in nude mice with the left limb as the controls. The sciatic nerve function was measured weekly by monitoring the gross behavior,limb function,and sciatic nerve index. All mice were euthanized six weeks after tumor cells injection,and the sciatic nerve and the tumor were excised for histopathological analysis. Results Mice began to develop the right hind limb dysfunction one week after injecting the cancer cells in diabetic group and 2 weeks after injection in normal glucose group. And 4/6 of mice developed the complete paralysis five weeks after tumor implantation in diabetic group,and only 1/6 in normal glucose group. The right paw span decreased more significantly in diabetic group than that in normal group six weeks after tumor injection( P < 0.05). Tumor diameter at the injection site was larger significantly in diabetic group than that in normal group(P <0.05). HE and immunohistochemical staining showed that the cancer tissue penetrated the nerve tissue in an invasive manner and did not simply compress the nerve tissue. Conclusion The in vivo model of sciatic neural invasion by PanCa cells in diabetic nude mice is a feasible method and could be used in the study how hyperglycemia promotes the perineural invasion in pancreatic cancer.%目的 诱导裸鼠糖尿病模型,构建糖尿病裸鼠坐骨神经肿瘤浸润模型,观察高血糖对胰腺癌神经浸润的影响. 方法 12只3-5周龄裸小鼠分成高糖组和血糖

  12. Preliminary Establishment of Transplanted Human Chronic Myeloid Leukemia Model in Nude Mice%移植性慢性髓系白血病裸鼠模型的初步建立

    Institute of Scientific and Technical Information of China (English)

    李先敏; 丁昕; 章龙珍; 岑建农; 陈子兴

    2011-01-01

    慢性髓系白血病(chronic myeloid leukemia,CML)是一种起源于造血干细胞的恶性克隆性疾病,CML干细胞被认为是导致疾病发生、发展并最终急变的根源,目前尚缺乏稳定的动物模型证明CML干细胞的存在.本研究旨在通过建立CML裸鼠模型,探讨人CML细胞在BABL/c裸小鼠体内的生物学行为,并使CML干细胞在裸鼠体内富集成为可能.对4至6周龄的BALB/c裸鼠进行切脾(splenectomy,S),环磷酰胺腹腔注射(cytoxan intraperitoneal injection,c)及全身亚致死剂量照射(sublethal irradiation,I)等预处理(SCI)后,经尾静脉接种(5 -8)×107个人CML慢性期患者单个核细胞.对4至6周龄的BALB/c裸鼠进行全身致死剂量照射(lethal irradiation)后,经尾静脉接种5×106同源裸鼠骨髓细胞和(5 -8)×107个人CML慢性期患者单个核细胞.应用RT-PCR、塑胶包埋病理切片以及流式细胞术等检测裸鼠各脏器及骨髓中人CML细胞浸润情况,并比较两种建模方法的优劣.结果表明,CML细胞能浸润至经SCI预处理的裸鼠骨髓体内,但目前成功率还很低,仅为通过BABL/c裸鼠建立人CML动物模型的一个开端.而经致死剂量预处理裸鼠,CML细胞未能浸润至骨髓.结论:人CML慢性期白血病细胞能在经SCI预处理的裸鼠体内形成白血病,为建立CML动物模型寻找到新的方向.%Chronic myeloid leukemia (CML) is a malignant clonal disease derived from hematopoietic stem cells. CML stem cells were thought to be the root which could lead disease development and ultimately rapid change. However, a stable animal model for studying the characteristics of CML stem cells is currently lacking. This study was aimed to establish a transplanted human CML nude-mice model to further explore the biological behavior of CML stem cells in vivo, and to enrich CML stem cells in nude mice by series transplantation. The 4-6 weeks old BALB /c nude mice pretreated by splenectomy (S), cytoxan intraperitoneal

  13. Establishment of three human pancreatic cancer orthotopic xenograft nude mice models and serum metabolomics%三种原位种植入胰腺癌裸鼠模型的建立及其血清代谢组学

    Institute of Scientific and Technical Information of China (English)

    胡伟泽; 李志水; 冯江华; 林贤超; 文实; 白建喜; 黄鹤光

    2016-01-01

    目的 应用代谢组学的方法,分析三种不同分化程度人胰腺癌细胞株原位种植胰腺癌裸鼠模型血清与正常裸鼠血清之间的代谢差异.方法 分别将三种人胰腺癌细胞株SW1990(中分化)、BxPC-3(低-中分化)、Panc-1(低分化)接种于裸鼠皮下.皮下成瘤后,取皮下癌组织原位移植于裸鼠胰腺,从而建立裸鼠原位种植胰腺癌模型.造模成功后,采集血清标本,然后采用基于核磁共振的代谢组学技术,联合多变量统计分析处理,筛选出三种胰腺癌裸鼠模型与正常裸鼠血清标本的差异代谢物.结果 三种裸鼠原位种植癌模型均成功构建.SW1990组成瘤率为79%(11/14),病死率为7% (1/14);BxPC-3组成瘤率为93% (13/14),无死亡;Panc-1组成瘤率为86%(12/14),病死率为7%(1/14).三种胰腺癌裸鼠血清中肌酸、丙氨酸、谷氨酰胺、1-甲基组氨酸、异亮氨酸、乳酸、苯丙氨酸、色氨酸及缬氨酸水平均显著高于正常裸鼠,而甘油磷酸胆碱及葡萄糖水平显著低于正常裸鼠.三种胰腺癌裸鼠血清中异亮氨酸及缬氨酸水平随肿瘤分化程度的降低而升高.结论 采用原位种植的方法可建立稳定可靠且成瘤率较高的裸鼠胰腺癌模型.胰腺癌裸鼠与正常裸鼠两者糖代谢、脂质代谢及氨基酸代谢存在显著差异.不同人胰腺癌原位种植裸鼠模型血清中具有某些相同的代谢物,可作为诊断胰腺癌的潜在标志物.%Objective To analyze the metabolic profile in serum between normal and orthotopic xenograft nude mice burdened with three human pancreatic cancer cell lines,which were differentiated differently.Methods Human pancreatic cancer lines SW1990,BxPC-3 and Panc-1 were subcutaneously injected into the nude mice,respectively.When the tumor volume reached 1.0 cm3,the nude mice were euthanized and the tumor tissues were removed and implanted to the pancreas to establish the orthotopic xenograft mice model.The serum

  14. Preparation of chitosan-polyaspartic acid-5-fluorouracil nanoparticles and its anti-carcinoma effect on tumor growth in nude mice

    Institute of Scientific and Technical Information of China (English)

    Dan-Ying Zhang; Xi-Zhong Shen; Ji-Yao Wang; Ling Dong; Yong-Li Zheng; Li-Li Wu

    2008-01-01

    AIM: To prepare chitosan-polyaspartic acid-5-fluorouracil (CTS-Pasp-5Fu) nanoparticles and investigate its anti-carcinoma effect and toxicity.METHODS: CTS-Pasp-5Fu nanoparticles were synthesized by ionic gelatification. Male BABL/c nude mice were injected with SGC-7901 gastric carcinoma cell line mass to establish a human gastric carcinoma model. They were randomly allocated into 4 groups: CTS-Pasp-5Fu (containing 5-Fu 1.25 mg/kg), 5-Fu (1.25mg/kg), CTS-Pasp and normal saline groups. Tumor weight was measured and assay of colony forming unit-granulocyte and macrophage (CFU-GM) was performed. The structural change of cells and tissues was observed and the bax and bcl-2 genes were detected.RESULTS: Compared with normal saline, the inhibition rates of tumor growth for the CTS-Pasp, 5-Fu and CTS-Pasp-5Fu groups were 5.58%, 58.69% and 70.82%, respectively. The tumor inhibition rates for the CTS-Pasp, 5-Fu and CTS-Pasp-5Fu groups were 5.09%, 65.3% and 72.79%, respectively. There was a significant decrease in the number of CFU-GM formation and increase of total bilirubin, and alanine aminotransferase in the 5-Fu group, but no change in those of the other three groups. There was no change in white blood cell count and creatinine among the four groups. Pathological section of liver and nephridial tissues showed that the damage in the 5-Fu group was more severe than that in the CTS-Pasp-5Fu group. 5-Fu and CTS-Pasp-5Fu groups could both down-regulate the Bcl-2 expression and up-regulate the Bax expression to different extent, and the accommodate effect of CTS-Pasp-5Fu was more obvious than 5-Fu.CONCLUSION: The tumor inhibition rate of CTS-Pasp-5Fu nanoparticles is much higher than that of 5-Fualone.

  15. Establishment of the adbominal cavity metastasis model of human ovarian carcinoma cisplatin-resistant cell in nude mice%人卵巢癌顺铂耐药细胞裸鼠腹腔转移模型的建立

    Institute of Scientific and Technical Information of China (English)

    黄守国; 孔北华; 杨瑞芳; 江森

    2003-01-01

    目的探讨建立人卵巢癌顺铂耐药细胞裸鼠腹腔转移模型的方法.方法人卵巢癌细胞株3AO和顺铂耐药细胞株3AO/cDDP细胞体外培养.4×106个3AO、3AO/cDDP分别接种于裸鼠腹腔96h后,各随机分为2组,分别腹腔内注射生理盐水和顺铂(cDDP),观察各组裸鼠的致瘤率、生存期和生存延长率.采用流式细胞技术观察转移瘤LRP、MRP基因的表达情况.转移瘤瘤体行病理学检查.结果3AO、3AO/cDDP细胞的裸鼠致瘤率差异无显著性,P>0.05;cDDP能提高3AO荷瘤鼠的生存期及生存延长率,与3AO/cDDP荷鼠相比,差异有显著性,P<0.05;3AO/cDDP转移瘤的LRP、MRP基因的表达水平显著高于3AO转移瘤,P<0.05;病理学检查提示裸鼠腹腔转移瘤细胞具人恶性特征.结论该方法建立裸鼠卵巢癌腹腔转移模型具有成瘤率高的特点,并能保持顺铂耐药特征.%Objective:To explore the method of establishment of the abdominal cavity metastasis model of cisplatin- resistant human ovarian carcinoma cells in nude mice. Methods: Human ovarian carcinous cell strain 3AO cells and cisplatin- resistant cell strain 3AO/cDDP cells were cultured in vitro. Nude mice were planted with 3AO and 3AO/cDDP cells 4 × 106 in abdominal cavity respectively, then were divided into 2 groups at random in 96 h,treated with intraperitoneal injection of normal saline and cDDP. The rate of tumor formation, survival period, survival prolong rate of tumor- bearing nude mice were evaluated. LRP and MRP gene expression were estimated by flow cytometry (FCM). Tumor was examined with pathological diagnosis. Results: The tumor formation rates of 3AO and 3AO/cDDP cells in nude mice were equal, P >0.05. Compared with 3AO/cDDP, cDDP could prolong the survival period and enhance the survival prolong rate of 3AO tumor- bearing nude nice, P < 0.05. LRP and MRP gene expression level in 3AO/cDDP metastasis tumor were significantly higher than that in 3AO metastasis tumor, P

  16. 裸鼠颅内小细胞肺癌移植瘤模型的建立%Establish of intracranial small cell lung cancer xenograft model in nude mice

    Institute of Scientific and Technical Information of China (English)

    吴涛; 张爱琴; 陈波; 卢红阳

    2015-01-01

    Objective To establish an intracranial xenograft model of small-cell lung cancer (SCLC) in nude mice for providing animal model for SCLC related experimental research. Methods LTEP/P human SCLC cells were cultured and passaged for 3~4 generations, and then 1ml cells of 1×108 cells /ml were collected. After fourteen nude mice were anes-thetized, a dental drill was used to drill a small hole in the skull of every mouse. And then, 3μl cells were extracted through a 10μl syringe and slowly inoculated into the brain of BALB/C SPF mice by stereotaxic instrument. The mice were raised in SPF environment and killed by cervical dislocation at 7th day and brains tissues were taken for pathology detecting. Results All mice regained consciousness, gradually recovered and resumed eating within one hour after surgery. At 5th day, the mice appeared poor appetite and low active while the mice appeared sluggish, unresponsive and one mouse was died at 7th day. Pathological examination confirmed that SCLC cells were visible in the brain tissues of 13 nude mice. Con-clusion It is feasible to establish a stable and reliable intracranial SCLC xenograft model by inoculating cells into the brains of nude mice through stereotaxic instrument.%目的:建立裸鼠颅内小细胞肺癌(SCLC)移植瘤模型,为今后开展SCLC相关实验研究提供动物模型。方法培养LTEP/P人SCLC细胞株,传代3~4代,收集细胞,并制成1×108/ml 的细胞悬液共1 ml。14只裸鼠麻醉后,用牙科钻在裸鼠颅脑钻一小孔,然后用10μl微量注射器抽取3μl肿瘤细胞悬液,利用立体定位仪缓慢接种于BALB/C SPF裸鼠颅内,放置入SPF环境内继续饲养,观察7 d后脱颈处死,取完整脑组织,行病理检测。结果所有裸鼠在术后1h内逐渐苏醒并恢复活动和饮食,第5天出现活动、饮食减少,第7天出现神软、萎靡、反应迟钝等症状,并死亡1只。病理检测证实所有裸鼠脑组织内可

  17. Effect of PAMAM-mediated endostatin gene therapy on human endometriosis in nude mice%PAMAM介导内皮抑素基因治疗对裸鼠人子宫内膜异位症的作用

    Institute of Scientific and Technical Information of China (English)

    张红霞; 王宁宁; 谭金凤; 洪珊珊; 丁慧娟; 刘斌; 黄建昭; 梅卓贤; 庄广伦

    2009-01-01

    Objective To explore the effect of endostatin (ES) gene therapy mediated by polyamidoamine (PAMAM) on human endometriosis in nude mice. Methods One hundred and twenty nude female BALB/c mice were subcutaneously transplanted with human endometrium fragments for the establishment of endometriosis model. They were divided into four treatment groups: ES transfection group (n=33, a mixture of 65μg PAMAM and 20μg ES gene was injected into the lesion of nude mice); PAMAM group (n=30, a mixture of 65μg PAMAM and 20μg sterile saline was injected into the lesion of nude mice); normal saline group (n = 27, 85μl sterile saline was injected into the lesion of nude mice); blank group (n=30, nothing was injected). Each group was then divided into 2 subgroups, i. e. day 1 treatment and day 14 treatment subgroups. All nude mice were sacrificed 1 week after treatment. Ovaries and uterus were weighed, number of ovarian follicles was obtained, and ES, VEGF protein and MVD in nude mice were analyzed by immunohistochemistry. Results The ES expression was significantly higher in day 1 subgroup of ES transfection group than in the day 1 subgroups of other three groups (P0. 05). The ES expression was higher, VEGF expression was lower, MVD was less, and the volume of lesions was smaller and weight was lighter in the day 14 subgroup of ES transfection group than those in the day 14 subgroups of other three groups (P0. 05). Conclusion PAMAM-mediated endostatin gene therapy is effective for endometriosis given 14 days after model establishment, without producing side effect on heart, liver, kidney and reproductive organ in nude mice.%目的 探讨聚酰胺-胺型树枝状高聚合物(PAMAM)介导内皮抑素(ES)基因抗血管生成对裸鼠人子宫内膜异位症(EMs)的治疗作用及时机.方法 120只BALB/c雌性裸鼠经皮下移植法建立人子宫内膜异位症模型后,分为以下4组:ES转染组(n=33),病灶局部注射20μg pcDNA3.1(+)-hES+65μg PAMAM混合液85

  18. Histological changes of skin and its relationship with wound healing in diabetic nude mice%糖尿病裸鼠的皮肤组织改变及其与创面愈合的相关性

    Institute of Scientific and Technical Information of China (English)

    黄昕; 沈向前; 吴守成; 曹谊林

    2012-01-01

    目的 研究糖尿病裸鼠的皮肤组织改变及其与皮肤创面愈合的相关性.方法 采用150 mg/kg链脲佐菌素(STZ)一次性腹腔注射建立糖尿病裸鼠模型.对正常对照组裸鼠(n=20)和诱导成模后4周的糖尿病裸鼠(n=20)分别切取背部直径为1.8 cm的全层皮肤.采用苏木精-伊红(HE)染色,观察裸鼠皮肤的组织学改变并测量真皮层和表皮层厚度.采用苦味酸天狼猩红染色并分析相对胶原含量;应用氧化酶法测量皮肤组织糖含量.于术后第3、5、7、14和21天观察创面的愈合率.结果 糖尿病组裸鼠的皮肤真皮层和表皮层厚度较正常对照组明显变薄,真皮层相对胶原含量也明显少于正常对照组,差异均有统计学意义(P<0.05或P<0.01).糖尿病组裸鼠的血糖浓度和皮肤糖含量均高于正常对照组,差异有统计学意义(P<0.01);皮肤组织糖含量与血糖浓度呈正相关(r =0.951,P<0.01).糖尿病组裸鼠在术后第3、5、7、14和21天的创面愈合率显著低于正常对照组,差异有统计学意义(P<0.01).结论 应用STZ诱导的糖尿病裸鼠模型的皮肤组织改变明显,这些改变可能与局部糖基化终末产物蓄积,导致糖尿病皮肤创面不易愈合有关.%Objective To observe the histological changes of skin and explore its relationship with wound healing in diabetic nude mice. Methods Diabetic nude mice models were established by intraperitoneal injection of 150 mg/kg STZ. Full-thickness skin of 1. 8 cm in diameter was obtained from the dorsum of normal control rats ( n = 20) and diabetic nude mice (n = 20) 4 weeks after model establishment. HE staining was used to observe the histological changes of skin, and the thickness of dermis and epidermis was measured. Picrosirius red staining was employed to analyse the relative content of collagen in dermis. The cutaneous content of glucose was determined by glucose oxidase method. The wound closure rates were calculated 3 d, 5

  19. Suppression of Type 1 Insulin-like Growth Factor Receptor Expression by Small Interfering RNA Inhibits A549 Human Lung Cancer Cell Invasion in vitro and Metastasis in Xenograft Nude Mice

    Institute of Scientific and Technical Information of China (English)

    Jianfang QIAN; Aiqiang DONG; Minjian KONG; Zhiyuan MA; Junqiang FAN; Guanyu JIANG

    2007-01-01

    Cancer invasion and metastasis, involving a variety of pathological processes and cytophysiological changes, contribute to the high mortality of lung cancer. The type 1 insulin-like growth factor receptor (IGF-1R), associated with cancer progression and invasion, is a potential anti-invasion and anti-metastasis target in lung cancer. To inhibit the invasive properties of lung cancer cells, we successfully down-regulated IGF-1R gene expression in A549 human lung cancer cells by small interfering RNA (siRNA)technology, and evaluated its effects on invasion-related gene expression, tumor cell in vitro invasion, and metastasis in xenograft nude mice. A549 cells transfected with a plasmid expressing hairpin siRNA for IGF-1R showed a significantly decreased IGF-1R expression at the mRNA level as well as the protein level. In biological assays, transfected A549 cells showed a significant reduction of cell-matrix adhesion,migration and invasion. Consistent with these results, we found that down-regulation of IGR-1R concomitantly accompanied by a large reduction in invasion-related gene expressions, including MMP-2,MMP-9, u-PA, and IGF-1R specific downstream p-Akt. Direct tail vein injections of plasmid expressing hairpin siRNA for IGF-1R significantly inhibited the formation of lung metastases in nude mice. Our results showed the therapeutic potential of siRNA as a method for gene therapy in inhibiting lung cancer invasion and metastasis.

  20. Influence of gonadotropin-releasing hormone agonist on the effect of chemotherapy upon ovarian cancer and the prevention of chemotherapy-induced ovarian damage: an experimental study with nu/nu athymic mice

    Institute of Scientific and Technical Information of China (English)

    Qiong-yan LIN; Yi-feng WANG; Hui-nan WENG; Xiu-jie SHENG; Qing-ping JIANG; Zhi-ying YANG

    2012-01-01

    Background and objective:Gonadotropin-releasing hormone (GnRH) plays an important role in the regulation of ovarian function and ovarian cancer cell growth.In this study,we determined whether administration of the GnRH agonist (GnRHa),triporelin,prior to cisplatin treatment affects cisplatin and/or prevents cisplatin-induced ovarian damage.Methods:nu/nu mice were injected with ovarian cancer OVCAR-3 cells intraperitoneally.After two weeks,the mice were treated with saline (control),cisplatin,GnRHa,or cisplatin plus GnRHa for four weeks.At the end of the experimental protocol,blood,tumor,ovary,and uterine tissues were resected for hematoxylin and eosin (H&E) staining,immunohistochemical analyses of Ki67,nuclear factor-κB (NF-κB),and caspase-3,transmission electron microscopy of apoptosis,or enzyme-linked immunosorbent assay (ELISA) analyses of anti-Mullerian hormone (AMH).Results:Cisplatin treatment effectively inhibited tumor growth in mice treated with human ovarian cancer cells; however the treatment also induced considerable toxicity.Immunohistochemical analyses showed that Ki67 expression was reduced in cisplatin-treated mice compared to control (P<0.05),but there was no statistically significant differences between cisplatin-treated mice and cisplatin plus GnRHa-treated mice (P>0.05),while expressions of NF-κB and caspase-3 were reduced and induced,respectively,in cisplatin-treated mice and cisplatin plus GnRHa-treated mice.Apoptosis occurred in the GnRHa,cisplatin,and cisplatin plus GnRHa-treated mice,but not in control mice.Ovaries exposed to GnRHa in both GnRHa mice and cisplatin-treated mice (combination group) had significantly more primordial and growth follicles and serum levels of AMH than those in the control mice and cisplatin-treated mice (P<0.05).Conclusions:Administration of GnRHa to mice significantly decreased the extent of ovarian damage induced by cisplatin,but did not affect the anti-tumor activity of cisplatin.

  1. Study on effect of survivin antioligonucleotide on subcutaneous transplanted Xunwei lung adenocarcinoma nude mice model%Survivin反义核苷酸对宣威肺腺癌移植瘤裸鼠模型作用的研究

    Institute of Scientific and Technical Information of China (English)

    王巍炜; 洪志鹏; 李高峰; 王绍佳; 陈瑞彬; 张继朋

    2012-01-01

    目的 选用宣威肺腺癌细胞裸鼠移植瘤模型,采用survivinmRNA的反义寡核苷酸(ASODN)抑制宣威肺腺癌细胞,观察其疗效,为进一步临床研究提供实验依据.方法 建立宣威肺腺癌细胞XWLC-05裸鼠皮下移植瘤模型,选取48只成瘤裸鼠,随机分为:对照组、单纯脂质体转染(LIP)组、survivin正义寡核苷酸(SODN)组、survivinASODN组,通过皮下移植瘤内多点注射后,观察裸鼠一般情况、移植瘤体积,计算抑瘤率等.病理学检测各组肿瘤的变化以及对心脏、肝脏、肾脏的影响.结果 survivinASODN组注射survivinASODN后,裸小鼠表现为生长速度较为缓慢,质量低于其他3组(P>0.05),其生长抑制率高于其他3组(P>0.05).而对照组、LIP组、survivinSODN组在肿瘤质量及生长抑制率方面均无明显差异.病理检查见瘤组织中有大量的细胞坏死灶.各组裸鼠均未出现死亡,病理检查重要脏器未见明显损害.结论 survivinASODN能够抑制裸鼠皮下移植瘤的生长,未对其他脏器产生明显损害.%Objective By selecting transplanted Xunwei lung adenocarcinoma nude mice model, to adopt survivinnmRNA anti-sense oligonucleotide to inhibit Xunwei lung adenocarcinoma cells and to observe its effects to provide the experiment evidence for further clinical study be offered in clinical treatment. Methods After modeling subcutaneous transplanted Xunwei lung adenocarcinoma cell XWLC-05 nude mice,48 nude mice were selected and devided into 4 groups randomly: control group (blank) , Lip group (simple liposome) , survivin-SODN group (injecting sense oligonucleotide) and survivin-ASODN group (injecting antisense oligonucleotide). We injected different drugs according to different groups. Then the general activity of nude mice in different groups was observed and the tumor size was measured. Also,the antineoplastic rates in different groups were calculated. The pathological methods were used to analyse the effects of 4

  2. 三种癌裸鼠移植瘤肝脾转移的比较研究%A Comparative Study on the Liver and Spleen Metastasis of Three Transplanted Carcinomas in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    褚芳; 余华; 方铝; 周艳艳; 郑国安; 范其坤; 丁琦

    2012-01-01

    Objective To observe and compare the liver and spleen metastasis of transplanted human ovarian cancer, gastric cancer and colon cancer in nude mice. Method The human ovarian cancer, gastric cancer and colon cancer were transplanted to the nude mice. The growth rate of the solid tumors, the survival time, and the pathological changes in the liver and spleen metastasis of three transplanted carcinomas were observed. Results The rates of tumor formation and the liver metastasis of xenografted human ovarian cancer, gastric cancer and colon cancer in nude mice were 100% . The spleen metastasis rate of human ovarian cancer was 100% , that of gastric cancer was 62. 5% , and that of colon cancer was 75% . The tumor growth rate of solid tumor of human ovarian cancer in nude mice was higher than that of solid tumor of gastric cancer and colon cancer, and spleen metastasis of human ovarian cancer was rapider with a short survival time. There were differences in the pathological changes in the liver and spleen metastasis of three transplanted carcinomas. Conclusion The models of liver and spleen metastasis of transplanted human ovarian cancer, gastric cancer and colon cancer in nude mice can reproduce clinical processes of the liver and spleen metastasis of three transplanted carcinomas, which makes for the studies on biological mechanism of liver and spleen metastasis of human ovarian cancer, gastric cancer and colon cancer and anti-metastasis.%目的 利用人卵巢癌、胃癌、结肠癌裸鼠移植瘤动物模型观察比较肝脾转移情况.方法 分别将人卵巢癌、胃癌、结肠癌实体瘤移植到裸鼠皮下,在建立人卵巢癌、胃癌、结肠癌裸鼠实体瘤模型的基础上,观察裸鼠实体瘤生长速度、存活时间及肝脾转移病理形态学变化.结果 人卵巢癌、胃癌、结肠癌实体瘤移植到裸鼠皮下,移植成瘤率、肝转移率皆为100%;卵巢癌脾转移100%;胃癌脾转移62.5%;结肠癌脾转移75%.人

  3. Effect of Moxibustion on DPC4 and ki67 Expression of Pancreatic Carcinoma in Nude Mice%艾灸对胰腺癌裸鼠移植瘤DPC4、ki67表达的影响

    Institute of Scientific and Technical Information of China (English)

    仲丽丽; 孙忠人

    2015-01-01

    目的:观察艾灸对胰腺癌荷瘤裸鼠移植瘤DPC4、ki67表达影响的实验研究,并探讨艾灸抗胰腺癌的可能作用机制。方法:将16只裸鼠均接种BxPC-3细胞构建胰腺癌裸鼠移植瘤的动物模型,随机分为模型组和艾灸组。接种后次日给予麦粒灸裸鼠大椎穴至14天后结束治疗,取出肿瘤组织。采用免疫组化法检测肿瘤组织中DPC4、ki67蛋白的表达。结果:与模型组相比,艾灸组中DPC4蛋白表达升高,而ki67表达显著降低( P<0.05)。结论:艾灸对肝癌裸鼠移植瘤的生长有明显的抑制作用,其机制可能与上调肿瘤组织中DPC4、下调ki67表达水平有关。%Objective:To observe the efficacy of DPC4 and ki67 in the expression of pancreatic carcinoma in nude mice treated by moxibustion and explore the possible mechanism of antitumor through moxibustion.Meth-ods:16 nude mice were inoculated with BxPC-3 cells to construct pancreatic carcinoma xenograft models and were divided into a model group and a moxibustion group randomly.On the next day give mice moxibustion at Dazhui point.After the treatment for 14 days,the tumor tissues in nude mice were removed.Use immunohisto-chemical method to detect the protein expression of DPC4 and ki67 in tumor tissues.Results:Compared with the model group,the DPC4 expression was significantly higher and ki67 expression was lower (P<0.05).Con-clusion:Moxibustion has a significant inhibition on the growth of transplanted tumor and the mechanism may be related to the up-regulation of the expression level of DPC4 and down-regulation of the expression level of ki67 in tumor tissues.

  4. 不同转移潜能MG63骨肉瘤细胞亚株裸鼠肺转移模型的建立%Establishment of nude mice model of human osteosarcoma cell MG63 with different potential of metastasis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To establish a nude mice model of human osteosarcoma lung metastasis. Methods: The growth of human osteosarcoma cell sublines M8 and M6 was determined by MTT assay. 2 × 107 cells were injected into the tail vein of nude mice. Mice were sacrificed started on week 4 after injection, and lung metastases were evaluated under both macroscopic and microscopic observation with HE staining. Results: The growth of low-metastatic subline M6 was lower than high-metastatic sublines M8. Seventeen mice after injected M8 had occurred lung metastases while only one mice had occurred in M6 group. Moreover, M8 cells within metastases were arrangement disorder with variable nuclear hyperchromasia.Conclusion: A mouse model for human osteosarcoma cancer lung metastasis can be established by injection different ability of metastasis MG63 cells into tail vein.

  5. Establishment of the tracing bone marrow reconstituted nude mice model%辐射诱发裸小鼠骨髓功能毁损与示踪骨髓移植重建其功能的研究

    Institute of Scientific and Technical Information of China (English)

    陈骅; 郭辰; 沈云天; 陈列松; 罗良生; 陆朝晖; 黄强

    2013-01-01

    目的 建立辐射诱发裸小鼠骨髓功能毁损与示踪骨髓移植重建的动物模型.方法 分别用4、6、8、10Gy X线辐照裸小鼠,检测辐照后第1、3、5、7、14、21天小鼠血象变化,确定适合裸小鼠骨髓功能毁损的辐照剂量.用确定剂量辐照后1周进行尾静脉移植表达绿色荧光蛋白(GFP)裸小鼠的骨髓细胞(2×10 7个/只),通过实时检测其在外周血中的分布,并比较移植前后外周血白细胞和骨髓细胞,以评价骨髓功能.结果 8 Gy辐照后裸小鼠外周血白细胞为(0.1375 ±0.0510)×109/L,骨髓细胞是辐照前的(31.73±2.56)%.辐照后1周骨髓移植鼠外周血白细胞在28 d达到(12.46 ±0.68)× 109/L,恢复到辐照前水平[(12.89±1.04)×109/L,P>0.05].外周血中GFP+细胞占(63.0±0.6)%.结论 8 Gy是建立裸小鼠骨髓功能重度毁损重建较为适合的辐照剂量;尾静脉注射GFP+供体骨髓细胞,能有效示踪受体骨髓功能重建主要依赖于供体的骨髓细胞.%Objective To establish the green fluorescent protein (GFP) + bone marrow reconstituted nude mice model.Methods Different doses (4,6,8,10 Gy) X-ray were used to irradiate the nude mice.The hemogram was detected separately 1,3,5,7,14 and 21 days after irradiation in order to confirm the proper irradiation dose for bone marrow damage.One-week after irradiation with such dose,allogeneic transplantation with GFP + bone marrow cells (BMCs) (2 × 107 cells/mice) were executed through the caudal vein.The proportion of GFP + donor cells in peripheral blood was tested.White blood cells (WBCs) of peripheral blood and BMCs were compared before and after transplantation.Results After irradiation with 8 Gy,the number of peripheral blood WBCs was (0.1375 ±0.0510) × 109/L,and BMCs were [(31.73 ±2.56)%] of pre-irradiation nude mice.At 28th day after BMCs transplantion,the number of peripheral blood WBCs was (12.46 ± 0.68) × 109/L and recovered to the level pre-irradiation (12.89 ± 1

  6. Influence of As2O3 combined with ginsenosides Rg3 on inhibition of lung cancer NCI-H1299 cells and on subsistence of nude mice bearing hepatoma

    Institute of Scientific and Technical Information of China (English)

    Jian-Bo Che; Zhong-Hua Liu; Hong-Bing Ma; Yong Li; Hui Zhao; Xiao-Hui Li; Wei-Chao Liu; Gong-Ning Shi

    2014-01-01

    Objective:To study the effect of arsenic trioxide(As2O3) combined with ginsenosidesRg3 on inhibiting theNCI-H1299 lung cancer cells and subsistence in nude mice bearing hepatoma. Methods:MTT method was used to measure the inhibition effect ofAs2O3 combinedRg3 onNCI-H1299 cells, and the proliferation inhibiting effect was observed via establishing the transplanted tumor modelin vitro.A total of40 tumor-bearing nude mice were randomly divided into normal saline group,As2O3,Rg3 andAs2O3+Rg3 group.Transplantation tumor model of lung cancer in nude mice was constructed, followed by injection of certain concentrations of normal saline, As2O3, ginseng saponinRg3 andAs2O3+Rg3 every day.The survival duration and the tumors size of the mice were recorded and theKaplan-Meier curve was made; microscopic observation of apoptosis of tumor cellsin vivo was done usingTUNEL staining.Results:After72 h of injection, inhibition rate of tumor cell in normal saline group,As2O3 group,Rg3 group andAs2O3+Rg3 group was(5.66±0.31)%,(65.58±4.75)%,(44.69±3.32)% and(82.67±5.43)%, respectively.Inhibition rate of tumor cell inAs2O3 group,Rg3 group andAs2O3+Rg3 group was significantly higher than that of normal saline group(P<0.01); inhibition rate of tumor cells ofAs2O3+Rg3 group was significantly higher than that of the two groups givenAs2O3 orRg3 alone(P<0.01).The tumor volume of As2O3 group,Rg3 group andAs2O3+Rg3 group shrank to(65.38±3.25)%,(77.68±3.43)% and(42.65±3.55)% of the original, tumor volume of saline group was1.21 times of the original size(P<0.01);Median survival of saline group,Rg3 group,As2O3 group were significantly shorter than that of As2O3+Rg3 group(P<0.01); co-ordinated intervention ability ofAs2O3+Rg3 onNCI-H1299 cell was significantly higher than that ofAs2O3 orRg3, separately.Conclusions:As2O3 combined with Rg3 can significantly inhibit proliferation ofNCI-H1299 cells in lung cancer, prolong survival of tumor-bearing nude mice, and promote tumor cell apoptosis, and

  7. Effect of morphine on growth of subcutaneous tumor of human gastric cancer cells in nude mice%吗啡对裸鼠人胃癌细胞皮下瘤生长的影响

    Institute of Scientific and Technical Information of China (English)

    周丽芳; 覃怡; 利莉; 杨一兰; 谢玉波

    2016-01-01

    目的 评价吗啡对裸鼠人胃癌细胞皮下瘤生长的影响.方法 SPF级雄性BALB/C裸鼠30只,4~5周龄,体重15~20 g,建立裸鼠人胃癌MGC-803细胞皮下瘤模型,采用随机数字表法分为3组(n=10):对照组(C组)、生理盐水组(N组)和吗啡组(M组).C组不作任何处理,M组腹腔注射吗啡20 mg/kg,1次/d,连续14d,N组腹腔注射生理盐水1.5 ml/kg.于给药后3d开始每2d测定肿瘤的长径和短径,计算肿瘤相对体积(RTV);第15天拉颈处死裸鼠取肿瘤组织,采用RT-PCR和Western blot法检测NF-κB活性、Bcl-2和Bax及其mRAN的表达.结果 与C组比较,M组各时点RTV减小,皮下瘤组织NF-κB活性降低,Bcl-2及其mRAN表达下调,Bax及其mRAN表达上调(P<0.05),N组各指标比较差异无统计学意义(P>0.05).结论 吗啡可抑制裸鼠人胃癌细胞皮下瘤的生长,其机制与促进肿瘤细胞凋亡有关.%Objective To evaluate the effect of morphine on the growth of subcutaneous tumor of human gastric cancer cells in nude mice.Methods Thirty SPF male BALB/C nude mice,aged 4-5 weeks,weighing 15-20 g,in which the model of subcutaneous tumor of human gastric cancer cell line MGC-803 was established,were randomly divided into 3 groups (n=10 each) using a random number table:control group (group C),normal saline group (group N),and morphine group (group M).The mice in group C received no treatment.Morphine 20 mg/kg was intraperitoneally injected once a day for 14 consecutive days in group M,while normal saline 1.5 ml/kg was given instead of morphine in group N.The caliper was used to measure the tumor size every 2 days starting from 3 days after beginning of administration,and the relative tumor volume was calculated.The nude mice were sacrificed on 15th day,and the tumor tissues were obtained for determination of nuclear factor-kappa B activity and Bcl-2 and Bax protein and mRNA expression by real-time reverse transcriptase polymerase chain reaction and Western blot.Results Compared

  8. Effect on growth and cell cycle kinetics of estradiol and tamoxifen on MCF-7 human breast cancer cells grown in vitro and in nude mice

    DEFF Research Database (Denmark)

    Brünner, N; Bronzert, D; Vindeløv, L L

    1989-01-01

    determined by repeated flow cytometric DNA analyses in vitro and in vivo and by the technique of labeled mitosis in nude mouse-grown tumors. Under in vitro conditions, estradiol induced a pronounced increase in S-phase fraction and cell number. TAM inhibited growth of MCF-7 cells with a concomitant increase...... cytometric DNA analysis and percentage of labeled mitosis investigations revealed no significant differences in the proliferation kinetics of TAM-treated and control tumors. Calculating the cell loss factor demonstrated an increase from 69% in control tumors to 107% in TAM-treated tumors. These experiments...

  9. Establishment of three orthotopic implantation nude mice models of colorectal cancer metastasis to liver%裸鼠原位种植大肠癌肝转移三种建模方法的比较

    Institute of Scientific and Technical Information of China (English)

    蔡健华; 赵任; 万方军; 刘坤; 于颖彦; 朱正纲

    2010-01-01

    目的 比较3种不同的人大肠癌裸鼠原位种植肝转移模型,建立稳定有效的人大肠癌裸鼠原位种植肝转移模型.方法 逐步传代法皮下成瘤传5代,采用84只BALB/C-nu/nu裸鼠,随机分为4组,结肠原位荷包缝合法和结肠原位纤维蛋白胶黏合法和结肠微注射1×106和1×105SW1116细胞法建立大肠癌裸鼠原位种植肝转移模型.各组裸鼠死亡后立即解剖观察原位以及肝脏、肺、脾脏、胰腺、肠系膜等脏器组织的转移并且进行苏木素-伊红(HE)染色进行镜下观察有无转移.结果 荷包缝合组和纤维蛋白胶组结肠原位种植肝转移成功率均为100%比微注射法50.0%和14.3%高,纤维蛋白胶法比其他两种方法所形成的结肠原位肿瘤和肝转移瘤均大而多.HE染色表明肝转移肿瘤性质与结肠原位种植瘤相同.结论 结肠原位纤维蛋白胶黏合法比较其他二种原位种植肝转移模型的手术成功率高,肝转移率高、操作简单.%Objective To establish and compare three orthotopic implantation nude mice models of colorectal cancer metastasis to liver. Methods Human SW1116 cell line was inoculated into 5 BALB/ C nude mice. Eighty-four nude mice were divided equally into pouch, fibrin glue, 1×106 cell and 1 × 105 cell microinjection groups. After animals were killed, the metastasis of cancer in situ, the liver, the lung, the spleen, the pancreas, and the mesentery was observed under the microscopy after HE staining. Results The metastasis rate in groups of pouch, fibrin glue, 1×1106 cell and 1×105 cell microinjection was 100% , 100% , 50. 0% and 14. 3% respectively. The liver metastasis tumor in fibrin glue group was bigger than other groups. HE staining indicated that the liver metastasis tumor was derived from colon tumor. Conclusion Among the three orthotopic implantation nude mice models of colorectal cancer metastasis to liver, the fibrin glue method has a high success rate of operation, a high

  10. 提高裸鼠体内人胎肝细胞移植物存活率的方法探讨%Methodological exploration of improving the survival rate of human fetal hepatocytes transplanted into nude mice

    Institute of Scientific and Technical Information of China (English)

    唐智敏; 詹春姣; 金文银; 李航森; 石淑仙

    2000-01-01

    Objectives To explore whether human fetal hepatocytes(HFH)transplanted into nude mice survived and study the methods for raising successful rate of transplantation.Methods The suspension of human fetal hepatocytes was transplanted into the abdominal cavity.liver.speen and mesenterium respectively.Three months later,histological observation was performed.Results The HFH could be found on the transplanting sites of spleen and mesenterium with only 10% successful rate of transplantation. Intraperitoneal injection of dexamethasone after transplantation could increase the Successful rate of the transplantation to 6/10.Under this circumstances.if HFH in cellular Sphere culture was used as transplantation material,successful rate of transplantation could reach 90%.Based on methods mentioned above,a lobe of liver in nude mice was resected,successful rate of transplantation could reach 100%,and HFH transplanted into the spleens of nude mice still survived 6 months after transplantation.Conclusions HFH transplanted in nude mice could survive for at least 6 months.If transplantationmaterials were made up into cellular sphere cultures,combining with using dexamethasone,the survival rate of transplantation might significantly be increased.%目的 探讨人胎肝细胞移植入裸鼠体内能否存活及提高移植物存活率的方法.方法 将人胎肝细胞悬液分别移植至裸鼠的腹腔、肝脏、脾脏及肠系膜,3个月后进行移植部位的组织学观察.结果 仅移植入脾脏和肠系膜的组中各有1只(1/10)受者可观察到存活的移植物,而移植入肝脏组无法区分裸鼠肝细胞和人胎肝细胞,其它组均未观察到移植物;移植后腹腔注射地塞米松,可将移植成功率提高到6/10;若将人胎肝细胞采用球体细胞培养技术制成细胞球团行脾脏内移植,术后腹腔注射地塞米松,则移植成功率可达9/10,术后6个月仍可见存活的移植物.结论 人胎肝细胞移植到

  11. Dynamic Contrast-Enhanced Magnetic Resonance Imaging Rapidly Indicates Vessel Regression in Human Squamous Cell Carcinomas Grown in Nude Mice Caused by VEGF Receptor 2 Blockade with DC101

    Directory of Open Access Journals (Sweden)

    Fabian Kiessling

    2004-05-01

    Full Text Available The purpose of our study was the investigation of early changes in tumor vascularization during antiangiogenic therapy with the vascular endothelial growth factor (VEGF receptor 2 antibody (DC101 using dynamic contrast-enhanced magnetic resonance imaging (DCE MRI. Subcutaneous heterotransplants of human skin squamous cell carcinomas in nude mice were treated with DC101. Animals were examined before and repeatedly during 2 weeks of antiangiogenic treatment using Gd-DTPA-enhanced dynamic T1-weighted MRI. With a two-compartment model, dynamic data were parameterized in "amplitude" (increase of signal intensity relative to precontrast value and kep (exchange rate constant. Data obtained by MRI were validated by parallel examinations of histological sections immunostained for blood vessels (CD31. Already 2 days after the first DC101 application, a decrease of tumor vascularization was observed, which preceded a reduction of tumor volume. The difference between treated tumors and controls became prominent after 4 days, when amplitudes of treated tumors were decreased by 61% (P = .02. In line with change of microvessel density, the decrease in amplitudes was most pronounced in tumor centers. On day 7, the mean tumor volumes of treated (153 ± 843 mm3 and control animals (596 ± 384 mm3 were significantly different (P = .03. After 14 days, treated tumors showed further growth reduction (83 ± 93 mm3, whereas untreated tumors (1208±822 mm3 continued to increase (P=.02. Our data underline the efficacy of DC101 as antiangiogenic treatment in human squamous cell carcinoma xenografts in nude mice and indicate DCE MRI as a valuable tool for early detection of treatment effects before changes in tumor volume become apparent.

  12. Chronotherapy by Ribozyme Targeted to Telomerase in Nude Mice with a Transplanted Tumor: Model for Human Hepatic Cancer%端粒酶核酶时间治疗肝癌裸鼠移植瘤研究

    Institute of Scientific and Technical Information of China (English)

    屈艺; 王正荣; 万朝敏; 黄翔; 母得志; Germaine CORNELISSEN; Franz HALBERG

    2008-01-01

    Objective To investigate therapeutic autcomes of using telomerase inhibitors to treat cancer at the presumably most and least opportune circadian stages basing on our earlier study. Methods Twenty-four BALB/C nude mice were synchronized to a regimen of LD12:12 for 4 wk. Hepatic cancer cells (SMMC-7721) were implanted into both flanks of each mouse.Two weeks after transplantation,the hTERT-5'RZ was used to treat the hepatic cancer transplanted into the nude mice daily for two weeks,the injection times being either 9 or 21 HALO.Results The tumor inhibition ratio of mice treated at 21 HALO (65%) was statistically significantly higher than that of mice treated at 9 HALO (48%). Telomerase activity was also reduced to a greater extent in mice treated with hTERT-5'RZ at 21 than at 9 HALO, that was at the time of maximal circadian telomerase activity. Conclusion Injection of ribozyme targeted to telomerase during the tumor's DNA synthesis is associated with a better inhibition of tumor growth and a better therapeutic outcome in hepatic cancer.%目的 探讨在端粒酶峰值时相与谷值时相施以端粒酶抑制剂治疗肝癌裸鼠移植瘤的疗效差异.方法 24只BALB/C裸鼠进行为期4 wk的LD12: 12节律同步化.移植肝癌细胞(SMMC-7721)于裸鼠以建立肝癌裸鼠移植瘤.在移植后 2 wk,瘤体内注射端粒酶抑制剂hTERT-5'RZ以治疗肝癌裸鼠移植瘤,注射时间点为9 HALO或21 HALO,持续2 wk.结果 21 HALO治疗组的肿瘤抑制率(65%)和端粒酶抑制率(90%)高于9 HALO治疗组的肿瘤抑制率(48%)和端粒酶抑制率(70%),差异具有统计学意义. 结论 在肿瘤DNA合成期注射以端粒酶为作用靶点的核酶能更好地抑制肝癌生长,具有更好的治疗效果.

  13. 内皮抑素对卵黄囊瘤裸鼠模型血管生长的影响%Effects of Endostatin Treatment on Yolk Sac Tumor Xenografts of Children in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    陈聪德; 吴碎春; 王浩; 陈肖鸣; 张华

    2012-01-01

    Objective Based on the establishment of Yolk Sac tumor xenografts of children in nude mice, we study the effects and mechanism of endostatin (ES) on YST'S tumor xenografts of children. Methods Fourty nude mice were inoculated with tissue of YST'S xenograft and five males and five feamales for each group. In high - dose ( HD) group,nude mice bearing cancer would be subcutaneouly and intratumorally injected ES by 1.5mg/(kg · d) for 14 days. In low -dose (LD) group,mice would be injected ES by 0.75mg/(kg · d) for 14 days. In experimental control group,mice be injected isolonic Nachloride by 25ml/(kg · d) for 14 days. And in blank control group, mice would not be injected. The volume of transplantation tumors was measured everyday. Tumor control rate and draw growth curve were detected. The differences of the tumor vessel between each group were obsorved. The expression of AFP and level of VEGF and MVD also be measured by immunohistochemistry. Results The duplication of malignant teratoma xenografts of children in nude mice was successful, and the quale of the transplantation tumors is steady. The speed of tumor growth of treatment groups was slower than control groups since the sixth day(P 0. 05 ). Treatment groups were lower than control groups in extent and magnitude of expression of VEGF(P 0. 05 ). For MVD,treatment groups were fewer than control groups(P 0.05 ) . Angiography of tumor showed that vascular distribution density was HD group < LD group < experimental control. Conclusion Endostatin could hindrance the effect of VEGF, thus to control angiogenesis,which thereby effectively iahibit YST'S xenografts of children in nude mice.%目的 通过动物实验验证血管生长在卵黄囊瘤裸鼠模型中的作用,以及内皮抑素对模型血管生长的影响.方法 建立卵黄囊瘤裸鼠模型,分别采用1.5mg/(kg·d)及0.75mg/( kg·d)两个浓度重组人血管内皮抑制素局部注射干预,并皮下及瘤内注射生理盐水25ml/( kg

  14. Comparisons of [{sup 18}F]-1-deoxy-1-fluoro-scyllo-inositol with [{sup 18}F]-FDG for PET imaging of inflammation, breast and brain cancer xenografts in athymic mice

    Energy Technology Data Exchange (ETDEWEB)

    McLarty, Kristin; Moran, Matthew D. [Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8 (Canada); PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Scollard, Deborah A.; Chan, Conrad [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Sabha, Nesrin; Mukherjee, Joydeep; Guha, Abhijit [Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, University of Toronto, ON, M5G 1X8 (Canada); McLaurin, JoAnne [Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, M5S 3H2 (Canada); Nitz, Mark [Department of Chemistry, University of Toronto, Toronto, ON, M5S 3H6 (Canada); Houle, Sylvain; Wilson, Alan A. [Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8 (Canada); PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Reilly, Raymond M., E-mail: raymond.reilly@utoronto.ca [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Toronto General Research Institute, University Health Network, Toronto, ON, M5G 2M9 (Canada); Department of Medical Imaging, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Vasdev, Neil, E-mail: neil.vasdev@utoronto.ca [Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8 (Canada); PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada)

    2011-10-15

    Introduction: The aim of the study was to evaluate the uptake of [{sup 18}F]-1-deoxy-1-fluoro-scyllo-inositol ([{sup 18}F]-scyllo-inositol) in human breast cancer (BC) and glioma xenografts, as well as in inflammatory tissue, in immunocompromised mice. Studies of [{sup 18}F]-2-fluoro-2-deoxy-D-glucose ([{sup 18}F]-FDG) under the same conditions were also performed. Methods: Radiosynthesis of [{sup 18}F]-scyllo-inositol was automated using a commercial synthesis module. Tumour, inflammation and normal tissue uptakes were evaluated by biodistribution studies and positron emission tomography (PET) imaging using [{sup 18}F]-scyllo-inositol and [{sup 18}F]-FDG in mice bearing subcutaneous MDA-MB-231, MCF-7 and MDA-MB-361 human BC xenografts, intracranial U-87 MG glioma xenografts and turpentine-induced inflammation. Results: The radiosynthesis of [{sup 18}F]-scyllo-inositol was automated with good radiochemical yields (24.6%{+-}3.3%, uncorrected for decay, 65{+-}2 min, n=5) and high specific activities ({>=}195 GBq/{mu}mol at end of synthesis). Uptake of [{sup 18}F]-scyllo-inositol was greatest in MDA-MB-231 BC tumours and was comparable to that of [{sup 18}F]-FDG (4.6{+-}0.5 vs. 5.5{+-}2.1 %ID/g, respectively; P=.40), but was marginally lower in MDA-MB-361 and MCF-7 xenografts. Uptake of [{sup 18}F]-scyllo-inositol in inflammation was lower than [{sup 18}F]-FDG. While uptake of [{sup 18}F]-scyllo-inositol in intracranial U-87 MG xenografts was significantly lower than [{sup 18}F]-FDG, the tumour-to-brain ratio was significantly higher (10.6{+-}2.5 vs. 2.1{+-}0.6; P=.001). Conclusions: Consistent with biodistribution studies, uptake of [{sup 18}F]-scyllo-inositol was successfully visualized by PET imaging in human BC and glioma xenografts, with lower accumulation in inflammatory tissue than [{sup 18}F]-FDG. The tumour-to-brain ratio of [{sup 18}F]-scyllo-inositol was also significantly higher than that of [{sup 18}F]-FDG for visualizing intracranial glioma xenografts in

  15. Hymenolepis nana: immunity against oncosphere challenge in mice previously given viable or non-viable oncospheres of H. nana, H. diminuta, H. microstoma and Taenia taeniaeformis.

    Science.gov (United States)

    Ito, A; Onitake, K; Sasaki, J; Takami, T

    1991-04-01

    When mice, previously given oral inoculation with viable oncospheres of the heterologous cestode species (Hymenolepis diminuta, H. microstoma, Taenia taeniaeformis) and the homologous one (H. nana), were challenged with oncospheres of H. nana 4 days after the primary inoculation, they showed strong and complete resistance to H. nana challenge, respectively. However, the resistance was not evoked in mice given either infective eggs of Toxocara canis or non-viable oncospheres of all cestode species examined. Congenitally athymic nude mice given viable oncospheres did not show any resistance to H. nana either. Eosinophil infiltration around cysticercoids of H. nana in the intestinal villi appeared to be more prominent in mice previously given viable oncospheres of H. diminuta than in mice given non-viable oncospheres or PBS only. Some of the eosinophils in the villus harboring cysticercoid(s) of H. nana invaded the epithelia in the former, whereas all eosinophils remained in the lamina propria in the latter. There was almost no eosinophil infiltration in nude mice. Microscopic observations revealed that oncospheres of H. diminuta, which require beetles as the intermediate host like H. microstoma, could invade the mouse intestinal tissue. Therefore, it is strongly suggested that the strong cross resistance to H. nana in mice, induced by oncospheres of all heterologous cestode species, is thymus-dependent and due to oncospheral invasion into the intestinal tissue of mice.

  16. 大蒜素对胃癌细胞株及裸鼠移植瘤的抑制作用%Inhibitory Effect of Garlicin on Gastric Cancer Cells and Nude Mice Tumor Xenograft

    Institute of Scientific and Technical Information of China (English)

    王海燕; 许才绂; 王庆莉

    2001-01-01

    Objective To study the anticarcinogen mechanism of garlicin afterobservation of the effect of garlicin on gastric cancer cells.Methods Cultural cell lines of gastric cancer SGC-7901 and MGC-803 were used as the target cells to observe the effect of garlicin of different concertritions with different culture time on these cell lines by MTT assay.Two kinds of gastrical cancer cells with 10% bovine serum and 100mg.L-1 garlicin were cultured,and their changs of cell cycles after 4 and 8 hours were measured in vitro.In vivo study,garlicin were injected locally into the inplanted neoplasm of Balb/c nu/nu mice to observe the changs of the neoplasms and the living state after 7 and 14 days respectively when the nude mice tumor xenograft model were made.Results Garlicin had cytotoxic effect on these two kinds of gastrical cancer cells.When the mass concentritions of garlicin were 800mg.L-1 and 1000mg.L-1,the inhibiting rates of on SGC-7901 cells were 65.5% and 68.6% respectively(P<0.01,vs5-FU).When the mass concentritions of garlicin were 400mg.L-1,800mg.L-1 and 1000mg.L-1,the inhibiting rates on MGC-803 cells were 67.5%,75.3% and 79.5 respectively(P<0.01,vs5-FU).Culturing two kinds of gastrical cancer cells with bovine serum and 100mg.L-1 garlicin for 3 days,the inhibiting rates could come up to 85.2% and 96.7% respectively.Culturing two kinds of gastrical cancer cells with bovine serum and 100mg.L-1garlicin for 4 and 8 hours,the S phase of the cell cycles rose,and that of the MGC-803 cells rose more obviously.Injecting garlicin locally into the neoplasms in the seventh day when the nude mice tuor xenograft models were made,the neoplasm subsided in three nude mice,the neoplasm of one nude mice became very small.There were plenty of lymphocytes in the neoplasms,and the vasalium in neoplasm was scarce.Garlicin depressed the progress of the neoplasms when the nude mice tumor xenograft models were made by injecting locally in the fourteenth days,whose living state were better

  17. The establishment of orthotopic implant and metastatic models of human stomach cancer in nude mice under the microscope%显微镜下人胃癌裸鼠原位移植和转移模型的建立

    Institute of Scientific and Technical Information of China (English)

    林奇; 陈慧玉

    2012-01-01

      目的显微镜下建立一种能很好模拟人体内生物学行为的胃癌裸小鼠原位移植和转移模型.方法采用人胃癌SGC-7901细胞株在裸鼠皮下反复传5代形成实体瘤,显微镜下将人胃癌裸鼠皮下移植瘤块种植于裸小鼠胃壁,建立胃癌裸小鼠原位移植和转移模型16个,观察建立的模型肿瘤生长状况、移植成功率和自发转移的发生率,常规HE染色,观察胃癌原位移植瘤、胃癌淋巴结转移和肝转移的病理切片,电镜下观察肿瘤超微结构.结果胃癌裸鼠皮下移植瘤原位移植的原位成瘤率达100%(16/16),淋巴结广泛转移率为87.5%(14/16),肝转移发生率为75%(12/16),腹水形成率为12.5%(2/16).结论显微镜下建立原位移植和转移模型成功率高,且具有人胃癌自然生长过程的特点和生物学活性.%  Objective To develop a nude mouse model of human gastric cancer which can mimic its natural human biologic activities under the microscope. Methods Human gastric cancer SGC-7901 was cultured in nude mice repeatedly for 5 generations to get the Tumor subcutaneous solid tumor, which was then emulsified and orthotopicly implanted into the nude mouse stomach under the microscope to develop 16 implant-tumors. The tumor growth characteristic, tumor-take rates and metastatic rates were analyzed grossly. The gastric orthotopicaly transplantation, gastric cancer lymphatic metastasis and hepatic metastasis by HE staining, the ultrostructures, by electron microscopy were analyzed too.Results The tumor-take rate was 100%, the metastases of lymph nodes and livers were 87.5% and 75%, ascites formation is 12.5%. Conclusion To repeat the model under the microscope is easy and qualified, which can exhibiting natural growth characters and biological activities successfuly.

  18. 熊果酸对人肝癌SMMC-7721裸鼠移植瘤抑制作用的观察%Inhibitory effects of Ursolic acid on human hepatoma SMMC-7721 tumor xenograft in nude mice

    Institute of Scientific and Technical Information of China (English)

    韩旭鹤; 唐新娜; 丁一

    2012-01-01

    目的 观察熊果酸对人肝癌SMMC-7721裸小鼠移植瘤生长的抑制作用及其强度,为本药的进一步临床应用研究提供基础数据.方法 采用荷瘤裸小鼠作为移植性肿瘤实验动物模型.将裸鼠随机分为3组,每组8只,分别为阴性对照组、环磷酰胺阳性对照组和熊果酸组.阳性对照组给予环磷酰胺20mg/kg,熊果酸组给药剂量为4.5mg/kg,阴性对照组给予等量无菌注射用水,每日一次腹腔注射,连续14天.给药期间定期测定动物体重和瘤体积.实验结束后处死裸鼠,取出瘤体称重,计算肿瘤抑制率.结果 给药期间动物一般状况未见明显改变,饮食未见异常,体重较实验前有所增加.熊果酸组瘤体积缩小,瘤株抑瘤率达53.7%,阳性对照组的抑瘤率为39.2%,两组与阴性对照组比较,均有显著差异(P<0.05).熊果酸组和阳性对照组的相对肿瘤体积(RTV)分别为33.16±22.36,21.61±12.88,明显低于阴性对照组(62.09±32.80)(P<0.05),两组的相对肿瘤增殖率均小于60%.结论 熊果酸对人肝癌SMMC-7721裸小鼠移植瘤有明显的抑制作用.%Objective: To observe the inhibition effect and strength of ursolic acid on the human hepatoma SMMC - 7721 tumor xenografts in nude mice and provide base data to further clinical research. Methods: SMMC -7721 was injected subscaneously in nude mice to establish the xenograft tumor animal model. All 24 nude mice were equally divided into three groups randomly: the negative control group, cyclophosphamide positive control group and ursolic acid groups. The mice of positive control group and ursolic acid group were intraperitoneal injected cyclophosphamide by 20 mg/kg and ursolic acid by 4. 5mg/kg daily for a 14 - day continuous administration. Meanwhile, the mice of negative control group were intraperitoneal given the same amount of sterile water daily. During the administration, the weight of mice and the size of xenografts were measured regularly. All mice were

  19. Dynamic Observation on In vivo Bioluminescence Imaging of Experimental Metastatic Animal Models in Nude Mice%实验性肿瘤细胞转移动物模型的活体成像观察

    Institute of Scientific and Technical Information of China (English)

    闫明霞; 朱淼鑫; 刘蕾; 李静; 林河春; 赵方瑜; 姚明

    2012-01-01

    Objective To observe the tumor metastasis in deep organisms of the nude mice by in vivo bioluminescence imaging system. Methods The SMMC-7721-GFP/Luc cells with different concentrations were intravenously inoculated into the tail vein and spleen of the BALB/c-nu/nu mice, the distribution and expression of luciferase in nude mice were monitored by in vivo bioluminescence imaging system. Results The experimental metastatic animal models had been successfully established. The distribution and expression of luciferase ascended with cell concentration increased and decreased with the passage of time. Conclusion The in vivo bioluminescence imaging system may monitor the in vivo growth and metastasis of tumors and provide for studying the mechanisms of tumor metastasis and development of anticancer drug.%目的 利用小动物活体成像系统观察肿瘤细胞在动物体内的转移情况.方法 分别将不同浓度的绿色荧光蛋白(GPF)和荧光素酶(luciferase,Luc)双标的SMMC-7721细胞接种入裸小鼠尾静脉和脾,建立实验性转移动物模型,采用活体成像技术监测不同浓度的细胞在小鼠体内的转移情况,动态观察同一细胞于不同时间点在小鼠体内的转移情况.结果 成功建立了尾静脉接种肺转移及脾内接种肝转移的实验性转移动物模型,经小动物活体成像系统检测发现,随着接种细胞浓度的增加,荧光素的表达面积和强度逐渐增加,二者呈正比关系;随着接种时间的延长,荧光素的表达面积和强度逐渐减弱,二者呈成反比关系.结论 活体荧光成像系统可较好地观测肿瘤在动物体内深部脏器的转移情况,它将为肿瘤转移机制、抗转移治疗等研究提供有益的帮助.

  20. Role of hypoxia and glycolysis in the development of multi-drug resistance in human tumor cells and the establishment of an orthotopic multi-drug resistant tumor model in nude mice using hypoxic pre-conditioning

    Directory of Open Access Journals (Sweden)

    Duan Zhenfeng

    2011-02-01

    Full Text Available Abstract Background The development of multi-drug resistant (MDR cancer is a significant challenge in the clinical treatment of recurrent disease. Hypoxia is an environmental selection pressure that contributes to the development of MDR. Many cancer cells, including MDR cells, resort to glycolysis for energy acquisition. This study aimed to explore the relationship between hypoxia, glycolysis, and MDR in a panel of human breast and ovarian cancer cells. A second aim of this study was to develop an orthotopic animal model of MDR breast cancer. Methods Nucleic and basal protein was extracted from a panel of human breast and ovarian cancer cells; MDR cells and cells pre-exposed to either normoxic or hypoxic conditions. Western blotting was used to assess the expression of MDR markers, hypoxia inducible factors, and glycolytic proteins. Tumor xenografts were established in the mammary fat pad of nu/nu mice using human breast cancer cells that were pre-exposed to either hypoxic or normoxic conditions. Immunohistochemistry was used to assess the MDR character of excised tumors. Results Hypoxia induces MDR and glycolysis in vitro, but the cellular response is cell-line specific and duration dependent. Using hypoxic, triple-negative breast cancer cells to establish 100 mm3 tumor xenografts in nude mice is a relevant model for MDR breast cancer. Conclusion Hypoxic pre-conditiong and xenografting may be used to develop a multitude of orthotopic models for MDR cancer aiding in the study and treatment of the disease.

  1. miR-29c suppresses pancreatic cancer liver metastasis in an orthotopic implantation model in nude mice and affects survival in pancreatic cancer patients.

    Science.gov (United States)

    Zou, Yongkang; Li, Jianwei; Chen, Zhiyu; Li, Xiaowu; Zheng, Shuguo; Yi, Dong; Zhong, Ai; Chen, Jian

    2015-06-01

    We investigated mechanisms of pancreatic cancer metastasis and defined the biological role of miR-29c in pancreatic cancer metastasis. After two rounds of cell selection in vivo, pancreatic cancer cells with various metastatic potentials derived from spontaneous liver metastases were used as a model of pancreatic cancer to determine the role of miR-29c in pancreatic cancer metastasis. Pancreatic cancer samples were analyzed for miRNA-29c expression, and these levels were associated with survival between groups. miR-29c suppresses cell migration and invasion by targeting the MMP2 3'UTR. Overexpression of miR-29c suppresses pancreatic cancer liver metastasis in a nude mouse orthotopic implantation model. miR-29c expression was associated with metastasis and pancreatic cancer patient survival. miR-29c plays an important role in mediating pancreatic cancer metastasis to the liver by targeting MMP2. Therefore, miR-29c may serve as a novel marker of pancreatic cancer metastasis and possibly as a therapeutic target to treat pancreatic cancer liver metastasis.

  2. 沙利度胺对人卵巢癌裸鼠皮下种植瘤抑瘤作用的研究%Study of thalidomide on the growth inhibition of ovary cancer SKOV-3 subcutaneous implanted in nude mice

    Institute of Scientific and Technical Information of China (English)

    杜娟; 黄学惠

    2011-01-01

    Objective : To study the effect of thalidomide used alone and in combi - nation with cisplatin ( DDP) on ovanan cancer cell subcutaneous implanted tumor gro - wth inhibition.Methods : Twenty ovarian cancer modle ubcutaneous implantted in nude m - ice was established and randomly divided into 4 groups, n =5 : thalidomide group:200mmg · kg -1d -1 , 0.2ml , ip ; DDPgroup : 0.2mg · kg-1 d -1 , 0.2ml , ip ; Combjned treatment group : both Thd and DDP, 0.2ml, ip; control group : saline solution , 0.2ml , ip.Af - ter the succesa of implant, MTD 0.8cm, administered two weeks , twice a week , total of 4 injection.Weight, MTD changes , the actions of nude mice , the response to extemal stimulation , food , the surface of skin tumor changes and measured tumor inhibition rate was obsewed in each group.Results : Compared with the control group, growth of tumor was significantly reduced in mice treated with thalidomide, DDP and combined treatment.( inhibition rate 57.47% , 42.18% , 71.37% ) ( P < 0.05 ) .Conclusion :Thalidomide can inhibit the growth of human ovarian cancer subcutaneous implanted in nude mice.In combination with DDP, thalidomide might prove the antitumor drug therapy.%目的:探讨沙立度胺(反应停,酞咪哌啶酮,thalidomide)对卵巢癌裸鼠皮下种植瘤的生长抑制作用.方法:建立20只卵巢癌裸鼠荷瘤模型,随机分为4组,每组5只:沙利度胺组:按200mg·kg-1d-1,0.2ml腹腔内注射.顺铂组:2mg·kg-1d-1,0.2ml腹腔内注射.联用组:顺铂与沙利度胺联合应用(顺铂2mg·kg-1d-1,沙利度胺200 mg·kg-1d-1,各0.2ml腹腔内注射).生理盐水组:每只0.2ml生理盐水腹腔内注射.4组给药方法均为自肿瘤种植成功后瘤体直径平均为0.8cm,开始给药,给药2周,每周2次,总共注射4次.观察各组裸鼠体重、皮下种植瘤瘤体直径均值(MTD)的变化,以及各组裸鼠的行动、对外界刺激的反应、饮食、及瘤体表面皮肤的变化,测量各组肿瘤的大小.结果:沙

  3. 乳香提取物抑制裸鼠胰腺癌生长的作用及机制研究%The Inhibitory Effect and Mechanism of Pancreatic Cancer in Nude Mice Model with Frankincense Ex-tract

    Institute of Scientific and Technical Information of China (English)

    倪效; 梁晓强; 张静喆

    2015-01-01

    目的::研究乳香提取物体内抑制胰腺癌的可能性及其机制。方法:利用人胰腺癌细胞株MIA PaCa-2体外扩增后种植于裸鼠皮下成瘤,将乳香提取物经裸鼠皮下注射,同时设PBS组为对照,观察肿瘤体积变化(其中乳香提取物治疗组6只,对照组5只),12 d后将肿瘤切除后测量肿瘤体积,固定瘤体后切片,通过标记磷酸化组蛋白H3(PHH3),原位末端转移酶标记技术(TUNEL)行免疫组化分析。结果:治疗组肿瘤体积为(76.67±24.11)mm3,对照组肿瘤体积为(204.80±101.19)mm3;治疗组PHH3阳性细胞数为197.5±40.4,对照组PHH3阳性细胞数为252.8±30.6;治疗组TUNEL阳性细胞数为316.7±117.3,对照组为TUNEL阳性细胞数为100.6±47.2;治疗组与对照组比较,P<0.05。结论:乳香提取物在体内可以抑制裸鼠胰腺癌的生长,促进胰腺癌细胞的凋亡。%Objective To investigate the inhibitory effect and mechanism of pancreatic cancer in nude mice model with Frankincense extract. Methods MIA PaCa-2 of pancreatic cancer cell lines were implanted into nude mice subcutaneously .The nude mice were randomly assigned to receive either PBS(control) or Frankin⁃cense extract injection subcutaneously (the number of treatment group was 6, while the control group was 5). Af⁃ter 12 days, tumors were removed . Tumor volume were mersured. Tumors were fixed and immunohistochemical analysis for PHH3 and TUNEL. Results The tumor size of the treatment group was (76.67 ± 24.11) mm3 while the control group was(204.80±101.19)mm3. The difference is statistically significant (p < 0.05). The number of PHH3-immunoreactive cells of treatment group was (197.5±40.4), while the control group was (252.8±30.6). The difference is statistically significant (P<0.05). The number of TUNEL positive cells in treatment group was (316.7 ± 117.3), while the control group was (100.6 ± 47.2). The difference is

  4. 三氧化二砷对裸鼠宫颈癌移植瘤的作用及机制%Effects and Mechanism of Arsenic Trioxide on Growth of Cervical Cancer in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    林晨; 拉莱·苏祖克; 史永华; 魏琴

    2011-01-01

    目的 研究三氧化二砷(arsenic trioxide,ATO,As2O3)对宫颈癌 HeLa 细胞裸鼠移植瘤生长的作用及机制.方法 建立裸鼠移植瘤模型,分为低浓度 As2 O3组[2mg/(kg·d)],高浓度As2O3 组[5mg/(kg·d)],顺铂(DDP)组[3mg/(kg·d)]及阴性对照组(0.9%氯化钠0.2ml/d),连续给药10d,观察抑瘤率及药物对裸鼠的影响.透射电子显微镜观察肿瘤的超微结构,免疫组织化学检测p-P38和Caspase-3的表达.结果 低浓度 As2 O3,高浓度 As2 O3及 DDP 的抑瘤率分别为22.95%、54.86%和54.48%,后两者的抑瘤率与阴性对照组的差异有统计学意义(P<0.05),但DDP的不良反应大.p-P38和 Caspase-3在As2 O3组的表达明显高于阴性对照组(P<0.05).结论 As2O3可通过诱导肿瘤细胞凋亡抑制宫颈癌移植瘤的生长.%Objective To explore the inhibitory effect of arsenic trioxide(ATO, As2O3 ) on the tumor growth of cervical cancer cell line HeLa subcutaneously implanted in nude mice and its mechanism.Methods Human cervical cancer xenografted model was established in nude mice. The tumor-bearing nude mice were randomly divided into the experimental groups: ATO low dose group [2mg/(kg ·d)], ATO high dose group [5mg/(kg · d)], DDP positive control group [3rng/(kg · d)], saline negative control group(0. 9%NaCl 0. 2ml/d). The drugs were administered intraperitoneally for 10 consecutive days. To observe the tumor inhibition rate and effects of drugs. Ultramicrostructure feature of tumor was observed under electron microscope. Immunohistochemistry was used to measure the expression of p-P38 and Caspase-3. Results Inhibited tumor volume of ATO low and high dose groups and DDP positive control group was 22. 95% ,54. 86% and 54. 48%, respectively. The inhibited effect of ATO 5mg/kg/d group was similar with DDP 3mg/kg/d group, but the toxic effect of DDP was higher than ATO. The expression of p-P38 and Caspase-3 was higher than negative control group (P <0. 05). Conclusion ATO can inhibit

  5. Ang2-siRNA 慢病毒干预裸鼠移植性恶性黑色素瘤的研究%Ang2-siRNA Lentivirus Interference on Melanoma Xenograft in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    王彪; 林建鸿; 张炜强; 张明凤; 刘照亮; 单秀英; 王美水; 庄福连

    2012-01-01

    目的 研究血管生成素2小干扰 RNA(Ang2-siRNA)对裸鼠移植性恶性黑色素瘤血管形成及其生长的影响.方法 建立人恶性黑色素肿瘤裸鼠异种移植瘤模型.在体内使用 pNL-EGFP-Ang2-siRNA 慢病毒干扰裸鼠移植性恶性黑色素瘤 Ang2 基因的表达,观察统计各组肿瘤(空白组、空载组、实验组)生长情况.应用实时荧光定量 RT-PCR 检测肿瘤组织中 Ang2 基因的 mRNA 表达水平;CD34 单克隆抗体作为血管内皮标志物,免疫组织化学法检测其表达,以评价肿瘤微血管密度.结果 成功建立了恶性黑色素瘤裸鼠异种移植瘤模型,实验组肿瘤 Ang2 基因 mRNA 水平、微血管密度、肿瘤体积显著小于空白组和空载组(P0.05).结论 pNL-EGFP-Ang2-siRNA 慢病毒能沉默Ang2 的表达,显著抑制恶性黑色素瘤血管的形成和肿瘤的生长,可能为临床恶性黑色素肿瘤的基因治疗开辟新的途径.%Objective Research the influence of Ang2-siRNA on angiogenesis and growth of transplanted melanoma tumors in nude mice. Methods Human malignant melanoma ( MM ) trans-plantation tumor model was established in nude mice . Interference of Ang2 gene expression by pNL-EGFP-Ang2-siRNA lentivirus in transplanted MM was observed and recorded by comparison of tumor growth between the PBS control group, the Vector control group , and the experimental RNAi group. The expression levels of Ang2 gene in transplanted tumors was detected by Real -time RT-PCR. CD34, as one of the vascular endothelial markers , was detected by CD34 monoclonal antibodies to evaluate the microvessel de Nsity of transplanted tumor using Immunohistochemical method. Results The human MM transplanted tumor nude mice model was successfully established . The Ang2 gene mRNA level, microvassel de Nsity, and tumor size in RNAi group were significantly deceased , compared to those in the PBS and Vector control groups (P 0. 05 ) . Conclusion PNL-EGFP-Ang2-siRNA lentivirus can reduce

  6. 人脐血内皮祖细胞治疗裸鼠心肌梗死%Transplantation of endothelial progenitor cells from human cord blood into ischemic myocardium of nude mice

    Institute of Scientific and Technical Information of China (English)

    董永强; 徐家行; 张晓明; 朱水波; 刘高利; 殷桂林

    2010-01-01

    目的 探讨人脐血内皮祖细胞(EPCs)移植治疗裸鼠心肌梗死的可行性.方法 采用淋巴细胞分离液提取人脐血单个核细胞(MNCs),应用添加诱导因子的培养基于体外诱导分化并于培养7 d后进行鉴定.采用20只裸鼠建立心肌梗死模型后,将体外诱导分化7 d并摄取CM-Dil的内皮祖细胞通过尾静脉注射进行细胞移植到实验组,对照组注射培养基.2周后计数心梗区域新生毛细m管密度及心梗面积并于荧光显微镜下观察新生血管的荧光.结果 体外诱导7 d后贴壁细胞CD34阳性率达(50.48±5.17)%,CDl33阳性率达(19.12±4.37)%.实验组平均梗死面积为(8.27±1.64)%,对照组为(14.30±2.84)%(t=-4.78,P<0.05);实验组每高倍视野平均新生血管密度为14.29±1.38,对照组为10.17±1.72(t=4.71,P<0.01);行荧光显微镜下观察实验组新生血管有红色荧光.讨论人脐血单个核细胞在体外诱导分化为内皮祖细胞,进行细胞移植到建立心梗模型的裸鼠后可在心梗区域形成新生血管,从而并改善梗死部位心脏功能.%Objective To investigate the possibility of endothelial progenitor cells (EPCs) trans-plantation for the treatment of myocardial infarction of nude mice. Methods Mononuclear cells (MNCs) were isolated by lymphocyte separating medium from human cord blood and were cultured in DMEM with proper inducing factors. After 7 days, the attached cells were identified by the characteristic of EPCs. After establishing myocardial infarction model of 20 nude mice the attached cells taking CM-Dil were injected into vena caudalis. The control group was injected with non-serum culture medium, nfarcted size, apillary den-sity and fluorescence of new capillaries were measured 2 weeks after operation. Results After 7 days, the CD34 positive rate in the attached cells was (50.48±5. 17)% and CD133 rate was (19. 12±4. 37)%, respectively. Two weeks after operations, infarcted sizes of transplantation group was

  7. Preliminary trial of identification of brain structures in nude mice with green fluorescent protein expression by fluoroscope%荧光镜下界定绿色荧光裸小鼠脑结构部位

    Institute of Scientific and Technical Information of China (English)

    郑达理; 董军; 兰青; 黄强; 钱志远; 李如军; 王爱东; 崔宝乾; 陈延明; 费喜峰; 吴明霞; 霍红梅

    2012-01-01

    目的 探讨荧光镜下界定绿色荧光裸小鼠脑结构部位的可行性及优势所在.方法 取表达绿色荧光蛋白(GFP)的成年裸小鼠脑置于SLY脑切片模具中,切出1mm或0.9 mm厚的脑片,再分别对其进行25 μm厚的冰冻切片.荧光镜下观察切片的形态结构,结合《小鼠脑立体定位图谱》中小鼠脑解剖资料,在荧光镜下界定其解剖结构.观察结束后,全部切片行尼氏染色做对照.结果 依据脑内不同结构间的荧光色差可对其进行辨认:细胞核、尼氏小体密集区及神经束分布区为弱荧光信号;细胞核、尼氏小体密集区周围结构,如嗅球的丛状层、小脑的分子层为强荧光信号.切片经尼氏染色后,体视显微镜下观察到的脑结构与荧光镜观察的结果基本一致. 结论 荧光镜下界定绿色荧光裸小鼠脑结构部位可作为一个实验手段应用于荧光示踪实验的解剖定位研究.%Objective To explore the feasibility and advantage of fluoroscope in identification of brain structures in nude mice with green fluorescent protein (GFP) expression. Methods We laid the whole brain separated from 8-week adult nude mice with GFP expression into SLY mouse brain blocker to produce slices of 1 or 0.9 mm thickness; and then,25 μm-thickness frozen sections were cut.Fluoroscope was employed to observe the morphological structure to define their anatomic structures with reference to The Mouse Brain in Stereotaxic Coordinates compiled by Paxinos. After the observation,these frozen sections were performed Nissi staining for contrast. Results Different structures can be identified by their distinct fluorescence intensity:the dense areas of nuclei,Nissl bodies and nerve tract showed low fluorescence intensity; while the structures around the areas of nuclei and nerve tract,such as,the plexiform layer of olfactory bulb and the molecular layer of cerebella,showed high fluorescence intensity.The fluorescence intensity was

  8. MCF-7荷瘤裸鼠不同树突状细胞亚群凋亡的研究%Apoptosis of dendritic cell subsets in MCF-7 tumor-bearing nude mice

    Institute of Scientific and Technical Information of China (English)

    张还珠; 罗荣城

    2013-01-01

    目的:通过建立MCF-7荷瘤裸鼠模型,研究树突状细胞(DCs)不同亚群的凋亡,为设计新的免疫治疗方法和新的疫苗提供详尽信息.方法:建立MCF-7裸鼠模型,随机分为荷瘤组和对照组,肿块达5 mm后处死裸鼠,取骨髓单个核细胞进行DCs诱导、分化,流式细胞仪上检测表面分子标志CD86、CD83、MHC-Ⅱ及CD34,Annexin Ⅴ检测CD11c及CD123了解DCs亚群的凋亡率.结果:骨髓起源单个核细胞培养至第9天出现典型DCs形态特征,荷瘤组和对照组细胞均高表达CD86、CD83及MHC-Ⅱ,而CD34表达两组均较低.荷瘤组CD11c+ CD123-细胞为(52.01±1.43)%,对照组为(56.36±1.76)%;CD123+ CD11c-细胞荷瘤组为(32.19±1.71)%,对照组为(28.95±1.39)%.荷瘤组mDC凋亡率为(23.64±2.43)%,较对照组(20.05±2.49)%高,P<0.05.荷瘤组小鼠pDC凋亡率为(11.53±2.92)%,较对照组(14.96±2.96)%低,P<0.05.结论:MCF-7乳腺癌小鼠体内DCs存在mDC和pDC两种亚型,mDC凋亡率增加,使诱导Th1免疫反应能力减低;而pDC凋亡率减少,诱导体内免疫耐受的发生,机体抗肿瘤免疫反应能力因而下降.%OBJECTIVE:Establishing MCF-7 tumor-bearing mice and studying the apoptosis of DCs subsets,in order to give the particular information to design the new immune-therapeutic method and new vaccines in breast cancer. METH ODS:MCF-7 cell line was implanted subcutaneously in BALB/C nude mice to develop implant-tumor. Then the nude mice were randomly allocated into two groups. Mice were sacrificed when tumor size reached 5mm in diameter. Bone marrow-derived mononuclear cells were induced and differentiated. DCs were identified by flow cytometry. The apoptosis of DC subsets were verified by Annexin V using flow cytometry. RESULTS:The obvious morphologic characteristics of DCs were observed when the bone marrow-derived monoclear cell had been cultured for 9days. High level expressions of CD86, CD83 and MHC- II were similarly observed in two groups

  9. The effect of AD-VEGF-siRNA on the expression of vascular endothelial growth factor in osteosarcoma-bearing nude mice

    Institute of Scientific and Technical Information of China (English)

    Huaming Xue; Jiong Mei; Yihui Tu; Xuansong Cai; Guang Ojan; Mu Hu

    2008-01-01

    Objective: To explore the influence of AD-VEGF-siRNA on the expression of vascular endothelial growth factor (VEGF) in neoplasm and blood serum.Methods: Transplantable model of human osteosarcoma was successfully established by the way of subcutaneous injection of VEGF highly expressed human MG63 osteosarcoma cells.These mice were divided randomly into three groups: AD-VEGF-siRNA group, 15 mice; AD-EGFP group, 15 mice; PBS group, 15 mice.Three mice were additionally raised without any treatment.The drug was injected intratumorally 200 IJL at each time, once a day.The total dose of virus was 2×109 pfu.Three osteosarcoma-bearing mice of each group were sacrificed at 11th, 14th ,17th day after the implantation of MG63 cells.The expression of VEGF in implanted tumors and blood serum was detected by ELISA methods.Then the left mice were all sacrificed at the end of experiment (19th day).The expression of VEGF in implanted tumors was detected by RT-PCR and immune histochemistry methods, and that in implanted tumors and blood serum was detected by ELISA methods.Results: (1) Tumors in mice could be seen at 5th day from the implantation of MG63 ceils.(2)The expression of VEGF could be detected in all groups by RT-PCR and immune histochemistry, Which was much lower in the group receiving AD-VEGF-siRNA therapy than two control groups (P<0.05).(3) The expression of VEGF in blood serum of osteosarcoma-bearing mice was much higher than that of three healthy mice by ELISA (P<0.05).(4) The expression of VEGF in blood serum and neoplasm in AD-VEGF-siRNA group was much lower than that in two control groups (P<0.05).Conclusion: AD-VEGF-siRNA could effectively inhibited VEGF expression in vivo.This technology would bring some good references for our therapy of antiangiogenesis in osteosarcoma.

  10. Study on nude mice bearing human breast cancer of MCF-7%MCF-7细胞系乳腺癌裸鼠模型病理学特点及生物学性状的研究

    Institute of Scientific and Technical Information of China (English)

    刘建中; 谷俊朝; 俞巍

    2010-01-01

    目的 探讨荷人乳腺癌裸鼠移植模型的病理学特点及生物学性状,为乳腺癌病因学、发病学研究提供可靠的工具.方法 在裸鼠右侧腋窝注射人乳腺癌MCF-7细胞悬液0.1 mL(5×10~8个/mL),建立乳腺癌裸鼠动物模型.混合干预组小鼠,肿瘤接种部位旁皮下注射瘦素0.2 mL(15×10~4 ng/mL)和雌激素0.2 mL(0.15 mg/mL),每天1次;雌激素组注射雌激素0.2 mL(O.15 mg/mL);瘦素组注射瘦素0.2 mL(15×10~4ng/mL);空白组注射0.9%氯化钠溶液,每日观察肿块生长情况及肿瘤体积变化.宰杀取材,观察肿瘤组织学特征.结果 (1)空白组肿瘤移植成功率为33.3%(10/30),瘦素组为46.7%(14/30),模型失败.混合干预组肿瘤移植成功率为96.7%(29/30),雌激素组为93.3%(28/30),两组间无明显差异(P>0.05);(2)混合干预组裸鼠平均肿瘤最长径明显优于雌激素组,差异具有统计学意义(Pnude mice, to discuss the feature of pathology and biology of breast cancer,and give help to establish tools of pathogen research. Methods Human breast cancer cells MCF-7 were subcutaneously injected into the right armpit of nude mice to establish human breast cancer models.The mice were divided into composite group, estrogen group, leptin group and the blank group (30 in each). In the composite group,estrogen and leptin were injected into peripheral region of the tumor daily.In the estrogen group,estrogen was injected.In the leptin group, leptin was

  11. 前药热化疗对裸鼠结肠癌肝转移的作用%The influence of tissue specific CD/5-FC combined with thermotherapy on colon carcinoma liver metastasis in nude mice

    Institute of Scientific and Technical Information of China (English)

    黎成金; 王羊; 王烈; 涂小煌; 王瑜; 张宝明

    2008-01-01

    Objective To explore the effect of CD/5-FC system combined with thermotherapy on liver metastasis of colon carcinoma. Methods Forty-five nude mice were divided into 3 groups randomly. Different treatments were administrated, then liver metastasis rate, the number of liver metastasis nodules, the pathologic changes of the tumor tissues ,and apoptosis index of tumor cells were analyzed in every group respectively. The expression of CD gene in tumor tissues were detected by real-time RT-PCR and Western blot. Results Liver metastasis rate, number of metastasis nodules and tumor cell apoptosis index were 100%, (4.6±1.3) ,4.59% in control group, 40%, (2.2±0.9), 9.87% in 5-FC group and 20%, (0.5±0.8), 17.40% in 5-FC thermotherapy group respectively. Conclusion Inhibition of liver metasta-sis of colon cancer cells LoVo transfected with CD gene combined with thermotherapy can be observed evi-dently in nude mice.%目的 观察胞嘧啶脱氨酶/5-氟胞嘧啶(CD/5-FC)系统热化疗对裸鼠结肠癌肝转移的作用.方法 45只裸鼠随机分为3组,分别给予不同的治疗方法,观察各组肝转移率、肝转移瘤数目、病理学变化、肿瘤细胞凋亡指数,检测肿瘤组织中CD基因的表达情况.结果 对照组、5-FC治疗组、5-FC热疗组平均肝脏转移瘤数和肝脏转移率分别为4.6000±1.2649、2.2000±0.9189、0.5000±0.8498;100%、40%、20%;肿瘤细胞凋亡指数平均为4.59%、9.87%和17.40%,5-FC热疗组可见较多的凋亡小体形成.结论 CD/5-FC系统热化疗对裸鼠转CD基因LoVo细胞结肠癌肝转移有明显的抑制作用.

  12. Effect of whole-body irradiation of mice on the number of background plaque-forming cells.

    Science.gov (United States)

    Anderson, R E; Lefkovits, I; Söederberg, A

    1983-08-01

    Mice were exposed in whole-body fashion to several doses of radiation and killed at various times thereafter for a determination of the number of background plaque-forming cells (PFCs) as assayed on either sheep erythrocytes or bromelain-treated autologous mouse erythrocytes. Increased numbers of both types of PFC were found in the irradiated groups. These increases were dependent on radiation dose and time after exposure. They did not appear to be caused by a disruption of normal lymphocyte traffic or a switch in immunoglobulin isotype. An increased number of PFCs on bromelain-treated mouse RBCs but not on sheep RBCs were found in irradiated congenitally athymic nude mice. On the basis of this and related observations, background PFCs on bromelain-treated mouse RBCs and on sheep RBCs appear to fall under different forms of homeostatic control.

  13. 人瘢痕疙瘩成纤维细胞裸鼠荷瘤模型的建立%Establishment of a keloid model in nude mice with human keloid-derived fibroblasts

    Institute of Scientific and Technical Information of China (English)

    朱莲花; 万红双; 金明姬; 方宇辉; 李周娜; 金哲虎; 高钟镐

    2014-01-01

    目的 建立一种简单、成功率高的人瘢痕疙瘩裸鼠荷瘤模型.方法 27只雌性BALB/c裸鼠随机分为5组,A、B、C组每组5只,在每只裸鼠腋窝下接种人瘢痕疙瘩成纤维细胞和Matrigel胶混悬液0.1 ml,细胞浓度分别为1.0×104个/μl Matrigel胶(A组)、3.0×104个/μl Matrigel胶(B组)、5.0×104个/μl Matrigel胶(C组).取C组成形瘤块修剪成若干个5 mm×5 mm×5 mm大小的组织块移植于D组裸鼠(8只)的腋窝皮下;E组裸鼠(4只)皮下注射100μl Matrigel胶作为对照组.A、B、C组出瘤后30 d、D组瘤块移植后30 d肉眼观察瘤体的形成过程及变化,并在第31天处死裸鼠进行组织病理学检查,分析其移植后成形的瘤体组织学变化及裸鼠的心、肝、脾、肺、肾组织的变化.结果 A、B、C组裸鼠成瘤率为100%,出瘤时间分别为(90.20±3.96)d、(61.00±2.92)d、(39.60±3.20)d.出瘤30 d时3组瘤体体积分别为(288.34±25.29) mm3、(1 370.63±105.24) mm3、(1 940.98±184.37) mm3,3组差异有统计学意义(F=138.74,P< 0.05).D组裸鼠成形瘤块移植后瘤块体积先略增大后逐渐减小,移植第14天始持续增大,8只中7只成瘤.E组裸鼠未见瘤体形成.组织病理学检查,各组瘤体的组织形态在镜下一致,与人瘢痕疙瘩组织相似,未见其他脏器组织学改变及转移瘤灶.结论 裸鼠皮下接种人瘢痕疙瘩成纤维细胞可建立瘢痕疙瘩裸鼠荷瘤模型,而且已成瘤组织修剪成一定体积再次移植于裸鼠皮下也可以建立瘢痕疙瘩裸鼠荷瘤模型.%Objective To establish a simple and efficient method for developing a keloid model in nude mice with human keloid-derived fibroblasts.Methods Twenty-seven female BALB/c nude mice were randomly divided into five groups with 5,5,5,8 and 4 mice in group A,B,C,D and E respectively.The mice in group A,B and C were inoculated with 0.1 ml of suspension containing human keloid-derived fibroblasts at concentrations of 1.0 × 104,3.0 × 104

  14. Chronic Pseudomonas aeruginosa lung infection in normal and athymic rats

    DEFF Research Database (Denmark)

    Johansen, H K; Espersen, F; Pedersen, S S

    1993-01-01

    We have compared a chronic lung infection with Pseudomonas aeruginosa embedded in alginate beads in normal and athymic rats with an acute infection with free live P. aeruginosa bacteria. The following parameters were observed and described: mortality, macroscopic and microscopic pathologic change...

  15. New cancer-treatment model of photodynamic therapy combined with a type I topoisomerase inhibitor, CPT-11, against HeLa cell tumors in nude mice used by OPO parametric tunable laser

    Science.gov (United States)

    Yoshida, Takato O.; Matsuzawa, Eiji; Matsuo, Tetsumichi; Koide, Yukio; Terakawa, Susumu; Yokokura, Teruo; Hirano, Toru

    1995-03-01

    A new cancer-treatment model, photodynamic therapy (PDT) combined with a type I topoisomerase inhibitor, camptothecin derivative (CPT-11), against HeLa cell tumors in BALB/c nude mice has been developed using a wide-band tunable coherent light source operated on optical parametric oscillation (OPO parametric tunable laser). The Photosan-3 PDT and CPT-11 combined therapy was remarkably effective, that is the inhibition rate (I.R.) 40 - 80%, as compared to PDT only in vivo. The analysis of HpD (Photosan-3) and CPT-11 effects on cultured HeLa cells in vitro has been studied by a video-enhanced contrast differential interference contrast microscope (VEC-DIC). Photosan-3 with 600 nm light killed cells by mitochondrial damage within 50 min, but not with 700 nm light. CPT-11 with 700 - 400 nm light killed cells within 50 min after nucleolus damage appeared after around 30 min. The localization of CPT-11 in cells was observed as fluorescence images in the nucleus, particularly the nucleoral area produced clear images using an Argus 100.

  16. 人胰腺癌裸鼠皮下移植瘤模型MRI表现与病理对照研究%MRI Features and Pathology of Human Pancreatic Cancer Subcutaneously Implanted Tumor Model in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    张梅花; 杨晓春; 沈钧康; 赵永华

    2015-01-01

    目的 探讨人胰腺癌裸鼠皮下移植瘤磁共振成像(MRI)检查技术及其影像学表现的病理机制.方法 建立人胰腺癌Patu8988细胞株裸鼠皮下移植瘤模型20只,细胞接种后2、4、6、7、8周随机抽取4只荷瘤鼠,进行大体观察、MRI检查和病理检查.大体观察荷瘤鼠和肿瘤的生长后进行MRI扫描,MRI平扫后,腹腔注射钆贝葡胺后4min行增强扫描,观察肿瘤影像学表现和周围组织情况;MRI检查后处死荷瘤鼠,解剖瘤灶,进行病理学研究,并与MR图像进行对照.结果 肿瘤接种成功率为100%.2周时瘤灶T1WI和T2WI信号较均匀,4~8周时瘤灶T1WI呈均匀等信号或稍高信号,T2WI呈不均匀混杂信号,增强扫描瘤灶不均匀强化,以瘤灶周缘强化明显,内可见斑片状无强化区,随着肿瘤的生长,其内无强化区逐渐扩大.结论 常规MR扫描技术能对胰腺癌皮下移植瘤的发生发展进行动态观察,移植瘤MRI表现可从病理学角度进行解释.%Objective To investigate the MRI features of human pancreatic cancer subcutaneously implanted tu-mor in nude mice and the pathomechanism of the MRI features. Methods Twenty nude mice were subcutaneously injected with human pancreatic cancer cells Patu8988 to establish the animal model. Every 4 mice were randomly sampled at 2, 4, 6, 7, and 8 weeks after inoculation of the cells to conduct gross observation, MR scanning, and pathological examination. After gross observation, the bearing tumors were scanned by MR and enhanced MR(4 min after Gd-BOPTA injection), and then the mice were sacrificed for pathological examination. MRI findings were compared with pathological findings. Results The successful rate of inoculation was 100%. The signal of two-week-old tumors showed iso-intensity on T1WI and T2WI, the signal of four- to eight-week-old tumors showed iso-intensity or slight hyper-intensity on T1WI, and mix-intensity on T2WI. The tumors were intensified at 4min postinjection of the

  17. Immunohistology of carcinoembryonic antigen (CEA)-expressing tumors grafted in nude mice after radioimmunotherapy with 131I-labeled bivalent hapten and anti-CEA x antihapten bispecific antibody.

    Science.gov (United States)

    Gautherot, E; Kraeber-Bodéré, F; Daniel, L; Fiche, M; Rouvier, E; Saï-Maurel, C; Thedrez, P; Chatal, J F; Barbet, J

    1999-10-01

    We have developed a pretargeting strategy, called the Affinity Enhancement System (AES), which uses bispecific antibodies (BsF(ab')2) to target radiolabeled bivalent haptens to tumor cells. We performed several radioimmunotherapy (RIT) experiments in nude mice grafted with LS174T colon carcinoma or TT medullary thyroid cancer. Mice were treated with 131I-labeled di-DTPA-indium-tyrosyl-lysine bivalent hapten (75-112 MBq) administered 15-48 h after anti-CEA x anti-DTPA-indium BsF(ab')2. Immunohistological studies were performed on tumors at their minimal relative volume (TT), on stabilized tumor nodules (LS174T), and on regrowing tumors (TT and LS174T). Untreated tumors were used as controls. On microscopic examination, regrowing tumors (2 months posttherapy) were similar to untreated tumors with cells showing their respective typical morphology (large cells with a high nucleocytoplasmic ratio for TT, small and very undifferentiated cells for LS174T). However, regrowing tumors showed larger necrotic areas and a higher mitotic index correlated with Ki-67 antigen staining. Immunostaining for CEA was as strong as for controls. By contrast, the immunohistology of TT tumors at their minimal relative volume (1 month posttherapy) or of LS174T residual nodules (8 months posttherapy) showed decreased mitotic indices correlated with poor Ki-67 antigen staining. Some clusters of LS174T presented with features of glandular lumen, which suggested a more differentiated and less aggressive status. In TT tumors, CEA expression remained unchanged (80-100% membrane and cytoplasmic staining), whereas only 70% of the LS174T tumors were stained, with 58% loss of the membrane expression. Repeated treatment early after the tumor has reached its minimal relative volume should thus be efficient and improve the overall efficacy of AES RIT.

  18. Distribution of human hepatoma-specific antibody-directed immunonanoparticles in tumor-bearing nude mice%抗人肝癌抗体导向的载药毫微粒在荷瘤裸鼠体内的分布

    Institute of Scientific and Technical Information of China (English)

    肖笑荣; 刘晓波; 胡质毅; 蔡美英; 张萃

    2012-01-01

    目的 观察抗体导向免疫毫微粒在荷瘤裸鼠体内的分布.方法 采用氯胺T法将131I核素标记到人肝癌特异性抗体HAb18导向的阿霉素白蛋白免疫毫微粒;于皮下荷人肝癌SMMC-7721裸鼠模型体内,分别经尾静脉、腹腔或瘤体注射131I标记的免疫毫微粒,一定时间后处死裸鼠,取肿瘤、血、心、肝等组织,计算免疫毫微粒在各组织中的分布量.结果 经腹腔或尾静脉给药,免疫毫微粒主要分布于肝、脾等处,而在异位肿瘤处分布很少;经瘤体给药,免疫毫微粒主要分布于肿瘤处,在其他部位分布极少;比较肝癌特异性抗体免疫毫微粒、对照抗体免疫毫微粒及普通毫微粒在肿瘤中的分布,第12天后,肝癌特异性抗体免疫毫微粒的肿瘤滞留量明显高于其他两种毫微粒.结论 抗体导向的载药免疫毫微粒经腹腔、尾静脉给药无主动靶向结合异位肿瘤作用;但经瘤体给药能较好地滞留在肿瘤中.%Objective To observe the in vivo distribution of antibody-directed immunonanoparticles in tumor-bearing nude mice and then determine the optimal in vivo administered route of the immunonanoparticles . Methods Ammonia chroloric T technique was used for coupling radioisotope I to adrimycin-loaded human serum albumin immunonanoparticles linked with human hepatoma specific antibody HAb 18. The nude mice bearing human hepatoma xenograft subcutaneously were administered with labeled immunonanoparticles by tail vein , peritoneal cavity or intratumor route. The mice were sacrificed at the appointed time , their tumors , bloods , hearts etc. were weighted and then the distributive amounts of the labeled immunonanoparticles in these tissues were calculated . Results Following administration by tail vein or peritoneal cavity route , immunonanoparticles mainly concentrated in liver, spleen, etc, but few in the tumor xenografts. However, following administration by intratumor route , immunonanoparticles

  19. Inhibition of conventional chemotherapy combined with metronomic chemotherapy on breast cancer xenografts in nude mice%常规化疗联合节拍化疗对乳腺癌裸鼠移植瘤的实验研究

    Institute of Scientific and Technical Information of China (English)

    刘星; 陈伶; 史莉莉; 李丽

    2011-01-01

    microenvironment. It has been reported that metronomic chemotherapy enjoys obvious advantages in improving tumor microenvironment. The purpose of this study was to compare the antitumor effects in nude mice with human breast cancer with different cyclophosphamide chemotherapy regimens and to observe two balances: between pro-angiogenesis and anti-angiogenesis and between tumor cell proliferation and apoptosis. Methods: Breast ortho-topic transplantation tumor model was established. Twenty nude mice bearing carcinoma were divided into 4 groups randomly: metronomic chemotherapy group (LDM), conventional chemotherapy group (MTD), combination group (LDM+MTD) and control group. The general condition of mice was observed and the mice were weighed every other day, at the same time the volume of subcutaneous tumor was measured. WBC was counted every week. In the end, tumors were taken off and weighed to calculate inhibitory rates of each group. Immunohistochemistry was used to detect the tumor microvessel density (MVD), and the expressions of VEGF, TSP-1 and PCNA. TUNEL was used to detectthe apoptosis of the tumor cells. Results: All nude mice were in good condition throughout the trial period without significant side effects. Three chemotherapy regimens could inhibit the growth of xenografts in different degrees, whose inhibitory rates were 32.95%, 41.75% and 69.15%, respectively. LDM and MTD had similar tumor growth curve, while the xenografts in combination group appeared to grow significantly slower than the other groups. In the combination group and LDM group, xenografts expressed lower level VEGF and MVD and higher level TSP-1 than those in the other groups (P0.05). There was lower expression of PCNA in the combination group and MTD group than those in the LDM and control groups (P0.05). The apoptosis index (AI) in three chemotherapy groups had statically significant difference with control group (P<0.05). Furthermore, the AI in the combination group was the highest. Conclusion

  20. 骨膜蛋白在子宫内膜癌的肿瘤干细胞中裸鼠成瘤性的实验研究%Experimental study of periostin in the tumorigenesis of endometrial cancer stem cell for nude mice

    Institute of Scientific and Technical Information of China (English)

    柯毓敏; 周云清; 吴珠娜

    2015-01-01

    Objective To investigate the test of periostin in the tumori-genesis of endometrial cancer stem cell for nude mice. Methods Through immunomagnetic beads technique, periostin was extracted.Thir-ty nude mice adopted the subcutaneous injection of periostin+cells and periostin-cells in the left and right armpit.Flow cytometry was used to make a count of periostin cells.The ratio of periostin +cell was observed. Results The 35.7%(5/14) of nude mice had the periostin expression in the cytoplasm while periostin was not positively expressed in the nor-mal endometrial tissue.The tumor weight, volume and positive expre-ssion of periostin for nude mice with injection of positive periostin cells was significantly higher than that of injection of negative periostin cells (P<0.05).Conclusion For nude mice, periostin+is featured as tu-morigenesis while periostin -will not generate the tumor.%目的:探讨骨膜蛋白在子宫内膜癌的肿瘤干细胞中裸鼠成瘤特性。方法用免疫磁珠技术分离出骨膜蛋白,分别在30只裸鼠的左、右腋背部,皮下注射骨膜蛋白阳性细胞、骨膜蛋白阴性细胞,用流式细胞仪检测后进行计数,观察其中骨膜蛋白阳性细胞的比例。结果在35.7%(5/14)裸鼠胞浆内有骨膜蛋白表达,在正常子宫内膜组织中未见阳性表达;注射骨膜蛋白阳性细胞裸鼠的肿块重量、体积及瘤体骨膜蛋白阳性表达显著高于注射骨膜蛋白阴性细胞的裸鼠( P<0.05)。结论骨膜蛋白阳性的子宫内膜癌细胞在裸鼠体内具有成瘤性,而骨膜蛋白阴性细胞不具有成瘤性。

  1. The thymus reconstituted nude rat

    DEFF Research Database (Denmark)

    Hougen, H P; Klausen, B

    1987-01-01

    The monoclonal antibodies OX6, OX19, W3/13, OX7, OX8, and W3/25 were used to gain information about the distribution of different lymphocyte subpopulations in peripheral lymphoid organs of neonatally isogeneic and allogeneic thymus reconstituted nude rats. Splenic mitogen responsiveness, xenogene...... cell response is far better following isografting. We, therefore, conclude that isogeneic thymus grafting is an easy method of reconstituting the nude rat immunologically....

  2. A-NK 细胞对舌鳞癌裸鼠皮下移植瘤抑制作用的实验研究%The effects of A-NK cells on tumor growth of human tongue squamous cell carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    祝军; 刘红; 张真; 刁晓洁

    2014-01-01

    Objective:To explore the treatment effect of A-NK cells on the subcutaneously transplanted tumor of tongue squamous cell carcinoma in nude mice.Methods:Tca8113-Tb cells were subcutaneously transplanted into nude mice,14 tumor bearing mice were randomly assigned to 2 groups(n =7).The mice in control group were injected with normal saline,those in the experimental group were injected with A-NK cells.All animals were killed 33 days after tumor cell transplantation,The tumor volume and weight of the mice were measured and compared.Results:A-NK cells significantly inhibited tumor growth in nude mice in terms of the volume (P <0.05).After 15 -33 d of treatment the tumor weight(g)in the treated and control mice were 0.96 ±0.38 and 3.74 ±1.22 re-spectively(P <0.05).Conclusion:A-NK cells can inhibit the growth of Tca8113-Tb cell induced tumor in nude mice.%目的:探讨 A-NK 细胞治疗裸鼠舌鳞癌移植瘤的效果。方法:分离培养人 A-NK 细胞;建立舌鳞癌 Tca8113-Tb 细胞皮下移植瘤模型,随机分为2组(n =7)对照组裸鼠瘤旁注射生理盐水,实验组裸鼠瘤旁注射 A-NK 细胞,观察33 d 后,处死裸鼠,剥离移植瘤,称瘤重,绘制肿瘤生长曲线。结果:治疗15~33 d 时实验组肿瘤体积均小于对照组(P <0.05),观察33 d 后,实验组和对照组瘤重(g)分别是为0.96±0.38和3.74±1.22(P <0.05)。结论:A-NK 细胞在裸鼠体内具有抗肿瘤效应。

  3. Inhibitory effect of apigenin on the growth of human prostate cancer PC-3 cells transplanted tumor in nude mice%芹菜素对人前列腺癌裸鼠移植瘤的抑制作用

    Institute of Scientific and Technical Information of China (English)

    李卫林; 南存金; 王怡君; 木海琦; 杨森; 李峰; 陈映鹤

    2011-01-01

    目的 观察芹菜素对人前列腺癌PC-3细胞裸鼠移植瘤生长的影响.方法 通过皮下种植PC-3细胞建立人前列腺癌裸鼠移植瘤模型,成瘤后随机分为4组,对照组[二甲基亚砜(DMSO)+生理盐水(NS),0.2 ml/d]、芹菜素低剂量组(每天12.5 mg/kg)、芹菜素中剂量组(每天25mg/kg)、芹菜素高剂量组(每天50 mg/kg),每组6只,每日腹腔注射1次,共28次.通过测量移植瘤体积变化绘制生长曲线,根据终末瘤重比较计算抑瘤率.透射电镜观察组织细胞的超微结构变化.结果 根据不同组的体积变化,芹菜素中、高剂量组可抑制移植瘤的生长,与对照组和低剂量组比较,差异有统计学意义(P<0.05),但芹菜素低剂量组与对照组比较,移植瘤的生长无明显受抑制,差异无统计学意义(P>0.05).中剂量组终末瘤重(1.44±0.50)g,抑瘤率46.7%和高剂量组终末瘤重(0.46±0.17)g,抑瘤率83.0%,低于对照组终末瘤重(2.70±0.52)g,抑瘤率0.0%和低剂量组终未瘤重(2.68±0.41)g,抑瘤率0.7%,差异有统计学意义(P<0.05).但芹菜素低剂量组与对照组移植瘤的终末瘤重和抑瘤率比较,差异无统计学意义(P>0.05).透射电镜观察结果显示中、高剂量组的肿瘤细胞体积变小,细胞核固缩,染色质浓缩、边集,内质网水肿、空泡化,局部的细胞器溶解等凋亡和胀亡的细胞形态表现,而对照组和芹菜素低剂量组基本无此改变.结论 芹菜素中、高剂量组对裸鼠前列腺癌移植瘤的生长有抑制作用,其机制可能是通过凋亡和胀亡的形式使肿瘤细胞死亡从而起到抑制人前列腺癌裸鼠移植瘤的生长作用.%Objective To observe the effect of alcgenin on the growth of human prostate cancer PC-3 cells transplanted tumor in nude mice.Methods Human prostate cancer PC-3 cells cultured in vitro were subcutaneously inoculated into nude mice to establish transplanted tumor model.All tumor-bearing mice were randomly

  4. SphK1及其抑制剂对人胃癌裸鼠移植瘤的作用%Role of SphK1 in the growth of human gastric cancer xenograft in nude mice

    Institute of Scientific and Technical Information of China (English)

    苗怡然; 黄广清; 蔡红星; 王云; 单海霞; 朱正秋

    2013-01-01

    Objective To investigate the role of SphK 1 in the growth of human gastric cancer xenograft in nude mice and to explore its mechanism. Methods Human gastric cancer cells SGC -7901 were cultured in RPMI 1640 medium to exponential phase of growth and then transplanted under the skin of BALB /c nude mice to develop the tumor model of hu -man gastric cancer. After the model was successfully developed , 38 mice were randomly divided into four groups : normal saline (NS) control group, cisplantin (DDP) group, SKI - Ⅱ group, and SKI - Ⅱ combined with DDP group. All rats were given intraperitoneal injection of drugs on seven days for 3 times. The tumor mass volume was observed every 3 days and inhibition rate of tumor growth was also calculated . All nude mice in each group were killed at the 7th day after the injection of drugs and tumor were dislodged. Immunohistochemistry staining was used to detect the protein expression of SphKl, Bax and Bel - 2. The apoptosis of tumor was measured by terminal dUTP nick - end labeling ( TUNEL). Results The tumor model of human gastric cancer was successfully developed . SphKl and Bcl - 2 protein expression in SKI - Ⅱ combined with DDP group significantly decreased (P < 0.05 ). Compared with DDP group and SKI - Ⅱ group, Bax protein expression in SKI - Ⅱ combined with DDP group significantly increased (P < 0.05 ). As a result, SKI - Ⅱ combined with DDP could raise the rate of apoptosis and inhibit the growth of tumor model of human gastric cancer . Conclusion Sphkl can promote tumor cell proliferation through down -regulating the ratio of Bax/Bcl -2. SKI - Ⅱ has synergistic anti - tumor effect of cisplatin.%目的 研究鞘氨醇激酶-1(sphingosine kinase-1,SphK1)及其抑制剂在人胃癌裸鼠移植瘤生长中的作用,并探讨其作用机制.方法 对数生长期SGC7901细胞注射于裸鼠皮下建立人胃癌裸鼠移植瘤模型,建模成功后将裸鼠随机分为4组(每组8只),分别用生理盐水、SKI-

  5. Antitumor Mechanism Preliminary Studied by Proteome on Feiyanning Granule against Lung Cancer in Nude Mice%肺岩宁冲剂抗肺癌机制的初步探讨

    Institute of Scientific and Technical Information of China (English)

    王菊勇; 郑展; 王青; 郭净; 陈灵

    2011-01-01

    目的 研究肺岩宁冲剂治疗后裸鼠人肺癌细胞移植瘤组织的差异蛋白表达谱,初步探讨肺岩宁冲剂抗肺癌的分子机制.方法 将人肺癌细胞H460经皮下移植的荷瘤裸鼠16只随机分为两组,空白对照组(8只):灌服0.9%氯化钠溶液0.4ml×14天;肺岩宁冲剂组(8只):灌胃肺岩宁冲剂药液0.4 ml(含生药0.6 g)×14天.两组灌胃后第15天取移植瘤组织,提取细胞总蛋白,通过双向电泳分离、质谱分析和数据库检索鉴定蛋白表达谱的变化.结果 蛋白质组学分析结果显示,空白对照组裸鼠肿瘤组织细胞的蛋白组学有918个蛋白质点.肺岩宁冲剂组有970个蛋白质点,与空白对照组比较,有18个差异蛋白质点,其中表达上调的有9个,表达下调的有9个;按照功能可分为细胞周期相关蛋白、代谢相关蛋白、细胞信号转导分子、转录调控因子等.结论 肺岩宁冲剂可导致肿瘤组织蛋白质表达变化.%Objective To investigate the molecular mechanism at proteomic level of Fei-Yan-Ning Granule in nude mice with transplanted human lung carcinoma.Methods Nude mice with transplanted human lung carcinoma cell line H460 were randomly divided into control group and Feiyanning Granule treated group (FYN group).The total protein was isolated from carcinoma tissue of groups,and the changes of proteins expression profile of tumor tissues were evaluated by two-dimensional electrophoresis matrix-assisted laser desorption ionization-time of flight mass spectrometry and tandem mass spectrometry.Results As compared with the control group, eighteen differentially expressed proteins were identified unambiguously, among which 9 proteins were significantly up-regulated and 9 proteins were down-regulated, involving multiple scopes such as cell cycle, signal transduction, energy metabolism, protein synthesis,and cell receptors.Conclusion The antitumor effect of Feiyanning granule is multi-targeted, which elucidates part of the

  6. Preferential colonization of metastases by oncolytic vaccinia virus strain GLV-1h68 in a human PC-3 prostate cancer model in nude mice.

    Directory of Open Access Journals (Sweden)

    Ulrike Donat

    Full Text Available Recently, we showed that the oncolytic vaccinia virus GLV-1h68 has a significant therapeutic potential in treating lymph node metastases of human PC-3 prostate carcinoma in tumor xenografts. In this study, underlying mechanisms of the virus-mediated metastases reduction were analyzed. Immunohistochemistry demonstrated that virus-treatment resulted in a drastically decrease of blood and lymph vessels, representing essential routes for PC-3 cell migration, in both tumors and metastases. Thus, GLV-1h68 drastically reduced essential routes for the metastatic spread of PC-3 cells. Furthermore, analysis of viral distribution in GLV-1h68-injected tumor-bearing mice by plaque assays, revealed significantly higher virus titers in metastases compared to solid tumors. To elucidate conditions potentially mediating the preferential viral colonization and eradication of metastases, microenvironmental components of uninfected tumors and metastases were compared by microscopic studies. These analyses revealed that PC-3 lymph node metastases showed increased vascular permeability, higher proliferation status of tumor cells as determined by BrdU- and Ki-67 assays and lesser necrosis of PC-3 cells than solid tumors. Moreover, an increased number of immune cells (MHCII(+/CD68(+ macrophages, MHCII(+/CD19(+ B lymphocytes combined with an up-regulated expression of pro-inflammatory cytokines was observed in metastases in comparison to primary PC-3 tumors. We propose that these microenvironmental components mediated the metastatic tropism of GLV-1h68. Therefore, vaccinia virus-based oncolytic virotherapy might offer a novel treatment of metastatic prostate carcinomas in humans.

  7. Tissue distribution and cancer growth inhibition of magnetic lipoplex-delivered type 1 insulin-like growth factor receptor shRNA in nude mice

    Institute of Scientific and Technical Information of China (English)

    Minjian Kong; Xuebiao Li; Chunmao Wang; Chao Ding; Aiqiang Dong; Qunjun Duan; Zhonghua Shen

    2012-01-01

    The targeted delivery of therapeutic genes into specific tissues,as well as the determination of the biological fate and potential toxicity of nanoparticles,remains a highly relevant challenge for gene-based therapies.Type 1 insulin-like growth factor receptor (IGF-1R),an important oncogene,is frequently over-expressed in lung cancer and mediates cancer cell proliferation as well as tumor growth.In our previous studies,we have successfully applied gene delivery mediated by commercially available nanoparticles (CombiMAG) under a magnetic field,which suppresses IGF-1R expression in a non-small cell lung cancer cell line (A549) in vitro.In the present study,we aimed to investigate the biological distribution and target tumor suppression of magnetofection,as well as its potential toxicity via CombiMAG-carrying plasmids expressing green fluorescent protein (GFP) and short hairpin RNAs (shRNAs) targeting IGF-1R (pGFPshIGF-1Rs) in tumor-bearing mice.The peak expression in various organs appeared 48 h after transfection.Transgene expression via magnetofection was 3-fold improvement than via lipofection.On the 30th day after injection,the tumor size and weight of the CombiMAG-treated group (789.32 ± 39.43 mm3,105.5 ±6.1 mg) were significantly decreased compared with those of the lipofection group (893.83 ± 31.23 mm3,164.5 ±9.1 mg;P< 0.05),and the suppression rate was ~36%.After a 30-day observation,the injection of CombiMAG did not cause any apparent toxicity.Therefore,IGF-1R shRNA nanoparticles can be valuable and safe delivery agents for RNA interference therapy to tumors in vivo.

  8. 不同细胞促进脂肪移植存活的实验研究%Effects of different human adipose-derived cells in promoting human adipose tissue engraftment in nude mice

    Institute of Scientific and Technical Information of China (English)

    朱茗; 鲁峰; 高建华; 廖云君

    2012-01-01

    目的 探讨应用自人脂肪组织来源的不同细胞辅助脂肪移植,寻找促进移植物存活率的最佳种子细胞的有效方法,为干细胞进一步运用于临床提供实验依据.方法 从临床抽脂病人获取脂肪组织并提炼细胞,将0.3 ml待移植的脂肪颗粒分别与以下细胞进行混合处理:(1)低氧脂肪来源间充质干细胞(A组);(2)脂肪来源间充质干细胞(B组);(3)血管基质层细胞(SVFs)(C组);(4)加完全培养基的单纯脂肪颗粒为对照组(D组)脂肪颗粒与相应细胞混合后,注射移植于6只裸鼠背部皮下.术后3个月观察移植物情况,通过组织学、HE染色等方法进行分析.结果 A~D组湿重分别为(61.67±8.165)、(91.67±1.472)、(96.67±5.164)和(40.83±4.916)mg,A、B、C组脂肪存活率均高于D组(P<0.05),B、C两组之间比较差异无统计学意义(P>0.05)且都高于A组.A、B、C组血管密度均高于组D,且C组明显高于其他3组(P<0.05).A、B、C组存活脂肪细胞计数均高于D组,且B、C组最高(P<0.05),纤维组织计数均低于D组(P<0.05).结论 来源于人自体干细胞复合脂肪颗粒能够显著提高移植脂肪组织的成活率,其中血管基质层细胞及脂肪来源间充质干细胞移植脂肪的存活率最高.%Objective To explore the optimal seed cells derived from human adipose tissue for promoting the engraftment of transplanted adipose tissue in nude mice. Methods Human adipose tissue granules (0.3 ml) obtained from patients undergoing liposuction were mixed with hypoxic adipose-derived stem cells (ADCs, group A), ADCs (Group B), stromal vascular fraction (SVF) cells (group C), or pure adipose tissue granules in complete culture medium particles (group D). The mixtures were injected subcutaneously on the back of 6 nude mice, and the transplanted adipose tissues were harvested 3 months later to examine the engraftment using histological method and HE staining. Results The wet weights of the adipose

  9. 99Tcm标记Gd-DTPA-DG及其在裸鼠体内的生物分布%Radio-labeling of Gd-DTPA-DG with 99Tcm and its biodistribution in nude mice

    Institute of Scientific and Technical Information of China (English)

    黄占文; 张伟; 陈跃

    2011-01-01

    Objective To observe the stability and biodistribution of 99 Tcm radio-labeled a paramagnetic deoxy-glucose-type MR contrast agent diethylenetriamine pentaacetic acid-gadolinium salt deoxy-glucose(Gd-DTPA-DG) in tumor-bearing nude mice in vivo. Methods To form 99 Tcm-Gd-DTPA-DG , the labelling conditions such as Gd-DTPA-DG quality, SnCl2 · 2 H2 O dosage , the reaction medium pH value and reaction temperature were optimized by orthogonal experimental design. The radio-labeling efficiency was measured by thin layer chromatography(TLC). The bio-distribution was observed by the tumor and other major organs were taken out from nude mice at 10,30 min and 1, 2,4 , 24 h respectively after caudal vein injection of 99 Tcm-Gd-DTPA-DG. Results When taking 10 mg Gd-DTPA-DG,0. 6 mg SnCl2 · 2H2O,pH<2,adding 37 MBq Na99 TcmO4 ,then reacting in boiling water for 30 min, the radiochemical purity of 99Tcm-Gd-DTPA-DG can reach to 98. 5% and remain 96. 2% placed at room temperature for 6 h. 99TcmGd-DTPA-DG accumulated in the tumor to a higher level than other organ at 2 h,the uptake was about (1. 48±0. 12) %ID/g , and the radio-uptake ratio of tumor to muscle(T/NT)was reached 2. 91. Conclusion 99 Tcm labeled the paramagnetic MR contrast agent Gd-DTPA-DG is feasible. The labeled agent shows excellent tumor targeting in nude mice in vivo. 99 Tcm-Gd-DTPA-DG is potential for a SPECT(single photon emission computed tomography)-MRI dual-modality imaging probes.%目的 探讨锝(99Tcm)标记顺磁性脱氧葡萄糖类MRI对比剂二乙三胺五乙酸-脱氧葡萄糖钆盐(Gd-DTPA-DG)的稳定性及在荷瘤裸鼠体内的生物分布,寻找一种核素与磁共振双模式影像探针.方法 对 Gd-DTPA-DG进行99Tcm标记,并对需要的Gd-DTPA-DG、氯化亚锡(SnCl2·2H2O)用量,pH,温度采用正交实验设计,确定最佳标记条件.采用薄层纸层析法(TLC)分析标记率,体外放置6 h,观察标记物的稳定性.将标记的99Tcm -Gd-DTPA-DG注入裸鼠体内,10、30

  10. 丙戊酸抗裸鼠Kasumi-1细胞移植瘤血管新生的作用研究%Effect of Valproic Acid against Angiogenesis of Kasumi-1 Xenograft Tumor in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    王丽红; 张志华; 赵蕾; 朱翠敏; 赵立双; 郝长来

    2013-01-01

    This study was aimed to investigate the effect of valproic acid( VPA), a histone deacetylase inhibitor, on angiogenesis of acute myeloid leukemia in vivo and vitro, and to explore its molecular mechanism. Human t( 8 ;21) AML cell line Kasumi-1 cells were treated with VPA at different concentration for 3 d, the mRNA and protein expression levels of Angl and Angl were determined by semi-quantitative RT-PCR and Western blot respectively. Nude mice model with xenograft Kasumi-1 tumor was established by subcutaneous inoculation of Kasumi-1 cells. The CD34, Angl and Ang2 protein levels were analyzed by immunohistochemistry method. The mRNA and protein expression levels of Angl, Angl and VEGF were determined by semi-quantitative RT-PCR and Western blot. The results showed that in vitro, VPA at 3 mmol/L downregulated the Ang mRNA relative expression level for Angl from 0.360 ±0.116 to 0.040 ± 0.008, Ang2 from 0.540 ±0.049 to 0.146 ± 0.038. The animal experiment further verified that VPA 500 mg/kg, ip, for 14 d, reduced the relative expression of Angl, Ang2 and VEGF mRNA and proteins in Kasumi-1 tumor of nude mice, and reduced microvascullar density in xenograft tumor of nude mice (8.470 ±0.300 vs 2.600 ±0.200). It is concluded that VPA significantly inhibits tumor angiogenesis through the regulation of angiopoietins, thereby inhibits the proliferation and metastasis of leukemia cells.%本研究旨在探讨组蛋白去乙酰化酶抑制剂丙戊酸(VPA)体内、体外抑制急性髓系白血病血管新生及其作用机制.用不同浓度的VPA处理人t(8;21)急性白血病细胞株Kasumi-1细胞3d后用RT-PCR及Western blot分析细胞Ang1、Ang2 mRNA及蛋白水平的变化;建立Kasumi-1细胞裸鼠移植瘤模型,采用RT-PCR、Western blot的方法分析对照组和VPA治疗组瘤组织Ang1、Ang2、VEGF mRNA及蛋白水平的变化,免疫组织化学的方法分析瘤组织CD34及Ang1、Ang2蛋白水平的改变.结果表明,VPA 1-3 mmol/L处理3d

  11. 二甲双胍联合顺铂对人肺癌裸鼠移植瘤治疗作用的研究%Effects of metformin and cisplatin on human lung cancer xenograft in nude mice

    Institute of Scientific and Technical Information of China (English)

    陈玉琴; 陈刚

    2015-01-01

    Objective This study is designed to evaluate the effects of metformin combined with cisplatin on tumor growth,expressions of Survivin,matrix metalloproteinase-2 (MMP-2),and Ki67 in lung cancer xenograft on nude mice,to potentially develop new effective drugs for the treatment of lung caner.Methods Human lung cancer xenograft study model was established.The nude mice were randomly divided into metformin-treated group,cisplatin-treated group,metformin combined with cisplatin-treated group and control group.Forty-two days after administration,all the nude mice were sacrificed and tumor tissues were sampled.The expressions of Survivin,MMP-2,and Ki67 proteins in the tumor tissues were detected by immumohistochemical method.The expressions of Survivin,MMP-2,and Ki67 mRNA in the tumor tissue were detected by florescent real-time quantitative PCR.Results The tumor inhibition rate in metformin-treated group,cisplatin-treated group,and metformin combined with cisplatin-treated group was 28.97%,35.34%,and 54.65%,respectively.The expressions of Survivin,MMP-2,and Ki67 protein and mRNA in cisplatin-treated group and metformin combined with cisplatintreated group were lower than those in control group (all P <0.05).Compared with control group,the expressions of MMP-2 protein and mRNA in metformin-treated group were reduced (all P < 0.05).Compared with metformin-treated group and cisplatin-treated group,the expressions of Survivin,MMP-2,and Ki67 protein and mRNA in metformin combined with cisplatin-treated group were reduced (all P < 0.05).Conclusions Metformin could inhibit MMP-2 expression.Cisplatin or metformin combined with cisplatin can inhibit the expressions of Survivin,MMP-2,and Ki67.Combination drug of metformin and cisplatin can enhance the anti-tumor efficacy.%目的 研究二甲双胍联合常用的化疗药物顺铂对于人肺癌裸鼠移植瘤的抑瘤作用及对生存素(Survivin)、基质金属蛋白酶2(MMP-2)和Ki67分子表达的影响,致力于

  12. Impact of exogenous growth hormone on GH/IGF/IGFBP axis in colon cancer-bearing nude mice%生长激素荷人结肠癌裸鼠GH/IGF-I/IGFBP-3轴的影响

    Institute of Scientific and Technical Information of China (English)

    张毅; 梁道明; 李思齐; 袁勇; 赵辉; 陈嘉勇

    2013-01-01

    目的:探讨外源性生长激素(GH)对荷瘤裸鼠GH/胰岛素样生长因子(IGF)/胰岛素样生长因子结合蛋白3(IGFBP-3)轴的影响.方法:采用人结肠癌细胞株(HCT116)建立人结肠癌细胞裸鼠移植瘤模型.取48只荷瘤裸鼠随机均分为生理盐水处理组(NS组)、氟尿嘧啶处理组(FU组)、GH处理组(GH组),FU+GH处理组(FU+GH组).每组连续给药6d,在给药结束后24,72 h分别处死每组6只动物,取血及移植瘤标本,应用ELISA法检测血清GH,IGF-I,IGFBP-3含量和RT-PCR法检测移植瘤IGF-I,IGF-I受体(IGF-IR),IGFBP-3的mRNA表达.结果:ELISA结果显示,给药结束后24 h,GH组和FU+GH组血清GH,IGF-I,IGFBP-3含量较NS组与FU组明显升高(均P<0.05);给药结束后72 h,各组GH,IGF-I的水平无统计学差异(均P>0.05),但GH组和FU+GH组IGFBP-3水平仍高于NS组和FU组(均P<0.05).RT-PCR结果显示,给药结束后24 h,GH,FU,FU+GH组移植瘤组织IGF-I mRNA与IGF-IR mRNA的表达较NS组明显降低,而IGFBP-3 mRNA表达明显增加;给药结束后72 h,IGF-I mRNA与IGF-IR mRNA表达各组间无差别,但GH组,FU组和FU+GH组IGFBP-3 mRNA表达量仍明显高于NS组.结论:短期应用外源性GH所致GH/IGF/IGFBP-3轴的变化对人结肠癌移植瘤生长无促进作用.%Objective: To observe the impact of exogenous growth hormone (GH) on the axis of GH/insulin-like growth factor I (IGF-I)/insulin-like growth factor binding protein (GFBP) in colon cancer-bearing nude mice. Methods: Nude mice xenograft models of human colon cancer were established by using human colon cancer HCT116 cells. Subsequently, 48 tumor-bearing mice were equally randomized into normal saline treatment group (NS group), fluorouracil treatment group (FU group), GH treatment group (GH group) and FU plus GH treatment group (FU+GH group), and all treatment regimens were continued for 6 days. Mice were sacrificed to collect the blood and tumor xenograft samples at 24 and 72 h after the termination of regimens with 6

  13. 黄芩苷对高致瘤HL-60细胞裸鼠移植瘤模型的体内抑瘤作用和机制探讨%Effects of Baicalin on HL-60 Cell Xenografts in Nude Mice and Its Mechanism

    Institute of Scientific and Technical Information of China (English)

    郑静; 胡建达; 黄毅; 陈英玉; 李静; 陈步远

    2012-01-01

    This study was aimed to investigate the effects of baicalin on HL-60 cell xenografts in nude mice in vivo and explore its mechanism. Xenograft tumor model of HL-60 cells in nude mice was established, which was divided randomly into 6 groups: negative control group (injection of 5% NaHCO3), 25,50 and 100 mg/kg baicalin groups, combination group (50 mg/kg baicalin+ 2 mg/kg VP16) and positive control group(VP16 4 mg/kg). The nude mice with HL-60 cell xenografts were treated with drugs via intraperitoneal injection daily. After treatment for 14 days average weigh and inhibitory rate of transplanted tumor stripped from 5 nude mice in each group were calculated, and the ultrastructure change of xenografts cells were tested by transmission electron microscopy. Histopathologic examination was used to observed the change of main organs in nude mice. The expression of signaling molecular PDK/Akt proteins extracted from xenografts was detected by Western blot. The effects of baicalin on overall survival time in nude mice with HL-60 cell xenografts were evaluated. The results showed that baicalin could inhibit the growth of transplanted tumors in dose-dependent manner. There were more necrotic and apoptotic cells in mice of baicalin-treated groups and combination group than that in mice of negative control group. Baicalin could inhibit the proliferation of HL-60 cells in vivo by down-regulating the PI3K/Akt/Mtor signal pathway, where the expressions of p-Akt, Mtor and p-Mtor proteins decreased compared with negative control group, and no significant difference of Akt expression was found between different groups. Compared with negative control group, the median survival time of mice in combination group was more prolongated (P <0.05). It is concluded that baicalin can inhibit growth and induce apoptosis of HL-60 cell xenografts in nude mice, and prolong median survival time of nude mice. The possible mechanisms may be related to inhibition of Akt activity and down

  14. 靶向超声微泡对结肠癌新生血管分子成像的实验研究%Molecular imaging of tumor angiogenesis with VEGFR2 targeting microbubbles in colon cancer bearing nude mice

    Institute of Scientific and Technical Information of China (English)

    位红芹; 何洁; 杨莉; 纪丽景; 张霞; 王冬晓; 文戈; 谷英士; 李颖嘉

    2013-01-01

    Objective To evaluate the effect of tumor neovascularization imaging in a nude mouse model of colon cancer by contrast ultrasound molecular imaging (UMI) of VEGF receptor 2 (kinase insert domain receptor,KDR).Methods Targeted microbubbles (MBt) were built by conjugating K237,a small peptide with high affinity for KDR,to liposome microbubbles through a biotin-avidin bridge.Control microbubbles (MBc) with control peptide were prepared by the same method.Nude mice models of LS174T human colon cancer were established.MBt and MBc were injected intravenously in twelve mice in random order with an interval of 30 min.MBt were injected in another six mice after K237-peptide blocking.UMI was performed in all mice at 5 min postinjection to observe the imaging difference and measure the video intensity (Ⅵ) of tumor tissues in different groups.One-way analysis of variance and the least significant difference t test were performed to analyze the difference of tumor VI in the groups with MBt,MBc and K237 blocking.Immunohistochemistry was applied to detect the expression and distribution of KDR in tumor tissue and adjacent tumor tissues.Results K237 peptide was successfully conjugated to the surface of microbubbles through biotin-avidin mediation.Ultrasound imaging signal of the tumor was high in the MBt group,while there were no significant enhancement in the groups of K237 blocking and MBc.The VI in MBt,MBc and K237 blocking groups was significantly different (F =39.130,P < 0.01).There was a significant difference of VI in the MBt group compared to the MBc group (30.18 ± 9.56 vs 8.28 ± 4.74,t =6.91,P <0.01).In the K237 blocking group Ⅵ was significantly lower than that in the MBt group (9.23 ± 3.44 vs 30.18 ± 9.56,t =4.91,P < 0.01).Immunohistochemistry results showed that KDR was highy expressed in tumor tissue.Conclusions KDR-targeting liposome contrast microbubbles may specifically and efficiently link to tumor vascular endothelial cells in vivo.Thus it may be

  15. Experimental study on effect of recombinant human growth hormone combined with chemotherapy on stomach neoplasms implanted in nude mice%重组人生长激素联合氟尿嘧啶对人胃癌裸小鼠皮下移植瘤作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    Fangfang Shi; Suyi Li

    2007-01-01

    Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neoplasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stomach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5-FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index(PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.

  16. 抗VEGFR-2嵌合Fab抗体对裸鼠肝癌原位移植瘤的治疗作用%Therapeutical effect of chimeric anti-VEGFR-2 Fab antibody on orthotopic xenograft of hepatocellular carcinoma in BALB/c nude mice

    Institute of Scientific and Technical Information of China (English)

    李倩君; 潘峰; 王丙剑; 朱进; 张建民; 吴亚夫; 周传文

    2013-01-01

    目的 检测抗血管内皮生长因子受体2 (VEGFR-2)嵌合Fab抗体对裸鼠肝癌原位移植瘤的治疗作用.方法 40只4周龄雄性BALB/c裸鼠建立肝癌H22细胞移植瘤模型后随机均分为Fab抗体(A)组和生理盐水对照(B)组.比较两组裸鼠生存时间、移植瘤病理变化及微血管密度(MVD).结果 成功建立裸鼠H22肝癌原位移植瘤模型,HE染色显示肝细胞肝癌.A组裸鼠中位数生存时间明显长于B组(20.0 d vs.14.0 d)(P<0.01);A组肝脏实体瘤内MVD较B组显著减少(8.65±1.79 vs.25.64±1.53)(P<0.05).结论 抗VEGFR-2嵌合Fab抗体对裸鼠肝癌原位移植瘤有治疗作用.%Objective To investigate the therapeutical effect of chimeric anti-vascular endothelial growth factor receptor(VEGFR)-2 Fab antibody on orthotopic xenograft in BALB/c nude mice. Methods The orthotopic xenograft model of hepatocellular carcinoma H22 cells was established in 40 nude mice, which were equally randomized into two groups of A (treated with chimeric anti-VEGFR-2 Fab antibody) and B(treated with normal saline). The survival time, pathological changes and microvessel density(MVD) in H22 xenografts were compared between two groups. Results An orthotopic xenograft model of hepatocellular carcinoma was successfully created in nude mice, which was confermed as hepatocellular carcinoma by hematoxylin-eosin staining. The mean survival time was longer in group A than that in group B(20. 0 d vs. 14. 0 d) (P<0. 05). MVD in the xenografts was less in group A than that in group B(8. 65±1. 79 vs. 25. 64±1. 53) (P<0. 05). Conclusion The chimeric anti-VEGFR-2 Fab antibody has some therapeutical effect on an orthotopic xenografts in nude mice.

  17. Effects of shRNA targeted inhibition of Midkine expression on the tumorigenic ability of MDA-MB-231 cells in nude mice%shRNA靶向抑制MK表达对MDA-MB-231细胞裸鼠体内成瘤能力的影响

    Institute of Scientific and Technical Information of China (English)

    韩正杰; 张鹏; 孙卓; 巩玉森; 刘慧; 王庆苓

    2016-01-01

    目的:探讨中期因子(Midkine,MK)基因表达对人乳腺癌MDA-MB-231细胞株裸鼠体内成瘤性的影响。方法将转染pSilencer-3.1-H1-MK(MK KD组)和pSilencer-3.1-H1-NC(NC组)质粒的乳腺癌细胞分别接种于雌性BALB/c裸鼠右侧前肢腋部皮下,然后于接种第7、14、21、28和35天观察测量肿瘤大小。结果与NC组相比,MK KD组裸鼠肿瘤形成时间长,并且肿瘤生长速度慢,瘤体重量轻、体积小(P<0.05)。结论抑制MDA-MB-231乳腺癌细胞MK基因的表达,可以抑制裸鼠体内成瘤能力。%Objective To investigate the effects of Midkine ( MK) expression on the tumorigenic ability of MDA -MB-231 cells in nude mice.Methods Plasmids pSilencer -3.1-H1-MK (Group MK KD) and pSilencer-3.1-H1-NC ( Group NC) were transfected into MDA 231 cells which were then inoculated in the right side of female BALB /c nude mice.The tumor size was measured on Days 7, 14, 21, 28 and 35.Results Compared with Group NC, nude mice in Group MK KD showed longer time to develop tumor , with a slower rate of tumor growth , lower tumor volume and weight (P<0.05).Conclusion The inhibition of MK gene expression in MDA -MB-231 cells can inhibit the growth of tumor in nude mice .

  18. Inhibitory effects of thymoquinone on human pancreatic carcinoma orthotopically implanted in nude mice%百里醌抑制胰腺癌裸鼠原位移植瘤生长的实验观察

    Institute of Scientific and Technical Information of China (English)

    王咏梅

    2011-01-01

    Objective To explore the anti-neoplastic and anti-metastatic effects of thymoquinone on the model of human pancreatic carcinoma established by surgical orthotopic implantation (SOI) in nude mice.Methods After a 3-week implantation,40 mice were randomized into 4 groups:control group,feed with 1% ethanol; low-dose thymoquinone group (L-TQ 5 mg/kg BW daily by i.g.),high-dose thymoquinone group ( H-TQ 20 mg/kg BW daily by i.g.) and gemcitabine group ( GEM 100 mg/kg BW twice a week by i.p.) (n=10 each). All treatment sessions lasted for 2 weeks. At Week 8 post-implantation,tumor weight,inhibition rate and the presence of metastasis were evaluated respectively after sacrificing. Immunohistochemistry was used to detect the positive expressions of Ki-67,XIAP (X-linked inhibitor of apoptosis protein) and MMP-9 (matrix metalloproteinase 9) in tumors.Results Thetumor growth-inhibiting rates of L-TQ group,H-TQ group and GEM group were 42.57%,64.11% and54.77% respectively.The rates of metastasis in L-TQ group and H-TQ group were 60% and 50% versus GEM group ( 100% ).And the differences had statistical significance ( P< 0.05 ).The positive rates of Ki-67in group L-TQ and group H-TQ were 37% ±3% and 32% ±2% versus group.GEM (55% ±4% ).And the differences had statistical significance (P<0.05 ).The positive rates of XIAP in group L-TQ and group H-TQwere 30% ± 3% and 28% ± 5% versus group GEM (56% ± 4% ).And the differences had statistical significance (P<0.05).The positive rates of MMP-9 in group L-TQ and group H-TQ were 57% ± 7% and 53% ± 2% versus group GEM ( 73% ± 4% ). And the differences had statistical significance (P<0.05).Conclusion Thymoquinone has the anti-neoplastic and anti-metastatic effects on the human pancreatic carcinoma in nude mice.And the above effects may be correlated with the down-regulated expressions of XIAP and MMP-9.%目的 观察百里醌对胰腺癌裸鼠原位移植瘤生长和转移

  19. Treatment of brain glioblastoma multiforme with pcDNA3.1-Egr. 1p-p16 combined with gamma knife radiation: An experimental study on nude mice

    Directory of Open Access Journals (Sweden)

    Liu Wenke

    2013-01-01

    Full Text Available Background: High post-operative recurrence and poor prognosis are likely to be related to the infiltrative growth of the glioblastoma multiforme (GBM. Objectives: The primary objective of this study is to investigate the possible synergistic effect of the combined treatment of gamma knife radio-surgery (GKRS and gene therapy for GBM and secondary objective is to explore the role of GKRS for the temporal and spatial regulation of the gene expression. Materials and Methods: The study performed on 70 nude mice and randomly divided into seven groups. Subcutaneous injection of human GBM tumor cells (T98G was carried out to establish the animal models. Various doses of liposome-mediated pcDNA3.1-Egr. 1p-p16 recombinant plasmid were transfected through intra-tumor injection. GKRS was scheduled following the plasmid transfection. Tumor volumes were measured every 4 days after the treatment. Subcutaneous tumor nodule specimens were collected to analyze the cell apoptosis and p16 gene expression using terminal-deoxynucleoitidyl transferase mediated nick end labeling staining and reverse transcription-polymerase chain reaction. Tumor volumes, levels of cell apoptosis and p16 gene expression were compared between groups. Results: Rates of tumor growth were significantly lower in the pcDNA3.1-Egr. 1p-p16 plasmid + GKRS groups than that in the remaining groups 28 days following the GKRS management. The p16mRNA expression was noted in both of the pcDNA3.1-Egr. 1p-p16 plasmid group and the pcDNA3.1-Egr. 1p-p16 plasmid + GKRS with marginal-dose of 20 Gy group. The level of messenger ribonucleic acid expression was higher in the pcDNA3.1-Egr. 1p-p16 plasmid + GKRS with the marginal-dose of 20 Gy group, with a markedly increased apoptotic and necrotic cells, than that in the pcDNA3.1-Egr. 1p-p16 plasmid group. Conclusions: In animal studies, pcDNA3.1-Egr. 1p-p16 in combination with GKRS is a preferable management option for the GBM to the sole use of GKRS or gene

  20. 茯苓多糖对人胃癌裸鼠移植瘤的抑制效应研究%Inhibitory Effect of Pachyman on Human Gastric Cancer of Xenografts in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    林丽霞; 薛银萍; 陈燕; 梁国瑞; 熊晨

    2015-01-01

    目的:探讨茯苓多糖对人胃癌裸鼠移植瘤的抑制效应及部分作用机制。方法用体外培养的SGC-37901人胃癌细胞株制作皮下荷瘤裸鼠模型40只,随机分为5组:茯苓多糖低、中、高剂量组[予茯苓多糖400、200、100 mg/( kg·d)],环磷酰胺组[予环磷酰胺20 mg/( kg·d)],对照组(予相同体积生理盐水),每组8只。均予灌胃给药。观察各组肿瘤重量的变化并计算抑瘤率及肝、脾指数;采用免疫组化染色法研究肿瘤组织的凋亡情况以及凋亡相关基因Bax及Bcl-2表达的变化。结果与对照组比较,用药各组的瘤质量均显著降低( P0.05)。环磷酰胺组、茯苓多糖各组与对照组Bax蛋白PI比较升高明显(P0. 05 ) . PI values of Bax protein in Pachyman groups and Cyclophosphamide group were significantly in-creased compared with that in the control group (P<0. 05);PI values of Bax protein in Pachyman groups were signifi-cantly lower than that in Cyclophosphamide group (P<0. 05), and the PI values of Bax protein were increased with the increasing Pachyman concentration in Pachyman groups (P<0. 05). Conclusion Pachyman has inhibitory effect on or-thotopic transplantation tumor of gastric carcinoma in nude mice, and the mechanisms may be obtained by improving the immune system and regulating the Bcl-2/Bax protein at the same time so as to promote apoptosis of tumor cell.

  1. Rearrangement and junctional-site sequence analyses of T-cell receptor gamma genes in intestinal intraepithelial lymphocytes from murine athymic chimeras.

    Science.gov (United States)

    Whetsell, M; Mosley, R L; Whetsell, L; Schaefer, F V; Miller, K S; Klein, J R

    1991-12-01

    The molecular organization of rearranged T-cell receptor (TCR) gamma genes intraepithelial lymphocytes (IEL) was studied in athymic radiation chimeras and was compared with the organization of gamma gene rearrangements in IEL from thymus-bearing animals by polymerase chain reaction and by sequence analyses of DNA spanning the junction of the variable (V) and joining (J) genes. In both thymus-bearing mice and athymic chimeras, IEL V-J gamma-gene rearrangements occurred for V gamma 1.2, V gamma 2, and V gamma 5 but not for V gamma 3 or V gamma 4. Sequence analyses of cloned V-J polymerase chain reaction-amplified products indicated that in both thymus-bearing mice and athymic chimeras, rearrangement of V gamma 1.2 and V gamma 5 resulted in in-frame as well as out-of-frame genes, whereas nearly all V gamma 2 rearrangements were out of frame from either type of animal. V-segment nucleotide removal occurred in most V gamma 1.2, V gamma 2, and V gamma 5 rearrangements; J-segment nucleotide removal was common in V gamma 1.2 but not in V gamma 2 or V gamma 5 rearrangements. N-segment nucleotide insertions were present in V gamma 1.2, V gamma 2, and V gamma 5 IEL rearrangements in both thymus-bearing mice and athymic chimeras, resulting in a predominant in-frame sequence for V gamma 5 and a predominant out-of-frame sequence for V gamma 2 genes. These findings demonstrate that (i) TCR gamma-gene rearrangement occurs extrathymically in IEL, (ii) rearrangements of TCR gamma genes involve the same V gene regardless of thymus influence; and (iii) the thymus does not determine the degree to which functional or nonfunctional rearrangements occur in IEL.

  2. 5-氨基乙酰丙酸光动力治疗裸小鼠胃移植癌的实验研究%Photodynamic therapy for human gastric cancer using 5-aminolaevulinic acid-induced protoporphyrin IX:an in-vivo study in athymic nude mice

    Institute of Scientific and Technical Information of China (English)

    侯东生; 刘文沛; 叶劲松; 陈光春; 刘衍民

    2004-01-01

    目的探讨以5-氨基乙酰丙酸(5-ALA)作为光敏剂对胃癌进行光动力治疗(ALA-PDT)的疗效,为胃癌的综合治疗寻找有效的手段.方法接种胃癌细胞MGC-803于裸小鼠皮下,建立胃移植癌模型,以5-ALA(100mg/kg体重)作为光敏剂,采用瘤内局部注射和口服两种不同方式给药,继以波长630 nm的激光照射肿瘤局部,观察光动力治疗后肿瘤的生长速度和组织形态学变化.结果接受光动力治疗的两组肿瘤生长速度明显减慢,肿瘤表面可见坏死,组织学检查见肿瘤组织有广泛坏死,两种给药途径,其疗效差异无显著性(P>0.05).结论 5-ALA光动力治疗对胃癌有杀伤作用,这将为胃癌的综合治疗提供有效的手段.

  3. A nude mouse model of endometriosis and its biological behaviors

    Institute of Scientific and Technical Information of China (English)

    WANG Dan-bo; ZHANG Shu-lan; NIU Hui-yan; LU Jing-ming

    2005-01-01

    @@ Endometriosis (EM) as a common and intractable gynecological disease is characterized by unknown etiology and complex pathologic changes. Many factors of the disease are uncertain at the molecular level and it is difficult to study clinically. In this study, we attempted to establish a nude mice model of EM for dynamical observation of the genesis and development of the disease, morphological changes in tissue, and biological behaviors.

  4. Effect of ketogenic diet on growth of human colon cancer cells in nude mice%生酮饮食对人结肠癌裸鼠皮下移植瘤生长的影响

    Institute of Scientific and Technical Information of China (English)

    郝光伟; 王海玉; 何德明; 陈榆升; 吴国豪; 张波

    2014-01-01

    Objective:To observe the effect of ketogenic diet on the growth of human colon cancer cells in nude mice and to de-termine its possible mechanisms. Methods:A total of 24 male BALB/C nude mice were injected subcutaneously with the tumor cells of the colon cancer cell line HCT116. These animals were randomized into two feeding groups. One group was fed with a ketogenic diet (KD group;n=12), and the other group was given a standard diet (SD group;n=12) ad libitum. Experiments were completed upon at-taining a target tumor volume of 600 mm3 to 700 mm3. The two diets were compared based on body weight, serum glucose, ketone body, insulin, tumor growth, and survival time, which is the interval between tumor cell injection and attainment of target tumor vol-ume. Results:The tumor growth was significantly more delayed in the KD group than in the SD group. Tumors in the KD and SD groups reached the target tumor volume at 33.8 ± 6.7 days and 24.8 ± 3.1 days, respectively. The ketone body in the KD group was ele-vated with a slight reduction in serum insulin, and the difference in serum glucose in the two groups was insignificant. Importantly, the KD group had significantly larger necrotic areas and less vessel density than the SD group. Conclusion:The application of an unre-stricted ketogenic diet delayed tumor growth in a mouse xenograft model. Further studies are needed to address the mechanism of this diet intervention and its effect on other tumor-relevant functions, such as invasive growth and metastasis.%目的:观察生酮饮食对人结肠癌裸鼠皮下移植瘤生长的影响;探讨生酮饮食可能的作用机制。方法:24只雄性BALB/C裸鼠皮下注射人结肠癌HCT116细胞系后随机分成2组,分别给予正常饮食(standard diet,SD)及生酮饮食(ketogenic diet,KD),两组饮食均不限制总量。当肿瘤体积达到600~700 mm3时实验终止,并将接种当日至肿瘤达到目标体积的时间定义为肿瘤生长期

  5. Antitumor Effect of BCG on Growth of Transplanted Human Myeloid Leukemia HL-60 Cells in Nude Mice%卡介苗抑制裸鼠白血病移植瘤生长及抗肿瘤的实验研究

    Institute of Scientific and Technical Information of China (English)

    王媛媛; 王玲珍; 孙立荣

    2011-01-01

    This study was purposed to explore the anti-leukemia effect of bacillus calmette-guerin vaccine (BCG) on the human myeloid leukemia cell xenograft models.An animal model was established by inoculating the human myeloid leukemia HL-60 cells into the BALB/c (8 - 10 weeks of age) nude mice.The mice were randomly divided into two groups: control group and experimental group.Nude mice in control group were injected with physiological saline, while those of experimental group were given BCG and inactivated BCG respectively.The tumor growth was assayed by using caliper.The survival time of nude mice was determined.Necrotic extent and morphological changes of tumor were observed and examined by HE staining and immunohistochemical method.The results indicated that on 5th -7th days after tumor inoculated, 2 -3 mm tumor mass could be observed.The tumor volume increased over the time.HE staining of tumor tissues showed that there were different degrees of tumor necrosis in BCG group and inactivated BCG group.Immunohistochemistry results demonstrated that CD20 positive cells were obviously observed in the necrotic area of BCG group, compared with the control group and inactivated BCG group.It is concluded that human myeloid leukemia HL-60 cells have been successfully transplanted in nude mice, and the systemic metastasis occurs along with the prolongation of time.BCG inoculation can delay the tumor growth and prolong the survival time of nude mice with leukemia, suggesting that BCG has an antitumor effect.%本研究通过建立人白血病突变株细胞异种移植模型探讨卡介苗(bacillus calmette- guerin vaccine,BCG)的抗白血病作用.对8-10周龄的BALB/c裸鼠皮下接种1×107/ml人急性髓系白0细胞,于4-6天可形成皮下浸润的白血病裸鼠模型,随后将其分为2组:对照组和实验组.对照组于肿瘤内接种生理盐水,实验组又分为T1组(BCG组)、T2组(灭活的BCG组).观察各组裸鼠带瘤生存情况,以及通过对肿瘤组织

  6. Inhibition of compound AG4 fromArdisia gigantifolia Stapf. on xenograft tumor growth of human nasopharyngeal carcinoma in nude mice%走马胎中化合物AG4对人鼻咽癌细胞裸鼠移植瘤的影响

    Institute of Scientific and Technical Information of China (English)

    陈超; 孙艳; 董宪喆; 郭代红; 郑小丽; 穆丽华; 刘屏

    2015-01-01

    目的:研究走马胎中化合物AG4对人鼻咽癌细胞裸鼠移植瘤生长的影响。方法:建立人鼻咽癌细胞裸鼠皮下移植瘤模型,以抑瘤率为指标研究化合物AG4的体内抑瘤作用及AG4干预对裸鼠的一般情况(体质量、活动、食欲等)的影响;同时采用实时荧光定量PCR法观察AG4对肿瘤内凋亡相关基因表达的影响。结果:阳性药顺铂组(2.00 mg·kg-1)对荷瘤裸鼠的抑瘤率为49.41%,3.02 mg·kg-1AG4组的抑瘤率为42.34%,AG4对裸鼠体质量及肝、脾、肾的脏器指数没有明显影响;AG4能明显升高Bax和Bad基因的相对表达量,降低Bcl-2基因的相对表达量。结论:AG4在裸鼠体内对人鼻咽癌细胞有较强的抑制作用,对裸鼠没有明显的毒副作用,其作用机制可能与激活线粒体途径诱导肿瘤细胞凋亡有关。%Objective:To investigate the influence of compound AG4 derived fromArdisia gigantifolia Stapf. on xenograft tumor of human nasopharyngeal carcinoma (NPC) in nude mice.Methods: Human NPC nude mice model were established, and the inhibition rate (IR) was the index to evaluate the tumor growth suppression of AG4in vivo. Simultaneously, general conditions (weight, action, appetite) of nude mice and the expression of Bcl-2, Bad and Bax mRNA by real time PCR method were observed during AG4 interference.Results: The IR of positive control group (cisplatin 2.00 mg·kg-1) and AG4 group (3.02 mg·kg-1) was 49.41% and 42.34% respectively. The effect of AG4 on the weight lose of nude mice was not significant comparing with negative control group, and the toxicity of AG4 to the vital organs (liver, spleen and kidney) and immunity index (spleen index) was not obvious in short period. AG4 could increase the Bax and Bad mRNA expression, and decrease the Bcl-2 mRNA expression.Conclusion:AG4 had obvious inhibition effects on xenograft tumor in human NPC nude mice, and with no outstanding adverse effects, the mechanisms

  7. Experiment study on bioluminescent signal in orthotopic and heterotopic brain tumors in nude mice%裸鼠原位和异位脑肿瘤生物发光信号成像实验研究

    Institute of Scientific and Technical Information of China (English)

    步星耀; 章翔; Walter E. Laug

    2006-01-01

    目的应用生物发光成像技术,非侵入性地连续检测活体裸鼠原位和异位脑肿瘤发展演进过程.方法用SMPU-R-MND-luc载体转染人脑肿瘤U87MG细胞系,形成具有高荧光素酶活性的细胞克隆.在裸鼠脑内和胁腰部皮下植入持续表达荧光素酶的肿瘤细胞,建立原位和异位脑肿瘤模型,用影像学资料显示肿瘤部位.用光子发射定量分析动态监测肿瘤生长情况.结果成功地建立了表达荧光素酶活性的原位和异位脑肿瘤动物模型.采集反映肿瘤生长的生物发光信号,肿瘤细胞植入后不同时间点的发光信号值呈显著正相关,而且原位和异位脑肿瘤间存在明显差异.但生物发光脑肿瘤生物发光信号值在第4 d和第14 d时无显著差异.结论体内生物发光成像可以非侵入性地动态检测活体内脑肿瘤演进过程,为研究肿瘤发展机制及最佳治疗策略的选择提供了新的手段和工具.%Objective To investigate the bioluminescent signal in orthotopic and heterotopic brain tumors in nude mice for noninvasive monitoring on progression of brain tumor in vivo.Methods The human brain tumor cell line U87MG cells were transduced by using the SMPU-R-MND-luc vector then a clone with high luciferase activity was cloned and used for in vivo experiments. Tumor cells were implanted into the brains and flanks of the animals, and whole body images revealing tumor location were obtained. Tumor burden was monitored over time by quantity of photon emission.Results Orthotopic brain tumor and heterotopic flank tumor models were established by implanting constitutively expressing luciferase tumor cells in the brains and flanks of the animals. The magnitude of bioluminescence from firefly luciferase measured in vivo correlated with the time after injection of luciferin, indicating that the time of post-injection signal quantification was of special importance. Furthermore, the time courses in the heterotopic and

  8. Effect of TET on Xenografted Tumor of Human Bladder Cancer BIU-87 Cells on Nude Mice%粉防己碱对人膀胱移行细胞癌BIU-87细胞裸鼠移植瘤的实验研究

    Institute of Scientific and Technical Information of China (English)

    李永生; 赵诚; 胡钊

    2012-01-01

    OBJECTIVE To investigate the effects of tetrandrine(TET) on the xenografted tumor of the human bladder cancer BIU-87 cell line on nude mice. METHODS Fourteen nude mice which had been inoculated with BIU-87 cells by subcutaneous injection into the right legs were divided into the PBS control group(7 mice) and the 25 μg·mL-1 TET group(7 mice). After a month of transplantating tumor cell, mice were given PBS or TET into the tumor once every 3 days. Tumor volumes were measured every 3 days. RT-PCR was used to detect Bcl-2 and Bax mRNA expressions. The expressions of survivin and Capseae-3 were detected by Western-blot. RESULTS TET could inhibite the growth of xenografted tumor of human bladder cancer BIU-87 cells on nude mice, the inhibitory rate was 66.6%. RT-PCR analysis showed that TET significantly reduced tumor Bcl-2 mRNA expression and increased Bax mRNA expression (P<0.05); Western-blot showed that after TET treatment, the survivin protein markedly dropped, and Capseae-3 protein expression increased significantly (P<0.05). CONCLUSION TET can inhibite the growth of xenografted tumor of human bladder cancer BIU-87 cells on nude mice. The molecular mechanism may be reducing the expressions of Bcl-2, survivin, and increasing the expression of Bax, Capseae-3.%目的 研究粉防己碱(TET)对人膀胱移行细胞癌BIU-87细胞株裸鼠移植瘤的作用机制.方法 14只裸鼠右后腿背侧皮下接种BIU-87移植瘤细胞后随机分为磷酸盐缓冲液(PBS)对照组(7只)和25 μg·mL-1 TET治疗组(7只).接种1个月后开始,每3 d一次于肿瘤局部注射给予PBS或TET,每3d测量1次肿瘤大小;RT-PCR检测Bcl-2、Bax mRNA表达;Western-blot分析survivin、Capseae-3蛋白表达.结果 TET对人膀胱癌BIU-87细胞裸鼠移植瘤的生长具有抑制作用,抑制率达66.6%.RT-PCR检测结果显示,与PBS对照组相比,TET能明显下调移植瘤Bcl-2 mRNA的表达,上调Bax mRNA的表达(P<0.05); Western-blot结果显示经TET处理

  9. 恶性横纹肌样瘤(MRT)的起源研究——高变异率HeLa细胞致裸鼠产生MRT的实验研究%Studies of the Origin of Malignant Rhabdoid Tumor(MRT)——Experimental Researches on the MRT Evolving in Nude Mice Inoculated with Violently Variable HeLa Cells

    Institute of Scientific and Technical Information of China (English)

    张德礼; 夏耕田; 高步先; 何旭玉; 白晓鸿; 黄高升; 李六金; 刘尚高

    2000-01-01

    致癌性;HeLa细胞染色体遗传特征决定致瘤性质,细胞染色体数目变异大小和致癌/致瘤性强弱相关,致瘤性由弱到强的顺序依次为KB株,X株和NM20/X株,但H株有例外,尚待进一步实验确定。%Under the prerequisite that the incidence of cancer or tumor in negatively?controllednudemiceinoculatedsubcutaneously with feline or canine kidney cell cultures purified in vitro at passage 3 or higher (the modal chromosome number of FKC on passage 3 was 38 of diploid at the rate of 80%) was 0%(0/22) and 0%(0/10) respectively, and the incidence of progressively negative growing tumor in controlled nude mice inoculated subcutaneously with repeatedly-frozen-andthawed-HeLa cell cultures of X strain was 20%(1/5), the negative growing malignant tumor (MT) was found in half of the nude mice inoculated subcutaneously with HeLa cell cultures of H strain(with modal chromosome number of 78±2 of sub-tetraploid at the rate of 40%), the progressively-growing malignant tumor was found in all the other 40 nude mice inoculated subcutaneously with HeLa cell cultures of other strains, with the incidence of MT in nude mice with KB strain (with modal chromosome number of 60±3 of hyperdiploid at the rate of 72%~76%) 10/10, the incidence of poorly-differentiated MT originated from epithelia in nude mice with X strain (with modal chromosomal number of 62±3 of hyperdiploid at the rate of 69%) 25/25, and the incidence of MRT in nude mice with in vitro cultured tumor cell NM20/X strain (with modal chromosome number of 68±3 of both hyperdiploid and subtetraploid at the rate of 52%) 5/5. After being continuously cultivated for 20 passages in vitro, HeLa cell of X strain was subcutaneously inoculated into nude mice and cultivated for 1 passage in vivo within 15 days, and then the developed growing MT was collected as HeLa cell of NM20/X strain on passage 0 and continuously cultivated for 11 passages to prepare for

  10. Effect of N-cadherin knock-down on tumor formation of EC9706 cells in nude mice%RNAi沉默N-cadherin表达对EC9706细胞裸鼠移植瘤生长的影响

    Institute of Scientific and Technical Information of China (English)

    李克; 刘莺; 刘文静; 侯新芳; 何素英; 王居峰

    2011-01-01

    AIM: To explore the effect of N - cadherin knock - down on the biological behavior of EC9706 cells in vivo.METHODS: The control vector pEGFP - MSCVneo and recombinant retroviral vector pMSCVneo/N - cadherin plasmids were transfected into esophageal squamous cell carcinoma( ESCC ) cell line EC9706 according to the manufacturers instructions.Stable EC9706 cell clones were selected using selection medium containing G418.Untreated EC9706 cells, control vector - transfected EC9706 cells and N - cadherin RNAi - transfected EC9706 cells were inoculated subcutaneously into the right flank of BALB/c mice ( 5 for each group ), respectively.When tumors became palpable, the diameters of the tumors were measured with a caliper each week after subcutaneous implantation, and the volume ( mm3 ) and weight ( g ) of the tumors were also calculated.Immunohistochemistry and Western blotting were employed to examine the expression levels of E - cadherin, N - cadherin and MMP - 9 in the tumor tissues.The cell apoptosis was analyzed by TUNEL method.RESULTS: Compared with untreated group and control vector group, there was an obvious decrease in the volumes and weights of the tumors in N - cadherin RNAi group ( P < 0.05 ).No difference of E - cadherin expression in the 3 groups was observed.However, the expression of N - cadherin and MMP - 9 in N - cadherin RNAi group was apparently reduced, and the positive number of cell apoptosis was obviously increased in N - cadherin RNAi group ( 106.81 ± 6.47 ) as compared with that in untreated group ( 51.55 ±4.68 ) and control vector group ( 54.17 ± 5.26 ).CONCLUSION: N - cadherin knock - down inhibits the tumor formation of EC9706 cells in nude mice by decreasing MMP - 9 expression , resulting in less degradation of ECM and less aggression of the cancer cells.N - cadherin is an important factor in the progression and metastasis of ESCC,and may serve as a potential molecular target for biotherapy of ESCC.%目的:探讨RNAi沉默N-cadherin表

  11. Preparation of 99mTc-Gd-DTPA-BMA and its bio-distribution in nude mice bearing tumor%99mTc-Gd-DTPA-BMA的制备及其在荷瘤裸鼠体内的生物学分布

    Institute of Scientific and Technical Information of China (English)

    曹丰; 陈跃; 黄占文; 丁志凌; 张伟

    2011-01-01

    目的 探讨以99mTc标记Gd-DTPA-BMA的可行性及其在荷瘤裸鼠体内分布的特征.方法 采用氯化亚锡还原法,用99mTc标记Gd-DTPA-BMA,TLC法测定99mTc-Gd-DTPA-BMA的放射化学纯度,将标记物注入荷A549肿瘤裸鼠体内,分别行SPECT显像及MRI增强成像,并测定其体内分布.结果 99mTc-Gd-DTPA-BMA放射化学纯度为99.2%,室温放置6 h后放射化学纯度大于95%.该标记物主要通过肾脏排泄,注射后肿瘤组织在SPECT及MRI下均能获得较好的显示或增强,且在肿瘤组织中具有较高的每克组织百分注射剂量率.结论 作为一种潜在的双模式显像剂,99mTc-Gd-DTPA-BMA值得进一步研究.%Objective To explore the feasibility of using 99mTc labeled Gd-DTPA-BMA, and to observe its characteristics of distribution in nude mice bearing tumor. Methods The labeled compounds were prepared by reducing 99mTc in the presence of Gd-DTPA-BMA with stannous chloride (SnCl2). The radiochemical purity was determined by TLC. 99mTc-Gd-DTPA-BMA was injected into nude mice bearing A549 tumor. SPECT and MR imaging were performed, respectively. The in vivo bio-distribution in nude mice was observed. Results The radiochemical purity of 99mTc-Gd-DTPA-BMA was 99.2%,and remained more than 95 % within 6 h at room temperature. 99mTc-Gd-DTPA-BMA imaging and bio-distribution experiments showed that the marker was excreted by renal. After inject 99mTc-Gd-DTPA-BMA, SPECT and MRI showed the tumor tissue or enhancement clearly, and high percentage of the injected dose per gram of tissues mass was noticed. Conclusion As a potential dual-modal imaging agent, 99mTc-Gd-DTPA-BMA is worthy of further research.

  12. Chaiqiyigan granula enhances Taxol-induced growth inhibition of hepatocellular carcinoma xenografts in nude mice: an in vivo fluorescence imaging study%柴芪益肝颗粒联合紫杉醇抑制裸鼠肝癌生长的在体成像研究

    Institute of Scientific and Technical Information of China (English)

    游敏玲; 罗满芳; 廖蔚茜; 胡世平; 许文学; 靖林林

    2012-01-01

    Objective To study the effects of Chaiqiyigan Granula (CG) and Taxol on the growth of hepatocellular carcinoma (HCC) xenografts and expression of Bax, p53 and VEGF in nude mice. Methods Whole-body fluorescence imaging was used to visualize the growth of HCC in nude mice bearing hepG2/EGFP cell xenograft. Irnmunohistochemistry was used to determine the content of Bax, p53 and vascular endothelial growth factor (VEGF) in the tumor tissues. Results Compared with normal saline, Taxol alone and in combination with CG significantly inhibited the growth of HCC xenografts in the nude mice. The combined treatment with CG and Taxol produced a stronger inhibitory effect on the tumor growth than Taxol alone in the third and fourth weeks. The volume and weight of the xenografts were decreased in the combined treatment group compared with those in saline treatment group. CG combined with Taxol increased the expression of Bax and reduced the expression of p53 and VEGF in the tumor xenografts. Conclusion CG can enhance the inhibitory effects of Taxol on the growth of HCC xenografts, and this effect is related to the up-regulation of Bax and down-regulation of p53 and VEGF expression in the tumor.%目的 探讨柴芪益肝颗粒(CG)和紫杉醇(taxol)对裸鼠异位肝癌的作用及对Bax、p53和VEGF表达的影响.方法 应用转染及G418筛选构建单克隆Hep G2/EGFP细胞系,细胞注射至裸鼠形成异位肝癌模型,应用荧光成像技术在体观察在柴芪益肝颗粒合Taxol作用下肿瘤的生长,用免疫组化法检测肿瘤组织中Bax、p53、VEGF的表达.结果 与对照组相比,Taxol组和Taxol+CG组在3周和4周时降低肝癌增殖速度,Taxol+CG组抑制作用显著优于Taxol组比.Taxol+CG组增加Bax表达,降低p53表达和VEGF表达.结论 柴芪益肝颗粒明显增强Taxol对裸鼠异位肝癌生长的抑制作用,其作用与增加Bax表达、抑制p53、VEGF表达相关.

  13. 重组腺病毒bcl-xs基因对人卵巢癌裸鼠移植瘤作用的研究%腺病毒科;癌基因;卵巢肿瘤;癌,Ehrlich瘤;肿瘤,实验性 Therapeutic effects of adenovirus-bcl-xs gene to the ascites tumor of nude mice model of human ovarian carcinoma

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To investigate the effects of adenovirus-bcl-xs gene on the ascites tumor growth inhibition and survival rate of nude mice with human ovarian carcinoma transplanted intraperitoneally. Methods Making an adenovirus-bcl-xs gene vector infected in JH293T cell and reproduced in it. After having detected the inhibitory potential of adenovirus-bcl-xs gene on NUTU-19 cell we use it to transfer intraperitoneally to ascites tumor model of human ovarian carcinoma transplanted in nude mice. Detected the ascites formation, the survival time and survival rate of nude mice with the human ascites tumour. The weight and toxic-adverse systemically effects of nude mice was observed and morphology of adenovirus was observed by electromicroscope and the gene expression was detected by immunocellchemistry. Results  The adenovirus-bcl-xs gene could reproduce in JH293T cell and had inhibitory potential on NUTU-19 cell. the survival time of nude mice was longer and the survival rate was higher, and the time of ascites formation was retarted. There was no obvious alternation in the weight and systemic toxic-adverse effects observed. Conclusions The data suggestes that the transfer of adenovirus-bcl-xs gene to the ascites tumour of nude mice with human ovarian carcinoma could improve the survival rate of nude mice and retard the time of ascites formation. It may be a useful method of gene therapy in the treatment of ovarian carcinoma.%目的 观察重组腺病毒bcl-xs基因(adv-bcl-xs基因,简称bcl-xs基因)对人卵巢癌裸鼠移植瘤的生长抑制和荷瘤裸鼠生存率的影响,为卵巢癌的基因治疗提供实验基础。方法 采用以复制缺陷型腺病毒bcl-xs基因感染的人胚肾细胞,使bcl-xs基因在人胚肾细胞内扩增,扩增后的bcl-xs基因感染大鼠卵巢癌细胞株NUTU-19,观察bcl-xs基因对NUTU-19细胞的生长抑制作用并检测其病毒滴度后,将bcl-xs基因导入人卵巢癌裸鼠移植瘤中,观察bcl-xs

  14. Effects of juglone on growth of human hepatocellular carcinoma BEL-7402 xenografts in nude mice%胡桃醌不同给药途径对人肝癌细胞BEL-7402裸鼠皮下移植瘤生长的影响

    Institute of Scientific and Technical Information of China (English)

    陈丽; 张建; 汪思应; 黄德武; 顾为望

    2011-01-01

    目的 采用裸鼠皮下移植瘤模型,通过不同给药途径对胡桃醌抗肿瘤活性和毒性进行评价.方法建立人肝癌BEL-7402细胞裸鼠皮下移植瘤模型,通过腹腔注射和局部注射两个给药途径观察胡桃醌抑制肿瘤生长的效果.结果 ①以600、300和150 μg/kg胡桃醌腹腔注射于人肝癌BEL-7402细胞裸鼠皮下移植瘤模型,发现该剂量胡桃醌对肿瘤生长没有明显的影响;NK细胞活性检测发现,600、300μg/kg胡桃醌对裸鼠免疫功能有影响(P均<0.01),150 μg/kg胡桃醌则没有影响(P>0.05);与阳性对照组(5-Fu)相比,600 μg/kg胡桃醌组NK细胞活性差异无显著性(P>0.05),300和150 μg/kg胡桃醌组NK细胞活性差异有显著性(P <0.05,P<0.01),结果提示胡桃醌对小鼠免疫系统有一定的损伤作用.②以4.5、3和1.5 mg/kg胡桃醌腹腔注射于人肝癌BEL-7402细胞裸鼠皮下移植瘤模型,抑瘤率分别为为78.24%、66.57%、48.94%;4.5、3 mg/kg胡桃醌的抑瘤作用可与阳性对照组比拟(P均>0.05).但4.5 mg/kg胡桃醌组裸鼠出现明显的皮下脂肪减少、消瘦,并有死亡现象.③以pH 7.4和pH 4.0的600、300和150 μg/kg胡桃醌人肝癌BEL-7402细胞裸鼠皮下移植瘤模型局部给药,结果发现不同pH(pH7.4或4.0)600、300μg/kg的胡桃醌局部注射抑瘤作用与阳性对照组(5-Fu)组差异无显著性(P>0.05),而不同pH的150μg/kg胡桃醌抑瘤作用不明显.同一浓度不同pH药物的抑瘤作用差异无显著性(P均>0.05),但pH 4.0的胡桃醌组肿瘤细胞肝转移较少.结论 胡桃醌不同给药途径均可抑制人肝癌BEL-7402细胞裸鼠皮下移植瘤的生长,但有一定的毒副作用,药物安全范围较小.%Objective To evaluate the inhibitory effect and toxicity of juglone administered via different routes on the nude mice model bearing subcutaneously transplanted tumor. Methods Human hepatocellular carcinoma BEL-7402 cells were subcutaneously injected

  15. Biological functions of the nude mice subcutaneous tumor established by MDA-MB-468 and SK-BR-3 breast cancer cells%MDA-MB-468和SK-BR-3乳腺癌细胞建立裸鼠皮下种植瘤的生物学功能

    Institute of Scientific and Technical Information of China (English)

    赵期康; 吴颖; 莫雪丽; 熊兵红

    2015-01-01

    characteristics in to the subcutaneous transplantation tumor in nude mice.To judge the impact of biological function of adriamycin on two breast cancer cell subcutaneous implanted tumor in nude mice.Methods 80 nude mice were randomly divided into group MDA-MB-468 and group SK-BR-3,group MDA-MB-468 mice subcutaneous injection of breast cancer cells MDA-MB-468,SK-BR-3 mice by subcutaneous injection of breast cancer cell line SK-BR-3,with 40 rats in each group.Selection of half the number of mice by subcutaneous injection of the cells grown in nude mice right groin area,1 daily injections for 4 weeks after injection,mice were sacrificed and the tumor body.Two groups of nude mice tumor volume measurement,calculation of tumor volume inhibition rate,remove the other half mice in two groups in a mouse model of adriamycin,will slow preparation into two groups of mice subcutaneous tumor model by injection,daily 1 times,continuous injection for 4 weeks.Observation of two nude mice,the growth of the dietandmental status,tumor record,mice were killed after 4 weeks,the tumor volume,the tumor size was measured.The apoptosis index of tumor cells was detected by TdT-mediated dUTP nick end labeling (TUNEL) in two groups of mice tumor tissue,to observe the effect of adriamycin on the two groups of breast cancer cell cycle and apoptosis.Results (1) Tumor growth:at eighth weeks,two groups of mice tumor volume were (3.212 ±0.151) and (2.924 ±0.316) cm3,the difference was statistically significant between the two groups (t =2.758,P < 0.05).Results the tumor volume inhibition rate.(2) After adriamycin injection:two groups of mouse model of breast cancer after injection of adriamycin,subcutaneous tumors stopped growing and gradually narrowing,4 weeks later,the tumor volume was statistically significant difference between the two groups of mice (x2 =2.14,P < 0.05),detection index of tumor cell apoptosis by TUNEL,there was statistical significance the difference between the two groups (x2 =3.59,P

  16. 小干扰RNA抑制卵巢癌模型裸鼠移植瘤葡萄糖调节蛋白94的表达及意义%Small interfering RNA inhibits glucose regulated protein 94 expression in transplantable models of human ovarian carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    张丽颖; 徐爱丽; 李佩玲; 艾丽敏

    2014-01-01

    BACKGROUND:After glucose regulated protein 94 (GRP94) was knockout in model mice of transplanted tumor, cel ular adhesion is terminated, thus stimulating the proliferation of liver-derived cel s and promoting the development of liver cancer. We speculate that GRP94 plays a protective role against liver cancer. OBJECTIVE:To investigate the expression of endoplasmic reticulum molecular chaperone GRP94 mRNA and protein with smal interfering RNA technique in nude mice model of transplantable human ovarian carcinoma, and to explore the effect of GRP94 mRNA and protein expression on the growth of transplanted tumor. METHODS:The gene sequences of human GRP94 were obtained from Gene Bank. psiSTRIKETM/GRP94 was constructed, which is eukaryotic expression vector control ed by the U6 promoter of human RNA polymerase Ⅲ. The transplantable model of human ovarian carcinoma in nude mice was established using human ovarian cancer HO-8910 cel line. The eukaryotic expression vector was transfected into the transplanted tumors in nude mice, and the growth of the tumor was observed. The nude mice models were divided into three groups, specific smal interfering RNA group, non-specific smal interfering RNA group and saline control group. The volumes of the subcutaneous tumor were determined. RT-PCR and immunohistochemistry were used to detect the mRNA and protein expression of GRP94 respectively. RESULTS AND CONCLUSION:The recombinant plasmid of RNA interference specific for GRP94 was successful y constructed. The subcutaneous tumors appeared in al the nude mice 5 days after transplantation. The diameter of subcutaneous tumors was 7-10 mm 14 days after transplantation. The growth of subcutaneous tumors in nude mice with interference specific for GRP94 treatment was significantly decreased as compared with non-specific smal interfering RNA group and control group (P  目的:应用小干扰RNA技术抑制裸鼠卵巢癌模型皮下移植瘤内质网分

  17. Study on tissue distribution of 1, 2- [bis ( 1,2-benzisoselenazolone-3(2H)-ketone)]-ethane in nude mice and SD rats%乙烷硒啉在大鼠和结肠癌荷瘤裸鼠体内的组织分布研究

    Institute of Scientific and Technical Information of China (English)

    周海燕; 孟志云; 窦桂芳; 何铁强; 楼雅卿; 章国良

    2012-01-01

    目的:考察抗肿瘤新药乙烷硒啉在大鼠和结肠癌荷瘤裸鼠体内的组织分布规律.方法:采用荧光分光光度法和液相色谱-质谱联用法分别测定SD大鼠和人结肠癌LS174T细胞荷瘤裸鼠灌服乙烷硒啉后各组织中药物浓度经时变化.结果:大鼠灌服乙烷硒啉2h后,药物广泛分布于各组织,以胃肠及其内容物、肝、肾中含量最高;24 h肝肾组织硒浓度分别为(6.14±0.87)和(6.93±0.94) μg·g-1,同时间点血液中硒浓度为(4.43±1.65) μg·mL-1;48 h后除肾脏外,其他各组织硒浓度数值均低于血硒浓度.结肠癌裸鼠给药后1h即可见原形药迅速分布于各组织,至24 h肾脏药物浓度达峰值,而其他组织中药物浓度显著降低,至48 h肿瘤中仍可检测出较高药物浓度.结论:乙烷硒啉口服给药后在大鼠和结肠癌荷瘤裸鼠体内均可广泛分布,并对肿瘤组织具有一定选择性,其组织分布特点可能与药物的代谢排泄途径相关.%Objective; To investigate the characteristics of tissue distribution of 1 ,2-[ bis ( 1 ,2-benziso-selenazolone-3 (2H)-ketone) ]-ethane ( BBSKE ) in nude mice and SD rats. Methods: An atomic fluorescence spectrometry ( AFS) was applied to determine the concentrations of selenium in SD rats after administration of BBSKE, and HPLC-MS/MS was applied to determine the concentrations of BBSKE in nude mice after administration of BBSKE. Results; Selenium was observed to widely distribute in various tissues at 2 h after administration of BBSKE in rats. It was shown that selenium mainly existed in the digestive tract including stomach, small intestine, large intestine and their contents, kidney and liver. After 24 h, the concentrations of selenium in liver and kidney were (6.14±0.87) and (6.93 ±0.94) μg· g-1 , respectively, while the average concentration of selenium in plasma was (4.43 ±1.65) μg·mL-1. After 48 h, selenium concentration reduced in other tissues except kidney. Similarly

  18. 脂肪干细胞复合Ⅰ型胶原对裸鼠移植组织生长的影响%Effects of adipose tissues derived stem cells compounding with type I col-lagen on growth of transplanted tissue in nude mice

    Institute of Scientific and Technical Information of China (English)

    许颖溦; 刘林嶓; 徐永飞

    2014-01-01

    Aim:To observe the effects of compositing adipose tissues derived stem cells (ADSCs) with typeⅠcollagen on nude mice subcutaneous stratum .Methods: Three groups were divided depending on the selected material .Group A (ADSCs companding with type Ⅰcollagen), group B(pure fat particles), and group C(pure ADSCs).The same quantita-tive tissue was injected into one point of subcutaneous stratum of every nude mice , and marked accordingly .The number of nude mice used in the experiment was 12.The growth of the transplanted tissue was observed .The appropriate specimens were obtained three months later and the general observation ,mass(wet weight), and microvessel density(MVD) were ob-served.Results:The tissue of group A was absorbed least than the other 2 groups, the tissue of group B was absorbed more, the tissue of group C was absorbed most (F=47.619,P<0.001).Group A was heavier than group B and C (F=68.425,P<0.001).The MVD of group A was higher than group B and C (F=46.730,P<0.001).Conclusion: As a cellular scaffold, type Ⅰcollagen can promote the survival and growth of transplanted ADSCs , and can promote neovascu-larization in nude mice subcutaneous stratum .%目的:探讨脂肪干细胞( ADSCs )复合Ⅰ型胶原在裸鼠背部组织工程化软组织存活与生长的变化。方法:根据所选移植物不同,将实验分为ADSCs复合Ⅰ型胶原( A)、单纯脂肪颗粒( B)和单纯ADSCs( C)组。分别将3组移植物定量注射到每只裸鼠背部皮下,1只裸鼠每种组织复合物各注射一点,并做相应的分组标记,12只裸鼠均做同样处理。观察各移植组织的生长情况,3个月后获取移植组织标本,测量体积、湿重和微血管密度( MVD)。结果:①A组移植组织被吸收较少,体积最大;B组移植组织被吸收较多,体积较小;C组移植组织被吸收最多,体积最小;差异有统计学意义(F =47.619,P <0.001)。②A

  19. Inhibitory Effect of As2O3 on Nude Mice Ascitis Production Planted by Gastric Cancer Cell Line%三氧化二砷对人胃癌裸鼠腹腔种植 腹水生成的影响

    Institute of Scientific and Technical Information of China (English)

    张兴荣; 蔡洪培; 邓志华; 沈健伟

    2001-01-01

    目的:研究三氧化二砷 (As2O3)对人胃癌裸鼠腹腔种植腹水生成的影响及其作用机制。方法: 100只 BALB/C-nu/nu裸鼠腹腔内接种胃癌 MKN-45细胞株后,随机分为 5组,然后分别腹腔内注射生理盐水 (第 1组 )、表阿霉素 (第 2组 )及不同剂量的 As2O3(第 3、 4、 5组 ),观察癌细胞株对各组裸鼠的致瘤率、腹水生成量及生存时间;透射电镜观察 As2O3作用后腹腔内肿瘤细胞的形态学变化。结果:表阿霉素、低剂量 As2O3与生理盐水对照组相比可显著抑制裸鼠腹水的生成,延长生存期 (P<0.01);中高剂量 As2O3除上述作用外还可通过诱导肿瘤细胞凋亡消除腹腔内肿瘤细胞,抑制腹水产生,并使裸鼠寿命明显延长。结论: As2O3可通过诱导胃癌细胞凋亡而抑制或消除人胃癌裸鼠腹腔种植及腹水的生成,不同程度地延长生存期。%Objective: The aim of this study was to observe the effect of As2O3 on malignant ascites of nude mice and investigate its mechanism. Method: One hundred BALB/c-nu/nu nude mice were injected with MKN-45 gastric cancer cell line and were divided into 5 groups at random: Group 1, normal saline; Group 2, Epirubicin; Group 3-5, various concentration of As2O3. The rate of tumor formation, production of ascites and survival period were evaluated. Morphological changes of tumor cell were observed with electromicroscope. Result: Epirubicin and low dose of As2O3 obviously inhibited the production of ascites and prolonged the survival period of tumor-loading nude mice ( P<0.01). Mid to high doses of As2O3 eradicated cancer cells through the way of apoptosis. Conclusion: As2O3 could induce gastric cancer cell apoptosis, inhibit or eradicate production of ascites and prolong the survival period of nude mice that suffered from malignant ascites from metastasis

  20. 转染 p53基因对肺腺癌细胞株裸鼠 移植瘤生长的影响%Study on the Role of p53 Gene Transfer on Human Glandular Lung Cancer Cell Growth in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    李萍; 王北宁; 丁振若

    2001-01-01

    Objective: This study was designed to explore the significance and the role of wild-type p53 (wt-p53) gene and mutant p53 gene(mt-p53) transfer on human glandular lung cancer cell growth in nude mice. Methods: wt-p53 gene and mt-p53 gene were transfected and lipofectin-mediated into the human glandular lung cancer cell line GLC-82. And the growth of gene-transfected cell lines were observed in vitro and in vivo. Results: The colony number in the colong-forming experiment and the volume and weight in nude mice were greater in the mf-p53 tranfecting cells group than in the control group. The tumor resulting from the cells transfected with the wt-p53 gene grew more slowly and was smaller than that from control GLC-82 cells. In contrast, the tumor from the cells transfected with the mt-p53 gene grew faster than that produced by cells transfeted with the wt-p53 gene and that produced by control GLC-82 cells. Conclusion: The wild-type p53 gene could inhibit the glandular lung cancer cell growth in nude mice and the mutant p53 gene could enhance the glandular lung cancer cell growth in nude mice.%目的:探讨转染野生型 p53( wt-p53)和突变型 p53( mt-p53)基因对人肺腺癌细胞株 GLC-82裸鼠移植瘤生长的影响。方法:采用脂质体介导法,分别将 wt-p53和 mt-p53基因导入人肺腺癌细胞株 GLC-82,在裸鼠体内、体外实验中检测转导细胞的生长状况和裸鼠致瘤性。结果:转染 mt-p53 基因的细胞株 G418筛选的细胞集落数、 3H-TDR掺入实验、软琼脂平皿细胞集落数,以及裸鼠瘤组织重量和体积均高于对照组( P<0.01),而转染 wt p53基因的细胞株均显著低于对照组( P< 0.01),表明导入 wt p53基因的细胞株瘤细胞生长速度明显低于对照组细胞株和导入 mt p53基因的细胞株,即导入 mt p53基因的细胞株瘤细胞生长速度最快,而导入 wt p53基因的细胞株瘤细胞

  1. 反义miRNA-21/ rAV-Tumstatin病毒载体对裸鼠膀胱癌生物学行为的影响%The biological behaviour influence of Anti-sense miRNA-21/ rAV- Tumstatin viral vector on nude mice bladder cancer

    Institute of Scientific and Technical Information of China (English)

    李然伟; 魏巍; 刘禄成; 温都苏; 陈秀玲

    2012-01-01

    目的 探讨反义miRNA-21/ rAV-Tumstatin病毒载体对裸鼠膀胱癌生长及转移的影响.方法 通过构建裸鼠原位膀胱癌移植瘤模型并灌注携带基因的腺病毒载体,观察肿瘤生长及盆腔淋巴结转移情况,同时采用免疫组化法检测肿瘤细胞增殖和凋亡指数.结果 肿瘤大小:治疗组为(14.60±5.31)mm2,对照组为(58.92±7.16)mm2,两组比较P<0.01;肿瘤细胞增殖率:治疗组为41.30%,对照组94.70%,两组相比P<0.05;凋亡指数治疗组和对照组分别是30.18和9.53,两者比较P<0.05;治疗组5只中无一只发生盆腔淋巴结转移,而对照组3只出现转移(60.0%),两组比较P<0.01.上述各项组间差异均有统计学意义.结论 反义miRNA-21/rAV-Tumstatin病毒载体对人膀胱癌裸鼠原位移植瘤具有良好的靶向性,能够通过抑制肿瘤细胞增殖和加速肿瘤细胞凋亡,遏制实验性裸鼠膀胱移植癌模型的生长转移,从而为该载体用于人类膀胱癌的治疗提供了一定的实验依据.%Objective To investigate the influence of anti-sense miRNA-21/ rAV-Tumstatin viral vector on nude mice bladder cancer growth and metastasis. Methods To establish nude mice situ bladder cancer model and pour into adenovirus vector with gene,observe the growth of tumor cell and transfer of pelvic cavity lymphaden, simultaneously use immunohistochemisty detecting proliferation and apoptotic index of tumor cell. Results Tumor size: treatment group(14. 60+5. 31)mm2, control group(58. 92 + 7. 16)mm2, two groups compare P<0. 01 ;proliferation rate of tumor cell: treatment group 41. 30% ,control group 94. 70% , two groups compare P<0. 05 ;apoptotic index of treatment and control group arc 30. 18 and 9. 53, two groups compare P<0. 05;no one happen pelvic cavity lymphaden metastasis in 5 treatment group,but control group 3 happen mctastasis(60. 0%),tow groups compare P<0. 01. The difference of a-bovc-mentioned each groups have statistical significance. Conclusion Anti

  2. Effect of Proton Pump Inhibitors on Cancer Cachexia in Nude Mice Bearing SGC-7901 Gastric Adenocarcinoma%质子泵抑制剂对SGC-7901胃腺癌裸小鼠癌性恶病质的作用

    Institute of Scientific and Technical Information of China (English)

    沈永华; 陈敏; 沈卫东; 黄淑玲; 张丽莉; 邹晓平

    2011-01-01

    背景:癌性恶病质是癌症晚期最重要的并发症之一.质子泵抑制剂(PPIs)目前广泛用于治疗酸相关疾病,有研究显示其对恶性肿瘤细胞具有化疗增敏和诱导凋亡作用.目的:探讨PPIs对裸小鼠癌性恶病质的改善作用及其可能机制.方法:予BALB/c nu/nu裸小鼠皮下注射人胃腺癌细胞株SGC-901建立癌性恶病质模型并予PPIs干预(奥美拉唑治疗组和泮托拉唑治疗组),同时设立不予干预的癌性恶病质组和非荷瘤空白对照组,每组11只裸小鼠.观察各组裸小鼠的一般情况、肿瘤体积以及与癌性恶病质的发生、发展密切相关的血清细胞因子肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平.结果:两组PPI治疗组裸小鼠体质量下降受抑,摄食、饮水量明显高于癌性恶病质组,血清TNF-α、IL-6水平明显低于癌性恶病质组,差异均有统计学意义(P<0.05),肿瘤体积则与癌性恶病质组无明显差异.结论:PPIs对裸小鼠的癌性恶病质有明显改善作用,其机制可能与改变体内细胞因子水平有关.%Background: Cancer cachexia is one of the most important complications of advanced cancer. It has been reported that proton pump inhibitors (PPIs), currently used in the treatment of acid-related diseases, can increase the sensitivity of cancer cells to cytotoxic agents and induce cancer cell apoptosis. Aims: To investigate the improvement effect of PPIs on cancer cachexia in nude mice and its possible mechanism. Methods: Thirty-three BALB/c nu/nu nude mice were injected with human gastric adenocarcinoma cell line SGC-7901 subcutaneously to induce cancer cachexia, and then randomized to receive omeprazole, pantoprazole or normal saline treatment (Ome-treated group, Pan-treated group, and cancer cachexia group), respectively; 11 nude mice without any intervention served as blank controls. The general condition, tumor volume and the serum levels of two cachexia-associated cytokines, tumor

  3. 纳秒脉冲治疗裸鼠皮下移植瘤抗癌机制研究%Anti-cancer mechanism of nanosecond Pulsed Electric Fields on xenografts in nude mice

    Institute of Scientific and Technical Information of China (English)

    彭巧; 赵雪; 姚陈果; 唐均英

    2013-01-01

    To investigate the anticancer effect of nanosecond Pulsed Electric Fields (nsPEF) on human melanoma A375 cell xenograft in nude mice. Tumor size was detected by vernier caliper. The cell apoptosis was detected by DNA agarose gel eleetrophoresis and termina I deoxynucleotidyl transferase- mediated dUTP nick end - labeling (TUNEL) assay;Tumor morphology was observed with HE staining; The expression of microvessel density (MVD) 、 vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) were detected by SP immunohistochemistry. Results showed that tumor growth inhibition rate was 42.6% at 4d after nsPEF treatment. DNA ladder were observed more typically in 4d group than other two groups; The apoptosis rate of tumor cells in 4d group was the most highest than other group detected by TUNEL. Tumor turned grey immediately after treatment; A few of necrosis cells were found in 2h group, while numerous necrosis were found in 4d group; The slate of blocking of capillary vessel was found significantly in 4d group. The expressions of MVD, VEGF and PCNA were significantly lower in 4d group than the other two groups, while no significant difference were found between 2h group and control group. The result indicated that the inhibitory effects of nsPEF may be related to inducing cell apoptosis, reducing blood flow in a short time, decreasing the angiogenesis and discouraging tumor revascularization and tumor cell' s proliferative activity.%本研究探讨了纳秒级陡脉冲(nsPEF)对人恶性黑色素瘤A375细胞裸鼠皮下移植瘤模型可能的抗癌机制.通过用游标卡尺测量裸鼠皮下瘤大小,估算抑瘤率.用琼脂糖凝胶电泳、TUNEL法检测肿瘤细胞在纳秒脉冲电场下的细胞凋亡情况,并用HE染色观察细胞形态变化.通过免疫组化法检测瘤体内微血管密度MVD、微血管形态、血管生长因子VEGF和增殖细胞核抗原PCNA的表达.结果发现nsPEF治疗后4d肿瘤生长抑制率达42

  4. Investigation of Abscopal and Bystander Effects in Immunocompromised Mice After Exposure to Pencilbeam and Microbeam Synchrotron Radiation.

    Science.gov (United States)

    Fernandez-Palomo, Cristian; Schültke, Elisabeth; Bräuer-Krisch, Elke; Laissue, Jean Albert; Blattmann, Hans; Seymour, Colin; Mothersill, Carmel

    2016-08-01

    Out-of-field effects are of considerable interest in radiotherapy. The mechanisms are poorly understood but are thought to involve signaling processes, which induce responses in non-targeted cells and tissues. The immune response is thought to play a role. The goal of this research was to study the induction of abscopal effects in the bladders of NU-Foxn1 mice after irradiating their brains using Pencil Beam (PB) or microbeam (MRT) irradiation at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. Athymic nude mice injected with F98 glioma cells into their right cerebral hemisphere 7 d earlier were treated with either MRT or PB. After recovery times of 2, 12, and 48 h, the urinary bladders were extracted and cultured as tissue explants for 24 h. The growth medium containing the potential signaling factors was harvested, filtered, and transferred to HaCaT reporter cells to assess their clonogenic survival and calcium signaling potential. The results show that in the tumor-free mice, both treatment modalities produce strong bystander/abscopal signals using the clonogenic reporter assay; however, the calcium data do not support a calcium channel mediated mechanism. The presence of a tumor reduces or reverses the effect. PB produced significantly stronger effects in the bladders of tumor-bearing animals. The authors conclude that immunocompromised mice produce signals, which can alter the response of unirradiated reporter cells; however, a novel mechanism appears to be involved.

  5. 皮下移植和皮下注射构建子宫内膜异位症皮下模型的比较研究%Comparison between two experimental methods of reproduction of subcutaneous endometriosis model in nude mice

    Institute of Scientific and Technical Information of China (English)

    王宁宁; 庄广伦; 董愉; 张红霞; 丁慧娟; 洪珊珊; 谭金凤; 刘斌; 黄建昭; 梅卓贤; 周灿权

    2009-01-01

    Objective To compare the results of two experimental methods, namely subcutaneous transplant and subcutaneous injection, in reproducing endometriosis in nude mice, and study the differences in angiogenesis related factors. Methods Nude mice were divided two groups: in group A, the human endometrium fragments were transplanted into subcutaneously, and in group B the human endometrium suspension was subcutaneously injected. Each group was then divided into two subgroups according to inplantation time (2 and 4 weeks) : group A1 and group A2, and group B1 and group B2. Vascular endothelial growth factor (VEGF) and microvessel density (MVD) were detected by SP method, and the weight and volume of ectopic focus between different groups were compared. Results At the same time points (2 week or 4 week), the volume of ectopic focus showed no significant difference between group A and group B (P> 0. 05), but the weight of ectopic focus was significantly higher in group A than in group B (P0. 05), but the VEGF expression and MVD in gland cells were significantly higher in Al and Bl groups at 2 weeks compared with that at 4-week point in A2 and B2 groups (P0.05),A组异位病灶重量较B组明显增加(P0.05).两组在2周时病灶腺体中VEGF表达及MVD均明显高于4周时(P<0.05).结论 两种方法均可成功构建裸鼠人子宫内膜异位症模型,并可观察血管新生情况,以皮下移植造模效果较好.

  6. Non-invasive imaging of GFP-luciferase labeled orthotopic prostate cancer model in nude mice using bioluminescence system%可发光可连续检测原位前列腺癌模型的建立

    Institute of Scientific and Technical Information of China (English)

    宋超; 廖文彪; 杨嗣星; 王玲珑

    2012-01-01

    Objective To develop preclinical orthotopic model in nude mice for sensitive prostate cancer cell tracking during tumor progression using bioluminescent technique.Methods The human prostate cancer cell line PC3 cells were transduced with green fluorescent protein (GFP) -luciferase fusion gene by a lentivirus vector which can express high activity of luciferase and GFP.Stably transduced GFP-LucPC3 monoclonal cells were got with Blasticidin selection.Labeled or normal tumor cells ( 5 × 106 ) were implanted into the flanks of 6 animals to build up an intradermal xenograft prostate cancer model,which provided prostate cancer graft to build the orthotopic prostate tumor model,and to confirm the tumorigenesis ablitiy of GFP-Luc-PC3.Tumor tissue from the either PC3 or GFP-Luc-PC3 line tumors was harvested and cut into pieces of about 2 mm3.These were grafted into the anterior prostates of 24 male animals which were randomly divided into two groups.The tumor growth was monitored by both WIS 200 and ex vivo tumor weight analysis 2,4,6 and 8 weeks after tumor tissue grafting.The bioluminescent signal values as well as tumor weight was measured,and their relationship was analyzed accordingly.Results A GFP-LucPC3 cell line was established which had the same growth pattern as well as tumorigenesis ability as normal PC3 cells.There was a positive linear correlation between bioluminescent signal and cell number with the coefficient factor r =0.997.In orthotopic prostate cancer model,all 12 mice in GFP-Luc-PC3 group developed prostate tumor,from which the bioluminescent signal could be recorded.In normal PC3 group,there was no significant bioluminescent signal.The bioluminescent values (photons/second) in vivo were (69.13298±2.07900) E+05,(82.66208±1.231 00) E+05,(91.94257±2.321 00) E+05 and ( 130.643 40 ± 3.247 00) E + 05 respectively 2,4,6 and 8 weeks after tumor tissue implantation.The tumor weight ex vivo was ( 9.67 ± 1.07 ),( 12.47 ± 2.12),( 16.45 ± 2.57 ),and ( 21

  7. Gene modified Ecoli DH5 for the treatment of liver metastasis of colon cancer in nude mice%经基因改造大肠杆菌DH5对裸鼠结肠癌肝转移灶的治疗效果

    Institute of Scientific and Technical Information of China (English)

    姜宏华; 周辉; 张纪伟; 莱代莉; 子树明; 徐佶; 杜鹏; 杨宝仁; 崔龙

    2012-01-01

    Objective The operon of formic dehydrogenase gene which was sensitive to hypoxia, the promoter of lux gene which could perceive the difference of cell density, and diphtheria toxin gene were constructed by synthetic AND gate methods. Then all these kinds of gene were imported into auxotrophy Ecoli DH5α mutagenized by N-Methyl-N'-nitro-N-nitrosoguanidine (NTG), which was eventually injected into nude mice with colon cancer. And the efficacy of this gene modified Ecoli DH5α on the liver metastasis of colon cancer was observed. Methods The plasmid was constructed and imported into auxotrophy Ecoli DH5α, and then the Ecoli DH5α was injected into 10 nude mice to observe the toxicity, and was injected into 20 nude mice with liver metastasis of colon cancer to observe the efficacy. Results Ten mice injected with wild type of Ecoli DH5α were all dead, and only one was dead of those injected with auxotrophy Ecoli DH5α. The size of liver metastasis of colon cancer in mice injected with auxotrophs Ecoli DH5α which contained plasmid was smaller than that contained no plasmid. Conclusion The auxotrophs Ecoli DH5α is safe for normal mice, and has chemotaxis and anti-tumor effect toward cancer foci.%目的:利用"与"门(AND gate)方法对缺氧敏感的甲酸脱氢酶基因操纵子、能感知细胞密度差异的lux基因转录启动子、白喉毒素基因等基因进行构建,导入NTG诱导的减毒营养缺陷型DH5α大肠杆菌(Ecoli DH5α),注射入荷瘤鼠,观察其对结肠癌肝转移灶的作用.方法:先构建质粒,然后导入诱变后DH5α大肠杆菌,注射入10只裸鼠体内,观察其毒性.后对20只结肠癌肝转移的荷瘤鼠注射后观察疗效.结果:注射野生型DH5α大肠杆茵10只裸鼠均死亡,而注射营养缺陷型DH5α大肠杆茵只有1只死亡,与未转染质粒的营养缺陷型DH5α大肠杆菌相比,注射含质粒的营养缺陷型DH5α大肠杆菌荷瘤鼠的癌转移灶大小明显小于对照组.结论:含"与"

  8. Human Cord Blood Mononuclear Cell Transplantation in the Treatment of Radioactive Experimental Study of Premature Ovarian Failure in Nude Mice%人脐血单个核细胞移植治疗放射性裸鼠卵巢早衰

    Institute of Scientific and Technical Information of China (English)

    党建红; 金志军; 葛军辉; 胡电; 彭飞

    2012-01-01

    This study was aimed to explore the feasibility and effects of human cord blood cell transplantation for the treatment of premature ovarian failure (POF) in nude mices. Methods:Thirty female nude mouse were randomly divided into three groups,Normal control group (n=35) and premature ovarian failure (POF plus vehicle,n=35); POF plus cell transplantation (HCMNCs were implanted into the bilateral ovarian,n=35). Cobalt-60 irradiation was used to establish POF models. HCMNCs were isolated by ficoll density gradient centrifugation, and labled by BrdU. Four weeks after transplantation, the nude mice were sacrificed for determination of serum E2, FSH, LH, histological and immunochemical examination of the bilateral ovaries. Results:The transplanted HCMNCs survived in transplantation group and participated the repair process in ovaries. The serums of E2, FSH, LH of the transplantation group were compared with POF control group. E2 significantly increased(P<0.05), FSH decreased significantly (P<0.05) ,LH decreased significantly (P<0.05). And also found the number of follicles recovered. Conclusions:HCMNCs can be successfully transplanted into nude mice ovaries, and can improve the recovery of ovarian function.%目的:探讨人脐血单个核细胞(HCMNCs)移植治疗卵巢早衰(POF)的可行性及疗效.方法:雌性BALB/C裸鼠105只,随机分为空白对照组、POF对照组、POF+人脐血单个核细胞移植组.钴60γ射线照射建立POF模型,聚蔗糖(Ficoll)密度梯度离心法制备HCMNCs悬液,并以5-溴-2'-脱氧尿苷(BrdU)标记.POF造模成功后,移植组双侧卵巢内注入标记的HCMNCs悬液,POF对照组双侧卵巢内注入同等量的达尔伯克改良伊格尔氏低培养基(L-DMEM)培养液,空白对照组未行任何处理.移植后4周,酶联免疫吸附试验(ELISA)法测定血清雌二醇(E2)、卵泡刺激素(FSH)、黄体生成激素(LH)水平变化,并取卵巢组织行苏木素-伊红(HE)染色、BrdU组化染色,观察卵巢卵泡数目

  9. Radiosensitization effect of cyclooxygenase-2 inhibitor NS398 on radioresistant esophageal cancer cell xenografts in nude mice%NS398对放射抗拒食管癌裸鼠移植瘤的放射增敏作用

    Institute of Scientific and Technical Information of China (English)

    车少敏; 张晓智; 陈鑫; 杨蕴一; 惠蓓娜

    2012-01-01

    Objective To investigate the radiosensitization effect of cyclooxygenase-2 inhibitor NS398 on radioresistant esophageal cancer cell xenografts in nude mice. Methods The model of xenograft tumor was established by subcutaneous inoculation of cell suspensions into the nude mice. We compared the tumorigenetic ability between esophageal EcalO9 cells and EcalO9R 50 Gy cells (which received a total irradiation dose of 50 Gy). The EcalO9R 50 Gy cell-bearing nude mice were divided randomly into 4 groups: NS398 treatment group, radiation group, NS398+radiation group and the control group. The volume and weight change of tumors were recorded during the 14 days of intervention. The tumor inhibition rate and radiosensitization ratio (E/O) were calculated. Results Ecal09R 50 Gy cells displayed 40 times higher tumorigenetic ability than EcalO9 cells in vivo. The treatment of NS398 plus radiation could significantly inhibit the growth of Ecal09R 50 Gy cell nude xenografts, particularly with the most obvious decrease of tumor volume and weight (P<0.05). The E/O of 1.5 mg/kg NS398 was 1.61 O1.4). Conclusion NS398 could enhance the radiosensitivity of radioresistant Ecal09R 50 Gy cells in vivo, and more in-depth signal conduction mechanisms need further study.%目的 研究COX-2抑制剂NS398对放射抗拒食管癌细胞裸鼠移植瘤的放射增敏作用.方法 采用食管癌细胞悬液裸鼠皮下接种法建立裸鼠移植瘤模型,比较食管Eca109细胞和放射抗拒Eca109R 50 Gy细胞(接受总剂量50 Gy照射)的致瘤能力.选取接种Eca109R 50 Gy细胞荷瘤裸鼠,随机分为NS398组、放射组、NS398+放射组和对照组.在干预的14d中记录移植瘤体积、重量,计算各组肿瘤抑制率和NS398的放射增敏比值(E/O).结果 Eca109R 50 Gy细胞比Eca109细胞裸鼠体内致瘤能力高出40倍.NS398+放射治疗能显著抑制裸鼠移植瘤的生长,体积缩小和瘤重减轻最为明显(P<0.05).1.5 mg/kg NS398的放射增敏比值E/O=1.61(>1

  10. Inhibition effect of IP6 on subcutaneous transplantation of colon cancer in nude mice%IP6对结肠癌裸鼠皮下移植瘤细胞生长抑制及其机制的探讨

    Institute of Scientific and Technical Information of China (English)

    宋扬; 李敏

    2011-01-01

    目的:研究肌醇六磷酸(IP6)对HT-29细胞裸鼠皮下移植瘤生长的抑制作用.方法:建立HT-29细胞裸鼠移植瘤模型,随机分为对照组(生理盐水组)、低剂量IP6组和高剂量IP6组,用药20 d后处死小鼠.比较各组抑瘤作用和裸鼠一般状态的变化,透射电镜观察移植瘤细胞形体变化,TUNEL法检测移植瘤细胞凋亡情况,并运用RT-PCR、蛋白质印迹法检测移植瘤Bcl-2及Bax基因和蛋白的表达.结果:IP6组出现典型凋亡现象,PCR及蛋白检测也显示IP6可显著上调Bax蛋白的表达,下调Bcl-2蛋白的表达(P<0.05);在移植瘤质量和体积方面,用药组与对照组差异无统计意义,P>0.05,但用药组移植瘤呈现下降趋势.结论:IP6可能通过促进细胞凋亡而起到抑制和延缓肿瘤生长的作用,其机制可能与上调Bax蛋白表达和下调Bcl-2蛋白表达有关.%OBJECTIVE: To investigate the effect and mechanism of inositol hexaphosphate (IP6) on human colorectal cancer in nude mouse subcutaneous xenograft model. METHODS: The cell line HT-29 in log phase of human colorectal cancer was implanted subcutaneously in BALB/C nude mice to develop implant-tumor. Then the nude mice were randomly allocated into three groups. After treating with IP6, the tumor growth and general condition of the nude mice were observed. The volume and weight of implant-tumor were measured. Simultaneously, the electron microscope and TUNEL method were used to detect and determine the cell apoptosis, and RT-PCR method was used to detect the expression of Bcl-2 and Bax mRNA in the tumor tissue. Western blot method was used to detect the expressions of Bcl-2 and Bax protein in the tumor tissue. RESULTS: IP6 induced tumor cell apoptosis and significantly inhibited the expressions of Bcl-2 and raised the expression of Bax (P0. 05). CONCLUSIONS: IP6 can inhibit the growth of human colorectal cancer implanted tumor mildly. The mechanism of antitumor may be correlated with inducing

  11. 放射性核素骨显像支持下建立乳腺癌骨转移裸鼠莫型%Establishment of Nude mice model of breast cancer osseous metastasis under the support of radionuclide bone imaging

    Institute of Scientific and Technical Information of China (English)

    程旭锋; 刘胜; 杨顺芳; 刘琦

    2011-01-01

    Objective To estabish the animal model of breast cancer osseous metastasis. Methods MDA-MB-231BO was injected in left ventricle of hairless mice at the density of 0. 8 × 107/ml and 1.0 ×107/ml, respectively, and the nude mice model of breast cancer osseous metastasis was detected by radionuclide imaging and X-ray. The survival time, the rate of body weight descending, the extent of osseous metastasis and the rate of metastasis in the organs of the nude mice with breast cancer osseous metastasis were investigated. Results In the 0. 8 × 107/ml group and the 1.0 × 107/ml group, the nude mice model of breast cancer osseous metastasis was established successfully. The extent of osseous metastasis, the rate of body weight descending and the rate of metastasis number/total cellular score of MDA-MB-231BO in the 1.0 × 107/m]group were significantly increased as compared with the 0. 8 × 107/ml group ( P <0. 05 ,P <0. 01 ). The survival time in the 0. 8 × l07/ml group were longer than that in the 1.0 × 107/ml group significantly (P <0.05). The metastasis number of 1.0 × 107/nl group was greater than that of 0. 8 × 107/ml group and the detection rate of metastasis by radionuclide imaging was 100%. Conclusion The radionuclide imaging thchnology can diagnosis early hairless mice osseous metastasis. The nude mice model of breast cancer osseous metastasis was established at the MDA-MB-231BO at the density of 0. 8 × 107/nl successfully. The nude mice model simulated the pathologic progress of breast cancer osseous metastasis completely.%目的 建立人乳腺癌骨转移裸小鼠模型。方法 采用人乳腺癌骨高转移细胞株MDA-MB-231BO,运用细胞悬液浓度0.8×107/ml、1.0×107/ml进行左心室注射,放射性核素骨显像和X线分别检测建立的人乳腺癌骨转移裸鼠模型。观察两组裸小鼠造模后的生存时间、体质量下降率,及骨转移程度与各部位转移率。结果 在两组裸小鼠体内均建

  12. The nude mouse as an in vivo model for human breast cancer invasion and metastasis

    DEFF Research Database (Denmark)

    Brünner, N; Boysen, B; Rømer, J;

    1993-01-01

    Human breast cancer xenografts only rarely invade and metastasize in nude mice, and have therefore only had limited use as a model for studying mechanisms involved in breast cancer spreading. However, recent reports describe differences not only between various cell lines but also between strains...

  13. Stathmin siRNA抑制人胃癌SGC-7901细胞裸鼠移植瘤的生长并诱导细胞凋亡%Stathmin siRNA induces growth inhibition and apoptosis of human gastric carcinoma SGC-7901 cell xenografts in nude mice

    Institute of Scientific and Technical Information of China (English)

    张彩凤; 夏永华; 李贞娟; 周慧聪; 韩宇; 孙矗

    2012-01-01

    AIM: To investigate the effects of microtubule — destabilizing protein stathmin on the growth and apoptosis of human gastric carcinoma SGC —7901 cell xenografts in nude mice. METHODS: The model of xenograft was established by implanting 0. 1 mL gastric carcinoma SGC — 7901 cell suspension ( 5 x 10 /L ) into the nude mice. The model animals were randomly divided into 3 groups including PBS group ( treated with PBS ), control siRNA group ( treated with control siRNA at the final concentration of 100 nmol/L ) and stathmin siRNA group ( treated with stathmin siRNA at the final concentration of 100 nmol/L ) by intraperitoneal injection. The status of xenografted nude mice was observed for continuous 2 weeks. Subsequently, the expression of proliferative antigen Ki —67 was detected by immunohistochemistry, and TUNEL was utilized to analyze cell apoptosis. The protein expression of stathmin, Bcl —2 and Bax was determined by Western blotting in the tumor tissue of xenografted nude mice. RESULTS: siRNA targeting stathmin obviously inhibited the growth of nude mouse xenografts ( P < 0. 05 ), and the weight of nude mouse xenografts in stathmin siRNA group was significantly lower than that in PBS group and control siRNA group. Additionally, the proliferation index of Ki — 67 in stathmin siRNA group was markedly lower than that in PBS group and control siRNA group. The number of apoptotic cells in stathmin siRNA group was evidently higher than that in PBS group and control siRNA group. Furthermore, the protein expression levels of stathmin and Bcl — 2 in stathmin siRNA group were obviously down — regulated, and the expression of Bax protein was significantly increased compared with PBS group and control siRNA group. CONCLUSION: Stathmin may play an important role in cell proliferation and apoptosis in gastric carcinoma, indicating a molecular target for treating gastric carcinoma.%目的:探讨微管解聚蛋白stathmin对人胃癌SGC-7901细胞裸鼠移植瘤

  14. Studies on biodistribution and imaging of 188Re labeled insulin-like growth factor-1 analogue in nude mice bearing human pancreatic carcinoma%188Re-胰岛素样生长因子1类似物在荷人胰腺癌裸鼠体内分布及其显像研究

    Institute of Scientific and Technical Information of China (English)

    邓胜明; 张玮; 章斌; 罗贤文; 吴翼伟

    2008-01-01

    目的 研究188Re标记胰岛素样生长因子l类似物(IGF-1A)在荷人胰腺癌裸鼠体内的分布及其显像.方法 ①直接法标记188Re-IGF-1A并测定标记率.②建立荷人胰腺癌Patu8988裸鼠模型.③188Re-IGF-1A经瘤内注射荷人胰腺癌裸鼠瘤内,分别于注射后15 min、1 h、4 h、24 h、3 d、5 d进行SPECT平面显像.④188ReO4-经瘤内注射后15 min、1 h、2 h、4 h、24 h进行显像,取各时间组裸鼠(n=4)脏器和肿瘤组织,计算每克组织百分注入剂量(%ID/g)及肿瘤/非肿瘤组织放射性摄取比值(T/NT).结果 ①188Re-IGF-1A标记率为(94.07±0.32)%.②瘤内注射188Re-IGF-1A后,肿瘤部位放射性积聚量4 h内差异无统计学意义(F=1.622,P>0.05),且随时间延长,肿瘤与其他脏器的T/NT呈上升趋势,其中肿瘤/肌肉在5 d时最高,达到6531.79±4930.26.③瘤内注射188ReO4-后,在体内初始主要分布于甲状腺、胃、肿瘤、血液,随时间延长,肿瘤部位放射性计数迅速下降.④在24 h,瘤内注射188Re-IGF-1A组肿瘤及肾脏内%ID/g较188ReO4-组高,两者有统计学差异(t=5.877,t=13.287,P<0.01);两组肿瘤内%ID/g比值在24 h达到最高,为74.10倍.⑤瘤内注射188Re-IGF-1A后,SPECT平面显像见瘤内浓聚,5 d时仅见肿瘤部位显影.结论 188Re-IGF-1A对胰腺癌具有良好的亲和力,在肿瘤部位有较高的T/NT,可望作为胰腺癌治疗的药物.%Objective To evaluate the biodistribution and planar gamma carnera jmaging characteristics of 188Re labeled insulin-like growth factor 1 analogue(188Re-IGF-1A)in tumor-bearing mice.Methods ①To label IGF-1A with 188Re directly and to determine the labeling efficiency.②To establish nude mice model which beating human pancreatic carcinoma cell Patu8988.③To scan those nude mice at 15 min,1 h,4 h,24 h,3 d and 5 d after intratumor injection with 188Re-IGF-1A into their tumors.④To scan those nude mice at 15min,1 h,2h,4 h and24 h after intratumor injection with 188ReO4-into their

  15. Mechanisms of Arsenic Trioxide on Invasion and Adhesion of Human Breast Cancer Xenograft Tumor in Nude Mice%三氧化二砷影响人乳腺癌裸鼠移植瘤侵袭性和黏附性 Syk 机制

    Institute of Scientific and Technical Information of China (English)

    周艳; 吴振村; 程健君

    2015-01-01

    目的:探讨三氧化二砷(arsenic trioxide, AS2 O3)影响人乳腺癌裸鼠移植瘤侵袭性和黏附性 Syk作用机制。方法成功建立人乳腺癌裸鼠移植瘤模型,随机分为实验组(AS2 O3)和对照组(生理盐水)。7 d后观察肿瘤体积的变化,流式细胞术检测肿瘤组织细胞凋亡情况及两组荷瘤裸鼠肿瘤组织中基质金属蛋白酶-9(MMP-9)和细胞间黏附分子-1(ICAM-1)的表达情况。结果实验组荷瘤裸鼠肿瘤体积明显低于对照组,差异有统计学意义;实验组荷瘤裸鼠肿瘤组织细胞凋亡率明显高于对照组(P <0.01);实验组 ICAM-1表达明显高于对照组(P <0.05);实验组 MMP-9表达低于对照组(P <0.05)。结论AS2 O3对人乳腺癌裸鼠移植瘤具有明显的抑瘤作用,可降低肿瘤组织侵袭性增加其黏附性,其作用机制可能与蛋白酪氨酸激酶 Syk 的表达有关。%Objective To explore the mechanisms of arsenic trioxide (As2 O3 )on invasion and adhe-sion of human breast cancer xenograft tumor in nude mice.Methods Xenografted breast carcinoma in nude mice was established and the mice models were divided randomly into two groups,namely experi-mental (treated with AS2 O3 )and control group (treated with saline).After 7 days,the changes in xen-ograft tumor volume were measured,and the apoptosis of tumor cells were detected by flow cytometry. The expression of matrix metalloproteinase-9 (MMP-9)and intercellular adhesion molecular-1 (ICAM-1) were also detected using flow cytometry.Results The tumor volume of experimental group was signifi-cantly reduced compared with that of control group;while the tumor cell apoptosis of experimental group was higher than that of control group (P < 0.01 );Experimental group showed significantly increased ICAM-1 expression (P <0.05)and reduced MMP-9 expression (P <0.05)compared with control group. Conclusion As2 O3 could inhibit the growth of human breast cancer in

  16. Effects of anti-gene and antisense therapeutics on human prostate cancer xenograft in nude mice%反基因及反义寡核苷酸对人前列腺癌裸鼠移植瘤生长的抑制作用

    Institute of Scientific and Technical Information of China (English)

    张勇; 马毅; 卢汉平; 周祥福; 谢瑶; 高锦辉; 梁昌盛

    2008-01-01

    Objective To investigate the effects of triple-helix forming oligonucleotide (TFO) and antisense oligonucleotide (ASO) on androgen receptor (AR) expression and tumor growth of human prostate cancer xenografts in nude mice.Methods Thirty-two nude mice were inoculated with human prostate cancer cells of the line LNCaP-C4-2 were randomized into 4 equal groups:TFO treatment group,undergoing intra-tumor injection of TFO at the dose of 25 mg · kg-1 · (2d)-1 for 14 times,ASO treatment group, undergoing intra-tumor injection of ASO at the same dose for 14 times,SCO group,undergoing intra-rumor injection of sequence control oligonucleotide (SCO) at the same dose for 14 times,and control group.The body weight and xenograft tumor volume of the nude mice were monitored during the therapy.28 days later venous blood samples were collected to measure the level of prostate specific antigen (PSA) by radioimmunoassay and then the mice were killed with their tumors taken out to measure the weight,and RTPCR,immunohistochemistry,and radioligand binding assay were used to detect the AR gene mRNA and protein expression in the tumor tissues.Results By the end of experiment the volumes and weights of tumor of the ASO and ASO groups were all significantly lower than those of the control group ( all P 0.05 ) .Conclusion TFO shows significantly higher inhibitory effect on AR expression and tumor growth of human prostate cancer xenograft than ASO,and is a promising agent for prostate cancer gene therapy.%目的 探讨三螺旋形成寡核苷酸(TFO)和反义寡核苷酸(ASO)对人前列腺癌裸鼠移植瘤雄激素受体(AR)表达和肿瘤细胞生长的抑制作用.方法 32只荷LNCaP-CA-2前列腺癌移植瘤裸鼠随机分成4组:TFO治疗组、ASO治疗组、序列对照寡核苷酸(SCO)非特异性对照组和阴性对照组.采用瘤内注射给药,寡核苷酸用量25 mg/kg,隔天给药1次,共14次.观察裸鼠体重和肿瘤体积变化.测量移植瘤重量计算抑瘤率,放射

  17. Anticancer effects of combination of anti-EBV-LMP1 humanized antibody Fab and mitomycin C on nasopharyngeal carcinoma xenografts in nude mice%人源抗EB病毒潜伏膜蛋白1抗体Fab联合丝裂霉素C对鼻咽癌裸鼠移植瘤生长的抑制作用

    Institute of Scientific and Technical Information of China (English)

    毛圆; 张大为; 陈仁杰; 朱进; 冯振卿

    2011-01-01

    目的:观察联合应用人源抗EB病毒鼻咽癌潜伏膜蛋白1(latent membrane protein 1,LMP1)抗体Fab片段与丝裂霉素C(mitomycin C,MMC)对LMP1阳性鼻咽癌裸鼠移植瘤生长的抑制作用.方法:建立LMP1阳性鼻咽癌裸鼠移植瘤模型,20只成瘤裸鼠随机分成4组,即Fab组、MMC组、Fab+MMC组和对照组.腹腔注射药物,每3天1次,共5次.观察肿瘤生长、测量肿瘤体积,计算抑瘤率.免疫组化法检测肿瘤组织血管内皮生长因子(vascular endothelial growth factor,VEGF)表达、流式细胞术检测肿瘤细胞凋亡情况.结果:Fab组、MMC组和Fab+MMC组抑瘤率分别为18.90%、28.95%、49.12%.Fab组、Fab+MMC组VEGF表达量明显低于对照组(P0.05).MMC组、Fab+MMC组肿瘤细胞凋亡率分别为(11.84±1.50)%、(17.55±3.21)%,与对照组凋亡率(3.90±0.55)%相比,有显著差异(P0.05).结论:Fab及MMC均有抑瘤作用,联合使用效果优于单独使用,二者抑制肿瘤的作用途径不完全相同.Fab可能与抑制肿瘤血管生成有关,MMC可能与诱导肿瘤细胞凋亡增加有关.%Objective: To investigate the inhibitory activity of anti-latent membrane protein 1 (LMPl)antibody fragment (Fab) combined with mitomycin C (MMC) on nasopharyngeal carcinoma NPC-LMPl xenografts in nude mice. Methods:Nasopharyngeal carcinoma LMPl cells (5×lO6) were subcutaneously transplanted in to 20 nude mice, which were randomly divided into Fab group,MMC group, Fab+MMC group and control group. The mice were injected once every 3 days. After corresponding treatments for 5 times,the tumor inhibition rate was evaluated, vascular endothelial growth factor (VEGF) was measured with immunohistochemistry, and the apoptotic rates were analyzed by flow cytometry. Results:The tumor growth inhibition rates in Fab group, MMC group, Fab+MMC group were 18.90%,28.95% and 49.12%,respectively. VEGF in Fab group and Fab+MMC group significantly reduced and showed lower expression compared with control group (P

  18. Effect of Slug knock-down on tumor formation and metastasis of HCT116 cells in nude mice%RNA干扰Slug基因对HCT116细胞裸鼠移植瘤生长及转移的影响

    Institute of Scientific and Technical Information of China (English)

    钱江; 韩佳; 陈鹏; 朱春丽; 傅仲学

    2014-01-01

    Objective:To explore the influence of RNAi mediated Slug silencing on the growth and metastasis of colon cancer in nude mice.Methods: HCT116 colon cancer cells use for 24 five-week-old nude mice implanted subcutaneously , established colon cancer xenograft model in nude mice ,all divided into blank control group ,negative control group and the experimental group ,each group had eight nude mices.All group were injected with saline , negative plasmid and lentivirus vectors respectively.Tumor growth was observed and draw tumor curved growth ,changes in tumor growth and lymph node metastasis between the groups were observed ,Slug gene and protein expression were detected by immunohistochemistry ,qRT-PCR and Western blot analysis.Results: Slug gene shRNA intervention group compared with the control group and negative control group ,tumor grew slower ,tumor mass was significantly reduced (3.08±0.31 vs 7.37±1.18,7.46±1.16,P<0.01),experimental group of lymph node-positive rate was 36.3%( 4 /11 ) ,compared to the negative control group 77.8% ( 14/18 ) and the control group was 68.4% ( 13/19 ) ( P<0.01 ).Conclusion: Targeted Slug RNA interference can significantly inhibit the growth of colon cancer in nude mice ,lymph node metastasis and the expression of the gene protein in cancer tissue ,Slug may be a potential molecular target for colon cancer gene therapy.%目的:探讨通过靶向RNA干扰(RNA interference,RNAi)抑制Slug基因的表达,观测对荷瘤裸鼠结直肠癌生长及转移的影响。方法:利用结肠癌细胞株HCT116对24只5周龄裸鼠皮下种植,建立结肠癌裸鼠皮下移植瘤模型,设立空白对照组、阴性对照组及实验组三组,每组8只。分别注射生理盐水、阴性对照质粒及慢病毒载体,观察肿瘤生长情况,绘制肿瘤生长曲线,观察各组间肿瘤生长及淋巴结转移的变化,应用免疫组化、qRT-PCR和Western blot检测Slug基因和蛋白表达情况。结果:Slug基

  19. 人肝癌裸鼠NKG2D受体的表达及对NK细胞毒活性的影响%Expression of NKG2D receptor and its effects on the cytotoxicity of NK cells in nude mice with transplanted human hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    司文章; 周晓俊; 秦磊; 钱海鑫

    2013-01-01

    目的 通过研究原发性肝癌中NK细胞的细胞毒活性变化及其活化性受体NKG2D的表达,观察肝脏和脾脏组织病理变化,探讨NK细胞免疫抑制机制,为原发性肝癌的免疫治疗提供理论依据.方法 ①建立人肝癌裸鼠皮下-肝原位移植瘤模型:先用人肝癌细胞株Hep3B接种于裸鼠皮下,形成皮下移植瘤,然后用此移植瘤组织再接种于裸鼠肝内,建立肝原位移植瘤模型(间接肝原位移植瘤模型);②检测裸鼠原发性肝癌对NK细胞免疫活性的影响:分离裸鼠外周血、肝脏及脾脏组织NK细胞,LDH方法检测NK细胞的细胞毒活性,流式细胞技术检测不同组织NK细胞NKG2D表达百分率,H-E染色观察肝脏移植瘤对肝脏和脾脏淋巴细胞的影响.结果 ①外周血、肝脏及脾脏的NK细胞毒活性及NKG2D受体表达随着肿瘤生长逐渐下降,其中肝脏NK细胞毒活性及NKG2D表达下降明显;②荷瘤裸鼠肝脏癌组织与皮下瘤相同,癌组织异型性与时间呈正相关,脾脏淋巴小结在第4周增生明显,第8周小梁结构增多.结论 原发性肝癌通过下调NKG2D的表达,对NK细胞有免疫抑制作用,这种作用主要发生在肝脏,但对外周血和脾脏也有影响.%Objective To investigate the cytotoxicity of NK cells and the expression of active NKG2D receptor in hepatocellular carcinoma (HCC).Then,to observe the pathological changes of liver and spleen.Eventually,to study the immunosuppression mechanisms of hepatocellular carcinomas upon NK cells.Methods ① Establishment of the orthotopic transplantation tumor model from the subcutaneous model of human hepatocellular carcinoma in nude mice:Hep3B cells were subcutaneously transplanted to form subcutaneous transplantation tumors in nude mice.Then,the subcutaneous transplantation tumors were injected into liver to form the orthotopic transplantation tumor model (indirect orthotopic model) in nude mice.② The effects of the primary hepatocellular

  20. 三氧化二砷诱导人鼻咽低分化鳞癌BALB/C裸鼠移植瘤的细胞分化和凋亡的研究%Arsenic Trioxide Induced Differentiation and Apoptosis in Human Nasopharyngeal Carcinoma Xenografts in BALB/C Nude Mice

    Institute of Scientific and Technical Information of China (English)

    郑毓武; ZHENG Yuwu; 杜彩文; DU Caiwen; 李德锐; LI Derui; LIN Yingcheng; WU Mingyao

    2004-01-01

    Objective: To study the effect of arsenic trioxide (As2O3) on human poorly differentiated nasopharyngeal cancer cell line, CSNE-1, in vivo and its possible mechanism of action. Methods: CSNE-1ceils were established as xenografts in BALB/C nude mice. The tumor-bearing mice were treated with As2O3 at the dose of 5 mg/kg every day. The tumor growth was observed by tumor-growth curve. Morphologic changes were studied under light microscopy and electron microscopy. TUNEL was used to detect apoptosis. The expression of PCNA, p53, Bcl-2 and Bax were determined by immunohistochemistry. Results: The cell growth and proliferate activity were significantly inhibited by As2O3 at the dose of 5 mg/kg every day. Morphologic changes such as the formation of keratinization of tumor cells, decreased ratio of nuclear/cytoplasm, increased organelle and plasmic fibril in cytoplasm were identified. Cytodesma, desmosomes and micro-process were seen under light microscopy and transmission electron microscopy, which revealed that the cancer cells underwent differentiation. In addition, remarkable cell apoptosis were observed by TUNEL assay. Over expression of p53 and Bax was detected in the As2O3 treatment group when compared with control group. Conclusion: As2O3 inhibited proliferation of human poorly differentiated nasopharyngeal cancer cell CSNE-1 by inducing differentiation and apoptosis, which may be related to the up-regulation of p53 and Bax expression.

  1. 诺斯卡品逆转人卵巢癌裸鼠移植瘤对顺铂耐药的作用及机制%The reversal effect and action mechanism of noscapine on the drug resistant of cisplatin in nude mice with transplanted human ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    申薇; 梁冰锋; 李秀荣; 程建新; 李红方

    2014-01-01

    Objective To investigate the reversal effect and relative mechanism of noscapine ( NOS ) on the drug resistant of cisplatin ( DDP) in nude mice with transplanted human ovarian cancer cell line SKOV 3/DDP.Methods The animal models with transplanted human ovarian cancer were successfully established in 24 BALB/c nu/nu mice,then the mice were randomly divided into control group ,DDP group,NOS group and combined treatment group (NOS+DDP),with 6 mice in each group .The appetite and mental state of the nude mice in different groups were observed .The weight of the nude mice and size of the xenograft tumor were measured and tumor growth curve was drew .The xenograft tumor was made into single cell suspension fluid with nets rub method,and the cell cycle,cell apoptosis rate,the expression levels of XIAP,Caspase-3,Bcl-2 and Survivin proteins in tumor tissues were detected by flow cytometry .Results The xenograft tumor size in combined treatment group was significantly smaller than that in the other three groups ( P <0 .05 ) .As compared with those in control group and DDP group , the tumor cell apoptosis rate and cell percentage at G 2/M phase in combined treatment group were significantly increased ( P <0.05),however,the expression levels of XIAP,Bcl-2 and Survivin proteins were obviously decreased,but the expression levels of Caspase-3 protein were significantly increased ( P <0.05).Conclusion NOS can increase the sensitivity and reverse the drug resistance of xenograft tumor cells to DDP , and its action mechanism may be correlated with downregulation of expression levels of XIAP , Bcl-2 and Survivin protein , and with upregulation of expression levels of Caspase-3 protein in xenograft tumor tissues of nude mice .%目的:探讨微管抑制剂诺斯卡品( NOS )逆转人卵巢癌细胞株 SKOV3/DDP 裸鼠皮下移植瘤对顺铂( DDP)耐药的作用及其机制。方法建立人卵巢癌裸鼠移植瘤模型,分为对照组、DDP组

  2. siRNA沉默LKB1基因激活Hedgehog信号通路及对人乳腺癌裸鼠移植瘤模型生长的实验研究%Silencing LKB1 by siRNA activated Hedgehog signaling pathway and the growth of xenografted breast carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    庄志刚; 成小林; 蒋蓓琦; 傅韵; 李正东; 罗建民; 金伟

    2011-01-01

    目的 探讨应用小分子干扰RNA(small interfering RNA,siRNA)沉默抑癌基因LKB1对人乳腺癌细胞MDA-MB-231中Hedgehog信号通路相关因子的表达及人乳腺癌裸鼠移植瘤模型的肿瘤生长的影响.方法 构建LKB1基因siRNA质粒LKB1-siRNA;建立LKB1表达抑制的MDA-MB-435细胞模型;裸鼠乳晕皮下接种,建立人乳腺癌裸鼠移植瘤动物模型;成瘤后,观察肿瘤体积变化、裸鼠生存时间;并用Western印迹法检测瘤组织中LKB1和Hedgehog信号通路中信号肽Shh、Sufu、膜受体Ptch、Smo、转录因子Gli1、Hip 蛋白表达的变化.结果 LKB1-siRNA质粒组裸鼠的肿瘤体积明显增长(P<0.05);肿瘤内LKB1基因表达水平明显下降,而Hedgehog信号通路相关因子Shh、Gli1、Ptch、Smo的表达升高,Hedgehog信号通路抑制因子Sufu、Hip表达下降.结论 LKB1基因siRNA能够明显抑制人乳腺癌裸鼠移植模型的LKB1基因的表达,上调Hedgehog信号通路相关因子的表达,促进肿瘤生长.LKB1基因和Hedgehog信号通路在乳腺癌细胞中呈现负相关表达.%Objective To investigate the effect of silencing LKB1 by small interfering RNA(siR-NA) on the expression of the correlation factor of Hedgehog signaling pathways in human breast cancer MDA-MB-231 cells and the growth of xenografted breast carcinoma in nude mice. Methods Plasmids of siRNA for LKB1 gene were constructed. RNA interference technique was used to silence LKB1 gene in breast carcinoma cells,xenografted tumor model was established in nude mice by subcutaneous inoculation of MDA-MB-231 cells. The tumor volume and survival time of nude mice were recorded. The expression of LKB1, Shh, Sufu.Gli 1 ,Ptch,Smo and Hip was measured by Western blotting. Results The tumor size was significantly increased in LKBl-siRNA treated group(P <0. 01). Western blotting analysis showed that the expression of LKB1 in xenografted tumor was markedly decreased and the correlation factor of Hedgehog signaling pathways was

  3. 活体成像分析异硫氰酸荧光素标记Rituximab在荷淋巴瘤裸鼠体内的生物分布%In vivo imaging analysis of biodistribution of FITC-labeled Rituximab in lymphoma-bearing nude mice

    Institute of Scientific and Technical Information of China (English)

    张胜华; 程昕; 钟根深; 熊冬生; 邵荣光

    2010-01-01

    目的 应用活体动物体内光学成像系统观察抗体药物Rituximab在荷淋巴瘤裸鼠体内的生物分布.方法 制备FITC标记的Rituximab(FITC-Rituximab),用激光扫描共聚焦显微镜和流式细胞仪体外分析FITC-Rituximab与人淋巴瘤Raji细胞的亲和力;建立裸鼠淋巴瘤皮下移植瘤模型,应用活体动物体内光学成像系统观察FITC-Rituximab在荷瘤小鼠体内的分布.结果 流式细胞仪和激光扫描共聚焦显微镜检测证明FITC-Rituximab与淋巴瘤Raji细胞有较好的亲合活性,主要结合在细胞膜表面.体内活体动物光学成像分析表明,FITC-Rituximab在1 h内即可特异性地在肿瘤部位富集,3~4 h即可进入肿瘤组织内部并达到最大浓度富集,8~10 h后在肿瘤组织仍可观察到FITCRituximab的特异性的富集,而在其他组织器官没有可见的荧光存在;双侧皮下移植瘤模型再次证明FITC-Rituximab具有对CD20抗原过表达的淋巴瘤特异性结合能力.结论 动物活体成像系统能够准确地监测FITC标记Rituximab在荷瘤裸鼠体内的动态分布情况,该技术对实时分析抗体药物在荷瘤小鼠体内的靶向效果具有参考价值和指导意义.%Objective To conduct an in vivo optical imaging analysis of the biodistribution of antibody Rituximab in lymphoma tumor-bearing nude mice. Methods Laser scanning confocal microscope and flow cytometry were employed to determine the affinity of FITC-labeled Rituximab (FITC-Rituximab)with human lymphoma Raji cells. And the in vivo optical imaging system was used to analyze the biodistribution of FITC-Rituximab in lymphoma-transplanted xenograft nude mice. Results The results of flow cytometry and laser scanning confocal microscope demonstrated that FITC-Rituximab had remarkable affinity with lymphoma Raji cells and was mainly bound at cell membrane. The results of in vivo imaging analysis suggested that FITC-Rituximab could specifically accumulated at peritumor tissue less

  4. 重组人血管内皮抑素联合NP方案对人乳腺癌裸鼠移植瘤作用的实验研究%Experimental study of recombinant human endostatin combined with NVB-Cisplatin on human breast cancer xenografts in nude mice

    Institute of Scientific and Technical Information of China (English)

    程丽; 张幸平; 杨鸿捷; 周涛琪; 饶明月

    2011-01-01

    Objective:To evaluate the inhibitory effect of recombinant human endostatin(rh-ES) combined with NP treatment on tumor growth and antiagiogenesis in nude mice after xenograft of MCF-7 cell line. Methods:40 nude mice models with human breast carcinoma were divided into group NVB-Cisplatin (group A), group rh-ES (group B), group NVB-Cisplatin + rh-ES (group C)and control group(group D),each group had 10 nude mice. Group A was given NP treatment one cycle. Group B was given rh-Endostatin two cycles. Group C was given NP treatment one cycle combined with rh-Endostatin two cycles. Group D was given normal saline solution respectively. Rh-Endostatin was used two cycles,each cycle for 14 days,two cvcles interval 7 days. Tumor inhibition rate (TIR)and growth curve of each group was calculated and plotted. The vascular endothelial growth factor ( VEGF ) and microvascular density ( MVD ) expression were detected by immunohistochemistry. Results:TIR of A, B and C groups were 61.80%,64.79% and 88.95%. The TlR of group C was obviously higher than other two groups. Compared with VEGF expression,group C was significantly lower than group A and group D ( both P were 0.001 ). Compared with MVD, group C was significantly lower than other three groups. Conclusion:Rh-Endostatin combined NP treatment have synergistic effect, they can obviously inhibit tumor growth and angiogenesis.%目的:探讨重组人血管内皮抑素(Recombinant human endostatin,rh-ES)联合长春瑞滨+顺铂(NP方案)化疗对人乳腺癌裸鼠移植瘤的肿瘤生长及新生血管生成的抑制作用.方法:将40只荷瘤裸鼠随机分成NP方案组(A组)、rh-ES组(B组)、联合用药组(C组)和空白对照组(D组),每组10只.A组给予NP方案化疗1周期,B组给予rh-ES 2周期,C组给予rh-ES两周期加NP方案1周期,D组给予等剂量生理盐水.其中,rh-ES连续用药14 d为1周期,间隔7 d后重复1周期.计算各组抑瘤率,绘制肿瘤生长曲线.肿瘤组织进行免疫组化

  5. Effect of Vitamin K2 and Benazepril Combination Therapy on Gastric Cancer in Nude Mice%维生素K2联合苯那普利对裸鼠胃癌的治疗作用及其机制的研究

    Institute of Scientific and Technical Information of China (English)

    应卫星; 陈华; 李荣洲

    2012-01-01

    目的 通过建立胃癌裸鼠种植瘤模型观察维生素(Vit) K2联合苯那普利对人胃癌SGC -7901裸鼠种植瘤的影响,以探讨两者对胃癌细胞的作用及机制.方法 通过人胃癌SGC-7901细胞接种建立胃癌裸鼠种植瘤模型后,随机分成对照组、Vit K2组、苯那普利组和联合组,每组10只,灌胃2周后处死;TUNEL法检测各组胃癌细胞凋亡情况,免疫组化法检测血管内皮生长因子(VEGF)、caspase 3的蛋白表达情况.结果 与对照组相比,药物组能明显抑制瘤体生长,而联合组较单独药物组抑制作用更明显(P<0.05).联合组在抑制胃癌细胞生长和诱导胃癌细胞凋亡方面的作用均优于单独药物组(P<0.05).与对照组比,联合组的VEGF表达阳性率明显下降(P<0.05).结论 Vit K2与苯那普利联合能抑制裸鼠胃癌细胞生长,两者联合有协同作用,其机制可能为通过诱导细胞凋亡及抑制VEGF的表达.%BJECTIVE To investigate the effect of vitamin K2 combined with benazepril on human gastric cancer in nude mice. METHODS SGC-7901 human gastric cancer cells were implanted into BALB/c nude mice to establish the cancer model. Fourteen days after the subcutaneous implantation of cancer cells,40 nude mice were randomly divided into 4 groups; control group, vitamin K2 therapy group, benazepril therapy group and combination therapy group ( vitamin K2 + benazepril). After 14 d, the tumor growth was evaluated, apoptosis indices were examined by TUNEL assay, and VEGF and caspase 3 expression were assessed by immunohistochemical staining. RESULTS Compared to the control group, tumor weights were decreased and apoptosis indexes was significantly increased in the therapy groups (P < 0. 05 ) , the protein expression of caspase 3 were up-regulated, and VEGF were decreased in the therapy group (P <0. 05) ,and all the changes above were more significant in combination therapy group than vitamin K2 or benazepril group (P <0. 05

  6. 双氢青蒿素对人结直肠癌裸鼠移植瘤的抑制作用及机制研究%Antitumor Effect and Mechanism of Dihydroartemisinin on Colorectal Cancer in Nude Mice with Transplanted Tumor of Human Colorectai Cancer

    Institute of Scientific and Technical Information of China (English)

    战晓农; 黄燕; 王雷; 梁志; 李智

    2011-01-01

    目的 研究双氢青蒿素( Dihydroartemisinine,DHA)对人结直肠癌LoVo细胞裸鼠移植瘤的抑制作用及可能机制.方法将人结直肠癌LoVo细胞接种于Balb/c裸鼠皮下,建立结直肠癌模型.将造模成功裸鼠随机分为5组,即模型对照组,阳性对照组(5-Fu 20 mg/kg),DHA高、中、低剂量组(120,60,30 mg/kg).观察各组动物肿瘤的重量及抑瘤率;采用免疫组化SABC法测定各组裸鼠肿瘤组织B-cell lymphoma-leukemia-2 gene(Bcl-2)和血管内皮生长因子(VEGF)的表达.结果5-Fu组及DHA高、中剂量组的抑瘤率显著高于模型组(P< 0.01或P<0.05);5-Fu组和DHA高剂量组Bcl-2的阳性表达率显著低于模型对照组(P< 0.01或P<0.05);5-Fu组VEGF的阳性表达率显著低于模型对照组(P<0.05).结论双氢青蒿素具有较强的抗结直肠癌活性,其作用机制可能是抑制抗凋亡基因Bcl-2的表达,从而刺激结直肠癌细胞凋亡.%Objective To observe the antitumor effect and mechanisms of dihydroartemisinin(DHA) on transplanted tumor of colorectal cancer in nude mice. Methods Colorectal cancer animal models were established by subcutaneous injection of colorectal cancer LoVo cells suspension into the specific-pathogen free BALB/c nude mice. Then the BALB/c tumor-bearing nude mice were randomized into 5 groups: model group, 5-FU group (intraperitoneal injec tion of 5-FU 20 mg/kg for 5 days) , and high-, middle-and low-dose DHA groups (gastric gavage of DHA in the dose of 120, 60 and 30 mg/kg respectively for 14 days). The tumor mass weight and tumor-inhibition rate were examined after treatment. And the expression levels of Bcl-2 and vascular endothelial growth factor(VEGF) were detected by SABC immunohistochemical assay. Results After treatment, the tumor-inhibition rate were increased in 5-FU group and high-and middle-dose DHA groups(P < 0.01 or P < 0.05 compared with those in the model group). The positive expression rate of bcl-2 in 5-FU group and high

  7. Reduction of cathepsin B inhibits proliferation of xenografted human esophageal carcinoma cell line EC9706 in nude mice and the related molecular mechanism study%下调组织蛋白酶B对人食管鳞癌EC9706细胞裸鼠移植瘤的抑制作用及其机制

    Institute of Scientific and Technical Information of China (English)

    冯天平; 赵景志; 尹磊; 陈奎生; 李晟磊

    2013-01-01

    目的:研究下调组织蛋白酶B(cathepsin B,CB)对人食管鳞癌EC9706细胞裸鼠移植瘤的抑制作用并探讨其体内抗肿瘤机制.方法:建立裸鼠荷瘤模型,利用CB siRNA和对照siRNA注射荷瘤裸鼠,监测肿瘤生长变化,采用RT-PCR及Western blot法检测治疗前后瘤体内CB及黏附分子Syndecan-1表达的变化.结果:成功构建了CB siRNA转染荷瘤裸鼠模型.与对照siRNA组和空白对照组相比,CB siRNA组荷瘤裸鼠肿瘤体积下降,组间比较差异具有统计学意义(F=483.992,P<0.05).转染CB siRNA后,CB蛋白及mRNA表达均显著下调,组间比较差异具有统计学意义(F=733.255及932.681,均P<0.01),Syndecan-1蛋白及mRNA表达则均显著升高,组间比较差异具有统计学意义(F=404.234及1 509.951,均P<0.01).结论:CB siRNA可以有效抑制人食管鳞癌EC9706细胞裸鼠移植瘤的生长,并下调CB的表达和上调Syndecan-1的表达,本研究为食管鳞癌的分子治疗提供了一定的理论依据.%Objective To investigate the effect of cathepsin B (CB) reduction on tumor growth of xenografted human esophageal squamous cell carcinoma (ESCC) cell line EC9706 in nude mice and to explore the related molecular mechanism. Methods The xenografted tumor model was established, and the CB siRNA and control siRNA was injected into the xenografted nude mice, respectively. The tumor growth was determined. RT-PCR and Western blot assay were performed to detect CB and Syndecan-1 expressions in tumor tissue. Results After CB siRNA injection, the tumor volume was decreased significantly in the CB siRNA group compared with that in the control siRNA group or the blank control group, respectively (F = 483.992, P < 0.05). The CB mRNA and protein expression was lower in the CB siRNA group than that in the control siRNA group or the blank control group, respectively, and there was significant difference among the three groups (F = 733.255 and 932.681, both P < 0.01). Furthermore, Syndecan-1 m

  8. Effects of recombinant human growth hormone on vascular endothelial growth factor expression of human gastric carcinoma xenografts in nude mice%重组人生长激素对荷人胃癌裸鼠移植瘤血管内皮生长因子表达的影响

    Institute of Scientific and Technical Information of China (English)

    程璐; 林岩; 曹鹏; 蒋苏豫; 李苏宜

    2010-01-01

    xenografts in nude mice with different expressions of growth hormone receptor (GHR). Methods Immunocytochemical method was used to pick out one GHR-positive and one GHR-negative cell line. Then the cells were subcutaneously injected into 24 nude mice separately. The nude mice bearing two different kinds of human gastric caicinoma were equalges of body weight and tumor volume of nude mice were recorded. Serum concentrations of VEGF in peripheral blood were analyzed by ELISA. VEGF protein and mRNA expression in tumor tissue were detected by immunohistochemistry and RT-PCR, respectively. Results We chose SGC-7901 as GHR positive group, and MKN-45 as the negative one. For nude mice bearing GHR + SGC-7901 xenografts, the tumor volumes were significantly larger in rhGH groups than in control group (P < 0.05), and the high-dose rhGH group revealed greater effect (P < 0. 05).Body weights were not significantly different among three groups (P > 0. 05). Serum VEGF concentration was (252.94 ± 15.32) ng/L in the high-dose rhGH group, which was significantly higher than that in control group [(49.94 ± 5.73) ng/L] and low-dose rhGH group [(167.60 ± 9.54) ng/L] (P < 0.05). Moderate positive staining with VEGF was observed in the control group, while VEGF staining was strong in rhGH administration groups. The relative expression of VEGF mRNA for the high-dose rhGH group was 0. 6470 ± 0. 0447, which was significantly higher than that in control group (0. 3230 ± 0. 0258)and low-dose rhGH group (0. 412 ± 0. 0351)(P < 0.05). While for nude mice bearing GHR-MKN-45 xenografts, the body weights of the rhGH-administrated groups were significantly higher than that of control group (P < 0.05), while tumor growth, serum VEGF concentration, and the expressions of VEGF mRNA and protein in tumor tissue were not significantly different (P > 0.05).Conclusions rhGH can promote tumor growth and increase the expression of VEGF in the GHR-highly-expressed SGC-7901 xenograft tumor model

  9. 靶向纳米造影剂C225-USPIO标记裸鼠鼻咽癌移植瘤MR成像研究%Studies on MR Imaging of Nude Mice Bearing Nasopharyngeal Carcinoma Xenograft by Using Targeted Nano-Contrast Agent C225-USPIO

    Institute of Scientific and Technical Information of China (English)

    钱莹; 龙国贤; 刘东伯; 胡国清

    2012-01-01

    Objective: This work aimed to design epidermal growth factor receptor-targeted contrast agent C225-USPIO and to evaluate its magnetic resonance imaging (MRI) capability to mark the nasopharyngeal carcinoma xenograft in nude mice. Methods: C225-USPIO was designed by conjugating ultra-small superparamagnetic iron oxide (USPIO) nanoparticles with cetuximab (C225). The diameter of C225-USPIO was detected. Nasopharyngeal carcinoma cells SUNE1 5-8F with EGFR overexpression were transplanted into the ventral subcutaneous site of the right rear thigh of 12 nude mice. When the diameter of a transplanted tumor reached 5 mm, the nude mice were randomly divided into two groups, i.e., the experiment group (Group One) and the control group (Group Two), with 6 mice in each group. C225-USPIO and USPIO were separately injected into the mice through the caudal vein. MRI T2 weighted image (T2WI) scanning was conducted 0, 8, 24 and 72 h after the injection. The nano-contrast agent distribution in the tumor tissues was detected. Results: The diameter of the contrast agent ranged from 45 run to 50 nm. MRI results showed that compared with the value of T2WI signal intensity 0 h after the contrast agent injection, the T2 value of the xenograft tumor in Group One was slightly decreased 8 h after the injection (P>0.05). The value was significantly decreased 24 h after the injection (P<0.05), and no apparent change in the T2 value was observed 72 h after the injection (P>0.05). In Group Two, no significant changes in the T2 value of xenograft tumor after the USPIO injection were observed at each time point. No significant iron particles were found in the tumor tissue 72 h after the injection. Conclusion: C225-USPIO particles could pass through blood capillaries and could be applied for MR imaging in vivo. In addition, they can reduce MRI T2 signal intensity of the xenograft in nude mice with a certain specificity and targeting property.%目的:制备针对EGFR的靶向纳米造影剂C225

  10. Establishment of a high metastatic potential human hepatocellular carcinoma orthotopic transplantation model with palliative liver resection in nude mice%高转移MHCC97H细胞裸鼠原位移植瘤姑息性肝癌切除模型的建立

    Institute of Scientific and Technical Information of China (English)

    黄修燕; 黄自丽; 许永华; 黄新余; 周俭; 叶胜龙; 樊嘉; 汤钊猷; 郑起

    2013-01-01

    Objective To construct a high metastatic potential human hepatocellular carcinoma (HCC)orthotopic transplantation model with palliative liver resection in nude mice.Methods A human HCC orthotopic nude mice model was established by administering a single inoculation of the highly metastatic MHCC97H tumor tissue (size 2 mm × 2 mm × 2 mm) into the left liver lobe.At day 14 post-inoculation,a random group of the mice received palliative liver resection; the unresected mice served as controls.Changes in expression levels of 113 genes with metastasis-related functions were evaluated in the residual HCC tissues.At day 35 post-resection,a random group of the mice were sacrificed by cervical dislocation and a comprehensive metastases examination was performed.The remaining mice were used to observe life span.All statistical analyses were performed by the SPSS v17.0 software,and significance was defined as P < 0.05.Results The nude mouse model of highly metastatic HCC with palliative liver resection was successfully established.Incidences of intrahepatic and abdominal metastases were higher in the palliative resected group (vs.unresected group:11.7 ± 4.7 vs.6.3 ± 2.8,t =-2.412,P < 0.05 and 9.8 ± 3.4 vs.5.2 ± 2.6,t =-2.641,P < 0.05respectively).In addition,the palliative resected group showed significantly enhanced pulmonary metastasis (vs.unresected group:14.3 ± 4.7 vs.8.7 ± 4.7,t =-2.348,P < 0.05).Differential gene expression levels were found for MTSS1,TGFβ1,SMAD2,IL-1β,and MMP7,and were situated in the central position of gene function net of residual HCC.The life-span of the palliative resected group was significantly longer than that of the unresected group (60.8 ± 2.7 vs.51.3 ± 1.4days,x2=12.850,P<0.01).Conclusion The highly metastatic human HCC nude mouse model with palliative liver resection that was successfully constructed in this study represents a useful investigational tool to assess the biological characteristics of residual cancer and to

  11. A high-resolution map of the chromosomal region surrounding the nude gene

    Energy Technology Data Exchange (ETDEWEB)

    Blackburn, C.C.; Griffith, J.; Morahan, G. [Royal Melbourne Hospital, Victoria (Australia)

    1995-03-20

    The nude mutation produces the apparently disparate phenotypes of hairlessness and congenital thymic aplasia. These pleiotropic defects are the result of a single, autosomal recessive mutation that was previously mapped to a 9-cM region of murine chromosome 11 bounded by loci encoding the acetylcholine receptor P subunit and myeloperoxidase. In this study, exclusion mapping of a panel of congenic nude strains was used to place the nude locus between the microsatellite loci D11Nds1 and D11Mit8. The relative distance from nude to each of these loci was determined by analyzing a large segregating cross. Thus, nude lies 1.4 cM distal to D11Nds1 and is 0.5 cM proximal to D11Mit8. Mice that carried recombinational breakpoints between D11Nds1 and D11Mit8 were further analyzed at the loci Evi-2 and D11Mit34, which placed nu 0.2 cM proximal to these markers. D11Nds1 and Evi-2/D11Mit34 thus define the new proximal and distal boundaries, respectively, for the nu interval. We also report the typing of the above microsatellite markers in the AKXD, AKXL, BXD, CXB, and BXH recombinant inbred strains, which confirmed the relative order and separation of loci in this region. 47 refs., 3 figs., 1 tab.

  12. PRP结合组织工程皮肤修复裸鼠巨大创面的实验研究%Combining Platelet-Rich Plasma and Tissue Engineer Skin in the Treatment of Large Skin Wound on Nude Mice

    Institute of Scientific and Technical Information of China (English)

    张莉; 郁淼; 王浩; 严钰锋; 姚莉韵

    2012-01-01

    Objective: To investigate the effects of tissue engineered skin in combination with PRP and other preparations on the repair of large skin wound on nude mice. Methods: Platelet-rich plasma (PRP) from venous blood wase prepared by density gradient centrifugation. Large skin wounds were created surgically on the dorsal part of nude mice. The wounds were then treated with either artificial skin, tissue engineered skin, tissue engineered skin combined with basic fibroblast growth factor, and tissue engineered skin combined with epidermal growth factor or tissue engineered skin combined with PRP. Tissue specimens were collected at different time intervals post surgery. HE, PAS stains and immunohistochemistry were performed to assess rate of wound healing. Results: Macroscopic observations, HE/PAS staining and immunohistochemistry revealed that the tissue engineering skin in combination with the PRP group showed the most satisfactory wound recovery out of the five groups.%目的:探讨富血小板血浆(platelet-rich plasma,PRP)结合组织工程皮肤对裸鼠巨大创面修复的影响.方法:首先,利用密度梯度离心法制备富含生长因子的浓缩血小板的血浆,并测其所含生长因子的量;其次,在裸鼠的背侧部分构建大面积皮肤创面,分别用人工真皮,组织工程皮肤,碱性成纤维细胞生长因子组织工程皮肤,表皮生长因子组织工程皮肤和PRP结合组织工程皮肤修复裸鼠巨大创面;最后,手术后不同时间间隔收集组织标本,采用HE染色,PAS染色和免疫组化等方法评估创面愈合情况.结果:PRP结合组织工程皮肤组创面修复愈合情况最好.

  13. 131Ⅰ标记抗CD20单克隆抗体不同给药途径对荷瘤裸鼠的放射免疫治疗实验%Experimental Research on Radioimmunotherapy of 131Ⅰ-labeled Anti-CD20 Monoclonal Antibody to Nude Mice Xenografted Tumor

    Institute of Scientific and Technical Information of China (English)

    左强; 罗宇玲; 罗荣城

    2011-01-01

    Objective To investigate the therapeutic efficacy of radioimmunotherapy of iodine-131 labeled Rituximab using intratumor injection(IT)in nude mice with xenografted raji cells tumor. Methods Iodine-131 labeled Rituximab was carried out by IODO-GEN method. The nude mice bearing raji cells tumor were divided into six groups based on the injected marked-drugs. The size of the tumor was measured every 2~3 day and the inhibition rates of different groups were calculated. Results The tumor inhibition rates of 131 I-Rituximab IT group were higher than those of IP group, 131 I-IgG IT group and cell control group(P<0. 05). 131 I-Rituximab with intratumor injection in different dose showed that inhibition rate of low dose group was lower than that of high group, while there was no significant difference(P>0. 05). Conclusion lodine-131 labeled Rituximab with intratumor injection showed the highest radioimmunotherapy efficacy which offered the experimental evidence for clinical application in the futrue.%目的 探讨131Ⅰ-Rituximab经瘤内注射对荷人Burkitt's淋巴瘤细胞系Raji细胞移植瘤裸鼠放射免疫治疗疗效.方法 131Ⅰ标记物的标记采用IODO-GEN碘化标记;按预定治疗方案分别注入含有131Ⅰ标记物,开始治疗前及治疗后每天用游标卡尺测量肿瘤长、短径,计算肿瘤体积,依公式计算肿瘤生长抑制率.结果 131Ⅰ-Rituximab瘤内注射组肿瘤抑制率显著高于腹腔注射组、131Ⅰ-IgG瘤内注射组以及对照细胞组(P0.05).结论 131Ⅰ-Rituximab经瘤内途径给药可以获得更好的放射免疫治疗效果,为下一步临床应用奠定了基础.

  14. 瘤体内注射32磷一玻璃微球对裸鼠人肝癌移植瘤的抗癌效应研究%Study on the antitumor effect of phosphorus - 32 glass microspheres intrattmoral injected to the implanted human hepatocellular carcinoma mass of nude mice

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    目的 研究瘤体内注射32磷-玻璃微球(32P-GMS)对裸鼠人肝癌移植瘤的抗癌作用。方法动态观察治疗组和对照组裸鼠的肿瘤生长状况,分批处死,取瘤体及其邻近组织进行光镜和电镜观察。结果与对照组相比,14 d治疗组抑瘤率为59.7%~93.6%(P<0.01)。瘤体吸收剂量为7 320Gy,肿瘤细胞可被一次性杀死;吸收剂量为1 830~3 660Gy时,瘤细胞大多损伤坏死,并出现分化较好的瘤细胞;吸收剂量为366Gy或更低时,仍残存有增殖活跃的瘤细胞。结论瘤体内注射1 830~3 660Gy的32P-GMS,可对人肝癌移植瘤产生最佳抗癌效应。%Objective To study the antitumor effect of phosphorus- 32 glass microspheres (~P-GMS) intratumoral injected to the implanted human hepatocellular carcinoma cell mass of nude mice. Method After dynamically observing the growth of tumor for 3 d~28 d, the experimental fifty- two Balb/c tumor loaded nude female mice in both control and treated group were killed in batches, andthen the tumors and their nearby tissues were examined by light and electron microscopy. Results In comparing with the control group, the treatment group attained the tumor inhibiting rates of 59.7 % ~ 93.6% ( P < 0.01 ) at 14 d. As the mass having the absorbed dose of 7 320 Gy, the tumor cells were completely destroyed. When the absorbed doses ranged from 1 830 Gy to 3 660 Gy, most of the tumor cells showed the evidences of injury or necrosis, but some well- differentiated tumor cell and enhanced effect of the auto - immunocytes ap- peared. As the absorbed dose being 366 Gy or less, some tumor cells still remained their active proliferative ability. Conclusion When32p- GMS of 1 830Gy~ 3 660 Gy were intratumoral injected to the experimental model of implanted hepatocellular carcinoma cells, it pro- duced excellent anticancer effect

  15. The significance of T cells, B cells, antibodies and macrophages against encephalomyocarditis (EMC)-D virus-induced diabetes in mice.

    Science.gov (United States)

    Kounoue, Etsushi; Izumi, Ken-ichi; Ogawa, Shuichiro; Kondo, Shiori; Katsuta, Hitoshi; Akashi, Tomoyuki; Niho, Yoshiyuki; Harada, Mine; Tamiya, Sadafumi; Kurisaki, Hironori; Nagafuchi, Seiho

    2008-01-01

    In order to clarify the significance of protective mechanisms against encephalomyocarditis (EMC) virus-induced diabetes in mice, we studied the relative importance of T cells, B cells, antibodies and macrophages in the prevention of virus-induced diabetes. Neither T cell-deficient athymic nude mice nor B cell-deficient microMT/microMT mice showed an enhanced clinical course of EMC-D virus-induced diabetes, indicating that neither T cells nor B cells played a major role in the protection against EMC-D-virus-induced diabetes. Transfer of a large amount of antiserum to EMC-D-virus-infected mice protected the development of diabetes only when transferred within 36 h of infection, the timing of which was earlier than that for the production of natural neutralizing antibodied. Since pretreatment of mice with the macrophage-activating immunopotentiator Corynebacterium parvum (CP) completely prevented the development of diabetes, we studied the clinical outcome of EMC-D-virus-infected mice pretreated with CP. Mice treated with CP showed reduced proliferation of EMC-D virus in the affected organs, including the pancreas, while the levels of development of neutralizing antibody and serum interferon were not enhanced compared with the controls. Finally, we studied the macrophages derived from mice pretreated with CP and found that they inhibited the growth of EMC-D virus in vitro more than those derived from non-treated and thioglycolate-treated mice. Taken together, it can be suggested that neither T cells nor B cells, which have to do with adaptive immunity, play a significant role in the pathogenesis of EMC-D-virus-induced diabetes, while innate immunity, which is dependent on activated macrophages, contributes to in vivo resistance against EMC-D-virus-induced diabetes.

  16. Effect of Small Needle-knife Therapy on the Fibroblasts in Human Hypertrophic Scar Tissues Transplanted into Nude Mice%针刀松解法对移植于裸鼠的人皮肤增生性瘢痕组织中成纤维细胞的影响

    Institute of Scientific and Technical Information of China (English)

    唐岩; 聂芳菲; 陈东明; 赵霞; 李枫; 毕振伍; 唐军民

    2012-01-01

    Objective To discuss the effect of small needle-knife therapy on the biological characteristics of fibroblasts of the hypertrophic scar tissues subcutaneously transplanted into nude mice by detecting the expressions of PCNA, collagen type I and Ⅲ , bcl-2 and bax in the fibroblasts. Methods To establish the animal model of hypertrophic scar on nude mice, 6 samples of hypertrophic scar tissues without cuticle were respectively divided into three pieces and transplanted subcutaneously into the back of 18 nude mice. Ten days after the operation, the mice were treated with saline (control group) , 0. 1 mg/ml triamcinolone (triamcinolone group ) , or small needle-knife ( small needle-knife group ) , respectively ( n = 6 in each). After 14-day treatment, pathological changes and the number of the fibroblasts positively expressed PCNA, I collagen, Ⅲ collagen , bcl-2 and bax in the hypertrophic scar tissues were detected by HE staining and immunohistochemistry. Results HE staining showed that, compared with the control group (913. 33 ± 148. 95)/mm2 , the number of fibroblast were reduced in the triamcinolone (853. 33 ±62. 82)/mm2 and small needle-knife groups (863. 33 ±75. 28)/mm , but no significant difference was found among the groups (P > 0. 05). Immunohistochemistry indicated that, in the triamcinolone and small needle-knife groups, the number of fibroblast that were positively stained with PCNA, and I and Ⅲ collagen were significantly lower than those in the control (P 0. 05 ). Conclusions Small needle-knife therapy can inhibit the proliferating, synthesizing and secreting abilities of the fibroblasts in hypertrophic scar tissues transplanted into nude mice. It has no influence on the expressions of bcl-2 and bax in the fibroblasts in human hypertrophic scar tissues,nor on the bcl-2/bax ratios.%目的 观察针刀松解法对移植于裸鼠皮下人增生性瘢痕成纤维细胞增殖细胞核抗原(proliferation cell nuclear antigen,PCNA

  17. Effect of fentanyl on expression of VEGF-A and MMP-9 in subcutaneous tumor of human gastric cancer in nude mice%芬太尼对裸鼠人胃癌皮下瘤VEGF-A和MMP-9表达的影响

    Institute of Scientific and Technical Information of China (English)

    陈秋妙; 管恩健; 杨一兰; 利莉; 谢玉波

    2016-01-01

    目的 评价芬太尼对裸鼠人胃癌皮下瘤血管内皮生长因子A(VEGF-A)和基质金属蛋白酶9(MMP-9)表达的影响.方法 SPF级雄性BALB/C裸鼠30只,4~5周龄,体重15~20 g,建立裸鼠人胃癌MGC-803细胞皮下瘤模型,采用随机数字表法将其分为6组(n=5):对照组(C组)、生理盐水组(NS组)和芬太尼0.05、0.10、0.20、0.40 mg/kg组(F1组、F2组、F3组和F4组).F1组、F2组、F3组和F4组分别腹腔注射相应剂量芬太尼,1次/d,连续14 d;NS组给予等容量生理盐水1.5 ml/kg.停止给药后1d处死裸鼠,取肿瘤组织,透射电子显微镜观察皮下瘤的超微结构,采用免疫组织化学染色法和Western blot法测定VEGF-A和MMP-9的表达,采用RT-PCR法测定VEGF-A和MMP-9的mRNA表达.结果 C组和NS组皮下瘤组织细胞形态结构未见异常,F1组、F2组、F3组和F4组皮下瘤组织细胞呈现核肿胀、染色质边集、核碎裂甚至出现凋亡小体.与C组比较,F1组、F2组、F3组和F4组皮下瘤组织VEGF-A和MMP-9及其mRNA表达下调(p<0.05),NS组各指标比较差异无统计学意义(P>0.05);F1组、F2组、F3组和F4组间皮下瘤组织VEGF-A和MMP-9及其mRNA表达比较差异无统计学意义(P>0.05).结论 芬太尼抑制裸鼠人胃癌皮下瘤生长和转移的机制与下调VEGF-A和MMP-9的表达有关.%Objective To evaluate the effect of fentanyl on the expression of vascular endothelial growth factor A (VEGF-A) and matrix metallopeptidase-9 (MMP-9) in the subcutaneous tumor of human gastric cancer in nude mice.Methods Thirty SPF male BALB/C nude mice,aged 4-5 weeks,weighing 15-20 g,in which the model of subcutaneous tumor of human gastric cancer cell line MGC-803 was established,were randomly divided into 6 groups (n =5 each) using a random number table:control group (C group),normal saline group (NS group) and fentanyl 0.05,0.10,0.20 and 0.40 mg/kg groups (F1-4 groups).The mice in group C received no treatment.Fentanyl 0.05,0.10,0.20 and 0.40 mg

  18. 重组人腺病毒p53对裸鼠人胃癌细胞移植瘤的抑制效果及不良反应%The curative effects and side effects of recombinant human adenovirus p53 on transplanted gastric cancer cells in nude mice

    Institute of Scientific and Technical Information of China (English)

    谢忆山; 伍龙; 刘少平; 彭春伟; 李雁

    2013-01-01

    目的 探讨重组人腺病毒p53(rAd-p53)对胃癌细胞裸鼠移植瘤的抗肿瘤效应及相关不良反应.方法 将胃癌细胞SGC-7901注射于裸鼠皮下制成动物模型,分别用rAd-p53和盐酸表阿霉素(EPI)进行治疗.rAd-p53治疗组剂量为10μl浓度1012vp/ml,EPI治疗组剂量为1.25mg/kg,各组每3周给药7次,以生理盐水为对照组.结果 与对照组比较,rAd-p53治疗组和EPI治疗组肿瘤抑制率分别为80%和60%,差异有统计学意义(P<0.01);rAd-p53和EPI治疗组之间比较差异无统计学意义(P>0.05).没有实验动物死亡,rAd-p53治疗组2只裸鼠出现肝脏不良反应,EPI治疗组1只裸鼠心脏不良反应,上述反应均有病理学观察证实.结论 裸鼠体内实验证实rAd-p53对胃癌细胞具有抗肿瘤效应,但应注意其肝脏不良反应.%Objective To investigate the inhibitory and side effects of recombinant Adenoviruswtp53 (tAd-p53) SGC-7901 on gastric cancer cells in vivo.Methods SGC-7901 cells were subcutaneously injected into the nude mice to establish xenograph models,which were treated with Gendicine,a recombinant human Ad-p53 injection (rAd-p53),and epirubicin hydrochloride (EPI),a cytotoxic chemotherapy agent.Results As compared with the blank control,treatment with rAd-p53 at the dose of 10 μl of 1012 vp/ml and EPI at the dose of 1.25 mg/kg,7 times every 3 weeks,resulted in 80% and 60% of tumor growth inhibition,respectively.The difference in rAd-p53 and EPI therapy group was not statistically significant.No animal death was observed,although 2 nude mice in rAd-p53 group developed liver toxicity and 1 nude mouse in EPI group developed cardiac toxicity,and the results were validated histopathologically.Conclusion The rAd-p53 has tumor inhibitory effect on gastric cancer cells,but the liver toxicity should be considered seriously.

  19. Promoting neovascularization of adipose tissue derived stem cells compoun -ding with different cellular scaffold in nude mice subcutaneous stratum%脂肪来源干细胞复合不同生物支架在裸鼠皮下的促血管化作用

    Institute of Scientific and Technical Information of China (English)

    徐永飞; 张建文; 暴志国; 李静怡; 王耀聪; 许颖溦

    2013-01-01

    目的:探讨脂肪来源干细胞复合不同生物支架在裸鼠皮下的促血管化作用。方法:根据所选支架的不同,将实验分为4组,A组为脂肪颗粒,B组为透明质酸钠,C组为Ⅰ型胶原支架,分别按体积比1:1与25×106 mL-1的脂肪来源干细胞混合,D组为单纯脂肪来源干细胞,将4组试剂注射到12只裸鼠皮下构建软组织,每只裸鼠各注射4个点,3个月后获取相应标本,测定湿质量、存活率、微血管密度。结果:4组间湿质量、存活率、微血管密度比较,差异均有统计学意义(F=47.523、48.425和47.619,P均<0.05),且A、B、C组湿质量、存活率、微血管密度均高于D组(P均<0.05)。结论:脂肪来源干细胞复合生物支架可加速软组织血管化,且效果优于单纯脂肪来源干细胞。%Aim:To discuss the affection of promoting neovascularization of adipose tissue derived stem cells (ADSCs) compounding with different cellular scaffold in nude mice subcutaneous stratum .Methods:The experiment was divided into four groups depending on the selected scaffold .Group A,B and C were given fat particles, sodium hyaluronate, typeⅠcol-lagen,respectively, mixed with ADSCs at 25 ×106 mL-1 .Group D was given pure ADSCs .Four reagents were injected ran-domly into subcutaneous stratum of 12 nude mice to build soft tissue .Each nude muse was injected 4 points.The appropri-ate specimens were obtained three months later and wet weight , survival rate and microvessel density were detected .Re-sults:The differences were statistically significant regarding the wet weight , survival rate , microvessel density among the four groups(F=47.523,48.425,47.619,P<0.05).The wet weight, survival rate, and microvessel density of group A ,B and C were higher than those of group D (P<0.05).Conclusion: ADSCs compounding with cellular scaffold could pro-mote neovascularization in subcutaneous stratum ,and is better than pure

  20. Suppression of human colon tumor growth by adenoviral vector-mediated NK4 expression in an athymic mouse model

    Institute of Scientific and Technical Information of China (English)

    Jian-Zheng Jie; Jian-Wei Wang; Jian-Guo Qu; Tao Hung

    2007-01-01

    AIM: To investigate the suppressive effects of adenoviral vector-mediated expression of NK4, an antagonist of hepatocyte growth factor (HGF), on human colon cancer in an athymic mouse model to explore the possibility of applying NK4 to cancer gene therapy.METHODS: A human colon tumor model was developed by subcutaneous implantation of tumor tissue formed by LS174T cells grown in athymic mice. Fifteen tumorbearing mice were randomized into three groups (n = 5in each group) at d 3 after tumor implantation and mice were injected intratumorally with phosphate-buffered saline (PBS) or with recombinant adenovirus expressing β-galactosidase (Ad-LacZ) or NK4 (rvAdCMV/NK4) at a 6-d interval for total 5 injections in each mouse. Tumor sizes were measured during treatment to draw a tumor growth curve. At d 26 after the first treatment, all animals were sacrificed and the tumors were removed to immunohistochemically examine proliferating cell nuclear antigen (PCNA), microvessel density (represented by CD31), and apoptotic cells. In a separate experiment,15 additional athymic mice were employed to develop a tumor metastasis model by intraperitoneal injection(ip) of LS174T cells. These mice were randomized into 3 groups (n = 5 in each group) at d 1 after injection and were treated by ip injection of PBS, or Ad-LacZ, or rvAdCMV/NK4 at a 6-d interval for total two injections in each mouse. All animals were sacrificed at d 14 and the numbers and weights of disseminated tumors within the abdominal cavity were measured.RESULTS: Growth of human colon tumors were significantly suppressed in the athymic mice treated with rvAdCMV/NK4 (2537.4±892.3 mm3) compared to those treated by either PBS (5175.2±1228.6 mm3)or Ad-LacZ (5578.8±1955.7 mm3) (P<0.05). The tumor growth inhibition rate was as high as 51%.Immunohistochemical staining revealed a similar PCNA labeling index (75.1%±11.2% in PBS group vs 72.8%±7.6% in Ad-LacZ group vs 69.3%±9.4% in rvAdCMV/NK4 group) in all groups, but

  1. Targeting human prostate cancer with (111) In-labeled D2B IgG, F(ab')2 and Fab fragments in nude mice with PSMA-expressing xenografts

    NARCIS (Netherlands)

    Lutje, S.; Rij, C.M. van; Franssen, G.M.; Fracasso, G.; Helfrich, W.; Eek, A.; Oyen, W.J.G.; Colombatti, M.; Boerman, O.C.

    2015-01-01

    D2B is a new monoclonal antibody directed against an extracellular domain of prostate-specific membrane antigen (PSMA), which is overexpressed in prostate cancer. The potential of D2B IgG, and F(ab')2 and Fab fragments of this antibody for targeting prostate cancer was determined in mice bearing sub

  2. Targeting human prostate cancer with In-111-labeled D2B IgG, F(ab ')(2) and Fab fragments in nude mice with PSMA-expressing xenografts

    NARCIS (Netherlands)

    Lutje, Susanne; van Rij, Catharina M.; Franssen, Gerben M.; Fracasso, Giulio; Helfrich, Wijnand; Eek, Annemarie; Oyen, Wim J.; Colombatti, Marco; Boerman, Otto C.

    2015-01-01

    D2B is a new monoclonal antibody directed against an extracellular domain of prostate-specific membrane antigen (PSMA), which is overexpressed in prostate cancer. The potential of D2B IgG, and F(ab)(2) and Fab fragments of this antibody for targeting prostate cancer was determined in mice bearing su

  3. 微泡增强低频超声空化抑制裸鼠前列腺癌移植瘤%An Experimental Study on Anti-tnmor Effect of Microbubble-enhanced Low-frequency Ultrasound Cavitation on Prostate Carcinoma Xenograft in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    王宇; 胡兵; 张吉臻; 刁雪红; 沈智勇; 申锷

    2011-01-01

    目的 观察低频超声(20 kHz)辐照联合静脉注射微泡造影剂SonoVue对裸鼠前列腺癌(Du145)移植瘤的抑瘤效应,并探讨其可能的抑瘤机制.方法 通过细胞移植和瘤块移植方法建立24只裸鼠前列腺癌Du145移植瘤模型,随机分为超声微泡组、单纯超声组、单纯微泡组和对照组,每组各6只.超声微泡组:尾静脉注射0.2mLSonoVue的同时对瘤体行20 kHz超声辐照,辐照强度200 mW/cm2;单纯超声组:尾静脉注射生理盐水0.2mL,同时超声辐照2 min;单纯微泡组:尾静脉注射SonoVue 0.2 mL同时行假照,各组均隔天1次,共3次,对照组不做任何处理.治疗后测量瘤体大小,绘制瘤体生长曲线,计算抑瘤率.首次治疗后14 d剥离瘤体,通过光学显微镜、电子显微镜观察肿瘤组织病理改变.免疫组织化学方法观察CD34阳性染色血管,计算肿瘤微血管密度(micro vessel density,MVD),比较各组间MVD的差异.结果 24只裸鼠均成功植瘤.治疗后超声微泡组瘤体体积均数明显小于其他3组(P<0.05),抑瘤率为62.7%.光学显微镜下超声微泡组瘤体组织大部分损伤坏死,电子显微镜下超声微泡组肿瘤内微血管的内皮细胞损伤,线粒体肿大,基底膜断裂.超声微泡组瘤体内CD34阳性染色微血管数减少,其MVD值显著低于其他各组.结论 20 kHz低频超声辐照联合微泡造影剂SonoVue可有效抑制裸鼠人前列腺癌移植瘤的生长,其抑瘤机制可能是通过超声空化效应破坏肿瘤的微血管实现的.%Objective To investigate the anti-tumor effect induced by low-frequency ultrasound (20 kHz) radiation combined with intravenous injection of microbubbles on human prostate carcinoma xenograft in nude mice, and to discuss its probable mechanism. Methods Human prostate carcinoma xenograft model in 24 nude mice were established with human prostate carcinoma Dul45 cells inoculation and sub-graft through mice, which were randomly divided into ultrasound

  4. Effects of Prunella vulgaris L on the growth of hemangioma and the expression of Fas/FasL in nude mice%夏枯草对裸鼠血管瘤生长及Fas/FasL表达的影响

    Institute of Scientific and Technical Information of China (English)

    陈伟; 彭强; 刘铭; 杨春; 肖骁

    2014-01-01

    目的 观察夏枯草对裸鼠血管瘤生长及Fas/FasL表达的影响,探讨夏枯草对血管瘤的治疗作用及其可能机制.方法 采用组织块移植法制作婴幼儿血管瘤裸鼠异种移植动物模型.移植30 d后,在移植成功的65只裸鼠中,随机选取5只观察瘤体生长情况并测量瘤体大小作初始对照.余下的60只荷瘤裸鼠按数字随机法随机平均分为:凡士林组、夏枯草组和曲安奈德组,观察移植瘤体的生长变化情况.用药后7、14、21和28 d分别处死各组实验裸鼠5只,测量瘤体大小及行病理学检查,免疫组织化学染色检测Fas、FasL,TUNEL法检测细胞凋亡.利用统计学软件SPSS 20.0分析实验数据,P<0.05为差异有统计学意义.结果 药物干预后,夏枯草组、曲安奈德组瘤体体积均逐渐减小而同期凡士林组则不断增大,组间比较,差异均有统计学意义(P<0.05).干预后21 d,夏枯草组Fas表达阳性率为(49.71±3.67)%,FasL表达阳性率为(32.59±3.01)%,Caspase-8表达阳性率为(39.69±3.47)%;凡士林组3项阳性率分别为(29.01±2.53)%、(19.01±2.13)%和(17.11±1.69)%;曲安奈德组3项阳性率分别为(26.83±2.37)%、(16.97±1.81)%和(15.86±1.91)%,组间比较,夏枯草组阳性率均明显高于另2组(P<0.05).干预后7、14、21和28 d,夏枯草组细胞凋亡指数分别为14.75±2.29、26.69±3.12、38.71±3.81和53.65±4.63,曲安德组细胞凋亡指数分别为24.53±2.61、37.35±3.58、56.37±4.25和72.92±5.21,均明显高于干预前6.79±1.33及同期凡士林组(7.12±1.47、6.98±1.33、7.29±1.51和6.81±1.34),差异有统计学意义(P<0.05).结论 夏枯草外用可以促进裸鼠模型血管瘤瘤体的消退.其机制可能与Fas/FasL介导的细胞凋亡有关.%Objective To explore the effects of Prunella vulgaris L (PVL) on the growth of hemangioma.Methods Infant proliferative hemangioma blocks were implanted subcutaneously into nude mice hemangioma modeling

  5. 三氧化二砷联合华蟾素抗裸鼠人肝癌移植瘤血管新生的作用%Anti-angiogenesis Effect of Arsenic Trioxide plus Cinobufacin on Human Hepatocarcinoma Transplantation Model Nude Mice

    Institute of Scientific and Technical Information of China (English)

    刘琳; 陈宝安; 秦叔逵; 赵伟; 李苏宜; 邱少敏; 王南瑶

    2011-01-01

    Objective To study the anti-angiogenesis effect and toxicity of arsenic trioxide (As2O3) plus cinobufacin on transplanted human hepatocarcinoma in nude mice, and the acting mechanism of the treatment was explored as well. Methods Human hepatocarcinoma was transplanted in nude mouse, and the modeled mice were divided at random into 4 groups, 8 in each group. They were treated respectively with normal saline (GA), 2. 5 mg/kg As2O3 (GB), 5 mL/kg cinobufacin (GC) and 2.5 mg/kg As2O3 + 5 mL/kg cinobufacin (GD), by intraperitoneal injection for 21 days. The anti-tumor effects was evaluated by estimating general condition of nude mice, tumor size, microvessel density(MVD) level. Expressions of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor(EGFR) in tumor, in tumor tissue of mice as well as pathology of tumor were detected by immunohistochemistry assay, optical microscope, transmission electron microscope ( TEM), respectively. Moreover, blood routine and pathological examinations of liver and kidney were performed.Results The tumor weight and volume were 0. 65 ± 0. 25 g and 0. 44 ± 0. 14 cm3 in GB, 0. 70 ± 0. 27 g and 0. 46 ±0. 19 cm3 in GC, 0.42 ±0. 16 g and 0. 26 ±0. 11 cm3 in GD, all significantly lower than those in GA (1.06 ±0. 25 g and 0. 67 ±0. 17 cm3, P<0. 05). The coefficient of drug interaction (CDI) on tumor weight was 0. 97 and that on tumor size was 0. 86, all less than 1, showing the synergistic action between the two drugs. Expressions of VEGF and EGFR in tumor as well as the MVD were decreased in GB and GC, and the decreasing of these indices were even more significant in GD. Pathologic examination showed the growth of tumor in GB, GC and GD were all inhibited significantly. No obvious toxicity of the treatments to the hepatic, renal and hematopoietic systems in the nude mice was observed. Conclusions As2O3 and cinobufacini showed synergistic action in inhibiting human hepatocarcinoma in nude mice and the

  6. Establishment and investigation of human epithelial ovarian cancer subcutaneous and or﹣ thotopic models in nude mice%人上皮性卵巢癌细胞系SKOV3-luc裸鼠皮下及原位移植瘤模型的建立与研究

    Institute of Scientific and Technical Information of China (English)

    朱沁怡; 王昕婧; 汪希鹏

    2015-01-01

    目的::建立整体可视化人卵巢癌皮下和原位移植瘤模型,用于实时观察和分析人卵巢癌移植瘤发展和转移的规律,并比较两者的成瘤情况及生物学特性。方法:使用带有荧光素酶报告基因( Luciferase )的人上皮性卵巢癌细胞系SKOV3—luc分别接种于裸鼠右侧腋窝皮下和左侧卵巢内,建立人上皮性卵巢癌裸鼠皮下和原位移植瘤模型。实时观察卵巢癌细胞SKOV3—luc在裸鼠皮下和原位的生长情况,并切取肿瘤组织,应用病理组织学方法对裸鼠皮下移植瘤和原位移植瘤进行检测和评价。结果:人卵巢癌细胞系SKOV3—luc裸鼠皮下和原位移植瘤模型建立的成功率均较高。裸鼠皮下和左侧卵巢接种肿瘤细胞后,可通过活体成像实时观察肿瘤的生长情况,并且行定量分析肿瘤形成时间等。皮下移植瘤(皮下组)成瘤率为100%,左侧卵巢原位移植瘤(原位组)成功率为100%。注射后第7天,皮下组的肿瘤总荧光强度比值为(3.38±2.50)(Fold),原位组为(1.43±1.32)(Fold);第14天,皮下组为(15.73±11.70)(Fold),原位组为(6.44±7.26)(Fold),皮下组第7天和第14天的肿瘤总荧光强度比值均大于原位组(P<0.05)。结论:人上皮性卵巢癌裸鼠皮下移植瘤和卵巢原位移植瘤建模成功率高,并能很好地反应肿瘤的生物学行为,实时荧光成像便于观察肿瘤体内生长情况,为研究卵巢癌发展和转移提供了可靠的观察模型。%Objective:To establish and observe visualization models of subcutaneous and orthotopic growth of human epithelial ovarian cancer with nude mice. Methods:Human epi—thelial ovarian cancer SKOV3—luc cells cultured in vitro were injected in nude mice to establish and observe subcutaneous and orthotopic models in nude mice. The dynamic growth of the trans—planted tumors were observed by the whole—body fluorescent imaging technique. The tumor sam

  7. Study on the inhibitory effects and related toxicity of all-trans-retinoic acid combined with arsenic trioxide on transplanted tumor of human bladder neoplasms in nude mice%全反式维甲酸联合三氧化二砷抗膀胱癌作用及其毒副作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    周振玉; 张永; 陈家存

    2011-01-01

    目的 观察全反式维甲酸(ATRA)联合三氧化二砷(As2 O3)对膀胱癌细胞株BIU-87裸鼠移植瘤生长的抑制作用,及其毒副作用。方法建立人膀胱癌裸鼠皮下移植瘤模型40只,随机等分为4组:对照组,ATRA组,As2 O3组,ATRA和As2O3联合用药组;裸鼠瘤体内连续注射用药14d。停药后48 h检测血常规和肝、肾功能;处死裸鼠,测量移植瘤体积、重量,计算抑瘤率;移植瘤及心、肝、肾等组织HE染色,观察其病理变化;瘤组织免疫组化S-P法检测血管内皮生长因子(VEGF)表达、CD43标记的微血管密度MVD的表达。结果与对照组比较,As2 O3组及ATRA组移植瘤生长明显受到抑制(质量抑瘤率分别为43.77%,41.82%),两者联合用药后,抑制作用显著增强(质量抑瘤率为68.55%),抑瘤率差异具有统计学意义(x2 =26.81,P<0.01);As2O3组、ATRA组、联合用药组均不同程度下调VEGF表达(OD值分别为27.33±2.17,20.72±2.01,19.23±2.32,17.16±1.59)及MVD的表达(OD值分别为141.12±8.38,43.39±7.41,44.77±8.25,30.56±7.71),联合用药组下调最显著;各用药组均出现轻度白细胞抑制(t =3.16,3.08,3.37,P<0.01),联合用药组抑制程度与单一用药组比较差异无统计学意义(P>0.05),肝、肾功能各指标比较差异均无统计学 意义(P>0.05)。结论ATRA联合As2 O3在体内能够协同抑制膀胱癌BIU-87细胞移植瘤的生长和血管生成,仅有白细胞轻度抑制,对肝肾功能无毒副作用。%Objective To investigate the inhibitory effects and related toxicity of all-trans-retinoic acid(ATRA) combined with arsenic trioxide(As2O3) on transplanted human bladder neoplasms in nude mice.Methods The subcutaneously transplanted tumor models of human bladder neoplasms in nude mice were established and then it was randomly divided into four teams: Saline group, ATRA group, As2 O3 group and the combination of ATRA and As2 O3 group.Each group

  8. Effect of 5-aminolevulinic acid-mediated photodynamic therapy on human gastric cancer xenografts in nude mice in vivo%5-氨基乙酰丙酸介导的光动力学对裸鼠人胃癌移植瘤的治疗作用

    Institute of Scientific and Technical Information of China (English)

    周广军; 黄宗海; 俞金龙; 厉周; 丁涟沭

    2008-01-01

    Objective To investigate the effect of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) on human gastric cancer xenografts in vivo and to explore its potential tumoreidal mechanism. Methods Cultured MGC-803 human gastric cancer cells were injected below the skins of the nude mice to develop the tumor model. The tumor-bearing nude mice were examined under the Leica LT-9MACIMSYSPULS to detect the fluorescence. The tumor volume of day 1, 3, 7, 14, 21 after treatment were measured, and its histological changes were also studied. The tissues of the tumors in nude mice of the control group, light group, 5-ALA group and PDT group were examined with the electron microscope and apoptosis was detected by TUNEL assay. Results The tumor model was successfully developed. The tumor in the nude mice emited the red fluorescence under the Leica LT-9MACIMSYSPULS. The tumor volumes were (0.189±0.010)cm3, (0.183±0.011)cm3, (0.185±0.019) cm3, (0.182±0.015)cm3 for the control group, light group, 5-ALA group, PDT group, respectively at day 1 after treatment, while at day 3, (0.294±0.010)cm3, (0.280±0.013)cm3, (0.278±0.016)cm3, (0.183±0.014)cm3;at day 7, (0.409±0.016)cm3, (0.411±0.009)cm3, (0.407±0.015)cm3, (0.221±0.008)cm3;at day 14, (0.970±0.055)cm3 (0.976±0.054)cm3, (0.981±0.032)cm3, (0.318±0.005)cm3;at day 21, (1.495±0.059)cm3, (1.513±0.057)cm3, ( 1.524±0.063)cm3, (0.446±0.042)cm3(F=1003.086, P=0.000). The histology demonstrated that most tumor blood vessels were congested and necrosis developed after PDT while not in the control group, light group and 5-ALA group. Necrosis and apoptosis were observed in the cells of the tumors of the PDT group examined by TUNEL and electron microscope while not in the cells of the tumors of the other groups. Conclusions 5-aminolevulinic acid-mediated photodynamic therapy (PDT) can induce injury to human gastric cancer xenografts and inhibit the tumor growth while light only and 5-ALA only can not. 5-aminolevulinic

  9. Artificial vessel construction in nude mice by subcutaneous implantation of polyglicolide acid cocultured with vascular endothelial cells and smooth muscle cells%血管内皮细胞和平滑肌细胞-聚羟基乙酸复合物置入裸鼠皮下构建人工血管

    Institute of Scientific and Technical Information of China (English)

    刘阳; 张燕中; 陈瑾君; 殷德民; 曹颖; 许志成; 刘伟; 崔磊; 曹谊林

    2008-01-01

    BACKGROUND: A lot of researches have proved that polyglicolide acid (PGA), as a stent material, has been successfully used to construct engineered tissues, such as cartilage, bone and tendons, in nude mice or even big mammal. Whether the incubation of vascular endothelial cells and smooth muscle cells in the polyglicolide acid may subcutaneously construct vessel-like structure in nude mice needs a further study.OBJECTIVE: To verify the feasibility of forming vessel-like structure in the nude mice by subcutaneous implantation of polyglicolide acid cocultured with vascular endothelial cells and smooth muscle cells derived from newborn umbilical vein.DESIGN: Contrast study.SETTING: Tissue Engineering Key Laboratory, Medical College, Shanghai Jiao Tong University.MATERIALS: This study was performed at Tissue Engineering Key Laboratory, Medical College, Shanghai Jiao Tong University from January to June 2002. Belly band was derived from newborn babies in our department of obstetrics & gynecology. The parturien provided the informed consent, and this study was approved by the local research ethics committee. Twenty-six nude mice (3-4 weeks old, clean grade, irrespective of gender) were selected in this study. The animal experiment received confirmed consent from the local ethic committee. Polyglicolide acid was provided by Albany International Research Co.METHODS: Vascular endothelial cells and smooth muscle cells derived from newborn umbilical vein were incubated on a piece of polyglicolide acid to produce cell-material compound. In addition, the compound covered around the silicone tube to form a tube-like structural substance. Subsequently, the tube-like structural substance was subcutaneously implanted in 20 nude mice, which were regarded as an experimental group. And then, polyglicolide acid alone was subcutaneously transplanted in the rest 6 nude mice, which was regarded as a control group.MAIN OUTCOME MEASURES: Gross observations of cell-material compound by 2 and

  10. 异甘草酸镁对奥沙利铂在人胃癌裸鼠模型中抗肿瘤作用的影响研究%Effects of magnesium isoglycyrrhizinate on oxalipatin chemotherapy in subcutaneously transplanted tumor of human gastric in nude mice

    Institute of Scientific and Technical Information of China (English)

    郭曼; 赵园园; 何信佳; 于丽; 张蕊; 叶宝玲

    2015-01-01

    Objective:To explore the effect of magnesium isoglycyrrhizinate on oxalipatin chemotherapy in subcutaneously trans-planted tumor of human gastric in nude mice. Methods:A tumor model of human gastric carcinoma was created by subcutaneous inocu-lation of SGC-7901 cells into nude mice. The mice were randomly assigned to high-,medium-,low-dose magnesium isoglycyrrhizinate with oxaliplatin groups,oxaliplatin group,magnesium isoglycyrrhizinate group and glucose control group with tail intravenous injection of drugs for 14 days. The mice were sacrificed 24 hours after the last injection and tissue specimens were obtained. Weights and volumes of the tumors were detected. Tumor inhibition rate was calculated and liver functions were tested. Results:The anti-tumor rates in high-, medium-,and low-dose magnesium isoglycyrrhizinate with oxaliplatin groups and oxaliplatin group were significantly higher than that in the glucose control group(P<0. 05). The anti-tumor rates of high-,medium-,and low-dose magnesium isoglycyrrhizinate with oxalipla-tin groups were higher than that of oxaliplatin group(P<0. 05),which showed a dose dependent manner. Compared with oxaliplatin group,high-,medium-,and low-dose magnesium isoglycyrrhizinate with oxaliplatin groups received a lower level of AST and ALT( P<0. 01). Conclusion:Magnesium isoglycyrrhizinate has the potential to increase the anti-tumor effect of oxaliplatin,and shows an obvious protection of liver function.%目的::探讨异甘草酸镁对奥沙利铂在人胃癌裸鼠模型中抗肿瘤作用的影响。方法:建立人胃癌SGC-7901细胞裸鼠皮下移植瘤模型,并随机分为高、中、低剂量异甘草酸镁( MgIG)联合奥沙利铂( L-OHP)组,单纯L-OHP组,单纯MgIG组和葡萄糖对照组6组,连续尾静脉注射给药14 d,停药24 h后处死裸鼠,称取移植瘤质量,测量移植瘤体积,分别计算质量抑瘤率、体积抑瘤率,用TENEL法检测移植瘤组织的细胞凋亡率,并检测裸鼠肝功

  11. 5-ALA-PDT后鼻咽癌裸鼠荷瘤组织VEGF及HIF-1α表达改变的实验研究%Expressions of VEGF and HIF-1α in nasopharyngeal carcinoma tissues of nude mice after 5-ALA-PDT

    Institute of Scientific and Technical Information of China (English)

    谢莹; 韦正波; 张哲; 温文胜; 易翔; 黄光武

    2011-01-01

    OBJECTIVE: To investigate the different expressions of VEGF and HIF-1α in nude mice bearing nasopharyngeal carcinoma after 5-aminolevulinic acid-photodynamic therapy (5-ALA-PDT).METHODS: CNE-2 cells were implanted in the right flank of the BALB/c nude mice.When the size of tumor reached 0.1-0.15 cm3 ,the mice were administrated with 5-ALA intratumorally at a dose of 100 mg/kg and 3 - 3.5 h prior to laser irradiation (100 mW/cm2 ,100 J,630 nm), while the mice of the control group were under exposure to the same dose laser without 5-ALA used.VEGF and HIF-1α expressions in tumors in both 5-ALA-PDT and control groups were detected by real-time fluorescent quantitative PCR, immunohistochemistry, Western-blot 24 h and 14 d respectively after the exposure to laser.RESULTS: Both differences of HIF-1α mRNA and protein levels were not significant between the 5-ALA-PDT and control groups(P> 0.05).The expression of VEGF in the 5-ALA-PDT group prominently was down-regulated 14 d after PDT(80% positive rate) ,with slightly up-regulated 24 h after the exposure comparing to control group(40% positive rate).CONCLUSIONS: Down-regulation of VEGF in 14 d after 5-ALA-PDT can be the mechanism of inhibition of the development of NPC.This study shows no significant change of HIF-1α following 5-ALA-PDT.The further study will be clone to identify whether HIF-1α can regulate VEGF after PDT.%目的:探讨5-ALA光动力治疗后,裸鼠体内鼻咽癌组织中VEGF及HIF基因表达的改变.方法:鼻咽癌CNE2细胞接种到BALB/c裸鼠右腋下,当肿瘤长到0.1~0.15 cm3时,将动物随机分成3组,每组10只,局部给予5-ALA100 mg/kg,3~3.5h后激光照射(100 mW/cm2,100 J,630 nm),对照组相等激光剂量照射但不给药.分别用实时荧光定量PCR、免疫组化、蛋白质印迹法检测对照组、5-ALA-PDT后24 h及14 d裸鼠鼻咽癌负荷瘤中 VEGF及HIF-1α表达情况.结果:HIF-1α mRNA、蛋白水平在各组间表达差异无统计学意义,P>0.05,

  12. The effect of cisplatin on the lymphatic metastasis of cervical carcinoma xenografts model of nude mice and its mechanism%顺铂对宫颈癌裸鼠移植瘤模型淋巴转移的影响及作用机制

    Institute of Scientific and Technical Information of China (English)

    陈云飞; 王朝霞; 李莉

    2015-01-01

    Objective To detect the effect of cisplatin ( DDP ) on the lymphatic metastasis of cervical carcinoma and its mechanism.Methods The human cervical carcinoma xenografts model was established in 14 nude mice, which were randomly divided into control group were and DDP group with 7 cases in each group.Mice in control group were injected PBS, mice in DDP group were injected cisplatin.The lymphatic metastasis was observed, invasion of cervical cancer in lymph nodes and the internal were certified by pathological methods, the expression of Podoplanin and thymidine phosphorylase ( TP ) were detected by immunohistochemical method.Results Cisplatin had an inhibitory effect for lymphatic metastasis.The number and incidence of lymphatic metastasis of DDP group were lower than control group(P<0.05).The expression of Podoplanin and TP in DDP group were lower than the control group ( P <0.05 ) .Conclusion The lymphatic metastasis in nude mice were inhibited after treatment of cisplatin, the expression of Podoplanin and TP was down-regulated.The proliferation and invasion of xenografts was inhibited may be one of the mechanisms of cisplatin inhibited lymphatic metastasis of cervical carcinoma.%目的:探讨顺铂( DDP)对宫颈癌淋巴转移作用的影响及其作用机制。方法将14只裸鼠建立人宫颈癌裸鼠移植瘤模型后,随机分为对照组和顺铂组各7只,对照组裸鼠腹腔注射PBS缓冲液,顺铂组裸鼠腹腔注射顺铂。观察裸鼠淋巴转移情况,采用病理学方法认证淋巴结及淋巴结内部的宫颈癌浸润,采用免疫组化方法检测肾小球足突细胞膜黏蛋白(Podoplanin)和胸苷磷酸化酶(thymidine phosphorylase, TP)的表达。结果顺铂组对淋巴转移有明显抑制作用,顺铂组淋巴转移个数及淋巴转移率均低于对照组(P<0.05)。顺铂组Podoplanin和TP的表达低于对照组(P<0.05)。结论应用顺铂治疗后,对裸鼠淋巴转移有明显的抑制

  13. 多烯磷脂酰胆碱对奥沙利铂治疗人胃癌裸鼠模型效果影响及其机制%EFFECT OF POLYENE PHOSPHATIDYLCHOLINE TO OXALIPATIN THERAPY IN GASTRIC CARCINAOMA XENOGRAFFS IN NUDE MICE

    Institute of Scientific and Technical Information of China (English)

    王丹宁; 赵园园; 于丽; 张蕊; 赵东河; 姜韬

    2011-01-01

    Objective To explore the anti-tumor effect and machanism of polyene phosphatidylcholine with different concentrations with oxaliplatin on the growth of SGC-7901 cell subcutaneously implanted tumor in nude mice. Methads A tumor model of human gastric carcinoma was created by subcutaneous inoculation of SGC-7901 cells into nude mice. The mice were randomized to glucose group, oxaliplatin group, polyene phosphatidylcholine group, high-, medium-, and low-dose polyene phosphatidylcholine with oxaliplatin groups. The mice in each group received intraperitoneal injection of the drugs for 2 weeks, and were sacrificed 24 hours after the last injection and tissue specimen was obtained. Tumor inhibition rate was calculated, detecting the contents of SOD, cell cycle detected with flow cytometry, the expression of easpase-3, ERCC-1 and GST-π was determined with immunohistochemistry method. Results Compared with control group, oxaliplatin significantly inhibited tumor growth in vivo, polyene phosphatidylcholine did not inhibit tumor growth, the groups of different concentrations of polyene phosphatidylcholine and oxaliplatin could inhibit tumor growth, but compared with the group of oxaliplatin tumor inhibition rate was lower, with the growth concentration of polyene phosphatidylcholine, the content of SOD was heightened, expression of caspase-3, ERCC-1, GST-π were decreased. Conclusion Polyene phosphatidylcholine was antagonistic on oxaliplatin, showing dose dependent, the mechanism may be related to the up-regulation of the activity of caspase-3, ERCC-1 and GST-π.%目的 探讨人胃癌裸鼠模型中不同剂量多烯磷脂酰胆碱(易善复)对奥沙利铂治疗效果的影响及其机制.方法 将人胃癌细胞SGC-7901接种于裸鼠皮下,建立人胃癌裸鼠皮下移植瘤模型.随机分为6组:葡萄糖对照组、奥沙利铂组、易善复组及高、中、低剂量易善复联合奥沙利铂组.连续给药2周,停药24 h后处死裸鼠,称取瘤质量,计算

  14. Experimental study of different platinum alone or combined with taxanes or vinoreibine on nude mice implanted human non-small cell lung cancer NCI-H460 cells in vivo%不同铂类联合紫杉类或长春瑞滨对非小细胞肺癌荷瘤裸鼠抑瘤作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    秦叔逵; 黄勇; 隋东虎; 李进; 楼丽广

    2011-01-01

    目的 探讨洛铂(LBP)、顺铂(DDP)和卡铂(Cab)单用或联合紫杉醇(PTX)、多西他赛(DOC)和长春瑞滨(NVB)对非小细胞肺癌(NSCLC)荷瘤裸鼠的抑瘤作用.方法 选用人大细胞肺癌细胞株NCI-H460接种于裸小鼠皮下成瘤.单药抑瘤实验中设LBP(3.75、7.5、15 mg/kg)3组及Cab(60mg/kg)、DDP(5mg/kg)各1组;联合抑瘤实验设LBP(7.5mg/kg)、DPP(2.5mg/kg)分别与DOC(5mg/kg)、PTX(12mg/kg)、NVB(5mg/kg)联合共6组以及各自单药5组,每组均随机分配6只成瘤小鼠,经静脉d0、d7给药(PTX d0、d2、d4给药除外).各设1组对照组,每组12只.每周2~3次记录瘤体体积和裸鼠体重,并计算相对肿瘤增殖率(T/C).结果 (1)单药抑瘤实验中,LBP抑瘤效果与剂量相关,中、高剂量组的T/C分别为51.1%和36.3%,低于Cab组(51.6%),但LBP高剂量组有1只小鼠出现药物相关性死亡.对裸鼠体重的影响由大到小依次为:DDP组>LBP高剂量组>LBP中剂量组>Cab组>LBP低剂量组.(2)联合抑瘤实验中,LBP+PTX组的T/C最低,为24.4%,明显优于DDP+PTX组(P<0.05);LBP+DOC组和DDP+DOC组亦对小鼠体重有明显影响.结论 LBP单药对NCI-H460荷瘤小鼠的抑瘤作用呈剂量依赖性,介于DDP与Cab之间;而LBP联合PTX的抑瘤作用最强,明显优于DDP联合PTX及其他两药联合.%Objective To investigate the inhibitory effects of lobaplatin (LBP), cisplatin (DDP) and caboplatin ( Cab ) alone or combined with paclitaxel ( PTX ), docetaxel ( DOC ) and vinorelbine ( NVB ) respectively against nude mice bearing human non-small cell lung cancer(NSCLC) NCI-H460 cells in vivo.Methods NCI-H460 cells were implanted into nude mice.In monotherapy treatment study, the nude mice beating human NSCLC NCI-H460 cells were randomly divided into 5 groups with 6 mice in each group.In concomitant treatment study, the nude mice bearing human NSCLC NCI-H460 cells were randomly divided into 11 groups, and each group had 6 mice.The volume of tumor, the weight of nude

  15. Observation the inhibitory effect and expression of MMP -2, CD44v6 of common turmeric among tumor-bearing nude mice%温郁金对荷肿瘤裸鼠抑瘤作用和MMP -2、CD44v6表达影响的观察

    Institute of Scientific and Technical Information of China (English)

    王光亮; 张俊会

    2012-01-01

    Objective To study the inhibitory effect of common turmeric and the expression of MMP - 2 and CD44v6 proteins in human gastric SGC -7901 cell, explore the possible mechanisms on gastric cancer metastasis. Method Established nude mouse orthotopic transplantation mode of SGC - 7901 and then randomly divided the nude mouse into control group and common turmeric group. The tumor growth and metastasis were observed, the expression of MMP - 2 and CD44v6 proteins in the tumor tissue were detected by immunohisto-chemistry. Results The rate of successfully orthotopic transplantation was 100%. The weight of the tumors in common turmeric group was (2.73 ±0.92) g, in control group was (4. 09 ± 1.17) g, there was statistical significance between the two group (P <0.05) , The inhibitory rate of common turmeric group was 33. 25%. The metastasis of cavitas peritonealis, liver and lymph node in common turmeric group were significantly lower than those of control group (P < 0. 05) . Meanwhile, we found that the positive rates of MMP - 2 and CD44v6 expression in the common turmeric group were obviously lower than that in control group (P<0.05) . Conclusions Common turmeric can inhibit gastric cancer growth and metastasis in orthotopic transplantation model of nude mice, the mechanism might be related to down - regulation of MMP - 2 and CD44v6 expression.%目的 观察温郁金对胃癌细胞抑制作用和MMP-2、CD44v6蛋白表达的影响,探讨其抗胃癌细胞转移的作用机制.方法 以SGC - 7901胃癌细胞株建立胃癌裸鼠原位移植瘤模型,将裸鼠随机分为对照组(0.9%氯化钠溶液)及实验组(温郁金水煎剂).观察裸小鼠胃癌种植后肿瘤生长及转移灶情况,用免疫组化法检测2组肿瘤组织中MMP-2和CD44v6蛋白的表达.结果 2组荷瘤鼠胃壁均有肿瘤生长,荷瘤率100%,对照组瘤重(4.09±1.17) g,实验组瘤重(2.73±0.92) g(与对照组比较P<0.05),抑瘤率为33.25%;实验组肝、腹腔和淋巴结转

  16. Biodistribution in healthy KM mice and micro PET/CT imaging in U87MG tumor-bearing nude mice of a new 18F-labeled cyclic RGD dimer%新型18F-RGD二聚体的正常生物分布及U87MG荷瘤裸鼠小动物PET/CT显像研究

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    Background and purpose:Integrinαvβ3 receptor plays an important role in promoting, sustaining and regulating the angiogenesis. It is overexpressed on neovascular endothelial cells and tumor cells. RGD peptide specifically binds to integrinαvβ3, which could evaluate growth status and invasiveness of tumor. This study aimed to investigate the biodistribution in healthy KM mice and micro PET/CT imaging in U87MG tumor-bearing mice of 18F-E[c(RGDfK)2]. Methods: 18F-E[c(RGDfK)2] was produced using an automated synthesis module via a simple one-step 18F-labeling strategy of the precursor 4-NO2-3-TFMBz-E[c(RGDfK)2]. The percentage activity of injection dose per gram of tissue (%ID/g) was calculated at 0.5, 1, 2, 4 h post injection of the probe. Micro PET/CT images of U87MG tumor-bearing nude mice with or without 18F-E[c(RGDfK)2] blocking were acquired at each time point. Results: The labeling efficiency and radiochemical purity of 18F-E[c(RGDfK)2] were 10% and 98%, respectively. 18F-E[c(RGDfK)2] was excreted via renal route, with a high blood clearance. The other organs had background-level activity accumulation. At 1 h, the%ID/g of kidney, liver, intestine, muscle and blood was (1.02±0.16)%ID/g,(0.24±0.06)%ID/g, (0.35±0.03)%ID/g, (0.13±0.03)%ID/g and (0.11±0.03)%ID/g 18F-E[c(RGDfK)2] had initial high tumor uptake [(5.2±0.56)%ID/g] and good tumor-to-background contrast (5.36) at 1 h post injection. Tumor uptake for blocking group was lower than those without blocking, and T/M reduced to 1.57. Conclusion: 18F-E[c(RGDfK)2] appears a promising PET molecular imaging probe targeting integrin αvβ3, with high tumor uptake. It could be suitable for prognosis evaluation of integrin-positive tumor, selection of vascular targeting therapy and therapy effect monitoring.%  背景与目的:整合素αvβ3受体在促进、维持以及调节血管生成的过程中有着至关重要的作用,高表达于多种肿瘤细胞及新生血管内皮细胞。RGD多肽

  17. Insights on FoxN1 biological significance and usages of the "nude" mouse in studies of T-lymphopoiesis.

    Science.gov (United States)

    Zhang, Zhijie; Burnley, Preston; Coder, Brandon; Su, Dong-Ming

    2012-01-01

    Mutation in the "nude" gene, i.e. the FoxN1 gene, induces a hairless phenotype and a rudimentary thymus gland in mice (nude mouse) and humans (T-cell related primary immunodeficiency). Conventional FoxN1 gene knockout and transgenic mouse models have been generated for studies of FoxN1 gene function related to skin and immune diseases, and for cancer models. It appeared that FoxN1's role was fully understood and the nude mouse model was fully utilized. However, in recent years, with the development of inducible gene knockout/knockin mouse models with the loxP-Cre(ER(T)) and diphtheria toxin receptor-induced cell abolished systems, it appears that the complete repertoire of FoxN1's roles and deep-going usage of nude mouse model in immune function studies have just begun. Here we summarize the research progress made by several recent works studying the role of FoxN1 in the thymus and utilizing nude and "second (conditional) nude" mouse models for studies of T-cell development and function. We also raise questions and propose further consideration of FoxN1 functions and utilizing this mouse model for immune function studies.

  18. Effects of Celecoxib on Interleukin-6 and Interleukin-8 Levels in Xenografted Nude Mice with Human Triple-negative Breast Cancer%塞来昔布对人三阴性乳腺癌裸鼠体内白细胞介素6和白细胞介素8水平的影响

    Institute of Scientific and Technical Information of China (English)

    王玲; 李杰; 张璟; 曹娜娜; 单保恩

    2012-01-01

    Objective To evaluate the effects of celecoxib on interleukin-6 (IL-6) and interleukin-8 (IL-8 ) expression in established nude mice with human triple-negative breast cancer (TNBC). Methods Human TNBC MDA-MB-231 cells were injected into BALB/c nude mice subcutaneously. The mice were randomly divided into 4 groups,including the control group and three celecoxib groups (receiving 25,50,100 mg·kg-1·d-1,respectively). On the 42nd day,the tumor volume and tumor weight were measured and growth curves were analyzed. The serum level of IL-6 and IL-8 was detected by ELBA assay. The mRNAs and protein levels of IL-6 and IL-8 in tumor tissues were measured by RT-PCR and immunohistochemistry, respectively. Results Compared with control group, celecoxib at doses of 25,50 and 100 mg ·kg-1·d-' inhibited the tumor growth significantly (P < 0.05). The serum levels of IL-6 and IL-8 were notably decreased in different cele- coxib treatment groups. Meanwhile, the gene expression of IL-6 and IL-8 in tumor tissues was also markedly suppressed after celecoxib treatment. Conclusion Celecoxib can inhibit the secretion and expression of IL-6 and IL-8, thus preventing the progress of TNBC in vivo.%目的探讨塞来昔布对人三阴性乳腺癌(TNBC)裸鼠体内白细胞介素6(IL-6)和IL-8水平的影响.方法 人TNBC细胞MDA-MB-231接种于裸鼠背部皮下,建立人TNBC裸鼠移植瘤模型.随机分为对照组和塞来昔布低、中、高剂量组.42 d后观察裸鼠一般状况的变化、用药前后肿瘤生长情况及肿瘤质量变化;ELISA法检测各组裸鼠血清中IL-6和IL-8含量的变化;RT-PCR检测肿瘤组织中IL-6和IL-8 mRNA的变化;免疫组化法检测肿瘤组织中IL-6和IL-8蛋白表达的变化.结果 塞来昔布各组肿瘤大小和瘤重较对照组均明显减小,差异均有统计学意义(P<0.05).经塞来昔布治疗后,塞来昔布低、中、高剂量组裸鼠血清中IL-6和IL-8的含量明显降低,与对照组

  19. A tumor targeted therapy study of PcDNA-sTRAIL combined with 131I-angiostatin on lewis lung garcinoma nude mice%131I-血管抑素联合PcDNA-sTRAIL在荷瘤小鼠模型肿瘤靶向治疗的研究

    Institute of Scientific and Technical Information of China (English)

    张弦; 田琼; 魏龙晓; 周润锁; 徐海峰; 袁梦辉

    2012-01-01

    Objective :To build PcDNA-sTRAIL eukaryolic expression vector and amplify, purify it. Then observe the joint sntitumor effect of the PcDNA-sTRAIL combined with '" I -AS in Lewis Lung Carcinoma nude mice Methods ■ Through the PCR amplification and directional cloning technology to build PcDN A-sTR AIL eukaryotic express carrier, me '" 1 to mark AS. The mark rate could reach 85 'A and exhibit good in vitro stability. After successfully constructed a tumor-burdened nude mice model, then we got a tumor-burdened mice SPECT imaging. Next, we completed a tumor targeted therapy study of restructuring PcON A-sTRAIL combined with '" I -AS. Result the overage volume of tumor in the PcDNA-sTRAIL and '" I-AS combined treatment group is smaller the other single treated groups. Conclusion ?Thi* research firstly suggested the combined treatment of inhibiting tumor angiogenesis effect, promoting the tumor cell apoptosis effect, and radiation treatment to fight cancer. We expect we could not only take full advantages of the three methods, but also provide powerful experimental evidences for combination treatment of radionuclide and the immune therapy.%目的:构建PcDNA-sTRAIL真核表达载体并进行扩增、纯化,采用131I标记血管抑素(AS)并完成了PcDNA-sTRAIL与131I-AS在荷瘤裸鼠体内的联合抑瘤试验.方法;通过PCR扩增和定向克隆技术成功构建PcDNA-sTRAIL真核表达载体,采用131I标记血管抑素,标记率达85%且体外稳定性好,成功构建了荷瘤裸鼠模型,并进行了荷瘤小鼠联合治疗后SPECT显像和病理结果,完成PcDNA-sTRAIL与131I-AS在荷瘤裸鼠体内的联合抑瘤试验.结果:荷瘤小鼠PcDNA-sTRAIL与131I-AS联合用药治疗期间肿瘤平均体积较其他单独治疗组增长缓慢.结论:本研究将抑制肿瘤血管生成、促肿瘤细胞凋亡和放射性核素的内照射三重作用相结合并用于抗肿瘤治疗,期望不仅能充分发挥三者的优势,又能为核素内照射与免疫

  20. Yanghe Decoctions Impact on the expression of CD90 and its antitumor effect in nude mice bearing human breast cancer%阳和汤对裸鼠荷人乳腺癌组织中 CD90表达的影响及其抑瘤作用

    Institute of Scientific and Technical Information of China (English)

    窦建卫; 任翠翠; 郝云; 严然; 杨亦奇

    2015-01-01

    目的:探讨阳和汤对裸鼠荷人乳腺癌组织中 CD90表达及其抑瘤作用。方法:将人乳腺癌细胞培养接种于裸鼠第四乳腺脂肪垫,建立裸鼠荷人乳腺癌模型,随机将荷瘤裸鼠分为5组:空白对照组、环磷酰胺组、阳和汤低浓度组、阳和汤中浓度组、阳和汤高浓度组,并于接种后14 d 给药2周,给药结束后24 h 麻醉,拉颈处死裸鼠,剥离肿瘤组织,称取瘤质量并绘制瘤体生长曲线、计算抑瘤率及采用免疫组化法测定组织中 CD90的表达。结果:1)环磷酰胺组及阳和汤组 CD90表达均低于空白对照组,差异有统计学意义(P <0.05),而环磷酰胺组与阳和汤组比较差异无统计学意义(P >0.05),环磷酰胺组、阳和汤低浓度组、阳和汤中浓度组、阳和汤高浓度组的表达阳性率均数分别为0.34%、0.73%、0.52%及0.42%;2)环磷酰胺组及阳和汤组肿瘤体积及瘤质量均小于空白对照组,差异有统计学意义(P <0.05),而环磷酰胺组与阳和汤组比较差异无统计学意义(P >0.05),环磷酰胺组、阳和汤低浓度组、阳和汤中浓度组、阳和汤高浓度组的抑瘤率分别为63.64%、37.45%、47.64%及63.27%。结论:1)阳和汤对人乳腺癌组织中 CD90表达具有明显下调作用,可能是其抑制乳腺癌的作用机制之一;2)对人乳腺癌细胞的生长具有明显抑制作用。%Objective:To explore the effect of Yanghe Decoction on the expression of CD90 and its antitumor effect in nude mice bearing human breast cancer.Methods:The breast cancer cells were injected into the fourth mammary fat pads of nude mice,es-tablishing the model of nude mice bearing human breast cancer.Then the mice were randomly divided into 5 groups:blank control group,cyclophosphamide group,Yanghe Decoction low dose group,middle dose group and high dose group.After 14 days inocu-lation,model mice were

  1. Influences of coupled medicinal-Shechuangzi (Fructus Cnidii) and Buguzhi(Fructus Psoraleae)on survival time and bone injury in nude mice with breast cancer with bone metastasis%药对蛇床子—补骨脂对乳腺癌骨转移裸鼠生存时间与骨损伤的影响

    Institute of Scientific and Technical Information of China (English)

    程旭锋; 刘琦; 刘胜; 张新峰; 杨顺芳

    2012-01-01

    Objective To study the influences of coupled medicinal-Shechuangzi (Fructus Cnidii) and Buguzhi {Fructus Psorakae) on survival time, activity of osteoclast and bone injury in nude mice with breast cancer with bone metastasis, and discuss the best combination of the coupled medicinal in the treatment of breast cancer with bone metastasis. Methods The model of nude mouse was established by using left ventricle injection of MDA-MB-231BO cells. The effect of coupled medicinal-Shechuangzi and Buguzhi(2. 56 g/mouse) was observed taking zoledronic acid as a positive control medicinal. All nude mice (n =84) were randomly divided into(0.2 mg/kg) group A and group B (each n =42), and each group were randomly divided again into model group, zoledronic acid group, 4 parts Shechuangzi to 0 part Buguzhi group (4 to 0 group) , 0 part Shechuangzi to 4 parts Buguzhi group (0 to 4 group) , 1 part Shechuangzi to 3 parts Buguzhi group (1 to 3 group), 2 parts Shechuangzi to 2 parts Buguzhi group (2 to 2 group), 3 parts Shechuangzi to 1 parts Buguzhi group (3 to 1 group, each re =6). A normal group (n = 6) was additionally set into group B. The survival time was observed in group A after intervention by different proportions of medicinal. The samples were collected 6 weeks after intervention by different proportions of medicinal in group B. The changes of morphology and quantity of osteoclasts were observed after TRACP staining, and the expressions of genes and proteins of M-CSF and PTHrP were detected in bone metastasis focus. Results The survival time was significantly prolonged in all intervention groups in nude mouse model (P <0. 05, P <0. 01), and the effect was the best in 2 to 2 group, which was almost as the same as that in zoledronic acid group. The activity of osteoclasts was inhibited to some extent in all intervention groups (P < 0. 05, P < 0. 01 ) , and the effect was the best in 2 to 2 group, which was almost as the same as that in zoledronic acid group. The expressions of

  2. 人肺腺癌脑转移动物模型建立及显像的研究%An Experimental Study on the Chinese Lung Adenocarcinoma Cell Clone CPA-Yang1-BR with Brain Metastasis Potency in Nude Mice and In Vivo Imaging Research

    Institute of Scientific and Technical Information of China (English)

    雷贝; 曹杰; 沈杰; 赵兰香; 梁胜; 孟庆刚; 谢文晖; 杨顺芳

    2013-01-01

    Background and objective Lung cancer is the leading cause of cancer-related death in men and wom-en. It is also the most common cause of brain metastases. A brain metastasis model is diffcult to be established because of the presence of the blood-brain barrier (BBB) and the lack of optimal methods for detecting brain metastasis in nude mice. hTus, the establishment of a Chinese lung adenocarcinoma cell line and its animal model with brain metastasis potency and in vivo research is of great signiifcance. Methods CPA-Yang1 cells were obtained from a patient with human lung adeno-carcinoma by lentiviral vector-mediated transfection of green lfuorescence protein. Intracardiac inoculation of the cells was performed in nude mice, and brain metastatic lesions were detected using micro 18F FDG-PET/CT scanners, small animal in vivo imaging system for lfuorescence, radionuclide and X ray fused imaging, magnetic resonance imaging (MRI) with sense body detection, and resection. hTe samples were divided into two parts for cell culture and histological diagnosis. hTe process was repeated in vivo and in vitro for four cycles to obtain a novel cell clone, CPA-Yang1-BR. Results A novel cell clone, CPA-Yang1-BR, was obtained with a brain metastatic rate of 50%. hTe use of MRI for the detection of brain metasta-ses has obvious advantages. Conclusion An experimental Chinese lung adenocarcinoma cell clone (CPA-Yang1-BR) and its animal model with brain metastasis potency in nude mice were established. MRI with sense body or micro MRI may be used as a sensitive, accurate, and noninvasive method to detect experimental brain metastases in intact live immunodeifcient mice. hTe results of this study may serve as a technical platform for brain metastases from lung adenocarcinoma.%背景与目的肺癌脑转移是临床常见的严重并发症,由于脑部结构和功能的特殊性、脑转移检测方法的局限性,预后很差。本研究旨在筛选人肺腺

  3. GPR30下调对子宫内膜癌细胞及裸鼠移植瘤组织 PI3K/Akt信号通路的影响%Influence of down-regulation of GPR30 on PI3 K/Akt signaling pathway in endometrial carcinoma cells and tumor tissue of nude mice

    Institute of Scientific and Technical Information of China (English)

    雷冬梅; 郭瑞霞; 刘泇希; 葛新; 乔玉环

    2015-01-01

    目的:探讨G蛋白偶联受体(GPR 30)下调对子宫内膜癌细胞及裸鼠移植瘤组织PI3K/Akt信号通路的影响。方法:采用免疫细胞化学SP法观察子宫内膜癌细胞系HEC-1A和Ishikawa细胞中GPR30、Akt和磷酸化Akt (p-Akt)蛋白的定位。以pGFP-V-RS(对照)和pGFP-V-RS-GPR30(干扰)分别转染两种细胞,用蛋白印迹法检测两种细胞中GPR30、Akt及p-Akt蛋白的表达水平。构建裸鼠移植瘤模型(分别接种上述4种转染细胞,共4组),用免疫组化SP法检测4组裸鼠移植瘤组织中p-Akt蛋白的表达。结果:①HEC-1A和Ishikawa细胞中,GPR30、Akt和p-Akt蛋白阳性表达均呈棕黄色,定位于细胞质。②稳定转染pGFP-VR-S -GPR30的两种细胞株中GPR30和p -Akt的表达均下调( P<0.05)。③与接种转染pGFP-V-RS细胞的2组裸鼠相比,接种转染pGFP-V-RS-GPR30细胞的2组裸鼠移植瘤组织中p-Akt表达降低。结论:在子宫内膜癌细胞及裸鼠移植瘤组织中, GPR30下调可能抑制了PI3K/Akt通路的活化。%Aim:To investigate the influence of down-regulation of G protein-coupled estrogen receptor 30 ( GPR30 ) on activation of PI3K/Akt signaling pathway in endometrial carcinoma cells and tumor tissue of nude mice .Methods:The location of GPR30, Akt and p-Akt protein in HEC-1A and Ishikawa cells was detected by immunocytochemical SP method . The expression of GPR30 in HEC-1A and Ishikawa cells was down-regulated by transfection with pGFP-V-RS-GPR30, a GPR30 antisense expression vector , and the cells transfected with pGFP-V-RS were the control; the levels of GPR30,Akt and p-Akt were detected by Western blot .The nude mice were allocated into 4 groups and inoculated the above transfected cells, and immunohistochemistry was performed to observe the changes of the expression level of p -Akt in the xenograft tis-sue.Results:Immunocytochemical SP method showed that GPR 30, Akt and p-Akt was stained as brown and

  4. The Difference of Expression and Activity Circadian Rhythm of Bc1-2 in Tumor Cells of Nude Mice Bearing Lung Adenocarcinoma%荷人肺癌裸鼠上肿瘤细胞Bcl-2表达及其活性生物时间节律差异

    Institute of Scientific and Technical Information of China (English)

    王志东; 刘湘国; 洪秀琴; 田晓彩; 孔春初

    2012-01-01

    目的:探索荷人肺癌裸鼠上肿瘤细胞Bcl-2表达及其活性生物时间节律差异.方法:体外培养A549人肺癌细胞系,移植到裸小鼠身上,10天成瘤后,随机分为6大组,每大组再分2小组,每组4只,一组不给任何处理,设为对照,各组小鼠分别于光照后不同时间点取肿瘤细胞制成细胞悬液,固定染色后,用流式细胞仪以每个样品检测10000个细胞的数量检测单个细胞的荧光强度,用流式细胞仪检测细胞周期情况,单因素方差分析法检验各期细胞在6个时间点差异的显著性,用Cosinor法考察G1,S,G2,M期细胞在24h的分布是否符合余弦函数,即是否有时辰节律.按6个时间点取的肿瘤细胞,匀浆后裂解细胞,Western Blot法测定Bcl-2的表达.结果:1.结果发现肿瘤的生长曲线高峰出现在睡眠期中点,其次在活动期中点;G1、S、G2期细胞变化符合余弦节律;2.Bcl-2的表达在光照后7h和19h达到峰值,变化趋势与肿瘤细胞的周期性改变一致.结论:荷人肺癌裸鼠上肿瘤细胞的细胞周期可能随昼夜交替呈节律性变化,Bcl-2的表达变化与肿瘤细胞的节律性改变一致.%Objective: To explore the difference of the expression of Bcl-2 in tumor cells of nude mice bearing lung neoplasm and its activity circadian rhythm. Methods: Transplanted the A549 lung neoplasm cell lines which were cultured in vitro to nude mice. After tumorigenesis in 10 days, they were divided into 6 groups randomly. And then, every group was subdivided into 2 groups, with 4 mice each. One group served as control, and did not receive any treatments. As for other groups, the tumor cells of each group were made into cell suspension at different time points after irradiation. After fixing dye, 10000 cells in each sample were made out to detect single cell fluorescence intensity and the cell cycle by flow cytometry. Changes at six time-points of cells at each stage were detected by Single factor variance

  5. 癌胚抗原启动子驱动双自杀基因对裸鼠大肠癌移植瘤的作用%Cytosine deaminase and thymidine kinase double suicide gene system driven by carcinoembryonic antigen promoter for the treatment of colorectal carcinoma xenograft in nude mice

    Institute of Scientific and Technical Information of China (English)

    黄正接; 冯庆钊; 尤俊; 许林; 罗维远; 易文城; 曾岳岳; 罗琪

    2013-01-01

    Objective To explore the therapeutic efficacy of double suicide gene system driven by carcinoembryonic antigen (CEA) promoter (Cp-CDglyTK) on colorectal carcinoma xenograft in nude mice.Methods The plasmid pcDNA3.1 (-) Cp-CDglyTK was transfected into the CEA-positive SW480 and CEA-negative HeLa cells respectively.The expression of suicide gene was detected by RT-PCR.And the transfected cells were treated with 5-fluorocytosine (5-FC) and ganciclovir (GCV) at different concentrations and the cell-killing and bystander effects assayed by methyl thiazolyl tetrazolium (MTT).By a transplantation of cultivated cells,SW480 or HeLa cell lines were injected subcutaneously into right axillary of nude mice to establish 96 SW480 and 72 HeLa tumor animal models.Nude mice were completely randomized with statistical software according to tumor volume.For prodrug therapy,48 SW480-bearing mice were divided equally into 4 groups of Ⅰ-Ⅳ.At the same time,48 HeLa-bearing mice were divided equally into 4 groups of Ⅴ-Ⅷ.Groups Ⅰ & Ⅴreceived an intratumoral injection of PBS,groups Ⅱ & ⅥGCV and 5-FC intratumorally,groups Ⅲ & Ⅶ PBS intraperitoneally and groups Ⅳ & Ⅷ GCV and 5-FC intraperitoneally.Forty-eight SW480-bearing mice were divided equally into 4 groups of Ⅸ ~ Ⅻ and 24 Hela-bearing ones into groups of ⅩⅢ & ⅩⅣ in therapy experiment by suicide gene plus prodrug.Six groups received an intratumoral injection of liposome Lipofectamine (R) and plasmid CP-CDglyTK and then an intraperitoneal injection of drug.The groups of Ⅸ and ⅩⅢ received an injection of PBS,group Ⅹ GCV,group Ⅺ 5-FC and groups Ⅻ & ⅩⅣ GCV and 5-FC.The observation parameters included tumor bulk,tumor weight,survival time and treatment effect in each group.Results SW480 cells transfected by plasmid pcDNA3.1 (-) Cp-CDglyTK expressed CDglyTK gene.The inhibition rates of GCV and 5-FC were significantly higher than those of HeLa cells (59.87% ± 0.21% vs 9.90% ± 0.09

  6. Biodistribution and planar gamma camera imaging of {sup 123}I- and {sup 131}I-labeled F(ab'){sub 2} and Fab fragments of monoclonal antibody 14C5 in nude mice bearing an A549 lung tumor

    Energy Technology Data Exchange (ETDEWEB)

    Burvenich, Ingrid J.G. [Laboratory of Radiopharmacy, University of Ghent, B-9000 Ghent (Belgium)]. E-mail: ingrid.burvenich@ugent.be; Schoonooghe, Steve [Department of Biomedical Research, Flanders Institute of Biotechnology (VIB), University of Ghent, B-9000 Ghent (Belgium); Blanckaert, Peter [Laboratory of Radiopharmacy, University of Ghent, B-9000 Ghent (Belgium); Bacher, Klaus [Department of Medical Physics and Radiation Protection, Ghent University, B-9000 Ghent (Belgium); Vervoort, Liesbet [Laboratory of Radiopharmacy, University of Ghent, B-9000 Ghent (Belgium); Coene, Elisabeth [N. Goormaghtigh Institute of Pathology, Ghent University, B-9000 Ghent (Belgium); Mertens, Nico [Department of Biomedical Research, Flanders Institute of Biotechnology (VIB), University of Ghent, B-9000 Ghent (Belgium); Vos, Filip de [Laboratory of Radiopharmacy, University of Ghent, B-9000 Ghent (Belgium); Slegers, Guido [Laboratory of Radiopharmacy, University of Ghent, B-9000 Ghent (Belgium)

    2007-04-15

    Detection of antigen 14C5, involved in substrate adhesion and highly expressed on the membrane of many carcinomas, including lung cancer, provides important diagnostic information that can influence patient management. The aim of this study was to evaluate the biodistribution and planar gamma camera imaging characteristics of radioiodinated F(ab'){sub 2} and Fab fragments of monoclonal antibody (mAb) 14C5 in tumor-bearing mice. Methods: F(ab'){sub 2} and Fab 14C5 fragments were radioiodinated using the Iodo-Gen method. In vitro stability, binding specificity and affinity of {sup 125}I-labeled 14C5 fragments were studied in A549 lung carcinoma cells. Biodistribution, blood clearance and tumor-targeting characteristics of {sup 131}I-labeled 14C5 fragments and intact mAb 14C5 were studied in Swiss nu/nu mice bearing A549 lung carcinoma tumors. Planar gamma imaging illustrated the potential use of these {sup 123}I-labeled 14C5 fragments for radioimmunodetection (RID). Results: Saturation binding experiments showed highest affinity for {sup 125}I-labeled F(ab'){sub 2} fragments (K {sub d}=0.37{+-}0.10 nmol/L) and lowest affinity for {sup 125}I-labeled Fab fragments (K {sub d}=2.25{+-}0.44 nmol/L). Blood clearance studies showed that the alpha half-life (t1/2{alpha}) value for Fab, F(ab'){sub 2} and mAb 14C5 was 14.9, 21 and 118 min, respectively. The beta half-life t1/2{beta} value for Fab, F(ab'){sub 2} and mAb 14C5 was 439, 627 and 4067 min, respectively. {sup 131}I-Fab fragments showed highest tumor uptake 3 h after injection (2.4{+-}0.8 %ID/g), {sup 131}I-labeled F(ab'){sub 2} showed highest tumor uptake 6 h after injection (4.7{+-}0.7 %ID/g) and for {sup 131}I-labeled mAb highest tumor uptake was observed at 24 h (10.7{+-}2.3 %ID/g). In planar gamma imaging, both labeled fragments gave better tumor-to-background contrast than {sup 123}I-mAb 14C5. Conclusion: Fab and F(ab'){sub 2} fragments derived from intact mAb 14C5 have

  7. Targeting human prostate cancer with 111In-labeled D2B IgG, F(ab')2 and Fab fragments in nude mice with PSMA-expressing xenografts.

    Science.gov (United States)

    Lütje, Susanne; van Rij, Catharina M; Franssen, Gerben M; Fracasso, Giulio; Helfrich, Wijnand; Eek, Annemarie; Oyen, Wim J; Colombatti, Marco; Boerman, Otto C

    2015-01-01

    D2B is a new monoclonal antibody directed against an extracellular domain of prostate-specific membrane antigen (PSMA), which is overexpressed in prostate cancer. The potential of D2B IgG, and F(ab')2 and Fab fragments of this antibody for targeting prostate cancer was determined in mice bearing subcutaneous prostate cancer xenografts. The optimal time point for imaging was determined in biodistribution and microSPECT imaging studies with (111)In-D2B IgG, (111)In-capromab pendetide, (111)In-D2B F(ab')2 and (111)In-D2B Fab fragments in mice with PSMA-expressing LNCaP and PSMA-negative PC3 tumors at several time points after injection. All (111)In-labeled antibody formats specifically accumulated in the LNCaP tumors, with highest uptake of (111)In-D2B IgG and (111)In-capromab pendetide at 168 h p.i. (94.8 ± 19.2% injected dose per gram (ID/g) and 16.7 ± 2.2% ID/g, respectively), whereas uptake of (111)In-D2B F(ab')2 and (111)In-D2B Fab fragments peaked at 24 h p.i. (12.1 ± 3.0% ID/g and 15.1 ± 2.9% ID/g, respectively). Maximum LNCaP tumor-to-blood ratios were 13.0 ± 2.3 (168 h p.i.), 6.2 ± 0.7 (24 h p.i.), 23.0 ± 4.0 (24 h p.i.) and 4.5 ± 0.6 (168 h p.i.) for (111)In-D2B IgG, (111)In-F(ab')2, (111)In-Fab and (111)In-capromab pendetide, respectively. LNCaP tumors were clearly visualized with microSPECT with all antibody formats. This study demonstrates the feasibility of D2B IgG, F(ab')2 and Fab fragments for targeting PSMA-expressing prostate cancer xenografts.

  8. 慢病毒载体介导端粒酶逆转录酶小干扰RNA治疗肝癌的实验研究%Inhibitory effect of lentivirus transduced anti-telomerase siRNA therapy on hepatocellular carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    张勇; 高云; 席力森; 邓蕾; 殷爱红; 王学浩; 孙倍成

    2009-01-01

    Objective To study the efficacy of anti-telomerase siRNA in hepatocellular carcinoma both in vitro and in vivo. Methods Lentvims vectors contained anti-telomerase siRNA were conducted with a high performance homologous recombination system, and then were transduced into human hepatocellular carcinoma HepG2 cells. The telomerase activity was detected by RT-PCR, HepG2 cell proliferation was determined by MTT assay, and apoptosis was detected by TUNEL assay. The in vivo experiment was carried out by inoculation of HepG2 cells into nude mice and the tumor growth was measured and analyzed. Results The growth of transfected HepG2 cells was significantly inhibited and the inhibition rate was 57.5% at the 8th day after transfection. The telomerase activity was significantly suppressed in vitro. The growth of transfected human hepatocellular HepG2 tumor in the nude mice was also significantly inhibited. Conclusion The results of this study demonstrate that the growth of hepatocellular carcinoma cells is effectively inhibited by transfection of anti-telomerase siRNA both in vitro and in vivo.%目的 探讨慢病毒介导的端粒酶逆转录酶(hTERT)小干扰RNA(siRNA)对肝癌细胞生长的影响.方法 构建携带hTERT siRNA的慢病毒表达载体,在体外转染人肝癌HepG2细胞系,以MTT法测定细胞生长变化,半定量逆转录聚合酶链反应(RT-PCR)检测hTERT mRNA的表达.将转染hTERT siRNA的HepG2细胞,接种于裸鼠腋窝皮下,观察移植瘤生长情况.取移植瘤组织,常规HE染色,行组织学观察,应用原位末端标记(TUNEL)技术检测细胞凋亡情况.结果 hTERT siRNA转染HepG2细胞后,随着时间的延长,对细胞增殖的抑制作用逐渐增强,到第8天,干扰组细胞抑制率为57.5%,与对照组比较,差异有统计学意义(P<0.01).RT-PCR产物凝胶电泳图显示,hTERT siRNA转染后,肿瘤细胞的端粒酶活性明显下降.转染后72 h,干扰组hTERT mRNA的表达水平为0.035±0.007,

  9. 大麻素WIN55,212-2对裸小鼠肝癌移植瘤及PPARγ表达的影响%Effect of cannabinoid WIN55,212-2 on HepG2 tumor xenograft and PPAR-γexpression in nude mice

    Institute of Scientific and Technical Information of China (English)

    邓远斐; 许达才; 肖顺华; 赵青

    2015-01-01

    目的::探讨大麻素WIN55,212-2( WIN)对裸小鼠肝癌移植瘤及过氧化物酶体增殖物激活受体(PPARγ)、c-myc表达的影响。方法:采用5 mg/kg的WIN对荷瘤裸小鼠进行瘤周皮下注射干预15 d,每3天测量1次瘤体体重和体积,计算肿瘤体积和抑瘤率。荧光定量PCR和Western blotting测定HepG2移植瘤中PPARγ和c-myc的表达情况。结果:WIN对HepG2细胞移植瘤具有抑制作用,抑瘤率为66.00%,荧光定量PCR结果显示WIN抑制HepG2细胞移植瘤c-myc在mRNA水平的表达,促进HepG2细胞移植瘤PPARγ在mRNA水平表达。 Western blotting结果显示WIN抑制HepG2细胞移植瘤c-myc在蛋白水平的表达,促进HepG2细胞移植瘤PPARγ在蛋白水平表达。结论:WIN能够抑制HepG2细胞移植瘤的生长和c-myc的表达,并上调PPARγ的表达。%Objective:To investigate the effect of a cannabinoid, WIN55, 212-2 ( WIN ) , on HepG2 hepatocellular carcinoma xenografts and expression of peroxisome proliferators activated receptor ( PPAR-γ) and c-myc in nude mice. Methods :The tumor-bearing nude mice were injected subcutaneously around the tumor sites with 5 mg/kg WIN for 15 d. The weight and size of the tumor were measure every 3d for calculation of the tumor volume and tumor inhibition rate. PCR and western blotting assay were used to measure the expression of PPAR-γ and of c-myc in HepG2 tumor xenograft. Results:WIN showed inhibitory effect on the growth of HepG2 tumor xenograft, with an inhibition rate being 66.00%. Fluorescence quantitative PCR showed that WIN inhibited the expression of c-myc mRNA and promoted the expression of PPAR-γ mRNA in HepG2 tumor xenografts. Western blotting analysis showed that WIN inhibited the expression of c-myc proteins and promoted the expression of PPAR-γ proteins in HepG2 tumor xenografts. Conclusion:WIN may inhibit the growth of HepG2 tumor xenograft and c-myc expression, and upregulate the expression of PPAR-γ.

  10. 人脐带间充质干细胞对食管癌细胞EC9706增殖、迁移和对裸鼠移植瘤的抑制作用%Inhibitory effect of human umbilical cord mesenchymal stem cells on proliferation and migration of esophageal cancer EC9706 cells and the transplanted tumor in nude mice

    Institute of Scientific and Technical Information of China (English)

    姚文健; 白玉; 赵宝生; 刘尚国; 齐博

    2014-01-01

    Objective To investigate the inhibitory effect of human umbilical cord mesenchymal stem cells(hUCMSCs) on proliferation and migration of esophageal cancer EC9706 cells and the transplanted tumor in nudemice. Methods hUCMSCs were isolated and cultured in vitro. The phenotype of hUCMSCs was identified.hUCMSCs were indirectly co-cultured with EC9706 and the effect of co-culture on EC9706 proliferation andmigration was evaluated. Animal models of transplanted tumor were established in nude mice. hUCMSCs wereinfused via the tail vein and the effect of hUCMSCs on the tumor growth and metastasis was investigated. ResultsAt 9 to 14 days after cell adherence, the fibroblast-like cells were observed. Flow cytometry analysis revealed thatCD29 and CD44 were highly expressed on the plasma membrane of the passages 3 cells, with negative expression ofCD34, CD45 and HLA-DR. Results of MTT assay and cell scratch test showed that compared with the control group,the proliferation and migration of EC9706 in the experimental group were significantly inhibited, respectively. Theaverage tumor weight in the control group and in the experimental was (1.83 ± 0.33)g and (1.02 ± 0.15)g,respectively. The average number of metastasis nodules was 5.37 ± 1.12 and 1.29 ± 1.05 respectively, withsignificant difference. Conclusion hUCMSCs can inhibit the proliferation and migration of EC9706 cells andinhibit the growth and metastasis of transplanted tumor in nude mice.%目的:探讨人脐带间充质干细胞(hUCMSCs)对食管癌细胞EC9706增殖、迁移的抑制作用和对裸鼠体内移植瘤的抑制作用。方法:体外分离培养hUCMSCs,检测细胞表型;将其和EC9706间接共培养,观察对EC9706增殖、迁移能力的影响。建立动物模型,尾静脉注射hUCMSCs后观察移植瘤生长及转移情况。结果:细胞贴壁9~14 d 后可见成纤维样细胞,流式分析显示第5代细胞均表达 CD29、CD44,不表达 CD34、CD45和HLA-DR。 MTT法及

  11. 再生基因Ⅳ及其碳水化合物识别域促进裸鼠结直肠癌移植瘤血管的生成%Regenerating gene Ⅳ and its carbohydrate-recognition domain promote angiogenesis of colorectal carcinoma xenografts in nude mice

    Institute of Scientific and Technical Information of China (English)

    郭英; 李楠; 徐佳佳; 田晓强; 黄培林

    2011-01-01

    目的:探讨再生基因Ⅳ(regenerating geneⅣ,RegⅣ)及其碳水化合物识别域(carbohydrate-recognition domain,CRD)对裸鼠结直肠癌移植瘤血管生成的影响.方法:将已转染了重组质粒pcDNA3.1-RegⅣ、pcDNA3.1-RegⅣ△CRD、空载体质粒的人结肠癌LoVo细胞(分别命名为LoVo/RegⅣ、LoVo/RegⅣ△CRD、LoVo/negative)和自然生长状态的LoVo细胞分别接种于裸鼠皮下.RT-PCR法检测移植瘤组织中RegⅣ及RegⅣ△CRD mRNA的表达,免疫组织化学法检测移植瘤组织中血管内皮生长因子(vascular endothelial growth factor,VEGF)和CD34的表达,计数移植瘤组织中微血管密度(microvessel density,MVD).结果:LoVo/RegⅣ移植瘤组织中VEGF的表达水平高于其他3组,差异有统计学意义(P<0.05);LoVo/RegⅣ△CRD、LoVo和LoVo/negative组间VEGF的表达水平差异无统计学意义(P>0.05); LoVo/RegⅣ移植瘤组织中MVD值明显高于其他3组(P<0.05),LoVo/RegⅣ△CRD、LoVo和LoVo/negative移植瘤组织间MVD值差异无统计学意义(P>0.05).结论:RegⅣ基因参与调控结直肠癌的血管生成,其作用与CRD结构域密切相关.%Objective: To investigate the effect of regenerating gene IV (RegW) and its carbohydrate-recognition domain (CRD)on angiogenesis of colorectal carcinoma xenografts in nude mice. Methods: The LoVo human colorectal carcinoma cells were transfected with recombinant plasmids pcDNA3.1-Reg IV (LoVo/ReglV group), pcDNA3.1-RegIVACRD (LoVo/Reg lV △CRD group) or empty vector (LoVo/negative group), and then the LoVo/ReglV, LoVo/Reg lV △CRD, LoVo/negative and LoVo cells were transplanted subcutaneously in nude mice, respectively. The expression levels of RegIV and ReglV/△CRD mRNAs in xenograft tissues were detected by RT-PCR. The expression levels of vascular endothelial growth factor (VECF) and CD34 proteins in xenograft tissues were determined by immunohistochemistry assay. The microvessel density (MVD) in xenograft tissues was calculated

  12. 胎猪胰腺干细胞体外诱导分化为胰岛素分泌细胞及其移植治疗裸鼠糖尿病的研究%Fetal Porcine Pancreatic Stem Cells Differentiating into Insulin-producing Cells In vitro and Their Curative Effect on Diabetic Nude Mice

    Institute of Scientific and Technical Information of China (English)

    楚元奎; 曹晖; 王赟; 张翊华; 窦忠英

    2011-01-01

    Islet replacement therapy is limited by the shortage of donor islet cells.The aim of this article is to study the potential capacity of fetal porcine pancreatic stem cells(FPPSCs) as a xenograft donor cells.FPPSCs have a strong proliferation ability, and the expression of it's surface antigen was similar to the mesenchymal stem cells.It expressed not only the markers of pancreatic stem cells, but also the markers of ES cells.After 2 weeks induction using a serum-free protocol, the DTZ-positive islet-like cell clusters (ICC) were formed, and these ICCs expressed insulin and Glut-2.After induction, the expression of markers related to pancreatic stem cells decreased,while that related to insulin-producing cells increased, and the insulin and C-peptide content synthesized and secreted by FPPSCs increased remarkably(P<0.05).The blood glucose level of diabetic nude mice in differentiated cells transplantation group decreased, but quickly reached and maintained at a high level (>16.7 mmol/L).These results demonstrated that FPP SCs can be induced to differentiate into insulin-producing cells in vitro,and ameliorate the hyperglycemia of diabetic nude mice.It might provide unlimited resources for islet replacement therapy.%缺乏供体细胞制约着胰岛替代疗法在Ⅰ型精尿病治疗过程中的应用.本研究对实验室分离保存的胎猪胰腺干细胞(fetal porcine pancreatic stem cells,FPPSCs),体外诱导分化为胰岛素分泌细胞以及移植治疗裸鼠糖尿病的能力进行了深入研究,以探讨该细胞株作为异种供体细胞的潜力.研究结果表明,该细胞体外增殖活力旺盛,其形态及表面抗原表达特征与间充质干细胞极其相似,除表达胰腺干细胞相关标志外,FPPSCs还表达一些胚胎干细胞的相关标志.采用无血清诱导方案诱导2周后,FPPSCs形成DTZ染色阳性的胰岛样细胞团(islet-like cell cluster,ICC),该细胞团表达胰岛素、Glut-2等胰岛素分泌细胞功能相关的

  13. FOXN1 deficient nude severe combined immunodeficiency

    OpenAIRE

    Rota, Ioanna A.; Dhalla, Fatima

    2017-01-01

    Nude severe combined immunodeficiency is a rare inherited disease caused by autosomal recessive loss-of-function mutations in FOXN1. This gene encodes a transcription factor essential for the development of the thymus, the primary lymphoid organ that supports T-cell development and selection. To date nine cases have been reported presenting with the clinical triad of absent thymus resulting in severe T-cell immunodeficiency, congenital alopecia universalis and nail dystrophy. Diagnosis relies...

  14. 微球化人脐带Wharton胶间充质干细胞移植裸鼠皮下构建异位软骨%Cartilage construction in nude mice with microencapsulated stem cells derived from human umbilical cord Wharton’s jelly

    Institute of Scientific and Technical Information of China (English)

    杨建华; 刘舒云; 赵鹏; 卢世璧; 张莉; 黄靖香; 赵斌; 许文静; 郭全义

    2014-01-01

    背景:软骨细胞外基质具有众多的信号分子蛋白和因子,其成分和特性最接近天然软骨组织,因而其很可能是构建组织工程软骨的最理想原料。  目的:探讨海藻酸钙-软骨细胞外基质混合凝胶微球复合人脐带Wharton胶间充质干细胞在裸鼠皮下异位构建组织工程软骨的可行性。  方法:制备软骨细胞外基质微丝悬液,将人脐带Wharton胶间充质干细胞接种于海藻酸钙-软骨细胞外基质混合凝胶微球中体外培养后植入裸鼠背部皮下(实验组),以人脐带 Wharton 胶间充质干细胞混合于单纯藻酸盐凝胶微球作为对照组,于4周后取材进行大体和组织学苏木精-伊红、甲苯胺蓝、番红O及Ⅱ型胶原免疫组化观察。结果与结论:体外培养时微球中干细胞呈球形软骨细胞样形态,生长、增殖情况良好;实验组术后第4周取材可见外形呈类软骨样组织块,甲苯胺蓝、番红O及Ⅱ型胶原免疫组化染色阳性,镜下观察可见大量类软骨样细胞及类软骨陷窝样结构,植入的混合凝胶微球周围组织无明显炎症反应;对照组显示微球部分降解,周围仅有少量炎症细胞及淋巴细胞。结果可见海藻酸钙-软骨细胞外基质具有良好的组织相容性,复合干细胞形成的微球植入裸鼠皮下可以构建为类软骨样组织。%BACKGROUND:Cartilage extracelular matrix with a large number of signaling molecule proteins and factors is likely to be an ideal material for tissue engineering cartilage. OBJECTIVE: To investigate the possibility of calcium alginate and cartilage extracelular matrix combined with microencapsulated stem cels derived from human umbilical cord Wharton’s jely to construct ectopic tissue-engineered cartilage in nude mice. METHODS: Microfilament suspension of the cartilage extracelular matrix was prepared. Human stem cels derived from Wharton’s jely of the umbilical cord

  15. Effect of selenium dioxide united DDP on the human ovarian cancer cells xenografts in nude mice and its mechanism%二氧化硒联合顺铂对裸鼠皮下耐药细胞株SKOV3/CDDP移植瘤的影响及其作用机制

    Institute of Scientific and Technical Information of China (English)

    尹春华; 胡嘉; 杨茗芳; 刘丝荪; 宋矿余

    2012-01-01

    Objective To investigate the effect of the combination of selenium dioxide and cisplatin on the human o-varian cancer cells xenografts in nude mice and its mechanism. Methods Human ovarian cancer models were established by subcutaneously transplanting SKOV3/CDDP cells into nude mice, then dividing them into control group and treatment group. The treatment group were divided into DDP group, SeO2 group, DDP + SeO2 group. Sodium chloride was given in control group. Then the transplantation rate, growth rate, mean tumor inhibition rate and weight, appetite and mental state of the nude mice in different groups were observed. Flow cytometry was used to assess the degree of apoptosis in the tissues of the tumor. The level of P-gp in tumor cells was detected by HE staining and imimmohistochemical method. Results Mean tumor inhibition rate in DDP group, SeO2 group^DDP + SeO2 group was separately 48. 29% , 41. 69% , 72. 28% , mean apoptosis rate separately 25.92% , 24. 14% , 45.43%. The mean tumor inhibition rate and mean apoptosis rate in the DDP + SeO2 group were higher than those in DDP group or SeO2 group ( P < 0. 05 ). The cancer cells in the S phase were decreased in DDP + SeO2 group. The P-gp levels in SeO2 group and DDP + SeO2 group were lower than those in DDP group(P<0.05). Conclusions SeO2 and DDP have united effect on apoptosis of drug-fast ovarian, and SeO2 can inhibit the expression of P-gp, which may be one of the important mechanism of adding the sensitivity of drug-fast oophoroma to DDP.%目的 探讨二氧化硒(SeO2)联合顺铂(DDP)对裸鼠皮下耐药细胞株SKOV3/CDDP移植瘤的影响及其可能的作用机制.方法 将人卵巢癌SKOV3/CDDP细胞接种于SPF级雌性BALB/C裸鼠皮下,随机分成治疗组和对照组.治疗组分为DDP组、SeO2组、DDP联合SeO2组,分别给予DDP、SeO2、DDP+ SeO2腹腔注射,对照组给予生理盐水,观察各组成瘤率、生长率、平均抑瘤率,绘制肿瘤生长曲线.用流式细胞术检测肿

  16. Systematically Experimental Investigation on Carcinogenesis or Tumorigenicity of VERO Cell Lines of Different Karyotypes in Nude Mice in vivo Used for Viral Vaccine Manufacture%病毒疫苗制备用不同核型VERO细胞系在裸鼠体内致癌/致瘤性的系统实验研究

    Institute of Scientific and Technical Information of China (English)

    张德礼; 季梁; 李六金; 黄高升

    2004-01-01

    Many cell lines used for vaccine production have a potentially strong tumorigenic character.Some of those routinely used need to be checked at different passage numbers for this characteristic.Using HeLa cell cultures as positive controls,and primary canine kidney cell (CKC) or feline kidney cell (FKC) cultures purified in vitro on passage three as negative controls,the tumorigenicity of VERO cell sublines was tested in 219 nude mice.The master cell stocks (MCS) and working cell banks (WCB) of eight strains of VERO African green monkey kidney cell (AGMKC) line used for canine,feline and mink vaccine preparation were established in China.The hypo-tetra-ploid JA or hyper-diploid KA strain of VERO line was highly tumorigenic.These data showed a variable chromosome karyotype of VERO line,and contraindicated the use of JA or KA strain of VERO line for the preparation of attenuated viral vaccines.JA or KA strain of VERO line could be a substitute for HeLa line as a positive-control malignant tumor (MT) cell model.The non-carcinogenic YB,JC,M and JB strains of VERO line were therefore selected for the preparation of modified live rabies viral vaccine in place of BHK-21.The cell sub-lines are comparatively stable in terms of their heritable characters,and show little significant changes between passages.In summary,we have found that:1)the tumorigenicity of cell line is different among different-karyotypic cells;2)it is the genetic characteristics of chromosomes of cell lines that determines their tumorigenicity,but with species-specific carcinogenicity;3)the chromosome number variation of cell lines has positive relationship with their carcinogenesis;4)highly variable strains of tumor cell line can be selected quickly and successfully in nude mice by alternate cultivation in vitro and in vivo.Malignant rhabdoid tumor (MRT) was evolved in nude mice inoculated with violently variable HeLa or VERO cells.The importance of assessing the tumorigenicity in cell sublines used for

  17. Effect of peroxiredoxin Ⅰ gene silencing on the radiosensitivity of breast carcinoma MCF-7 cell xenograft in nude mice%沉默Peroxiredoxin I基因对乳腺癌裸鼠移植瘤放射敏感性的影响

    Institute of Scientific and Technical Information of China (English)

    郭启帅; 黄曦; 李少林

    2011-01-01

    To investigate the effect of peroxiredoxin I (Prx I) gene silencing on the radiosensitivity of breast carcinoma MCF-7 cell xenograft in nude mice and explore the mechanism. Methods MCF-7 cells were transfected with the recombinant plasmids pGPU6-PrxI and pGPU6-HK separately. The pGPU6-PrxI-trasnfected cells stably expressing Prx I shRNA and pGPU6-HK-transfected cells were inoculated subcutaneously into BALB/c nude mice. After exposure to ionizing radiation (IR) with 6 MV X-ray, the xenografts were harvested for measuring the tumor volume and mass, and the tumor inhibition rates were calculated. Immunohistochemistry was employed for detecting the expressions of Prx I and caspase-3 proteins. The ultrastructural changes of the tumor tissues following the exposure were observed using electron microscopy. Western blotting was used to analyze the expressions of γ-H2AX and Rad51 proteins. Results Following IR exposure, the pGPU6-Prx I-transfected cell xenograft showed a significantly delayed growth and smaller tumor volume as compared with pGPU6-HK xnegraft, with a tumor inhibition rate reaching 79.76%, significantly higher than that in non-exposed pGPU6-Prx I group (34.92%) and pGPU6-HK+IR group (56.94%) (P<0.05). The pGPU6-Prx I-transfected xenografts showed significantly increased tumor cell apoptosis and necrosis, down-regulated the expressions of Prx I and Rad51 proteins, and up-regulated the expressions of caspase-3 and γ-H2AX proteins; these changes were even more obvious after IR exposure, which caused a decrease of Rad51 protein by 84.8% and an increase in γ-H2AX protein by 5.6 folds compared with those in pGPU6-HK group (P0.05). Conclusion Prx I gene silencing can significantly enhance the radiosensitivity of breast carcinoma xenograft in nude mice possibly by increasing DNA damage and lowering the capacity of the cells for DNA repair. Prx I may serve as an ideal molecular target for radiosensitization of breast carcinoma.%目的 探讨Peroxiredoxin I(Prx I)

  18. Combined effects of porous hydroxyapatite and demineralized bone matrix on bone induction: in vitro and in vivo study using a nude rat model

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Hyup; Lee, Kyung-Mee; Baek, Hae-Ri; Jang, Soo-Jeong; Lee, Ji-Ho [Department of Orthopedic Surgery, Seoul National University School of Medicine, SMG-SNU Boramae Medical Center, Seoul 156-707 (Korea, Republic of); Ryu, Hyun-Seung, E-mail: spinelee@snu.ac.kr [Research and Development Center, CGBio Inc., Seong-Nam 462-120 (Korea, Republic of)

    2011-02-15

    Hydroxyapatite (HA) is an osteoconductive material used as a bone graft extender and demineralized bone matrix (DBM) has been used as a source of osteoinductive factors. A combination of DBM and HA is expected to create a composite with both osteoconductive and osteoinductive properties. This study examined the effect of a combination of DBM and HA on osteogenesis both in vitro and in vivo using an athymic nude rat abdominal muscle pouch model, and evaluated the possibility of HA as a carrier of DBM. Alkaline phosphatase (ALP) staining, ALP assay and measurements of the mRNA expression of ALP and Runx2 by RT-PCR were performed by transplanting human mesenchymal stem cells onto a plate. Five athymic nude rats each were assigned to one of two experimental groups (DBM/HA putty and only HA, i.e. 15 pouches per group). The muscle pouches were filled with DBM/HA putty or only HA. Radiographs were obtained at weeks 4 and 8, postoperatively. The animals were sacrificed at week 8 postoperatively and high resolution microCT was used to confirm the newly formed mineralized tissue. Each pouch was fixed, embedded, sectioned and processed for hematoxylin and eosin staining. The ALP value of the DBM/HA putty was higher than those of HA and control (p < 0.05, each). The expression of ALP mRNA appeared higher on the DBM/HA putty than on HA and control. MicroCT and histology examinations of the DBM/HA putty demonstrated the presence of newly generated mineralized tissues but there was no mineralized tissue in the HA cases. In conclusion, the DBM/HA putty indicated osteoblastic differentiation in vitro and showed ectopic mineralized tissue formation in the rat abdominal pouch model. These findings indicate that the DBM/HA putty can retain its oteoinductivity and HA can be used as a carrier of DBM.

  19. Inhibitory effect of oridonin on androgen independent prostate cancer xenografts in nude mice%冬凌草甲素对雄激素非依赖性前列腺癌裸鼠移植瘤的抑制作用

    Institute of Scientific and Technical Information of China (English)

    徐凯; 郭剑明; 刘宇军; 徐志兵; 王国民

    2012-01-01

    Objective To research the inhibition effect of oridonin on androgen independent prostate cancer (AlPCa) xenografts in nude mice and its mechanism. Methods DU145 cells were injected subcutaneously to 20 male BALB/c-nude mice and those mice were randomly divided into oridonin group and control group. From day 2 after the injection, the mice were fed with 0.9% saline solution in the control group and odidonin (15 mg·Kg-1·D-1) in the oridonin group every day. The average size of xenografts was measured every week from week 2 to week 7. At the end of week 7, all mice were executed and the tumors were removed. The Mrna expression of G1/S regulatory factor p 16, cell proliferation related factor interleukin (IL-6 and immune escape related factor indoleamine 2, 3-dioxygenase (IDO) were analyzed by reverse transcriptase polymerase chain reaction. Results The growth of xenografts in the oridonin group was significantly inhibited, and the tumors were significantly smaller than those in the control group from the end of week 3 to week 7 (all P<0.001). Compared with control group, the growth inhibiting rate of the tumors in the oridonin group was 58.12% at the end of week 7. After 7 weeks, the average level of p16 Mrna in the control group was lower than that in the oridonin group (0.46 vs. 0.95); the average level of IL-6 Mrna in the control group was high than that in the oridonin group (0.33 vs. 0.02); the average level of IDO Mrna in the control group was 0.08, but it could not be measured in the oridonin group because there were no obvious electrophoretic bands. Conclusion Oridonin can obviously inhibit the growth of DU145 cells, indicating that oridonin has the antitumor activity to AlPCa. It may be achieved by downregulating cell cycle, immune escape and IL-6 level.%目的 探讨冬凌草甲素对雄激素非依赖性前列腺癌(AIPCa)裸鼠移植瘤的抑制作用及其机制.方法 雄性裸小鼠20只,皮下接种DU145细胞,随机分成用药组和

  20. Study on Characteristics of Absorption into Blood of Common Cnidium Fruit-Malaytea Scurfpea Fruit in Breast Cancer Bone Metastasis Nude Mice Model%蛇床子-补骨脂在乳腺癌骨转移裸鼠模型中吸收入血特征的研究

    Institute of Scientific and Technical Information of China (English)

    程旭锋; 刘胜; 金惠; 张新峰; 刘琦

    2012-01-01

    目的:以蛇床子素和补骨脂素为靶标成分,从药物吸收入血角度探讨蛇床子-补骨脂配伍后疗效增加的机制.方法:采用左心室注射MDA-MB-231 BO细胞法建立裸鼠乳腺癌骨转移模型,给予不同配比的蛇床子-补骨脂药物煎液,采用HPLC-MS法测定裸鼠血浆中蛇床子素和补骨脂素,观察蛇床子-补骨脂配伍后蛇床子素和补骨脂素吸收入血的特征.结果:蛇床子组血浆中可发现蛇床子素离子峰;补骨脂组血浆中可发现补骨脂素分子及其离子峰信号;蛇床子-补骨脂(1∶3)组血浆中可发现蛇床子素分子及离子峰信号,未发现补骨脂素分子及离子峰信号,蛇床子-补骨脂(2∶2)组可发现蛇床子素和补骨脂素的分子及离子峰信号,蛇床子-补骨脂(3∶1)组可发现蛇床子素分子及离子峰信号,未发现补骨脂素分子及离子峰信号.结论:蛇床子素和补骨脂素均可被吸收入血;蛇床子与补骨脂1∶1配伍可促进补骨脂中补骨脂素的吸收入血.%Objective: To investigate the mechanism of curative effect increased of Common Cnidium Fruit-Malaytea Scurfpea Fruit compatibility based on osthole and psoralen as the target components absorbed into the bloodstream. Method: The breast cancer bone metastasis nude mice models were established by injecting MDA-MB-231BO cells into left ventricular, and they were given different combinations of Common Cnidium Fruit-Malaytea Scurfpea Fruit drugs decoction, osthole and psoralen in nude ice plasma were detected by HPLC-MS, and the characteristics of osthole and psoralen absorbed into the bloodstream were observed. Result; The plasma osthole's ion peak could be found in the plasmas of Common Cnidium Fruit group; the psoralen molecule and its ion peak signal could be found in the plasmas of Malaytea Scurfpea Fruit group; osthole molecule and its ion peak signal, but not psoralen molecule or its ion peak signal could be found in- the plasmas of Common