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Sample records for athymic nude mice

  1. Anomalies in the hormonal status of athymic nude mice.

    Science.gov (United States)

    Köpf-Maier, P; Mboneko, V F

    1990-01-01

    The serum levels of hormones that are known to influence growth, development, and differentiation of the skin and its appendages were analyzed in female haired (NMRI) and nude (NMRI, nu/nu) mice. Whereas the concentrations of testosterone, prolactin, and triiodothyronine did not differ in nude animals from those found in normal mice of the same age in the anestrous phase of the sexual cycle, the serum levels of estradiol, progesterone, and thyroxine were found in female nude mice at significantly lower levels than in normally haired animals. These results point to a hormonal situation that contributes to the poor fertility of homozygous (nu/nu) female mice and may promote impairment of growth and differentiation of skin and hair, resulting in the macroscopic nudity of athymic, nude mice. PMID:2370246

  2. A bone metastases model of anaplastic thyroid carcinoma in athymic nude mice

    International Nuclear Information System (INIS)

    Anaplastic thyroid carcinoma (ATC), an aggressive form of thyroid cancer, represents less than 2% of all thyroid cancers. The survival of patients with ATC remains low especially when accompanied with bone metastasis. This study aims to establish a reproducible animal model of bone metastasis of ATC which may be useful for further research on novel treatment strategy. Eight 6-8 week old female athymic nude mice were randomly selected. ATC cell line ARO cells were injected into the left ventricular cavity of each mouse respectively. Each mouse was imaged using a dedicated small-animal PET/CT scanner after successful injection of [18F]-FDG under deep anesthesia. Pathological examination was carried out to confirm the bone metastases of ATC. Histopathology established ATC bone metastases in five nude mice’s tibia. Similarly, PET image displayed significantly increased radioactivity (P<0.01) in the established bone metastasis compared with the control normal tibia. Both micro-PET/CT and histomorphometric measurement confirmed the bone metastases model of ATC in nude mice by left ventricular cavity injection of ARO cell line. The bone metastases model of ATC will thus facilitate the understanding of its pathogenesis and aid in the development of novel therapies.

  3. 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.

  4. Interferon gamma is involved in the recovery of athymic nude mice from recombinant vaccinia virus/interleukin 2 infection

    OpenAIRE

    1990-01-01

    Athymic nude mice recover from an infection with recombinant vaccinia virus (VV) encoding murine interleukin 2 (IL-2), but treatment with a mAb to IL-2 accentuated infection. Administration of a mAb against interferon gamma (IFN-gamma) to mice infected with the IL-2-encoding virus completely prevented the IL-2-induced mechanisms of recovery. Both asialo-GM1+ (NK) and asialo-GM1- (non-NK) cells were participants in the IFN-gamma-mediated recovery of nude mice from infection with the IL-2-encod...

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Detection of Corynebacterium bovis infection in athymic nude mice from a research animal facility in Korea

    OpenAIRE

    Kim, Tae-Hyoun; Kim, Dong-Su; Han, Ju-Hee; Chang, Seo-Na; Kim, Kyung-Sul; Seok, Seung-Hyeok; Kim, Dong-Jae; Park, Jong-Hwan; Park, Jae-Hak

    2014-01-01

    Corynebacterium (C.) bovis infection in nude mice causes hyperkeratosis and weight loss and has been reported worldwide but not in Korea. In 2011, nude mice from an animal facility in Korea were found to have white flakes on their dorsal skin. Histopathological testing revealed that the mice had hyperkeratosis and Gram-positive bacteria were found in the skin. We identified isolated bacteria from the skin lesions as C. bovis using PCR and 16S rRNA sequencing. To the best of our knowledge, thi...

  7. Improvement of epidermal differentiation and barrier function in reconstructed human skin after grafting onto athymic nude mice.

    Science.gov (United States)

    Higounenc, I; Démarchez, M; Régnier, M; Schmidt, R; Ponec, M; Shroot, B

    1994-01-01

    To determine whether epidermis reconstructed in vitro at the air-liquid interface on de-epidermized dermis has the capacity to normalize the expression of differentiation-specific markers, its lipid composition and stratum corneum barrier properties, human skin equivalents were transplanted onto athymic nude mice and investigated at different stages ranging from 1 to 4 months after grafting. Indirect immunofluorescence with species- or non-species-specific antibodies revealed that as early as 1 month after transplantation keratinization, and involucrin, loricrin and transglutaminase patterns were normalized. Human melanocytes were observed in the basal layer of the pigmented graft. As revealed by high-performance thin-layer chromatography and transmission electron microscopy after ruthenium tetroxide fixation, the lipid profile and the intracellular lamellar organization were similar to those found in natural epidermis. Transepidermal water loss measurements and penetration studies showed that the barrier properties of the reconstructed epidermis after transplantation were comparable to those of normal human skin. PMID:8154923

  8. Localization of pulmonary human sarcoma xenografts in athymic nude mice with indium-111-labeled monoclonal antibodies

    International Nuclear Information System (INIS)

    In order to study localization of metastatic tumors with a radiolabeled monoclonal antibody, a pulmonary metastases model was devised in athymic mice. Metastatic pulmonary sarcoma colonies were verified by histological examination. A murine monoclonal antibody (MAb 19-24) directed against a human sarcoma antigen was labeled with indium-111 (111In) by use of the linker 1-(p-isothiocyanatobenzyl)-diethylenetriaminepentaacetic acid (SCN-Bz-DTPA). MAb P3 was similarly labeled as a negative control. In the group given MAb 19-24, the percent injected dose per gram lung tissue bearing tumor colonies (30.1%, 29.6%, and 27.7% on Days 1, 2, and 3, respectively) was significantly (p less than 0.05) higher than in those receiving MAb P3. Hepatic activities of both 111In-MAb 19-24 and 111In-MAb P3 were low. The lungs with tumor colonies demonstrated clearest images on Day 3. The specific binding of 111In-SCN-Bz-DTPA-labeled MAb 19-24 to pulmonary xenografts without appreciable liver uptake indicates that it may be useful in the clinical localization of pulmonic metastatic lesions

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

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

    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)

  11. 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)

  12. Uptake of a nido-carboranylporphyrin by human glioma xenografts in athymic nude mice and by syngeneic ovarian carcinomas in immunocompetent mice

    International Nuclear Information System (INIS)

    A tetraphenylporphyrin bearing four dicarbollide ([B9C2H11]-) cages linked to the o-phenyl ring positions by anilide bonds, known as boronated tetraphenylporphyrin (BTPP), has been synthesized in excellent yield from tetra-(o-aminophenyl)porphyrin and carborane carbonyl chloride followed by base-assisted cage opening and ion exchange to give the highly water-soluble potassium salt. Preliminary studies showed that BTPP accumulates in liver and in a syngeneic ovarian carcinoma, but not in normal brain parenchyma, of mice infused with BTPP subcutaneously for 6 or 7 days via surgically implanted osmotic minipumps. In this study, the uptake of boron was measured in human gliomas xenografted subcutaneously to athymic nude mice in which BTPP was infused intraperitoneally or subcutaneously or both for 3 or 7 days by using similar minipumps. Immunocompetent mice bearing a syngeneic ovarian carcinoma were similarly infused to provide comparative data. Bulk concentrations of boron up to 18 μg/g of glioma and up to 45 μg/g of carcinoma were observed when up to 102 μg/g of tissue was present in the liver after 7 days of BTPP infusion. Glioma boron concentrations were increased by ∼80% on the average correspondingly greater amounts of BTPP were infused in only 3 days. Cell counts and chemical tests on blood samples from individual mice indicate that BTPP causes moderate hepatotoxicity and thromboxytopenia. This hepatohematic toxicity syndrome should be taken into account if BTPP or a similar agent is used for boron neutron-capture therapy (BNCT) of human malignancies

  13. 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.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  15. 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...

  16. Uninvolved Skin from Psoriatic Patients Develops Signs of Involved Psoriatic Skin after Being Grafted onto Nude Mice

    Science.gov (United States)

    Fraki, Jorma E.; Briggaman, Robert A.; Lazarus, Gerald S.

    1982-02-01

    Clinically involved psoriatic epidermis maintains its histological appearance, increased labeling index, and increased level of plasminogen activator after being grafted onto athymic nude mice. Uninvolved psoriatic epidermis develops increases in plasminogen activator activity after being grafted onto athymic nude mice; this is accompanied by an increased labeling index. Thus, psoriatic skin can develop markers of psoriasis independent of the host.

  17. 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.

  18. 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....

  19. 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.

  20. 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 ...

  1. 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.

  2. 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

    white pulp, and the interfollicular areas of Peyer's patches, are severely cell-depleted in the athymic nude rat. The lower lymphocyte content of these organs is not reflected in the lymphocyte counts of peripheral blood, but the lymphocyte counts of thoracic duct lymph are much lower than those found...... the thymic aplasia. Normal B-lymphocyte function has been found in both in vitro and in vivo tests, whereas the T-cell function is virtually absent both in vitro and in vivo. Non-MHC-restricted cells with killer activity like NK cells are present in the nude rat, and these cells function normally both...

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. Radionecrosis skin model induced an athymic mouse nude (Nu/Nu) for development of dermal-epidermal human substitute based regenerative therapy

    International Nuclear Information System (INIS)

    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)

  8. 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.

  9. Uptake of {sup 188}Re-{beta}-naphthyl-peptide in cervical carcinoma tumours in athymic mice

    Energy Technology Data Exchange (ETDEWEB)

    Arteaga de Murphy, Consuelo E-mail: cmurphy@data.net.mx; Pedraza-Lopez, Martha; Ferro-Flores, Guillermina; Murphy-Stack, Eduardo; Chavez-Mercado, Leonora; Ascencio, Jorge A.; Garcia-Salinas, Laura; Hernandez-Gutierrez, Salomon

    2001-04-01

    Radiolabelled somatostatin analogues have been used in diagnostic and therapeutic nuclear medicine to treat cancerous tumours. Lanreotide, a cyclic octapeptide, {beta}-naphthyl-peptide, with antiproliferative action on human small cell lung carcinoma was {sup 188}Re labelled and characterised, and its biodistribution was studied in mice. Molecular modelling indicates that the lipophilic radiopharmaceutical might be an oxo-rhenium (V) penta-coordinated complex. The implanted human cervical tumour of epidermoid origin was positive for cytokeratins and Vimentin. Uptake of {sup 188}Re-labelled peptide in the implanted tumour in athymic mice was 6.2{+-}2.9% and was rapidly cleared via the hepatobiliary system. {sup 188}Re-{beta}-naphthyl-peptide might be a potential therapeutic agent.

  10. 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.

  11. Radiolabeled porphyrin versus gallium-67 citrate for the detection of human melanoma in athymic mice

    International Nuclear Information System (INIS)

    We performed the biodistribution and imaging studies of 111In and 67Ga labeled tetra(4-N-methylpyridyl) porphine, (T4NMPYP), and compared it to that of 67Ga citrate in athymic mice bearing a human melanoma xenograft. The biodistribution results of both 111In and 67Ga labeled T4NMPYP (3, 6, 24, and 48 hours) were similar but differed from that of 67Ga citrate (48 hours). The optimum tumor uptake of both radiolabeled porphyrins was at 6 hours postinjection and was lower than the tumor uptake of 67Ga citrate at 48 hours postinjection. Kidney was the only organ showing higher uptake of radiolabeled porphyrin compared to that of 67Ga citrate. The imaging studies performed with 111In T4NMPYP and 67Ga citrate correspond to the biodistribution results. Osteomyelitis present in one mouse showed good localization of 111In T4NMPYP. 15 refs., 3 figs., 5 tabs

  12. An UVB-carcinogenesis model with KSN nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Ishigaki, Yasuhito; Nikaido, Osamu [Kanazawa Univ. (Japan). Faculty of Pharmaceutical Sciences; Suzuki, Fumio; Hayakawa, Jun-ichiro; Hiai, Hiroshi

    1998-03-01

    We established and characterized a systematic ultraviolet light-induced carcinogenesis model using KSN nude mice. We prepared five groups of KSN mice and exposed them six times a week to five levels of daily ultraviolet B (UVB) doses; 1340, 670, 320, 160 and 0 J/m{sup 2}/day. In 670, 320 and 160 J/m{sup 2}/day, the latency period tended to become shorter in proportion to the daily doses and prevalence data fitted well to log-normal distribution. In the log-log plot of days till 50% prevalence versus daily dose, we saw a linear relationship for 1 mm tumor diameter. From this analysis, we determined that days necessary to reach 50% prevalence is in proportion to the -0.49 power of daily dose. The average number of tumors per survivor correlated with prevalence data. Direct measured rates of tumor growth were independent of daily UVB-dose. Therefore we speculated that UV-irradiation did not affect tumor growth after its appearance. Most UVB-induced tumors were squamous cell carcinoma, the rest were spindle cell carcinoma, papilloma and mixed type. We concluded that our experimental data with nude mice was in accordance with data with hairless mice in nature. (author)

  13. Activity of Artemether and Mefloquine against Juvenile and Adult Schistosoma mansoni in Athymic and Immunocompetent NMRI Mice

    OpenAIRE

    Keiser, Jennifer; Vargas, Mireille; Doenhoff, Michael J.

    2010-01-01

    Immune effector mechanisms can enhance the activity of antischistosomal drugs. We examined the in vivo effect of single oral doses of the antimalarials artemether (400 mg/kg) and mefloquine (200 mg/kg), recently described to have promising antischistosomal properties, against juvenile and adult Schistosoma mansoni in T cell-deficient and in comparably infected age- and sex-matched immunologically intact control mice. Artemether and mefloquine are equally effective in athymic and immunocompete...

  14. Radiolabeled porphyrin versus gallium-67 citrate for the detection of human melanoma in athymic mice

    Energy Technology Data Exchange (ETDEWEB)

    Maric, N.; Chan, S. Ming; Hoffer, P.B.; Duray, P.

    1987-01-01

    We performed the biodistribution and imaging studies of /sup 111/In and /sup 67/Ga labeled tetra(4-N-methylpyridyl) porphine, (T4NMPYP), and compared it to that of /sup 67/Ga citrate in athymic mice bearing a human melanoma xenograft. The biodistribution results of both /sup 111/In and /sup 67/Ga labeled T4NMPYP (3, 6, 24, and 48 hours) were similar but differed from that of /sup 67/Ga citrate (48 hours). The optimum tumor uptake of both radiolabeled porphyrins was at 6 hours postinjection and was lower than the tumor uptake of /sup 67/Ga citrate at 48 hours postinjection. Kidney was the only organ showing higher uptake of radiolabeled porphyrin compared to that of /sup 67/Ga citrate. The imaging studies performed with /sup 111/In T4NMPYP and /sup 67/Ga citrate correspond to the biodistribution results. Osteomyelitis present in one mouse showed good localization of /sup 111/In T4NMPYP. 15 refs., 3 figs., 5 tabs.

  15. Different metastasis patterns of a human melanoma cell line in nude mice and rats: Influence of microenvironment

    International Nuclear Information System (INIS)

    The metastatic capacity of intravenously injected human FEMX-I melanoma cells in athymic nude mice and rats was compared. Young rats given 1 x 10(6) ascites tumor cells all died of lung tumors with a life span of 50 ± 10 days (mean± SD). In contrast, in accordance with previous findings, only extrapulmonary metastases developed in mice. This host-dependent difference in metastasis pattern permitted studies on the role of factors that may influence the organ specificity of metastases. The tissue distribution of 125I-labeled FEMX-I cells did not differ in the two nude species during the first 12 hours after cell injection. The plating efficiency of FEMX-I cells in soft agar was increased by the addition of conditioned medium prepared from rat lungs, resulting also in a significant increase in colony size. In contrast, conditioned medium prepared from mouse lungs reduced the clonogenic capacity of the FEMX-I cells in a dose-dependent manner. Conditioned media prepared from rat and mouse liver, kidney, and spleen tissues either inhibited or had no effect on colony formation. The results suggest that the unexpected differential metastatic patterns observed in vivo may reflect differences in the presence of growth-modulating paracrine factors in the host lungs

  16. A comparison of UVB-carcinogenesis between nude mice and nude beige mice

    Energy Technology Data Exchange (ETDEWEB)

    Ishigaki, Yasuhito; Yasuda, Kazuhiro; Hashimoto, Noriyoshi; Hayakawa, Jun-ichiro; Nikaido, Osamu [Kanazawa Univ. (Japan). Faculty of Pharmaceutical Sciences; Hiai, Hiroshi

    1998-06-01

    To gain an insight into the relationship between UVB-carcinogenesis and natural killer activity, we examined ultraviolet light-induced carcinogenesis in mice with high natural killer activity (KSN) and mice with natural killer deficiency (KSN-bg). We exposed mice six times a week to three levels of daily ultraviolet B (UVB) doses; 320, 160 and 0 J/m{sup 2}/day. During the latency period of skin tumor development in KSN mice, we detected no suppression of the natural killer activity at both 320 and 160 J/m{sup 2}/day. Even at 1340 J/m{sup 2}/day, we could not detect any significant suppression of NK activity in KSN mice. When we irradiated spleen cells in vitro, we observed NK activity suppression. Next, we compared the carcinogenic effects of UVB-irradiation on KSN and KSN-bg mice. At 320 J/m{sup 2}/day, we detected no significant differences between them. In contrast, at 160 J/m{sup 2}/day, KSN-bg mice showed a significantly higher rate of skin tumor induction than KSN mice (p<0.05). Most UVB-induced tumors were squamous cell carcinoma, the rest were spindle cell carcinoma, papilloma and mixed type. Our results suggest that NK activity plays a protective role against UVB-carcinogenesis from low daily-doses of UVB-irradiation. (author)

  17. 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

    Casein kinase II (CKII) activity in colorectal tumours was compared before and after heterotransplantation onto nude mice. The test revealed that the enzyme activity was about two-fold enhanced in the tumours isolated from the nude mice when compared to the respective primary tumours from which t...

  18. 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)

  19. 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.

  20. Biokinetics and dosimetry with 177Lu-DOTA-TATE in athymic mice with induced pancreatic malignant tumours

    Science.gov (United States)

    Rodríguez-Cortés, J.; de Murphy, C. Arteaga; Ferro-Flores, Ge; Pedraza-López, M.; Murphy-Stack, E.

    Malignant pancreatic tumours induced in athymic mice are a good model for peptide receptor targeted radiotherapy. The objective of this research was to determine biokinetic parameters in mice, in order to estimate the induced pancreatic tumour absorbed doses and to evaluate an `in house' 177Lu-DOTA-TATE radiopharmaceutical as part of preclinical studies for targeted therapy in humans. AR42J murine pancreas cancer cells expressing somatostatin receptors, were implanted in athymic mice (nD22) to obtain biokinetic and dosimetric data of 177Lu-DOTA-TATE. The mean tumour uptake 2 h post injection was 14.76±1.9% I.A./g; kidney and pancreas uptake, at the same time, were 7.27±1.1% I.A./g (1.71±0.90%/organ) and 4.20±0.98% I.A./g (0.42±0.03%/organ), respectively. The mean absorbed dose to tumour, kidney and pancreas was 0.58±0.02 Gy/MBq; 0.23±0.01 Gy/MBq and 0.14±0.01 Gy/MBq, respectively. These studies justify further dosimetric estimations to ensure that 177Lu-DOTA-TATE will act as expected in humans.

  1. 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)

  2. Human Cancer Xenografts in Outbred Nude Mice Can Be Confounded by Polymorphisms in a Modifier of Tumorigenesis

    OpenAIRE

    Zeineldin, Maged; Jensen, Derek; Paranjape, Smita R.; Parelkar, Nikhil K.; Jokar, Iman; Vielhauer, George A.; Neufeld, Kristi L.

    2014-01-01

    Tumorigenicity studies often employ outbred nude mice, in the absence of direct evidence that this mixed genetic background will negatively affect experimental outcome. Here we show that outbred nude mice carry two different alleles of Pla2g2a, a genetic modifier of intestinal tumorigenesis in mice. Here, we identify previous unreported linked polymorphisms in the promoter, noncoding and coding sequences of Pla2g2a and show that outbred nude mice from different commercial providers are hetero...

  3. 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.

  4. Refinement to radiotherapy by tumour-adapted procedures. Experimental investigations into human tumours using the athymic nude mouse and the colony forming test

    International Nuclear Information System (INIS)

    Any radiooncologic stratey designed to take account of biological and tumour-related factors through standardization and individual adjustments requires adequate knowledge about the reactions of different neoplasms to different splitdose regimens and, basically, about a tumour's responsiveness to various method of treatment. The nude mouse is a suitable model to study fractionation systems and combined treatments, while the colony forming test elucidates the sensitivity of one particular tumour to a selection of therapeutic procedures. (UHE)

  5. 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...

  6. 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.

  7. 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.

  8. Effects of targeting magnetic drug nanopar ticles on human cholangiocarcinoma xenografts in nude mice

    Institute of Scientific and Technical Information of China (English)

    Tao Tang; Jian-Wei Zheng; Bo Chen; Hong Li; Xi Li; Ke-Ying Xue; Xing Ai; Sheng-Quan Zou

    2007-01-01

    BACKGROUND: Targeting is a new therapeutic tool for malignant tumor as a result of combining nanotechnology with chemotherapeutics. The aim of our study was to investigate the effects of magnetic nanoparticles enveloping a chemotherapeutic drug on human cholangiocarcinoma xenografts in nude mice. METHODS:The human cholangiocarcinoma xenograft model was established in nude mice with the QBC939 cell line. The nude mice were randomly assigned to 7 groups. 0.9% saline or magnetic nanoparticles, including high (group 2), medium (group 4) and low (group 5) dosages, were given to nude mice through the tail vein 20 days after the QBC939 cell line was implanted. Calculations were made 35 days after treatment in order to compare the volumes, inhibition ratios and growth curves of the tumors in each group. Mice in each group were sacriifced randomly to collect tumor tissues and other organs for electron microscopy and pathological examination. RESULTS:The high and medium dosage groups were signiifcantly different from the control group (P CONCLUSION: Magnetic nanoparticles can inhibit the growth of human cholangiocarcinoma xenografts in nude mice.

  9. Human interferons inhibit experimental metastases of a human melanoma cell line in nude mice.

    OpenAIRE

    Ramani, P; Balkwill, F.R.

    1988-01-01

    Therapy with human lymphoblastoid interferon HuIFN-alpha(N1), or recombinant human interferon gamma, rHuIFN-gamma, inhibited experimental pulmonary metastases of the human melanoma cell line, DX3-azac, in BALB/c nude mice and significantly prolonged survival. The human IFNs had no effect on nude mouse lung and spleen NK cell activity, lung macrophage activity, haemoglobin or white cell counts. HuIFN-alpha(N1) had no effect on the levels of the IFN induced enzyme 2-5A synthetase in nude mouse ...

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

    Energy Technology Data Exchange (ETDEWEB)

    Maryanski, J.L. (Ludwig Inst. for Cancer Research, Epalinges, Switzerland); 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-2delta 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.

  11. 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.

  12. Spontaneous pulmonary metastasis of human cancer cells in X-irradiated and nonirradiated nude mice

    International Nuclear Information System (INIS)

    The effect of whole body X-irradiation on the spontaneous pulmonary metastasis of human cancer cells transplanted into adult nude mice was investigated. Human cancer cells were inoculated into footpads of adult nude mice following 3 Gy whole body X-irradiation. The incidence of pulmonary metastasis was increased in the irradiated mice. Cytotoxicity of splenocytes, particularly adherent cells, was lower in the irradiated mice than in the nonirradiated mice. Histological examinations revealed decreased mononuclear cell infiltration around the primary tumor and pulmonary metastatic foci in the irradiated mice. The suppressive effect of cytotoxicity of the splenocytes by whole body X-irradiation may thus relate to ensuing metastasis both in the phase of release and intravasation from the primary tumor and in the phase of lodgement and proliferation in the target organ. (author)

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

    International Nuclear Information System (INIS)

    Highlights: ► This study has revealed novel oncogenic functions of TIP-1 in human invasive breast cancer. ► Elevated TIP-1 expression levels in human breast cancers correlate to the disease prognosis. ► TIP-1 knockdown suppressed the cell migration and pulmonary metastasis of human breast cancer cells. ► 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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 hormone dependency. The results can be compared with successive steroid hormone receptor determinations in the tumor tissue....

  2. 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...

  3. 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.

  4. Morphofunctional evaluation of human skin preserved in glycerol and exposed to gamma radiation: a study in athymic mice

    International Nuclear Information System (INIS)

    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)

  5. 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)

  6. 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.``

  7. Interleukin 1-induced augmentation of experimental metastases from a human melanoma in nude mice

    International Nuclear Information System (INIS)

    This study has examined the effect of the cytokine interleukin 1 (IL-1) on metastasis formation by the human melanoma A375M in nude mice. We have found that human recombinant IL-1 beta (a single injection greater than 0.01 micrograms per mouse i.v. given before tumor cells) induced an augmentation of experimental lung metastases from the A375M tumor cells in nude mice. This effect was rapidly induced and reversible within 24 h after IL-1 injection. A similar effect was induced by human recombinant IL-1 alpha and human recombinant tumor necrosis factor, but not by human recombinant interleukin 6. 5-[125I]odo-2'-deoxyuridine-radiolabeled A375M tumor cells injected i.v. remained at a higher level in the lungs of nude mice receiving IL-1 than in control mice. In addition, IL-1 injected 1 h, but not 24 h, after tumor cells enhanced lung colonization as well, thus suggesting an effect of IL-1 on the vascular transit of tumor cells. These findings may explain the observation of enhanced secondary localization of tumor cells at inflammatory sites and suggest that modulation of secondary spread should be carefully considered when assessing the ability of this cytokine to complement cytoreductive therapies

  8. INHIBITION OF ANGIOSTATIN TO THE GROWTH AND METASTASIS OF GASTRIC CANCER IN NUDE MICE

    Institute of Scientific and Technical Information of China (English)

    刘炳亚; 陈雪华; 朱正纲; 林言箴; 卢伟新; 郭礼和; 朱丽华

    2002-01-01

    Objective To study the inhibition effect on tumor angiogenesis and metastasis of angiostatin, which generated from human plasminogen. Methods Plasminogen was isolated from human plasma by Sepharose chromatography and then catalyzed by elastase. Angiostatin was isolated by Sepharose 4B-Lysine chromatography. Nude mice model of metastatic gastric cancer was set up by intact tumor tissue implantation orthotopically. From the day of operation, mice received daily intraperitoneal injections of human angiostatin ,intact plasminogen, or saline, respectively. 24μg(1.2mg/kg) of angiostatin or plasminogen was given on the day of operation, followed by a daily dose of 12μg (O. 6mg/kg) via intraperitoneal injection for three weeks.Ten weeks after implantation, mice were sacrificed and autopsied. Microvascular density was measured by immunohistochemistry. Results Molecular weight of plasminogen isolated from plasma was 94KD. Plasminogen was catalyzed into two fragment peptides by elastase, which were 41 ~ 43KD and 51 ~ 53KD in molecular weight. Growth of the orthotopieally implanted tumor was significantly reduced in size in the mice treated with angiostastin with an inhibition rate of 54.0%. Tumor metastasis to the liver and peritoneum was also significantly inhibited by angiostatin with inhibition rate of 61.9% and 55.6% respectively. The microvaseular density was also decreased significantly in the angiostatin treated mice. Conclusion Angiostatin may be generated from plasma, and has inhibitory effect both on tumor growth and metastasis in nude mice model of human gastric cancer.

  9. 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

    thymic activity and diminished numbers of T lymphocytes in peripheral lymphoid tissues. The total number of cells in these tissues as well as the blast cell activity, were within normal limits. Bone marrow lymphocyte numbers and kinetics as well as blood lymphocyte levels in splenectomized and sham......-splenectomized normal animals were comparable. Blood lymphocyte numbers were at normal levels in splenectomized nude mice, in spite of reduced numbers of bone marrow and thoracic duct lymphocytes. It is suggested that increased number of newly-formed lymphocytes, found in lymph nodes and blood of splenectomized mice...

  10. 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.

  11. 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

  12. Experimental study of radiotargeting-therapy with small molecular polypeptide in nude mice bearing lung adenocarcinoma

    International Nuclear Information System (INIS)

    Background: Integrin signal transduction pathways provide an important basis for molecular targeting therapy of cancer in tumor growth, infiltration and transfer. Existing research data have shown that small molecular peptide labeled with radionuclide has good clinical application prospects, but the successful researches on lung cancer have not been reported so far. It is considered that the main reason is the lack of small molecule peptide for specific targeting lung cancer. Purpose: Based on the small molecular peptide cNGQGEQc for specifically identifying integrin α3 and β1 found previously, polypeptide cNGQGEQc is selected and radiolabelled with 131I. And the inhibitory effect of 131I-cNGQGEQc in nude mice bearing lung adenocarcinoma is observed. Methods: The coupling of cNGQGEQc and tyrosine was done in the processing of solid phase synthesis of small molecular peptide. Chloramine-T method was used for radiolabelling of cNGQGEQc with 131I. Twenty nude mice bearing NCI-H1975 were built and randomly divided into four groups with five mice in each group, including the group of 131I-cNGQGEQc, the group of 131I-cNAQAEQc, the group of 131I and the saline control group. The general condition was observed in nude mice bearing tumor after tail vein injection of corresponding drugs. And the tumor sizes after grafting were measured per 3 days in 30 days. The inhibitory rate of tumor in each group was calculated. Results: The labeling efficiencies of 131I-cNGQGEQc and 131I-cNAQAEQc were greater than 90% with the radiochemical purity of more than 95%, and 131I-cNGQGEQc had obvious inhibitory effect for transplantation tumor in nude mice bearing NCI-H1975 adenocarcinoma of lung. After a treatment for 30 days the tumor inhibitory rates were 60.93% for the group of 131I-cNGQGEQc, 11.63% for the group of 131I-cNAQAEQ and 10.70% for the group of 131I. Conclusion: 131I-cNGQGEQC has a good affinity and effective inhibit effect for the NCI-H1975 lung adenocarcinoma. Integrin is

  13. Pharmacokinetics and biodistribution of Erufosine in nude mice - implications for combination with radiotherapy

    International Nuclear Information System (INIS)

    Alkylphosphocholines represent promising antineoplastic drugs that induce cell death in tumor cells by primary interaction with the cell membrane. Recently we could show that a combination of radiotherapy with Erufosine, a paradigmatic intravenously applicable alkylphosphocholine, in vitro leads to a clear increase of irradiation-induced cell death. In view of a possible combination of Erufosine and radiotherapy in vivo we determined the pharmacokinetics and bioavailability as well as the tolerability of Erufosine in nude mice. NMRI (nu/nu) nude mice were treated by intraperitoneal or subcutaneous injections of 5 to 40 mg/kg body weight Erufosine every 48 h for one to three weeks. Erufosine-concentrations were measured in brain, lungs, liver, small intestine, colon, spleen, kidney, stomach, adipoid tissue, and muscle by tandem-mass spectroscopy. Weight course, blood cell count and clinical chemistry were analyzed to evaluate general toxicity. Intraperitoneal injections were generally well tolerated in all dose groups but led to a transient loss of the bodyweight (<10%) in a dose dependent manner. Subcutaneous injections of high-dose Erufosine caused local reactions at the injection site. Therefore, this regimen at 40 mg/kg body weight Erufosine was stopped after 14 days. No gross changes were observed in organ weight, clinical chemistry and white blood cell count in treated compared to untreated controls except for a moderate increase in lactate dehydrogenase and aspartate-aminotransferase after intensive treatment. Repeated Erufosine injections resulted in drug-accumulation in different organs with maximum concentrations of about 1000 nmol/g in spleen, kidney and lungs. Erufosine was well tolerated and organ-concentrations surpassed the cytotoxic drug concentrations in vitro. Our investigations establish the basis for a future efficacy testing of Erufosine in xenograft tumor models in nude mice alone and in combination with chemo- or radiotherapy

  14. 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.

  15. 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...

  16. Imaging of human melanoma xenografts in nude mice with a radiolabeled monoclonal antibody

    International Nuclear Information System (INIS)

    External photoscanning with display of radioactivity data as a color-scaled image detected xenografts of human melanoma in male nude inbred mice of BALB/c background 48 hours after injection of 131I-labeled monoclonal IgG 225.28S that is specific for human melanoma. A 131I-labeled polyclonal goat IgG against human melanoma-associated antigens could also image the tumor, but with this preparation there was considerable localization of radioactivity in normal tissues, resulting in less satisfactory tumor definition. Labeled normal mouse IgG did not image the melanoma grafts. Assay of radioactivity in tissues of melanoma-grafted mice confirmed tumor-specific localization of the antimelanoma antibodies. The tumor:blood ratio of radioactivity was 6.55 with the monoclonal antimelanoma IgG and 0.45 with the polyclonal IgG

  17. Establishing the Nude Mice Bone Metastasis Model of Lung Adenocarcinoma and Applying MicroCT into the Observation

    OpenAIRE

    Yongqi CUI; Geng, Qin; Gu, Aiqin; Miaoxin ZHU; Hanwei KONG; Sun, Lei; Liu, Lei; Yan, Mingxia; Yao, Ming

    2013-01-01

    Background and objective 50%-70% of patients with advanced lung cancer will develop bone metastases. The aim of this study is to establish the nude mice bone metastasis model of lung adenocarcinoma using A549, H1299, SPC-A-1 and XL-2, all of which own different invasion and migration abilities in vitro and supervise the bone metastases by MicroCT. Methods fifty BALB/C-nu/nu nude mice were grouped into five groups on average randomly. Cells of the four cell lines were injected into the left ca...

  18. 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.

  19. 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.

  20. 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.

  1. 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...

  2. 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....

  3. 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...

  4. 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.

  5. Angiostatin up-regulation in gastric cancer cell SGC7901 inhibits tumorigenesis in nude mice

    Institute of Scientific and Technical Information of China (English)

    Jing Wu; Yong-Quan Shi; Kai-Chun Wu; De-Xin Zhang; Jing-Hua Yang; Dai-Ming Fan

    2003-01-01

    AIM: To explore the influence of angiostatin up-regulationon the biologic behavior of gastric cancer cells in vitro andin vivo, and the potential of angiostatin gene therapy in thetreatment of human gastric cancer.METHODS: Mouse angiostatin cDNA was subcloned intothe eukaryotic expression vector pcDNA3.1(+) and identifiedby restriction endonucleases digestion and sequencing. Therecombinant vector pcDNA3. 1(+)-angio was transfected intohuman gastric cancer cells SGC7901 with liposome andparalleled with the vector control and the mock control.Angiostatin transcription and protein expression wereexamined by RT-PCR and Western blot in the stable celllines selected by G418. Cell proliferation and growth in vitroof the three groups were observed respectively undermicroscope, cell number counting and FACS. The cellsoverexpressing angiostatin, vector transfected and untreatedwere respectively implanted subcutaneously into nude mice.After 30days the size of tumors formed was measured, andmicrovessel density count (MVD) in the tumor tissues wasassessed by immunohistochemistry with the primary anti-vWF antibody.RESULTS: The recombinant vector pcDNA3.1(+)-angio wasconfirmed with the correct sequence of mouse angiostatinunder the promoter CMV. After 30 d of transfection andselection with G418, macroscopic resistant cell clones wereformed in the experimental group transfected with pcDNA3.1(+)-angio and the vector control. But no untreated cellssurvived in the mock control. Angiostatin mRNAtranscription and protein expression were detected in theexperimental group. No significant differences wereobserved among the three groups in cell morphology, cellgrowth curves and cell cycle phase distributions in vitro.However, in nude mice model, markedly inhibitedtumorigenesis and slowed tumor expansion were observedin the experimental group as compared with the controls,which was paralleled with decreased microvessel density inand around tumor tissues (P<0. 05).CONCLUSION: Angiostatin

  6. 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

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

    International Nuclear Information System (INIS)

    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. 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). 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. 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

  8. 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.

  9. 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.

  10. Tumor-targeting Salmonella typhimurium A1-R prevents experimental human breast cancer bone metastasis in nude mice

    OpenAIRE

    Miwa, Shinji; Yano, Shuya; Zhang, Yong; Matsumoto, Yasunori; Uehara, Fuminari; Yamamoto, Mako; Hiroshima, Yukihiko; Kimura, Hiroaki; Hayashi, Katsuhiro; Yamamoto, Norio; Bouvet, Michael; Tsuchiya, Hiroyuki; Hoffman, Robert M.; Ming ZHAO

    2014-01-01

    Bone metastasis is a lethal and morbid late stage of breast cancer that is currently treatment resistant. More effective mouse models and treatment are necessary. High bone-metastatic variants of human breast cancer cells were selected in nude mice by cardiac injection. After cardiac injection of a high bone-metastatic variant of breast cancer, all untreated mice had bone metastases compared to only 20% with parental cells. Treatment with tumor-targeting Salmonella typhimurium A1-R completely...

  11. 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

  12. Growth inhibition of human pancreatic cancer grafts in nude mice by boron neutron capture therapy

    International Nuclear Information System (INIS)

    Cell destruction in boron neutron capture therapy (BNCT) is due to the nuclear reaction between 10B and thermal neutrons to release alpha-particles (4He) and lithium-7 ions (7Li). The 4He kills cells in the range of 10 μm from the site of 4He generation. Therefore, it is theoretically possible to kill tumor cells without affecting adjacent healthy tissues, if 10B-compounds could be selectively delivered. We have described that 10B atoms delivered by immunoliposomes exerted cytotoxic effect on human pancreatic carcinoma cells (AsPC-1) in a dose-dependent manner by thermal neutron irradiation in vitro as reported previously. In the present study, the cytotoxic effect of a locally injected 10B compound solution or multilamellar liposomes containing a 10B compound to human pancreatic carcinoma xenograft in nude mice was evaluated after thermal neutron irradiation. AsPC-1 cells (1 x 107) injected subcutaneously into a nude mouse grew to a tumor weighing 100-300 mg after 2 weeks. At this time 200 μg 10B compounds was locally injected in the tumor and irradiated with 2 x 1012 n/cm2 thermal neutron. Tumor growth of 10B-treated groups was suppressed as compared with control group. Histopathologically, hyalinization and necrosis were found in the tumor tissues. For effective tumor destruction, 10B dose more than 60 μg was necessary. The tumor tissue injected with saline only and irradiated showed neither destruction nor necrosis. These data indicate that the accumulation of 10B atoms to the tumor site is mandatory for the cytotoxic effect by thermal neutron irradiation. (author)

  13. 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.

  14. In vivo imaging of human malignant mesothelioma grown orthotopically in the peritoneal cavity of nude mice.

    Science.gov (United States)

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

    2011-01-01

    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. PMID:21479131

  15. 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.

  16. 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.

  17. Pharmacokinetics of 99m Tc-EDDA/HYNIC-Lys-D-Phe-RGD in athymic mice with induced malignant tumors for integrin imaging

    International Nuclear Information System (INIS)

    Full text: Nuclear medicine imaging techniques are non-invasive and monitor the spatiotemporal distribution of molecular events. Radiolabeled RGD-peptides are currently investigated to target integrin receptors for in vivo tumor imaging. The αvβ3 integrin is a target structure involved in the angio genesis process which mediates the binding to extracellular matrix via different proteins such as vitronectin, fibronectin and von Willebrand factor. The aim of this research was to prepare [99mTc]-Lys-D-Phe-RGD and to evaluate its pharmacokinetics in athymic mice with three different induced malignant tumors. Tumor uptake values of 99mTc-Lys-D-Phe-RGD labeled via HYNIC and EDDA showed good ability to target αvβ3 integrin receptors in the three different kinds of tumors (breast, prostate and neuroendocrine). A high in vivo stability and favorable pharmacokinetic properties such as fast blood clearance, rapid renal excretion, low liver and muscle uptake and low intestinal excretion were observed. This study demonstrated that 99mTc-EDDA/HYNIC-Lys-D-Phe-RGD is a specific and potential radiopharmaceutical to image αvβ3 integrin receptors in a variety of tumors. (Author)

  18. Effect of phosphorus-32 glass microspheres on human hepatocellular carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    Dong-Sheng Zhang; Lu Liu; Li-Qiang Jin; Mei-Ling Wan; Qun-Hui Li

    2004-01-01

    AIM: To study the effects of phosphorus-32 glass microspheres (32P-GMS) on human hepatocellular carcinoma in nude mice.METHODS: Human liver cancer cell line was implanted into the dorsal subcutaneous tissue of 40 BALB/c nude mice.Then the 40 tumor-bearing BALB/c nude mice were allocated into treatment group (n=-32) and control group (n=8). In the former group different doses of 32P-GMS were injected into the tumor mass, while in the latter nonradioactive 31PGMS was injected into the tumor mass. The experimental animals were sacrificed on the 14th day. The ultrastructural changes of tumor in both treatment group and control group were studied with transmission electron microscopy (TEM)and stereology.RESULTS: In treatment group, a lot of tumor cells were killed and the death rate of tumor cells was much higher (35-70%). Ultrastructurally, severe nuclear damage was observed in the death cells. The characteristics of appoptosis such as margination of heterochromatin was also found in some tumor ceils. Besides, well differentiated tumor cells,degenerative tumor cells and some lymphocytes were seen.The skin and muscle adjacent to the tumor were normal. In control group, the tumor consisted of poorly differentiated tumor cells, in which there were only a few of dead cells (5%). Stereologicl analysis of ultrastructral morphology showed that Vv of nuclei (53.31±3.46) and Vv of nucleoli (20.40±1.84) in the control group were larger than those (30.21±3.52 and 10.96±2.52) in the treatment group respectively (P<0.01), and Vv of RER (3.21±0.54) and Vv of mitochondria (4.53±0.89) in the control group were smaller than those (8.67±1.25 and 7.12±0.95) in the treatment group respectively (P<0.01, 0.05). Sv of the membrane of microvilli and canaliculi (27.12 um2/100 um3±11.84 um2/100 um3) in the control group was smaller than that (78.81 um2/100 um3±19.69 um2/100 um3) in the treatment group (P<0.01). But Vv of lipid particles (3.71±1.97) and Vv of vacuoles (5.72±1

  19. 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.

  20. Effects of LY294002 on the invasiveness of human gastric cancer in vivo in nude mice

    Institute of Scientific and Technical Information of China (English)

    Chun-Gen Xing; Bao-Song Zhu; Xiao-Qing Fan; Hui-Hui Liu; Xun Hou; Kui Zhao; Zheng-Hong Qin

    2009-01-01

    AIM: To investigate the effects of class Ⅰ phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 on the invasiveness and related mechanisms of implanted tumors of SGC7901 human gastric carcinoma cells in nude mice.METHODS: Nude mice were randomly divided into model control groups and LY294002 treatment groups. On days 5, 10 and 15 after treatment,the inhibitory rate of tumor growth, pathological changes in tumor specimens, expression levels of matrix metalloproteinase (MMP)-2, MMP-9, CD34 [representing microvessel density (MVD)] and vascular endothelial growth factor (VEGF), as well as apoptosis indexes in tumor samples were observed.RESULTS: In this study, we showed that treating the tumors with LY294002 could significantly inhibit carcinoma growth by 11.3%, 29.4% and 36.7%, after 5, 10 and 15 d, respectively, compared to the control group. Hematoxylin & eosin staining indicated that the rate of inhibition increased progressively (23.51% ± 3.11%, 43.20% ± 3.27% and 63.28% ± 2.10% at 5, 10 and 15 d, respectively) along with apoptosis.The expression of MMP-2 was also downregulated (from 71.4% ± 1.6% to 47.9% ± 0.7%, 31.9% ± 0.9% and 7.9% ± 0.7%). The same effects were observed in MMP-9 protein expression (from 49.4% ± 1.5% to 36.9% ± 0.4%, 23.5% ± 0.9% and 7.7% ± 0.6%), the mean MVD (from 51.2% ± 3.1% to 41.9% ± 1.5%, 30.9% ± 1.7% and 14.9% ± 0.8%),and the expression of VEGF (from 47.2% ± 3.1% to 25.9% ± 0.5%, 18.6% ± 1.2% and 5.1% ± 0.9%) by immunohistochemical staining.CONCLUSION: The class Ⅰ PI3K inhibitor LY294002 could inhibit the invasiveness of gastric cancer cells by downregulating the expression of MMP-2, MMP-9, and VEGF, and reducing MVD.

  1. A Walnut-Enriched Diet Reduces the Growth of LNCaP Human Prostate Cancer Xenografts in Nude Mice

    OpenAIRE

    Reiter, Russel J.; Tan, Dun-Xian; Manchester, Lucien C.; Korkmaz, Ahmet; Fuentes-Broto, Lorena; Hardman, W. Elaine; Rosales-Corral, Sergio A; Qi, Wenbo

    2013-01-01

    It was investigated whether a standard mouse diet (AIN-76A) supplemented with walnuts reduced the establishment and growth of LNCaP human prostate cancer cells in nude (nu/nu) mice. The walnut-enriched diet reduced the number of tumors and the growth of the LNCaP xenografts; 3 of 16 (18.7%) of the walnut-fed mice developed tumors; conversely, 14 of 32 mice (44.0%) of the control diet-fed animals developed tumors. Similarly, the xenografts in the walnut-fed animals grew more slowly than those ...

  2. 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.

  3. 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.

  4. 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.

  5. Modulation of cell cycle regulatory protein expression and suppression of tumor growth by mimosine in nude mice.

    Science.gov (United States)

    Chang, H C; Weng, C F; Yen, M H; Chuang, L Y; Hung, W C

    2000-10-01

    Our previous results demonstrated that the plant amino acid mimosine blocked cell cycle progression and suppressed proliferation of human lung cancer cells in vitro by multiple mechanisms. Inhibition of cyclin D1 expression or induction of cyclin-dependent kinase inhibitor p21WAF1 expression was found in mimosine-treated lung cancer cells. However, whether mimosine may modulate the expression of these cell cycle regulatory proteins and suppress tumor growth in vivo is unknown. In this study, we examined the anti-cancer effect of mimosine on human H226 lung cancer cells grown in nude mice. Our results demonstrated that mimosine inhibits cyclin D1 and induces p21WAF1 expression in vivo. Furthermore, results of TUNEL analysis indicated that mimosine may induce apoptosis to suppress tumor growth in nude mice. Collectively, these results suggest that mimosine exerts anti-cancer effect in vivo and might be useful in the therapy of lung cancer. PMID:10995875

  6. Human eccrine sweat gland cells reconstitute polarized spheroids when subcutaneously implanted with Matrigel in nude mice.

    Science.gov (United States)

    Li, Haihong; Zhang, Mingjun; Chen, Liyun; Li, Xuexue; Zhang, Bingna

    2016-10-01

    Increasing evidence indicates that maintenance of cell polarity plays a pivotal role in the regulation of glandular homeostasis and function. We examine the markers for polarity at different time points to investigate the formation of cell polarity during 3D reconstitution of eccrine sweat glands. Mixtures of eccrine sweat gland cells and Matrigel were injected subcutaneously into the inguinal regions of nude mice. At 2, 3, 4, 5 and 6 weeks post-implantation, Matrigel plugs were removed and immunostained for basal collagen IV, lateral β-catenin, lateroapical ZO-1 and apical F-actin. The results showed that the cell polarity of the spheroids appeared in sequence. Formation of basal polarity was prior to lateral, apical and lateroapical polarity. Collagen IV was detected basally at 2 weeks, β-catenin laterally and ZO-1 lateroapically at 3 weeks, and F-actin apically at 4 weeks post-implantation. At week 5 and week 6, the localization and the positive percentage of collagen IV, β-catenin, ZO-1 or F-actin in spheroids was similar to that in native eccrine sweat glands. We conclude that the reconstituted 3D eccrine sweat glands are functional or potentially functional. PMID:27492422

  7. Human medullary thyroid carcinoma: cell cultures and xenotransplants in nude mice. Immunocytochemistry and calcitonin secretion.

    Science.gov (United States)

    Andry, G; Lothaire, P; Vico, P; Dumont, P; Libert, A; Degeyter, M; Larsimont, D; Saigo, P E; Body, J J; Atassi, G

    1989-12-01

    Occult primary and recurrent medullary thyroid carcinomas (MTC) detected only by elevated calcitonin levels in the peripheral blood, generally after pentagastrin-test stimulation, are difficult to localize. Some new imaging procedures with radionuclide tracers or radiolabelled monoclonal antibodies against carcinoembryonic antigen seem to bring some potentially therapeutic benefits. We report our results with cell cultures and xenotransplants of human MTC with the intention of establishing reproducible models in vitro and in vivo. Cell cultures secrete calcitonin at up to 1200 pg/ml for periods ranging from 3 to 13 weeks. Immunocytochemistry detects cytoplasmic granules positive for calcitonin in polygonal epithelioid cells with dendritic processes. Xenotransplants in nude mice fare better in the subcutaneous axilla than in the subrenal capsule assay. In the former location the tumor-take is good and calcitonin is detected in the blood of the tumor-bearing animals, at levels ranging from 286 to more than 20,000 pg/ml. These models would be potentially usable as targets for radionuclide tracers and/or radiolabelled monoclonal antibodies. PMID:2689238

  8. Novel immunocytokine IL12-SS1 (Fv) inhibits mesothelioma tumor growth in nude mice.

    Science.gov (United States)

    Kim, Heungnam; Gao, Wei; Ho, Mitchell

    2013-01-01

    Mesothelin is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed on the cell surface of malignant mesothelioma. Monoclonal antibodies against mesothelin are being evaluated for the treatment of mesothelioma. Immunocytokines represent a novel class of armed antibodies. To provide an alternative approach to current mesothelin-targeted antibody therapies, we have developed a novel immunocytokine based on interleukin-12 (IL12) and the SS1 Fv specific for mesothelin. IL12 possesses potent anti-tumor activity in a wide variety of solid tumors. The newly-developed recombinant immunocytokine, IL12-SS1 (Fv), was produced in insect cells using a baculovirus-insect cell expression system. The SS1 single-chain Fv was fused to the C terminus of the p35 subunit of IL12 through a short linker (GSADGG). The single-chain IL12-SS1 (Fv) immunocytokine bound native mesothelin proteins on malignant mesothelioma (NCI-H226) and ovarian (OVCAR-3) cells as well as recombinant mesothelin on A431/H9 cells. The immunocytokine retained sufficient bioactivity of IL12 and significantly inhibited human malignant mesothelioma (NCI-H226) grown in the peritoneal cavity of nude mice and showed comparable anti-tumor activity to that of the SS1P immunotoxin. IL12-SS1 (Fv) is the first reported immunocytokine to mesothelin-positive tumors and may be an attractive addition to mesothelin-targeted cancer therapies. PMID:24260587

  9. Novel immunocytokine IL12-SS1 (Fv inhibits mesothelioma tumor growth in nude mice.

    Directory of Open Access Journals (Sweden)

    Heungnam Kim

    Full Text Available Mesothelin is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed on the cell surface of malignant mesothelioma. Monoclonal antibodies against mesothelin are being evaluated for the treatment of mesothelioma. Immunocytokines represent a novel class of armed antibodies. To provide an alternative approach to current mesothelin-targeted antibody therapies, we have developed a novel immunocytokine based on interleukin-12 (IL12 and the SS1 Fv specific for mesothelin. IL12 possesses potent anti-tumor activity in a wide variety of solid tumors. The newly-developed recombinant immunocytokine, IL12-SS1 (Fv, was produced in insect cells using a baculovirus-insect cell expression system. The SS1 single-chain Fv was fused to the C terminus of the p35 subunit of IL12 through a short linker (GSADGG. The single-chain IL12-SS1 (Fv immunocytokine bound native mesothelin proteins on malignant mesothelioma (NCI-H226 and ovarian (OVCAR-3 cells as well as recombinant mesothelin on A431/H9 cells. The immunocytokine retained sufficient bioactivity of IL12 and significantly inhibited human malignant mesothelioma (NCI-H226 grown in the peritoneal cavity of nude mice and showed comparable anti-tumor activity to that of the SS1P immunotoxin. IL12-SS1 (Fv is the first reported immunocytokine to mesothelin-positive tumors and may be an attractive addition to mesothelin-targeted cancer therapies.

  10. Total Aglycones from Marsdenia tenacissima Increases Antitumor Efficacy of Paclitaxel in Nude Mice

    Directory of Open Access Journals (Sweden)

    Rui-Jing Zhu

    2014-09-01

    Full Text Available Marsdeniae tenacissimae Caulis (MTC is a Chinese herbal medicine used mainly for treatment of cancer, whose pharmacologically active constituents responsible for its in vivo activity and clinical efficacy have not been clearly elucidated. In this study, total aglycones of MTC (ETA showed the ability to sensitize KB-3-1, HeLa, HepG2 and K562 cells to paclitaxel treatment. More inspiringly, ETA markedly enhanced the antitumor activity of paclitaxel in nude mice bearing HeLa or KB-3-1 xenografts. Compared to treatment with paclitaxel alone, treatment with combination of paclitaxel and ETA achieved significant reduction in volume and weight of HeLa tumors (p < 0.05, and remarkable inhibition to the growth of KB-3-1 tumors (p < 10−6. ETA was characterized by the presence of a group of tenacigenin B ester derivatives, among which four reference compounds, 11α-O-tigloyl-12β-O-acetyltenacigenin B, 11α,12β-di-O-tigloyltenacigenin B, 11α-O-2-methylbutanoyl-12β-O-tigloyltenacigenin B, and 11α-O-(2-methylbutanoyl-12β-O-benzoyltenacigenin B, accounted for 42.14% of the total peak area of 19 detectable components assayed by HPLC. Our study has identified ETA as a promising sensitizer for cancer chemotherapy.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. Preclinical evaluation of new radioligand of cholecystokinin/gastrin receptors in endocrine tumors xenograft nude mice

    Science.gov (United States)

    Brillouet, S.; Caselles, O.; Dierickx, L. O.; Mestre, B.; Nalis, J.; Picard, C.; Favre, G.; Poirot, M.; Silvente-Poirot, S.; Courbon, F.

    2007-02-01

    The cholecystokinin(CCK)/gastrin 2 receptors (R-CCK2) are overexpressed in 90% of medullary thyroid cancers (MTC) and in 60% of small cell lung cancers but not or poorly in corresponding healthy tissues. They represent a relevant target for the diagnosis and internal targeted radiotherapy of these tumors. Although previous studies have demonstrated the feasibility of radiolabeled CCK/gastrin to target CCK-2 receptor-expressing tissues in animals and patients, some problems remained unsolved to identify an optimum candidate for in vivo targeting of R-CCK2-expressing tumors. By a rational approach and " in silico" drug design, we synthesized a new CCK-derivative with high affinity for the R-CCK2. The aim of this study was to achieve the radiolabeling of a new radioligand, to assess its efficacy using a published CCK radioligand ( 111In-DTPA-CCK8) as a control for the R-CCK2 targeting. This new CCK-derivative was radiolabeled with 111In. Nude mice, bearing the human MTC TT tumors and NIH-3T3 cell line expressing a tumorigenic mutant of the R-CCK2, were injected with this radiolabeled peptide. In vivo planar scintigraphies were acquired. Thereafter, biodistribution studies (%ID/g tissue) were done. The conditions of radiolabelling were optimized to obtain a radiochemical purity >90%. Scintigraphic images of xenograft mice showed significant tumor uptake with a target to nontarget ratio higher than two. These results were confirmed by the biodistribution studies which showed as expected a significant activity in the spleen, the liver and the kidneys. Therefore, this new radiolabeled compound is a promised new candidate for molecular imaging and internal radiotherapy for R-CCK2 tumor targeting.

  16. Thyrotropin dependent and independent thyroid cell lines selected from FRTL-5 derived tumors grown in nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Ossendorp, F.A.; Bruning, P.F.; Schuuring, E.M.; Van Den Brink, J.A.; van der Heide, D.; De Vijlder, J.J.; De Bruin, T.W. (Netherlands Cancer Institute, Amsterdam (Netherlands))

    1990-07-01

    FRTL-5 cells were used to set up a thyroid tumor model system in C3H nu/nu mice. FRTL-5 tumors could be grown in nude mice provided serum TSH levels were elevated. Persistent TSH elevation was obtained by administration of Na131I, rendering the mice hypothyroid. After 4 weeks FRTL-5 cells were injected sc resulting in tumor growth within 2 weeks in eight out of eight mice. Although the tumors showed an apparently undifferentiated histology, lacking normal follicular structures, they were functional since the tumors were capable of concentrating (131)iodine, as demonstrated by nuclear imaging. From one of the tumors a new cell line was isolated (FRTL-5/T) that, like the parental FRTL-5 cell line, was TSH dependent for growth. In a control group of six euthyroid nude mice FRTL-5 tumor growth could not be obtained with one exception. After 3 months one animal developed a small tumor that grew rapidly thereafter. This tumor was easily transplantable in other euthyroid nude mice, showed an undifferentiated histology, and was nonfunctional, as it could not concentrate (131)iodine. From this tumor two cell lines were derived: one cultured in the presence of TSH (FRTL-5/TP) and one in the absence of TSH (FRTL-5/TA). The cell lines were analyzed for TSH responsive functions and TSH receptor expression. Responsiveness to TSH in FRTL-5/T and the parental FRTL-5 cell line were similar for most thyroid specific functions tested. However, FRTL-5/T was less sensitive than FRTL-5 for TSH induced (3H)thymidine incorporation. Both cell lines had two classes of TSH binding sites with high and low affinity respectively. FRTL-5/TP and FRTL-5/TA were both able to grow in TSH free medium and were nonresponsive to TSH in vitro, as tested for (3H)thymidine and (3H)uridine incorporation, iodine uptake, thyroglobulin iodination, and thyroglobulin secretion.

  17. The effect of hyperbaric oxygenation on the viability of human fat injected into nude mice.

    Science.gov (United States)

    Shoshani, O; Shupak, A; Ullmann, Y; Ramon, Y; Gilhar, A; Kehat, I; Peled, I J

    2000-11-01

    Autologous free-fat injection for the correction of soft-tissue defects has become a common procedure in plastic surgery. The main shortcoming of this method for achieving permanent soft-tissue augmentation is the partial absorption of the injected fat, an occurrence that leads to the need for both overcorrection and repeated fat reinjection. Improving the oxygenation of the injected fat has been suggested as a means of helping to overcome the initial critical phase that occurs postinjection (when the fat cells are nourished by osmosis), increasing phagocyte activity, accelerating fibroblast activity and collagen formation, and enhancing angiogenesis. In addition, the hyperbaric oxygen-mediated decrement in endothelial leukocyte adhesion will decrease cytokine release, thereby reducing edema and inflammatory responses. The purpose of the present study was to examine the effect of hyperbaric oxygenation on improving the viability of injected fat. Adipose tissue obtained from human breasts by suction-assisted lipectomy was injected into the subcuticular nuchal region in nude mice. The mice were then exposed to daily hyperbaric oxygen treatments, breathing 100% oxygen at 2 atmospheres absolute (ATA) for 90 minutes. The duration of the administered hyperbaric oxygen therapy was 5, 10, or 15 days, according to the study group. Mice exposed to normobaric air alone served as the control group, and each group included 10 animals. The rats were killed 15 weeks after fat injection. The grafts were dissected out, weight and volume were measured, and histologic evaluation was performed. In all of the study groups, at least part of the injected fat survived, giving the desired clinical outcome. No significant differences could be found between the groups regarding fat weight and volume. Histopathologic examination of the dissected grafts demonstrated a significantly better integrity of the fat tissue in the group that received hyperbaric oxygen for 5 days (p = 0.047). This

  18. 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

  19. 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.

  20. Transplantation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells or Their Conditioned Medium Prevents Bone Loss in Ovariectomized Nude Mice

    OpenAIRE

    An, Jee Hyun; Park, Hyojung; Song, Jung Ah; Ki, Kyung Ho; Yang, Jae-Yeon; Choi, Hyung Jin; Cho, Sun Wook; Kim, Sang Wan; Kim, Seong Yeon; Yoo, Jeong Joon; Baek, Wook-Young; Kim, Jung-Eun; Choi, Soo Jin; Oh, Wonil; Shin, Chan Soo

    2013-01-01

    Umbilical cord blood (UCB) has recently been recognized as a new source of mesenchymal stem cells (MSCs) for use in stem cell therapy. We studied the effects of systemic injection of human UCB-MSCs and their conditioned medium (CM) on ovariectomy (OVX)-induced bone loss in nude mice. Ten-week-old female nude mice were divided into six groups: Sham-operated mice treated with vehicle (Sham-Vehicle), OVX mice subjected to UCB-MSCs (OVX-MSC), or human dermal fibroblast (OVX-DFB) transplantation, ...

  1. 不同化疗方案对MCF-7乳腺癌荷瘤裸鼠的抑瘤作用及对PCNA表达的影响%The effects of various chemotherapy regimens on the expression of PCNA and human breast cancer xenograft (MCF-7) transplanted in nude mice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To investigate the antitumor activity of different combination regimens to human breast cancer xenograft (MCF-7) transplanted in nude mice and the effects on the expression of PCNA, and to evaluate the value of PCNA as predictive factor for the response of chemotherapy and individualized treatment. Methods: (1) 88 nude mice models of human breast cancer xenograft (MCF-7) were established, and then were randomly divided into control group and 10 chemotherapy groups (each group, n = 8). Among them, the mice of 5 chemotherapy groups were treated intraperitoneally/orally by 5 combination chemotherapy regimens (CMF, CAF, NP, TP, Xeloda) respectively at 1/3 LD10 dosage schedule (dose lethal to 10%of the mice), and that in another 5 chemotherapy groups were treated at 2/3 LD10 dosage schedule. Control animals were administered intraperitoneally with normal saline. (2) The body weight of nude mice and transplanted tumor growth were observed and recorded, then inhibition rate of tumor growth was calculated. (3) The pathological features of transplanted tumor were studied under microscope. The expression of proliferating cell nuclear antigen (PCNA) was comparatively studied in chemotherapy group and control group by SP immunohistochemical method and flow cytometry analysis. Results: (1) Body weight, tumor weight and inhibition rate of tumor growth of athymic mice bearing cancer: Body weights and tumor weights of nude mice in every 2/3 LD10 chemotherapy group were significantly lower than those of the control group (P < 0.05), and the inhibition rates of tumor growth were 83.1%, 75.5%, 84.6%, 87.9% and 91.0%, respectively. Body weights of athymic mice in every 1/3 LD10 chemotherapy group were lower than that of the control (P < 0.05). The results showed that the 2/3 LD10chemotherapy groups could reflect the effect of combination chemotherapy on the nude mice and the clinical dependability was better. So the data of 2/3 LD10 chemotherapy groups were appropriated

  2. Radiobiological parameters of four glioblastoma compared to four other histological types of human tumor xenografts in nude mice

    International Nuclear Information System (INIS)

    Purpose/Objective: Glioblastoma Multiforme (GBM) is a highly malignant tumor of the central nervous system with aggressive biological behavior and a fatal clinical outcome. Several radiobiological parameters might contribute to these poor results. In this study, we investigated seventeen biological parameters of four GBM xenografts and compared the results with four other histological types of human tumor xenografts in nude mice. Methods and Materials: Most of the xenografts retained the individual histological features of their original tumor types. Four GBM xenografts (U87, HP555, MMC1 and HGL21), two squamous cell carcinomas (SCC21 and FaDu), one soft tissue sarcoma (STS26T), and colon cancer (HCT15) xenografts were used. The tumors were implanted in the hindleg of 5-6 Gy WBI nude mice. The following parameters were investigated for most of the xenografts: fractionated TCD50 (the dose of radiation which controls 50% of the tumors) using 30 fractions in 15 days. The parameters pO2, IFP (interstitial fluid pressure), Tpot, SF2 (plastic and Courtenay), PE (plating efficiency), D0, GSH, TCD50 single dose in oxic and hypoxic conditions, the rate of metastasis in SCID mice, VDT (volume doubling time), spontaneous apoptosis, induced apoptosis after 30 and 60 Gy and p53 over-expression. Results: Using the t-test, there was a significantly less spontaneous apoptosis in GBM xenografts when compared with the other histological types. However, no significant difference was found between both groups of xenografts in the remaining biological parameters investigated. Conclusion: These data demonstrate that, with the exception of spontaneous apoptosis, no significant difference was found in fifteen biological parameters between GBM xenografts and the other histological types implanted into the subcutaneous tissue of nude mice. The data suggests that the classical radiobiological parameters cannot explain the poor response of GBM to radiation. Supported by NCI Grant CA13311

  3. Failure-to-thrive syndrome associated with tumor formation by Madin-Darby canine kidney cells in newborn nude mice.

    Science.gov (United States)

    Brinster, Lauren R; Omeir, Romelda L; Foseh, Gideon S; Macauley, Juliete N; Snoy, Philip J; Beren, Joel J; Teferedegne, Belete; Peden, Keith; Lewis, Andrew M

    2013-08-01

    Tumors that formed in newborn nude mice that were inoculated with 10(7) Madin-Darby canine kidney (MDCK) cells were associated with a failure-to-thrive (FTT) syndrome consisting of growth retardation, lethargy, weakness, and dehydration. Scoliosis developed in 41% of affected pups. Pups were symptomatic by week 2; severely affected pups became moribund and required euthanasia within 3 to 4 wk. Mice with FTT were classified into categories of mild, moderate, and severe disease by comparing their weight with that of age-matched normal nude mice. The MDCK-induced tumors were adenocarcinomas that invaded adjacent muscle, connective tissue, and bone; 6 of the 26 pups examined had lung metastases. The induction of FTT did not correlate with cell-line aggressiveness as estimated by histopathology or the efficiency of tumor formation (tumor-forming dose 50% endpoint range = 10(2.8) to 10(7.5)); however, tumor invasion of the paravertebral muscles likely contributed to the scoliosis noted. In contrast to the effect of MDCK cells, tumor formation observed in newborn mice inoculated with highly tumorigenic, human-tumor-derived cell lines was not associated with FTT development. We suggest that tumor formation and FTT are characteristics of these MDCK cell inocula and that FTT represents a new syndrome that may be similar to the cachexia that develops in humans with cancer or other diseases. PMID:24209967

  4. A comparison of 111In- or 64Cu-DOTA-trastuzumab Fab fragments for imaging subcutaneous HER2-positive tumor xenografts in athymic mice using microSPECT/CT or microPET/CT

    OpenAIRE

    Chan, Conrad; Scollard, Deborah A; McLarty, Kristin; Smith, Serena; Reilly, Raymond M

    2011-01-01

    Background Our objective was to compare 111In- or 64Cu-DOTA-trastuzumab Fab fragments for imaging small or large s.c. tumor xenografts in athymic mice that display a wide range of human epidermal growth factor receptor-2 (HER2) expression using microSPECT/CT or microPET/CT. Methods Trastuzumab Fab were labeled with 111In or 64Cu by conjugation to 1,4,7,10-tetraazacyclododecane N, N', N'', N'''-tetraacetic acid (DOTA). The purity of 111In- and 64Cu-DOTA-trastuzumab Fab was measured by SDS-PAGE...

  5. 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.

  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. Small lymphocytes in peripheral lymphoid tissues of nude mice. Life-span and distribution

    DEFF Research Database (Denmark)

    Hougen, H P; Röpke, C

    1975-01-01

    The distribution of small lymphocytes according to life-span in the peripheral lymphoid tissues of the mouse mutant "nude" has been studied by means of auto-radiography and scintillation counting to evaluate the localization of B lymphocytes with varying life-span. The vast majority of the lympho......The distribution of small lymphocytes according to life-span in the peripheral lymphoid tissues of the mouse mutant "nude" has been studied by means of auto-radiography and scintillation counting to evaluate the localization of B lymphocytes with varying life-span. The vast majority...

  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. Immunoscintigraphy of human neuroblastoma xenografted in nude mice using a panel of 125I-labelled monoclonal antibodies

    International Nuclear Information System (INIS)

    Neuroblastoma is the most frequent tumour of the childhood under the age of 5. The staging and the follow up are achieved by MIBG scintigraphy, considered as the method of reference, but sometimes difficult to interpret. The availability of monoclonal antibodies against the ganglioside GD2, expressed on the cell membrane of neuroblastoma and neuro-endocrine cancers offers novel tools that deserve to be carefully explored. We investigated four mouse monoclonal antibodies (3 lgG3: BW704, 7A4, 60C3, and the lgG1 variant of BW704: MAK704), on nude mice xenografted with a human neuroblastoma (REM). Sixty one nude mice were included. The three former MAbs provided tumour imaging, the best results being obtained with BW704, followed by 7A4 and 60C3. MAK704 was disappointing. A control antiphosphorylcholine antibody (P51-1) did not give any tumour image in the three tested mice. Scintigraphy ratios tumour/liver and tumour/muscle reached 20 and 100 with BW704, respectively, on the 10th day. Good imaging quality was already obtained from the 24th h. The tumour uptake, calculated from radioactivity countings of resected samples, reached 22 ± 3% of injected dose per gram. These results let us hope that these antibodies could also provide highly contrasted images in humans and could open the way for therapeutic applications. (authors). 18 refs., 6 figs., 1 tab

  10. Establishing the Nude Mice Bone Metastasis Model of Lung Adenocarcinoma and Applying MicroCT into the Observation

    Directory of Open Access Journals (Sweden)

    Yongqi CUI

    2013-09-01

    Full Text Available Background and objective 50%-70% of patients with advanced lung cancer will develop bone metastases. The aim of this study is to establish the nude mice bone metastasis model of lung adenocarcinoma using A549, H1299, SPC-A-1 and XL-2, all of which own different invasion and migration abilities in vitro and supervise the bone metastases by MicroCT. Methods fifty BALB/C-nu/nu nude mice were grouped into five groups on average randomly. Cells of the four cell lines were injected into the left cardiac ventricle of mice in the four experimental groups (0.2 mL/mouse respectively; meanwhile, mice in the control group were injected with normal saline (0.2 mL/mouse in the same manner. Periodical radiological examination was carried out to supervise the variation of the mice since the second week after injection. When mice in each group became thin obviously, end the experiment of this group. Before the end, pathological sections of bone tissues were made. We classified the bone metastatic sites into axial skeleton and limb bone, in order to compare the metastatic rates of these two different parts. The bone metastatic abilities of the four cell lines was statistically analyzed by comparing the average time cost in the appearance of bone metastases and the percentage of bone metastases among the experimental groups. Results Different metastatic sites which had been identified both by MicroCT and pathological sections appeared in each group of the four experimental groups. By contrast, no metastasis was observed in the control group. The percentage of cancer metastasizing to axial skeleton was remarkably higher than the percentage of tumor metastasizing to the limb bone in each experimental group, which was consistent with the clinical regularity and characteristics of skeletal metastases with lung cancer. Thus, the model has been established triumphantly. However, there were no statistical differences in the average time consumed and skeletal metastatic

  11. 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...

  12. 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.

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

    International Nuclear Information System (INIS)

    The uptake of the rhenium-188 (188Re(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 188Re(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

  14. 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.

  15. 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.

  16. 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.

  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. Lymphocyte Reactivity Contributes to Protection Conferred by Specific Antibody Passively Transferred to Herpes Simplex Virus-Infected Mice

    OpenAIRE

    Oakes, John E.; Davis, William B.; Taylor, John A.; Weppner, William A.

    1980-01-01

    Passively acquired immunity to herpes simplex virus (HSV) was studied in antithymocyte serum (ATS)-treated mice and athymic nude mice to determine whether immunocompetent lymphocytes contribute to the protection observed after transfer of HSV-specific antibody to infected animals. Mice were given three intraperitoneal injections of 0.1 ml of ATS at 24-h intervals. This treatment reduced concanavalin A and lipopolysaccharide stimulation of lymphocytes harvested from these animals by 90% when c...

  19. 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.

  20. Effects of knockdown of miR-210 in combination with ionizing radiation on human hepatoma xenograft in nude mice

    International Nuclear Information System (INIS)

    Solid tumors usually develop local hypoxia, which renders them resilient to radiotherapy. MiR-210 is the most consistently and robustly induced miRNA under hypoxia and functions as a micro-controller of a wide range of cellular responses to hypoxia. Hence, it is important to investigate the effect of knockdown of miR-210 in tumorigenesis and evaluate the efficacy of knockdown of miR-210 in combination with radiotherapy on human tumor xenograft in nude mice. SMMC-7721 Cells with stable integration of the anti-sense miR-210 were generated through lentiviral-mediated gene transfer and were subcutaneously implanted into nude mice. Mice were monitored for tumor growth and survival after radiotherapy. MiR-210 expression in tumor tissues was assessed by real-time Reverse transcription-Polymerase Chain Reaction (RT-PCR). Protein expression of HIF-1α and miR-210 targeted genes in human hepatoma xenograft was assessed by Western blot. Tumors were analyzed for proliferation, apoptosis, and angiogenesis biomarkers by immunohistochemistry staining. Tumor growth was delayed in miR-210 downregulated xenograft. Knockdown of miR-210 increased protein expression of miR-210 targeted genes, but decreased HIF-1α protein in hepatoma xenograft. Knockdown of miR-210 in combination with radiotherapy is more effective than radiotherapy alone or miR-210 knockdown therapy alone in suppressing tumor growth and extending survival duration. Combined therapy decreased Ki-67-positive cells and CD31-positive cells and increased TUNEL-positive cells in tumor xenograft. Knockdown of miR-210 in combination with radiotherapy showed an enhanced anti-tumor effect on human hepatoma xenograft. Our experiments demonstrated specific inhibition of miR-210 expression might be a means to enhance the effectiveness of radiotherapy to human hepatoma

  1. 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

  2. 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...

  3. Inhibition of K562 cell growth and tumor angiogenesis in nude mice by transfection of anti-VEGF hairpin ribozyme gene into the cells

    Institute of Scientific and Technical Information of China (English)

    许文林

    2006-01-01

    Objective To explore the effect of anti-VEGF hairpin ribozyme gene on the tumor cell growth and tumor angiogenesis in nude mice. Methods The recombinant eukaryotic expression plasmid pcDNA-RZ containing anti-VEGF hairpin ribozyme gene and the empty vector plasmid pcDNA were introduced separately into K562 cells

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

    International Nuclear Information System (INIS)

    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. 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. 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. 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

  5. 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.

  6. Effect of all-trans retinoic acid combined with trichostatin A on the nude mice bearing human follicular thyroid carcinoma

    International Nuclear Information System (INIS)

    Objective: To study the changes of iodine uptake of the follicular thyroid carcinoma cell line (FTC-133) and nude mice bearing human follicular thyroid carcinoma after the induction with all-trans retinoic acid (ATRA), trichostatin A (TSA) or ATRA combined with TSA. Methods: After the induction with ATRA, TSA, or ATRA combined with TSA in different concentrations for 96 h, the iodine uptake of FTC-133 cells was observed. The concentrations for different groups were as follows: ATRA 1.0 ×10-6 mol/L(Alow group), ATRA 1.0 × 10-4 mol/L (Ahigh group), TSA 1.65 ×10-7 mol/L (T group), Alow + T group, Ahigh + T group and ethanol (control group). Cell quantities and morphology were observed by HE staining. FTC-133 cells were subcutaneously injected into nude mice. Twelve nude mice were randomly divided into 4 groups after tumor formation: ATRA group (2 mg/kg, intragastric administration), TSA group (10 mg/kg, intraperitoneal injection), combined therapy group (ATRA + TSA, the same doses as above) and saline control group (10 ml/kg, intragastric and intraperitoneal administration, respectively). Drugs were administered to the tumor-bearing mice according to the mouse body mass daily. At the 22nd day, the tumor-bearing mice were injected with 37 MBq 131I intraperitoneally. The biodistribution of 131I and gamma imaging were performed at 4, 6, 12 and 24 h after the injection respectively. Histopathological examinations of the tumor samples were taken after imaging completion. The results were analyzed by analysis of variance (ANOVA) with SPSS 13.0. Results: The cellular iodine uptake were (23 885 ± 616.0) and (13 849 ±728.2) counts · min-1 · 10-6 cells in the Alow + T group and Ahigh + T group respectively, and the data were (985 ± 84.2) - (17 600 ± 782.7) counts · min-1 · 10-6 in the other groups (F=600.879, P<0.001). The % ID/g of tumor at 6 h was 6.17 ±0.46 in the combined group and it increased to 9.34 ±0.61 at 12 h and 11.19 ± 0.98 at 24 h. The % ID/g of

  7. Biokinetics of 111In-DTPA-D-Phe1-octreotide in nude mice transplanted with a human carcinoid tumor

    International Nuclear Information System (INIS)

    The long time biokinetics of the radiolabeled somatostatin analogues 111In-DTPA-D-Phe1-octreotide was studied in nude mice transplanted with the human carcinoid tumor, GOT1. The results were compared with those from the patient with the original tumor. This patient has been diagnosed and later treated with 111In-DTPA-D-Phe1-octreotide. The animals received about 2 MBq 111In-DTPA-D-Phe1-octreotide (0.1 μg) by injection into a tail vein. The animals were killed 0.5 h-14 d after injection of the radiopharmaceutical. Tumor tissue and normal tissues were collected and weighed and measured for 111In activity. The 111In uptake in the tumor was higher than in all normal tissues except the kidneys. The tumor-to-normal-tissue activity concentration, TNC, increased with time for all normal tissues studied. These data were similar to those observed for the original tumor in the patient. The similar biokinetics for 111In-DTPA-D-Phe1-octreotide in the tumor-bearing mice and the patient makes this animal model suitable as a model for evaluation of therapy of somatostatin receptor (sstr) expressing tumors with radiolabeled somatostatin analogues. Furthermore, the increase with time of TNC both in mice and the patient indicates that long-lived radionuclides are preferred for therapy with radiolabeled somatostatin analogues

  8. The effectiveness of 125I seed interstitial brachytherapy for transplantation tumor of human pancreatic carcinoma in nude mice: an experiment in vivo

    International Nuclear Information System (INIS)

    Objective: To discuss the effectiveness and therapeutic mechanism of 125I interstitial brachytherapy for transplantation tumor of human pancreatic carcinoma in nude mice. Methods: The human pancreatic cell line Sw1990 was subcutaneously injected into the right lower limb partially dorsal area next to the groin of the immunodeficient BABL /c nude mice. The tumor was removed and cut into small pieces after it was formed,then the tumor pieces were inoculated in nude mice. The tumor developed to 8-10 mm in size after six weeks. A total of 16 nude mice with the suitable tumor size were used in this study. The 16 experimental mice were randomly and equally divided into two groups. The mice in study group (n = 8) were implanted with 125I seeds, while the mice in control group (n = 8) were implanted with ghost seeds. After the implantation both the long and short diameter of the tumors as well as the mouse body weight were measured every 4 days. The tumor weight was measured when the mouse was sacrificed. The paraffin-embedded samples were sent for histopathological examination. Apoptotic cells were checked with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. Expression of proliferating cell nuclear antigen (PCNA) was detected with immuno-histochemical staining. Results: The tumor grew slowly in the study group, but rapidly in the control group. The tumor weight in the study group and the control group was (2.68 ± 0.70)g and (4.68 ± 1.45)g, respectively, the difference between two groups was statistically significant (P = 0.021). The tumor inhibition rate was about 42.66%. No significant difference in body weight of nude mice existed between two groups both before and after the treatment (P > 0.05). Marked tumor necrosis was seen in study group, but no obvious, or only a little, tumor necrosis could be observed in the control group. The apoptotic index checked with the TUENL method in the study group and control group was (23.2 ± 1.9)% and

  9. The MRI study of supraparamagnetic ironic oxide loaded polymeric nano-vesicles in human colonic carcinoma xenograft in nude mice

    International Nuclear Information System (INIS)

    Objective: To synthesize the hydrophobic supraparamagnetic ironic oxide (SPIO) loaded and hydrophilic SPIO loaded polymeric nano-vesicles and to investigate the feasibility of using hydrophobic SPIO loaded and hydrophilic SPIO loaded polymeric nano-vesicles to display the tumor in MRI in vivo through animal experiments. Methods: The polymeric nano-vesicles were prepared from poly (D, L-lactic acid) (PDLLA) and poly (ethylene glycol) (PEG) by a multiple emulsion/solvent evaporation method. The hydrophobic SPIO and hydrophilic SPIO were loaded in the polymeric, nano-vesicles respectively., Eighteen nude mice models with human colorectal carcinoma xenograft were established. They were divided equally into three groups (n=6). The three groups of nude mice models were injected with water-soluble SPIO, hydrophobic SPIO loaded and hydrophilic SPIO loaded vesicle via the mice caudal vein respectively., Dynamic MRI scan were performed in all the mice models. T2WI signal intensity and T2 relaxation time were measured in the tumor, liver and muscle by using T2 mapping software. ANOVA of repeated measurement was used to analyze if there were significant differences of signal intensity changes among the three groups, while Bonferroni method was used for pair-wise comparison. Results: On T2WI, tumors showed decrease in signal intensity after hydrophobic or hydrophilic SPIO loaded polymeric nano-vesicle injection, while no signal intensity decrease was found in the tumor after water-soluble SPIO administration. The maximum percentage of signal intensity decrease in tumor caused by hydrophobic SPIO loaded and hydrophilic SPIO loaded vesicle were 11.00%, 11.40%, respectively. There was statistical significant difference of signal intensity changes among these three groups (F=10.96, P 0.05), The three agents could lead to signal intensity decrease in the liver. The maximum percentage of signal intensity decrease in liver caused by water-soluble SPIO, hydrophobic SPIO loaded and

  10. 健脾解毒复方中药对裸鼠肝癌模型PTEN/ERK1的影响%Effect of Jianpi Jiedu decoction to PTEN/ERK1 of athymic mice with hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    孙保国; 周厚明; 邓宜材; 黄红中; 陈泽雄; 张诗军

    2009-01-01

    目的:探讨肝癌裸鼠不同肝组织PTEN/ERK1的表达及健脾解毒复方中药对其的影响.方法:采用人肝细胞癌细胞株Bel-7402间接原位移植,造雄性肝癌裸鼠模型90只,造模24 h后随机分9组,即不同浓度复方中药A~G组,FT207化疗组,生理盐水组,10只裸鼠不造模作为正常对照组,给药每天1次,8周后处死裸鼠,免疫组化二步法检测肝组织、癌旁组织和癌组织PT]EN/ERKI的表达情况.结果:荷瘤裸鼠肝脏PFEN蛋白表达强度正常肝组织>癌旁组织>癌组织.中药组B,D,E组眦N在正常肝组织的表达高于生理盐水组、化疗组、正常照组,(P癌旁组织>肝组织,癌旁组织ERK1表达强度化疗组高于中药组和生理盐水组,癌组织ERK1表达强度生理盐水组和化疗组均高于中药C,D,E,G,F组.在癌组织中,PTEN和ERKl的表达呈负相关,(P<0.01).结论:在肝癌的发生发展过程中PTEN的缺失或突变可能导致了ERK1的过度活化,健脾解毒复方中药可能对PTEN/ERK1有良性调节作用.%Objective: To research the effect of Jianpi Jiedu decoction (JPJDT) to PTEN/ERK1 of athymic mice with hepato-cellular carcinoma. Method: N2 male BALB/c athymic mice models were built by Bel-7402 with an indirect method. Mter 24 h of postoperation, the 90 athymic mice were distributed randomly into JPJDT groups: A, B, C, D, E, F, G, NS, FT each group had 10 athymic mice. Another 10 male BALB/c athymic mice without HCC was treated by NS as normal control (DZ). Group A to G were treated by intragastric administration with JPJDT that had been deliquated into 7 kinds of density for 8 wk. Group NS were were treated by intragastric administration with Sodium Chloride for 8 wk. Group FT were were treated by intragastric administration with FT207 ( te-gafur) for 8 wk. At last, athymic mice were sacrificed. PTEN/ERKI was detected in hepatic tissue, latero-cancer tissue and cancer tissue by immunohistochemistry (PowerVision~(TM) two-step histostaining

  11. 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.

  12. Antitumor effects of inductive hyperthermia using magnetic ferucarbotran nanoparticles on human lung cancer xenografts in nude mice

    Directory of Open Access Journals (Sweden)

    Araya T

    2013-03-01

    Full Text Available Tomoyuki Araya,1 Kazuo Kasahara,1 Shingo Nishikawa,1 Hideharu Kimura,1 Takashi Sone,1 Hideo Nagae,2 Yoshio Ikehata,3 Isamu Nagano,3 Masaki Fujimura11Department of Respiratory Medicine, Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, 2Cooperative Research Center for Kanazawa University, 3Department of Information and Systems Engineering, Kanazawa University, Kanazawa, JapanBackground: The effects of inductive hyperthermia on lung cancer have yet to be fully investigated. Magnetic nanoparticles used in inductive hyperthermia are made-to-order and expensive. This study was performed to investigate the use of ferucarbotran in inductive hyperthermia and to clarify whether inductive hyperthermia using ferucarbotran promotes antitumor effects in vivo using a lung cancer cell line.Methods: We injected A549 cells subcutaneously into the right thighs of BALB/c nu/nu nude mice. Forty mice with A549 xenografts were then classified into three groups. Group 1 was the control group. All mice in groups 2 and 3 had ferucarbotran injected into their tumors, and mice in group 3 were then subjected to alternating magnetic field irradiation. We evaluated tumor temperature during the hyperthermic procedure, the time course of tumor growth, histologic findings in tumors after hyperthermic treatment, and adverse events.Results: Intratumor temperature rose rapidly and was maintained at 43°C–45°C for 20 minutes in an alternating magnetic field. Tumor volumes in groups 1 and 2 increased exponentially, but tumor growth in group 3 was significantly suppressed. No severe adverse events were observed. Histologic findings for the tumors in group 3 revealed mainly necrosis.Conclusion: Inductive hyperthermia using ferucarbotran is a beneficial and promising approach in the treatment of lung cancer. Ferucarbotran is a novel tool for further development of inductive hyperthermia.Keywords: inductive hyperthermia, ferucarbotran, magnetic

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Therapeutic effect against human xenograft tumors in nude mice by the third generation microtubule stabilizing epothilones.

    Science.gov (United States)

    Chou, Ting-Chao; Zhang, Xiuguo; Zhong, Zi-Yang; Li, Yong; Feng, Li; Eng, Sara; Myles, David R; Johnson, Robert; Wu, Nian; Yin, Ye Ingrid; Wilson, Rebecca M; Danishefsky, Samuel J

    2008-09-01

    The epothilones represent a promising class of natural product-based antitumor drug candidates. Although these compounds operate through a microtubule stabilization mechanism similar to that of taxol, the epothilones offer a major potential therapeutic advantage in that they retain their activity against multidrug-resistant cell lines. We have been systematically synthesizing and evaluating synthetic epothilone congeners that are not accessible through modification of the natural product itself. We report herein the results of biological investigations directed at two epothilone congeners: iso-fludelone and iso-dehydelone. Iso-fludelone, in particular, exhibits a number of properties that render it an excellent candidate for preclinical development, including biological stability, excellent solubility in water, and remarkable potency relative to other epothilones. In nude mouse xenograft settings, iso-fludelone was able to achieve therapeutic cures against a number of human cancer cell lines, including mammarian-MX-1, ovarian-SK-OV-3, and the fast-growing, refractory, subcutaneous neuroblastoma-SK-NAS. Strong therapeutic effect was observed against drug-resistant lung-A549/taxol and mammary-MCF-7/Adr xenografts. In addition, iso-fludelone was shown to exhibit a significant therapeutic effect against an intracranially implanted SK-NAS tumor. PMID:18755900

  18. The preparation of 99Tcm-J591 and its SPECT imaging of nude mice bearing human prostate cancer

    International Nuclear Information System (INIS)

    Objective: To study the binding performance of 99Tcm labeled anti-human prostatic specific membrane antigen (PSMA) monoclonal antibody J591 (99Tcm-J591) and prostate cancer cells in vitro,the biodistribution and SPECT imaging of 99Tcm-J591 in nude mice bearing human prostate cancer in vivo. Methods: The monoclonal antibody J591 was labeled with 99Tcm by improved Schwarz method.Labeled antibody was purified by Sephadex G-50. The labeling efficiency and radiochemical purity were measured by paper chromatography and trichloroacetic acid method. The binding performance of J591 and prostate cancer cells was measured by flow cytometry in vitro. The nude mice bearing PSMA-positive C4-2 prostate carcinoma xenografts served as experiment group, mice bearing PSMA-negative PC3 tumors served as control group. 6.2-8.5 MBq of 99Tcm-J591 (25 μg) was intravenously injected into mice. Gamma imaging was performed 2, 6, 12 and 24 h after injection, T/NT was calculated by ROI technique. After scanned 12 h post injection, 4 mice of the experiment group and 5 mice of the control group were sacrificed and the tracer in vivo biodistribution was measured by gamma-counting, and the % ID/g was calculated. Two-sample t test was carried out to validate significant difference of % ID/g between two groups. Results: The labeling efficiency and radiochemical purity of 99Tcm-J591 were (78.9±6.2)% and (92.3±5.1)%, respectively, and the specific activity of 99Tcm-J591 was 68.7 MBq/mg. The antibody J591 and 99Tcm-J591 could strongly combine with PSMA-positive C4-2 cells in vitro, and didn't combine with PSMA-negative PC3 cells in vitro. SPECT imaging results showed that radioactive concentration was obvious in tumor 6 h post injection, the concentration scope became large and the tumor image was clear 12 h post injection. T/NT was 1.9±1.1 at 2 h, 4.3±1.8 at 6 h, 5.6±2.7 at 12 h, 1.4±0.6 at 24 h, respectively. In the control group, no radioactivity concentration was found in tumor, and T

  19. Effects of Medicated Diet to Eradicate Helicobacter spp. on Growth, Pathology, and Infection Status in Rag1–/– and Nude Mice

    OpenAIRE

    Garrett, Caroline M; Muth, Dillon; Watson, Julie

    2014-01-01

    The use of a commercial 4-drug diet has been shown to eradicate Helicobacter spp. from immunocompetent mice and those with innate immunodeficiencies. However the efficacy of this diet has not been confirmed in mice with altered adaptive immunity. We hypothesized that an 8-wk treatment with medicated diet would eradicate H. hepaticus and H. typhlonius from young naturally infected nude and Rag1 mice lacking functional T cells (Foxn1nu) or T and B cells (B6.129S7-Rag1tm1Mom/J), respectively. We...

  20. 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.

  1. The effect of multidrug resistance modulator HZ08 on pharmacodynamics and pharmacokinetics of adriamycin in xenograft-nude mice.

    Science.gov (United States)

    Zhang, Yanyan; Feng, Yidong; Darshika, Kodithuwakku Nandani; Zhang, Bo; Hu, Yahui; Fang, Weirong; Li, Yunman; Huang, Wenlong

    2015-01-23

    To overcome MDR (multidrug resistance) of cancer mediated by P-gp (P-glycoprotein) has become a key strategy to improve the survival rate in clinic. Therefore, it is imperative to develop advanced modulators that have no side effects or interactions with cytotoxic drugs. HZ08, which acts as a P-gp inhibitor, shows a notable reverse effect with low cytotoxicity in vitro. Based on the previous results, the goal of this experiment is to elucidate the effect of HZ08 on pharmacodynamics and pharmacokinetics of adriamycin in tumor-bearing nude mice. Several criterions and methods, such as tumor weight and volume, in vivo imaging, western blot, immunohistochemistry as well as ATPase hydrolysis assay were selected to evaluate the reversing activity and mechanism of HZ08 on MDR; Furthermore, fluorescence detection assay was applied to determine the distribution of adriamycin in the blood and tissues. This study revealed that HZ08 potentiated the anti-tumor activity of adriamycin but with little effect on the expression of P-gp in vivo. Adriamycin accumulation in tumor was enhanced by HZ08 via ATPase activity inhibition. In addition, HZ08 did not alter the pharmacokinetic characteristic of adriamycin in plasma or tissues. In conclusion, HZ08 showed dramatic MDR reversing activity and had no influence on the pharmacokinetics of adriamycin. PMID:25459530

  2. Radiolabeling of substance P with Lutetium-177 and biodistribution study in AR42J pancreatic tumor xenografted Nude mice

    International Nuclear Information System (INIS)

    Pancreatic tumor (PT) is a neuroendocrine neoplasm that usually origin metastases in the respiratory and gastrointestinal tract. In recent years, new developments in targeted therapies have emerged and the presence of peptide receptors at the cell membrane of PT constitutes the basis of the clinical use of specific radiolabeled ligands. Substance P, an 11-amino acid peptide which has an important role in modulating pain transmission trough neurokinin 1 and 2 receptors (NKr), may play a role in the pathogenesis of PT, because approximately 10% of these tumors over express NKr. The aim of the present work was to produce a pure and stable SP analog (DOTA-SP) radiolabeled with Lutetium-177 (177Lu), and to evaluate its in vivo target to AR42J pancreatic tumor cells in Nude mice in other to verify if SP can be used in this pancreatic tumor detection and treatment. 177Lu (half-life 6.7 days) has both β and γ-emissions suitable for radiotherapy and imaging respectively. Substance P was successfully labeled with high yield (>99%) at optimized conditions and kept stable for more than 72 hours at 4 deg C and 24 hours in human plasma. Biodistribution studies showed that SP excretion was mainly performed by renal pathway. In addition, 177Lu-DOTA-SP showed higher uptake by tumor than normal pancreas, indicating the presence of NK receptors in AR42J pancreatic tumor. (author)

  3. Targeted therapy against human lung cancer in nude mice by high-affinity recombinant antimesothelin single-chain Fv immunotoxin.

    Science.gov (United States)

    Fan, Dominic; Yano, Seiji; Shinohara, Hisashi; Solorzano, Carmen; Van Arsdall, Melissa; Bucana, Corazon D; Pathak, Sen; Kruzel, Ewa; Herbst, Roy S; Onn, Amir; Roach, Jennifer S; Onda, Masanori; Wang, Qing-cheng; Pastan, Ira; Fidler, Isaiah J

    2002-06-01

    Several tumors, including mesothelioma and ovarian cancer, can overexpress mesothelin, a glycosylphosphatidylinositol-linked differentiation glycoprotein. The membrane-bound type of mesothelin is found in the blood of cancer patients at a very low level, which makes mesothelin a good candidate for targeted therapy of certain cancers. An antimesothelin disulfide-linked Fv (SS1 Fv) was fused to a truncated mutant of Pseudomonas exotoxin A to produce the recombinant immunotoxin SS1(dsFv)-PE38, which has a high binding affinity to mesothelin (Kd = 0.7 nM). Our studies in vitro showed that SS1(dsFv)-PE38 is significantly more cytotoxic to the high-mesothelin-producing NCI-H226 human non-small cell lung cancer cells than to human lung adenocarcinoma PC14PE6 cells, which do not express mesothelin. When administered at a nontoxic dose of 500 microg/kg on days 7, 9, and 11 to nude mice injected i.v. with the two human lung cancer cell lines, SS1(dsFv)-PE38 selectively inhibited experimental lung metastases produced by the mesothelin-producing NCI-H226 cells. Our data indicate that mesothelin-producing squamous cell carcinoma of the lung may be a good target for this immunotoxin. PMID:12479219

  4. Adenovirus-Mediated Herpes Simplex Virus Thymidine Kinase Gene Transfer Driver by KDR Promoter in Treatment of Experimental Human HepatocelLular Carcinoma in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    LI Bao-jin; ZHANG Chao; YI Yuan-xue; HAO Ying; LIU Xiao-ping; OU Qing-jia

    2007-01-01

    Objective: To investigate the therapeutic efficacy of adenovirus-mediated herpes simplex virus thymidine kinase (HSV-tk) gene transfer under the driving of KDR promoter (AdKDR-tk) in combination of ganciclovir (GCV) against human hepatocellular carcinoma in nude mice. Methods: HepG2 cell line was implanted subcutaneously into 32 nude mice, which were subsequently divided into 4 groups (n=8 each group): Ganciclovir group (Ⅰ), Ad group (Ⅱ), AdCMV-tk/GCV group (under the driving of CMV promoter) (Ⅲ) and AdKDR-tk/GCV group (Ⅳ). Then intratumoral injection of recombinant adenovirus or Ad was performed in all nude mice, and repeated 24 h later. For the following 10 d GCV was given at a dose of 100 mg/(kg·d), ip. All the treated animals were killed to evaluate the tumor weight and the histopathological changes and the microvessel density of tumors after the treatment was determined. Results: Compared with group Ⅰ, the tumor inhibitory rate was 12.3% in group Ⅲ and 24.5% in group Ⅳ; the inhibition rates were significantly different between group Ⅲ and Ⅳ (P<0.05). The mean MVDs in group Ⅰ, Ⅱ, Ⅲand Ⅳ were 37.4±8.6, 30.6±7.8, 27.6±7.1, and 10.7±4.1 (microvessels/mm2), respectively. Significant differences were found between group Ⅲ and Ⅱ (P<0.05), Ⅳ and Ⅱ (P<0.01), and Ⅳ and Ⅲ (P<0.01). Conclusion: Intratumoral injection of AdKDR-tk results in marked inhibition of HCC growth through inhibition angiogenesis in nude mice. It may be a new treatment approach for human HCC.

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

    OpenAIRE

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

    2013-01-01

    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.

  6. 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

  7. Combination of Albendazole and 2-Methoxyestradiol significantly improves the survival of HCT-116 tumor-bearing nude mice

    International Nuclear Information System (INIS)

    Albendazole (ABZ) is a microtubule-targeting anthelmintic with a remarkable activity against a variety of human cancer cells. In this study, we examined if the antitumor activity of ABZ could be enhanced by its combination with other microtubule-binding agents. The interactions between ABZ and microtubule-binding agents, paclitaxel, vinblastine, colchicine, and 2-methoxyestradiol were characterized using median effect analysis method in HCT-116 colorectal cancer cells and DU145 prostate cancer cell line. The mechanism underlying the synergistic interaction related to tubulin polymerization and apoptosis was then investigated. Finally, the effect of the combination therapy on the survival of HCT-116 tumor-bearing nude mice was evaluated. Among the tested drugs, a synergistic anti-proliferative effect was observed with the combination of low concentrations of ABZ plus colchicine and ABZ plus 2-methoxyestradiol (2ME). Exploring the mechanism of the interaction between ABZ and 2ME revealed that the combination therapy synergistically activated the extrinsic pathway of apoptosis. Consistent with in vitro results, the combination of low concentration of ABZ with 2ME prolonged the survival of mice-bearing HCT-116 tumors. High concentration of ABZ in combination with 2ME, however, proved to be less effective than ABZ alone. The combination of low doses of ABZ and 2ME has shown promising results in our pre-clinical model. Additionally, the finding that the combination of two microtubule-binding agents that share the same binding site can act synergistically may lead to the development of new therapeutic strategies in cancer treatment

  8. 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.

  9. Activity of a new vascular targeting agent, ZD6126, in pulmonary metastases by human lung adenocarcinoma in nude mice.

    Science.gov (United States)

    Goto, Hisatsugu; Yano, Seiji; Zhang, Helong; Matsumori, Yuka; Ogawa, Hirohisa; Blakey, David C; Sone, Saburo

    2002-07-01

    ZD6126 (ANG453) is a novel vascular targeting agent that selectively disrupts the cytoskeleton of endothelial cells in tumor. In mouse s.c. xenograft models, ZD6126 was found to induce selective occlusion of tumor blood vessels, cessation of tumor blood flow, and death of tumor cells because of the starvation of oxygen and nutrition. Here, we investigated whether ZD6126 inhibited the metastatic formation of human non-small cell lung cancer cells. PC14PE6 (adenocarcinoma) and H226 (squamous cell carcinoma) cells were injected into the tail vein of nude mice, and lung metastases were estimated. ZD6126 treatment involved either a single dose on 24 h before killing or daily doses from day 14 until the end of the experiment. Single treatment with i.p. injection of 200 mg/kg ZD6126 caused bleeding and necrotic changes in the tumor by 24 h. Histological analysis revealed that apoptotic tumor cells were markedly increased in the ZD6126-treated group. Moreover, ZD6126 induced the apoptosis of CD31-positive vascular endothelial cells in tumors but not in the normal lung parenchyma. When mice were treated daily with 100 mg/kg ZD6126 from day 14 until the end of the experiment, the lung weight was significantly less in the ZD6126-treated group than that of the control group, despite no difference in the number of metastatic nodules. These data suggest that ZD6126 could demonstrate its antitumor activity against both already established and early phase of lung cancer metastasis by causing the selective apoptosis of tumor endothelial cells and destruction of the tumor vasculature. PMID:12097279

  10. 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.

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

    International Nuclear Information System (INIS)

    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 [18F]fluoro-2-deoxy-D-glucose (FDG), 3'-[18F]fluoro-3'-doxythymidine (FLT) or 4'-methyl-[11C]thiothymidine (S-dThd) into the mouse models. In vitro cellular uptake of [14C]FDG and [3H]FLT and thymidine kinase 1 (TK1) 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 [11C]S-dThd was significantly higher than that of [18F]FDG. On the other hand, in sarcomatoid models, [18F]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 [14C]FDG and [3H]FLT and TK1 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: [18F]FLT and [11C]S-dThd seemed suitable for the epithelioid subtype and [18F]FDG seemed

  12. 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

  13. Studies on biodistribution and imaging of 188Re labeled insulin-like growth factor-1 analogue in nude mice bearing human pancreatic carcinoma

    International Nuclear Information System (INIS)

    Objective: To evaluate the biodistribution and planar gamma camera imaging characteristics of 188Re labeled insulin-like growth factor 1 analogue (188Re-IGF-1A) in tumor-bearing mice. Methods: (1)To label IGF-1A with 188Re directly and to determine the labeling efficiency. (2)To establish nude mice model which bearing human pancreatic carcinoma cell Patu8988. (3)To 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. (4)To scan those nude mice at 15 min, 1 h, 2 h, 4 h and 24 h after intratumor injection with 188ReO4- into their tumors. To calculate the tumor to normal tissue ratio (T/NT) and the percentages of injected dose per gram tissue (%ID/g) of different organs. Results: (1)The labeling efficiency of 188Re-IGF-1A was (94.07 ± 0.32)%. (2)The largest uptake of tumors was (42.38 ± 17.82)%ID/g at 4 h after injection of 188Re-IGF-1A. Then the tumor to normal tissue ratios 5ncreased and the largest tumor to muscle ratio was 6531.79 ± 4930.26 at 5 d after injection. (3) 188ReO4- was major distributed in thyroid glands, stomachs, tumors and blood in nude mice after injection at first. Then %ID/g decreased rapidly in tumors. (4) The difference of %ID/g was significant (t=5.877, t=13.287, P188Re-IGF-1A group than in 188ReO4- group. The largest ratio of tumors in the two groups was 74.10 at 24 h after injection. (5) After being injected, 188Re-IGF-1A formed clear images in tumors, 5 d later, nothing but tumors can be seen. Conclusions: 188Re-IGF-1A has good affinity with human pancreatic cancer, and the tumor to muscle ratios in nude mice is high. So 188Re-IGF-1A is expected to be used for targeting therapy of human pancreatic carcinoma. (authors)

  14. 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.

  15. Effects of soy isoflavone extracts on the growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in ovariectomized nude mice

    Institute of Scientific and Technical Information of China (English)

    WU Qian; JIN NianZu; YU Jing; ZHAO RenChen; YU ZePing; QIAO ShanLei; LU XiaoHe; ZHANG ChunWen

    2009-01-01

    In this study,we explored the effects of soy isoflavone extracts on the growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in ovariectomized athymic mice.The ovariectomized athymic mice were implanted with MCF-7 cells.They were fed with low,moderate and high doses of soy isoflavone extracts,at dietary concentrations of 6.25,12.5 and 25 g/kg,respectively.The expression of ki-67 was detected by immunohistochemistry.The pS2 expression in tumors was analyzed by real-time PCR.Estrogen level in the serum was measured by chemiluminescence enzyme immunoassay.Com-pared with the control group,dietary soy isoflavone extracts had a significant stimulatory effect on MCF-7 tumor growth in mice (P 0.05).The ki-67 and pS2 mRNA expressions in tumors were signifi-cantly increased by 6.25 and 12.5 g/kg dose of soy isoflavone extracts (P 0.05).And,estrogen level in serum of 6.25 and 12.5 g/kg dose groups was higher than that of control group (P 0.05).In conclusion,in the tested dietary concentration range soy isoflavone extracts had a stimulatory effect on tumor growth.6.25 and 12.5 g/kg doses of soy isoflavone extracts can increase the cell proliferation in tumors and induce estrogen-responsive pS2 expression.

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

    OpenAIRE

    You, Mi-Kyoung; Kim, Min-Sook; Jeong, Kyu-Shik; Kim, Eun; Kim, Yong-Jae; Kim, Hyeon-A

    2016-01-01

    BACKGROUND/OBJECTIVES The present study was conducted to examine the inhibitory effect of loquat leaves on MDA-MB-231 cell proliferation and invasion. MATERIALS/METHODS Female athymic nude mice were given a subcutaneous (s.c.) inoculation of MDA-MB-231 cells and randomly grouped to receive a s.c. injection of either 500 mg/kg ethanol, water extract or vehicle five times a week. Tumor growth, mitotic rate and necrosis were examined. MDA-MB-231 cells were cultured with DMSO or with various conc...

  17. 人结肠癌裸鼠肝转移模型的建立%Establishment and Comparison of Colon Cancer Liver Metastasis Models in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    袁岱岳; 郭忠英; 赵任; 黄宝玉; 梅广林; 朱建伟

    2011-01-01

    目的 建立人结肠癌裸鼠肝转移模型,用于肿瘤转移防治的实验研究.方法 30只裸鼠随机分为两组,分别用肝脏注射法和脾脏注射法建立结肠癌肝转移模型,术后待裸鼠濒临死亡或自然死亡时.观察其生存天数,解剖裸鼠,观察腹腔内转移情况和肝脏成瘤的情况.结果 两组裸鼠的肝脏成瘤率均为100%,生存期无明显差异.肝脏注射组裸鼠均于注射部位出现单一的巨大瘤结节,脾脏注射组裸鼠肝脏表面及切面见多发散在的转移瘤结节.两组的肝脏瘤组织细胞形态学相似,符合低分化腺癌的特征.结论 经脾注射法建立裸鼠结肠癌肝转移模型比较符合结肠癌体内肝转移过程的规律,是一种简便有效的、重复性好的方法.%Objective To develop a reliable colon cancer liver metastasis model in nude mice. Methods Thirty nude mice were divided into two groups randomly, which were the liver injection group and spleen injection group, respectively containing 15 nude mice. Colon cancer liver metastasis models were made by liver injection and spleen injection, respectively. The average survival time was recorded. The metastasis of nude mice was detected pathologically. Results Both of the incidence rates of liver metastasis in the two groups were 100%. Survival time of the two groups showed no statistics significance. Anatomical study showed that there appeared a single giant tumor nodule appeared at every injection site in the liver injection group while multiple metastasis appeared nodules in livers in the spleen injection group. The pathological results indicated that the tumor cells pattern of liver metastasis was similar in the two groups and was in accordance with poorly differentiated colon adenocarcinorna. Conclusion Intrasplenic injection of colon cancer cells, which closely mimic the natural metastatic process, is a reliable method for producing colon cancer liver metastasis in nude mice and should be proved

  18. Antitumor and radiosensitizing effects of (E)-2'-Deoxy-2'-(Fluoromethylene) cytidine, a novel inhibior of ribonucleotide diphosphate reductase on human colon carcinoma xenografts in nude mice.

    OpenAIRE

    Sun, Lin-Quan; Li, Ye-Xiong; Guillou, Louis; Mirimanoff, René-Olivier; Coucke, Philippe

    1997-01-01

    Antitumor and radiosensitizing effects of (E).2'-deoxy.2'-(fluromethyl ene) cytidine (FMdC), a novel inhibitor of ribonucleotide reductase, were evaluated on nude mice bearing s.c. xenografts and liver metastases of a human colon carcinoma. FMdC given once daily or twice weekly has a dose-dependent antitumor effect. The maximum tolerated dose In the mice was reached with 10 mgi'kg applied daily over 12 days. Twice weekly administration of FMdC reduced its toxicity but lowere...

  19. 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.

  20. Adipose stem cells' antagonism in glycosylation of D-galactose-induced skin aging of nude mice and its skin recovery function.

    Science.gov (United States)

    Wang, Haiying; Wei, Shuyue; Xue, Xinxin; You, Yuntian; Ma, Qiang

    2016-09-01

    This study aims to discuss adipose stem cells' (ASCs) antagonism in glycosylation of D-galactose-induced skin aging of nude mice and its skin recovery function; the study also aims to explore a new mechanism of anti-aging to provide clinical anti-aging therapy with new thoughts and methods. We selected 40 healthy specific pathogen-free (SPF) nude mice and divided them randomly into four groups which were: blank control group; D-galactose + phosphate buffer saline (PBS) group; D-galactose + ASCs treatment group; and D-galactose + aminoguanidine (AG) group. Results showed that the superoxide dismutase (SOD) level of mice in the D-galactose-induced model group (87.15 ± 4.95 U/g) decreased significantly compared with that of control group (146.21 ± 4.76 U/g), while malonaldehyde (MDA) level of mice in D-galactose induced model group (11.12 ± 2.08 nmol/mg) increased significantly compared with that of control group (5.46 ± 2.05 nmol/mg) (P bioluminescence, and they survive for a short time in the skin after transplantation, which provides a basis for the application of ASC transplantation in clinical practices. Moreover, ASCs can control glycosylation level of D-galactose-induced skin aging of nude mice, reverse expression of aging-related biomarkers as well as restrain formation of advanced glycation end products, which are similar to the effects of AG inhibitors of advanced glycation end products. Thus, ASCs can prevent glycosylation-induced skin aging as well as recover functions of skin. PMID:26916459

  1. 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

  2. Silencing of signal transducer and activator of transcription 3 expression by RNA interference suppresses growth of human hepatocellular carcinoma in tumor-bearing nude mice

    Institute of Scientific and Technical Information of China (English)

    Jing Li; Yun-Feng Piao; Zheng Jiang; Li Chen; Hai-Bo Sun

    2009-01-01

    AIM: To explore the effect of silencing of signal transducer and activator of transcription 3 (STAT3) expression by RNA interference (RNAi) on growth of human hepatocellular carcinoma (HCC) in tumorbearing nude mice in vivo.METHODS: To construct the recombinant plasmid of pSilencer 3.0-H1-STAT3-siRNA-GFP (pSH1-siRNASTAT3) and establish the tumor-bearing nude mouse model of the HCC cell line SMMC7721, we used intratumoral injection together with electroblotting to transfect the recombinant plasmid pSH1-siRNASTAT3 into the transplanted tumor. The weight of the nude mice and tumor volumes were recorded. STAT3 gene transcription was detected by semi-quantitative reverse transcription polymerase chain reaction (RTPCR).Level of protein expression and location of STAT3 were determined by Western blotting and immunohistochemical staining. STAT3-related genes such as survivin, c-myc, VEGF, p53 and caspase3 mRNA and protein expression were detected in tumor tissues at the same time. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was used to detect apoptosis of tumor cells.RESULTS: The weight of the treated nude mice increased, and the tumor volume decreased markedly compared with those of the mock-treated and negative control groups ( P < 0.01). The results of RT-PCR and Western blotting showed that mRNA and protein levels of STAT3 declined markedly in the treated group. The change in STAT3-related gene expression in tumor tissues at the mRNA and protein level also varied, the expression of survivin, VEGF and c-myc were obviously reduced, and expression of p53 and caspase3 increased ( P < 0.01). Most of the tumor tissue cells in the treated group developed apoptosis that was detected by TUNEL assay.CONCLUSION: Silencing of STAT3 expression by RNAi significantly inhibits expression of STAT3 mRNA and protein, and suppresses growth of human HCC in tumor-bearing nude mice. The mechanism may be related to down-regulation of survivin, VEGF

  3. 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.

  4. 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.

  5. Experimental study on selective cyclooxygenase-2 inhibitor combined with radiotherapy for human prostate carcinoma xenografts in nude mice

    International Nuclear Information System (INIS)

    Objective: To investigate the anti-tumor and radiation-enhancement effects and observe a coordinate repression of celecoxib, a selected cyclooxygenase -2 inhibitor in prostate carcinoma. Methods: An animal model of human prostate carcinoma in BALC/C male nude mice was establised by injecting suspension of PC-3 cells and the mice were randomly divided into 4 groups which were interfered with celecoxib, radiation, and both celecoxib and radiation respectively, with 6 rats in each group. The effect of treatment was assessed by tumor growth delay (TGD) and radiosensitization enhancement effector (EF); the tumor tissues were collected and assessed for the detection of cyclooxygense-2 mRNA and prostaglandin E2 by RT-PCR and ELISA, and histopathological changes of transplanted mouse's important organs were observed. Results: The time that the longest diameters of all tumors growing from 8.0mm to 12.0mm for the control group and the celecoxib group was(6.18 ± 0.72)d and(7.87 ± 0.76)d, respectively ,while the time for the radiation group and celecoxib + radiation group was (9.16 ± 0.89)d and (12.62 ± 1.28)d respectively. The growth of tumors was significantly different among these groups (P2 levels between the control group and other groups (P2 levels between the radiation group and celecoxib + radiation group (P>0.05). Significant correlations were found between the growth delayed by celecoxib and the drop of prostaglandin E2 levels (r=0.807); Analysis of variance showed that there was no significant difference in cyclooxygense-2 mRNA among these four groups (P > 0.05). No significant toxic pathological changes of transplanted mouse's important organs were observed. Conclusion: Our results suggest a coordinative repression between celecoxib and radiation in inhibiting human prostate carcinoma xenografts by the anti-tumor and radiation-enhancement, which is safe and effective in some extent and may contribute to enlighten the future study and clinical therapy of

  6. 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.

  7. Radiolabeling of anti-human prostatic specific membrane antigen antibody with 99Tcm and its biodistribution in nude mice bearing human prostate cancer

    International Nuclear Information System (INIS)

    Objective: To study the binding affinity of 99Tcm labeled anti-human prostatic specific membrane antigen (PSMA) monoclonal antibody (McAb) J591 to prostate cancer cells and the biodistribution of 99Tcm-J591 in nude mice bearing human prostate cancer. Methods: The McAb J591 was labeled with vTcm by improved Schwarz method and the labeled McAb was purified by Sephadex G-50. The binding affinity of J591 with prostate cancer cells was measured by Flow Cytometry. The nude mice bearing PSMA-positive C4-2 prostate carcinoma xenografts were served as experiment groups, mice with PSMA-negative pc3 tumors served as controls. The biodistribution of 99Tcm-J591 were carried out in both model nude mice. Results: The radiolabeling efficiency of 99Tcm-J591 was 78.9±6.2%, and radiochemical purity was more than 90% after purification. The 99Tcm-J591 showed a good combination with PSMA-positive C4-2 cells and no combination with PSMA-negative PC3 cells in vitro. The biodistribution results showed that 99Tcm-J591 was accumulated in tumor tissue during the 2-24 hours after injection in experiment groups, and no significant uptake in control group. The uptake of 99Tcm-J591 in tumor tissue reached a maximum 15.91±5.16 % ID/g in experimental group at 12h post-injection. There was a significant difference compared with controls (P0.05). Conclusion: The monoclonal antibody J591 exhibits an excellent immuno-reactivity and tumor targeting property, and it may be used in diagnosis and target therapy of prostate cancer. (authors)

  8. 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.

  9. 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.

  10. Imaging the microenvironment of pancreatic cancer patient-derived orthotopic xenografts (PDOX) growing in transgenic nude mice expressing GFP, RFP, or CFP.

    Science.gov (United States)

    Hoffman, Robert M; Bouvet, Michael

    2016-09-28

    We have developed a multi-color, imageable, orthotopic mouse model for individual patients with pancreatic cancer. The tumors are labeled by first passaging them orthotopically through transgenic nude mice expressing green fluorescent protein (GFP), red fluorescent protein (RFP), or cyan fluorescent protein (CFP). Passage of the tumors in these colored transgenic mice labels the stromal cells of the tumor. The cancer cells in the PDOX are labeled in situ with GFP by telomerase-dependent adenovirus OBP-401. The models are termed imageable patient-derived orthotopic xenografts (iPDOX). The tumors acquired brightly-fluorescent stromal cells from the transgenic host mice, which were stably associated with the tumors through multiple passages. The colored fluorescent protein-expressing stromal cells included cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs). This model enables powerful color-coded imaging of the interaction of cancer and stromal cells during tumor progression and treatment. PMID:26742463

  11. The effect of finasteride and dutasteride on the growth of WPE1-NA22 prostate cancer xenografts in nude mice.

    Directory of Open Access Journals (Sweden)

    Alexander B Opoku-Acheampong

    Full Text Available BACKGROUND: 5α-reductase 1 (5αR1 and 5α-reductase 2 (5αR2 convert testosterone into the more potent androgen dihydrotestosterone. 5αR2 is the main isoenzyme in normal prostate tissue; however, most prostate tumors have increased 5αR1 and decreased 5αR2 expression. Previously, finasteride (5αR2 inhibitor treatment begun 3 weeks post-tumor implantation had no effect on Dunning R3327-H rat prostate tumor growth. We believe the tumor compensated for finasteride treatment by increasing tumor 5αR1 expression or activity. We hypothesize that finasteride treatment would not significantly alter tumor growth even if begun before tumor implantation, whereas dutasteride (5αR1 and 5αR2 inhibitor treatment would decrease tumor growth regardless of whether treatment was initiated before or after tumor implantation. METHODOLOGY/PRINCIPAL FINDINGS: Sixty 8-week-old male nude mice were randomized to Control, Pre- and Post-Finasteride, and Pre- and Post-Dutasteride (83.3 mg drug/kg diet diet groups. Pre- and post-groups began their treatment diets 1-2 weeks prior to or 3 weeks after subcutaneous injection of 1×10⁵ WPE1-NA22 human prostate cancer cells, respectively. Tumors were allowed to grow for 22 weeks; tumor areas, body weights, and food intakes were measured weekly. At study's conclusion, prostate and seminal vesicle weights were significantly decreased in all treatment groups versus the control; dutasteride intake significantly decreased seminal vesicle weights compared to finasteride intake. No differences were measured in final tumor areas or tumor weights between groups, likely due to poor tumor growth. In follow-up studies, proliferation of WPE1-NA22 prostate cancer cells and parent line RWPE-1 prostate epithelial cells were unaltered by treatment with testosterone, dihydrotestosterone, or mibolerone, suggesting that these cell lines are not androgen-sensitive. CONCLUSION: The lack of response of WPE1-NA22 prostate cancer cells to androgen

  12. Effect of melphalan on growth curves and cell cycle distribution of four human small cell carcinomas of the lung grown in nude mice

    DEFF Research Database (Denmark)

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

    1986-01-01

    Four human small cell carcinomas of the lung grown in nude mice were exposed to melphalan. Two of the tumors were derived from subpopulations isolated by in vitro cloning from the same tumor biopsy. The chemosensitivity of the tumors was determined by calculating the specific growth delay. Drug......-induced changes in the cell cycle were detected by flow cytometric DNA analysis. The specific growth delay of the tumors was very different with the greatest differences between the two subpopulations originating from the same tumor. Melphalan induced a dose-related S phase accumulation in three sensitive tumors...

  13. Transplantation of human umbilical cord blood-derived mesenchymal stem cells or their conditioned medium prevents bone loss in ovariectomized nude mice.

    Science.gov (United States)

    An, Jee Hyun; Park, Hyojung; Song, Jung Ah; Ki, Kyung Ho; Yang, Jae-Yeon; Choi, Hyung Jin; Cho, Sun Wook; Kim, Sang Wan; Kim, Seong Yeon; Yoo, Jeong Joon; Baek, Wook-Young; Kim, Jung-Eun; Choi, Soo Jin; Oh, Wonil; Shin, Chan Soo

    2013-03-01

    Umbilical cord blood (UCB) has recently been recognized as a new source of mesenchymal stem cells (MSCs) for use in stem cell therapy. We studied the effects of systemic injection of human UCB-MSCs and their conditioned medium (CM) on ovariectomy (OVX)-induced bone loss in nude mice. Ten-week-old female nude mice were divided into six groups: Sham-operated mice treated with vehicle (Sham-Vehicle), OVX mice subjected to UCB-MSCs (OVX-MSC), or human dermal fibroblast (OVX-DFB) transplantation, OVX mice treated with UCB-MSC CM (OVX-CM), zoledronate (OVX-Zol), or vehicle (OVX-Vehicle). Although the OVX-Vehicle group exhibited significantly less bone mineral density (BMD) gain compared with the Sham-Vehicle group, transplantation of hUCB-MSCs (OVX-MSC group) has effectively prevented OVX-induced bone mass attenuation. Notably, the OVX-CM group also showed BMD preservation comparable to the OVX-MSC group. In addition, microcomputed tomography analysis demonstrated improved trabecular parameters in both the OVX-MSC and OVX-CM groups compared to the OVX-Vehicle or OVX-DFB group. Histomorphometric analysis showed increased bone formation parameters, accompanied by increased serum procollagen type-I N-telopeptide levels in OVX-MSC and OVX-CM mice. However, cell-trafficking analysis failed to demonstrate engraftment of MSCs in bone tissue 48 h after cell infusion. In vitro, hUCB-MSC CM increased alkaline phosphatase (ALP) activity in human bone marrow-derived MSCs and mRNA expression of collagen type 1, Runx2, osterix, and ALP in C3H10T1/2 cells. Furthermore, hUCB-MSC CM significantly increased survival of osteocyte-like MLO-Y4 cells, while it inhibited osteoclastic differentiation. To summarize, transplantation of hUCB-MSCs could effectively prevent OVX-mediated bone loss in nude mice, which appears to be mediated by a paracrine mechanism rather than direct engraftment of the MSCs. PMID:23215868

  14. 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

  15. Interventional therapy for human breast cancer in nude mice with 131I gelatin microspheres (131I-GMSs) following intratumoral injection

    International Nuclear Information System (INIS)

    The aim of this study was to investigate the effects of 131I gelatin microspheres (131I-GMS) on human breast cancer cells (MCF-7) in nude mice and the biodistribution of 131I-GMSs following intratumoral injections. A total of 20 tumor-bearing mice were divided into a treatment group and control group and received intratumoral injections of 2.5 mci 131I-GMSs and nonradioactive GMSs, respectively. Tumor size was measured once per week. Another 16 mice received intratumoral injections of 0.4 mci 131I-GMSs and were subjected to single photon emission computed tomography (SPECT) scans and tissue radioactivity concentration measurements on day 1, 4, 8 and 16 postinjection. The 20 tumor-bearing mice received intratumoral injections of 0.4 mci [131I] sodium iodide solution and were subjected to SPECT scans and intratumoral radioactivity measurements at 1, 6, 24, 48 and 72 h postinjection. The tumors were collected for histological examination. The average tumor volume in the 131I-GMSs group on post-treatment day 21 decreased to 86.82 ± 63.6%, while it increased to 893.37 ± 158.12% in the control group (P < 0.01 vs. the 131I-GMSs group). 131I-GMSs provided much higher intratumoral retention of radioactivity, resulting in 19.93 ± 5.24% of the injected radioactivity after 16 days, whereas the control group retained only 1.83 ± 0.46% of the injected radioactivity within the tumors at 1 h postinjection. 131I-GMSs suppressed the growth of MCF-7 in nude mice and provided sustained intratumoral radioactivity retention. The results suggest the potential of 131I-GMSs for clinical applications in radiotherapy for breast cancer

  16. 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.

  17. 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)

  18. 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.

  19. Biodistribution and radioimmunoimage of iodine-125 labeled anti-human ADAM15 polyclonal antibody in nude mice bearing human gastric carcinoma xenografts

    International Nuclear Information System (INIS)

    Objective: To investigate the biodistribution of Iodine-125 labeled anti-human ADAM15 polyclonal antibody in nude mice bearing human gastric carcinoma xenografts. Methods: The anti-human ADAM15 polyclonal antibody was labeled with I-125 using Chloramine-T method. The labeling efficiency and radiochemical purity of 125I-anti-ADAM15 antibody were measured. The SPECT planar imaging of nude mice bearing gastric carcinoma xenografts were performed at 1, 4, 8, 24, and 48 h post-injection and the biodistribution of 125I-anti-ADAM15 antibody was measured at 48 h after injection. Results: The labeling efficiency of 125I-anti-ADAM15 antibody was (75.16±9.43)% and its radiochemical purity was (99.44±0.21)% . Tumors could be cleanly visualized in SPECT planar images, and the radioactivity ratio of tumor to non-tumor tissue was 3.84±0.43 at 48 h post-injection. Conclusion: 125I-anti-ADAM15 antibody can target the gastric carcinoma in vivo, and provide good radioimmunoimages. (authors)

  20. 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.

  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. Ectopic bone formation of human bone morphogenetic protein-2 gene transfected goat bone marrow-derived mesenchymal stem cells in nude mice

    Institute of Scientific and Technical Information of China (English)

    汤亭亭; 徐小良; 戴尅戎; 郁朝锋; 岳冰; 楼觉人

    2005-01-01

    Objective: To evaluate the osteogenic potential of bone morphogenetic protein (BMP)-2 gene transfected goat bone marrow-derived mesenchymal stem cells (MSCs). Methods: Goat bone marrow- derived MSCs were transfected by Adv-human bone morphogenetic protein (hBMP)-2 gene(Group 1), Adv-beta gal transfected MSCs (Group 2)and uninfected MSCs(Group 3). Western blot analysis, alkaline phosphatase staining, Von Kossa staining and transmission electron microscopy were adopted to determine the phenotype of MSCs. Then the cells were injected into thigh muscles of the nude mice. Radiographical and histological evaluations were performed at different intervals. Results: Only Adv-hBMP-2 transfected MSCs produced hBMP-2. These cells were positive for alkaline phosphatase staining at the 12th day and were positive for Von Kossa staining at the 16th day after gene transfer. Electron microscopic observation showed that there were more rough endoplasmic reticulum, mitochondria and lysosomes in Adv-hBMP-2 transfected MSCs compared to MSCs of other two groups. At the 3rd and 6th weeks after cell injection, ectopic bones were observed in muscles of nude mice of Group 1. Only fibrous tissue or a little bone was found in other two groups. Conclusions: BMP-2 gene transfected MSCs can differentiate into osteoblasts in vitro and induce bone formation in vivo.

  3. Endostar combined with cryoablation for subcutaneous xenografted tumor model of lung adenocarcinoma cell line A549 in BALB/c nude mice: an experimental study

    International Nuclear Information System (INIS)

    Objective: To investigate the inhibitory effect of Endostar combined with cryoablation on Lung adenocarcinoma cell line A549 in BALB/c nude mice, and to discuss its interaction mechanisms. Methods: The lung adenocarcinoma A549 model in BALB/c nude mice were established. When the largest diameter of tumor reached 1.0 cm, a total of 24 mice were randomly and equally divided into 4 groups: control group, Endostar group, cryoablation group and cryoablation plus Endostar group. The largest diameter and the vertical diameter of the tumors were measured at different points of time after treatment. At the 21st day, the mice were sacrificed and the tumors were removed and the rate of tumor cell apoptosis, the microvessel density (MVD) and the expression level of vascular endothelial growth factor (VEGF) were determined by using immunohistochemistry method. The results were statistically analyzed. Results: The tumor growth velocity of the control group, Endostar group, cryoablation group and cryoablation plus Endostar group was (2.36.68±51.23)%, (220.02±30.61)%, (159.46±29.33)% and (103.34±25.50)%, respectively (P<0.01). The rate of apoptosis of the four groups was (21.67±2.34)%, (22.17±1.47)%, (38.33±1.37)% and (49.17±1.72)%, respectively (P<0.01). The MVD and the expression levels of VEGF of the cryoablation plus Endostar group were significantly lower than those of the other three groups (P<0.01). Statistical analysis revealed that a positive correlation existed between the express of VEGF and MVD. Conclusion: Endostar can obviously enhance the therapeutic efficacy of cryoablation on lung adenocarcinoma A549 in BALB/c nude mice. The underlying mechanisms may be the Endostar-inhibited angiogenesis through down-regulating the expression of VEGF, and the cooperative effect of Endostar and cryoablation on the promotion of tumor cell apoptosis. (authors)

  4. A third-generation matrix metalloproteinase (MMP) inhibitor (ONO-4817) combined with docetaxel suppresses progression of lung micrometastasis of MMP-expressing tumor cells in nude mice.

    Science.gov (United States)

    Yamamoto, Akihiko; Yano, Seiji; Shiraga, Minoru; Ogawa, Hirohisa; Goto, Hisatsugu; Miki, Toyokazu; Zhang, Helong; Sone, Saburo

    2003-03-01

    The lung is the common target organ of hematogenous metastasis that restricts the prognosis of cancer patients. MMPs play a pivotal role in metastasis by promoting tumor invasion and angiogenesis; therefore, a large number of MMPIs have been developed. Our purpose was to determine the therapeutic efficacy of a selective-spectrum MMPI, ONO-4817 (inhibits MMP-2 and MMP-9 but not MMP-1), against established lung micrometastasis in combination with a cytotoxic anticancer drug, DOC, in a nude mouse model. Human non-small cell lung cancer PC14PE6 (adenocarcinoma) or H226 (squamous cell carcinoma) cells, expressing MMP-2, MMP-9 and/or MMP-1, were injected i.v. into nude mice on day 0. Mice received a single injection of DOC on day 7 (after establishment of micrometastasis) and/or ONO-4817 mixed with food from day 7 to the end of experiments. Monotherapy with ONO-4817 or DOC inhibited formation of lung metastasis by PC14PE6 and H226 cells. In addition, combined use of ONO-4817 with DOC significantly suppressed the tumor burden of H226 and PC14PE6 cells in the lung and prolonged the survival of PC14PE6-bearing mice compared to ONO-4817 or DOC alone. These therapies did not affect the body weight or food intake of tumor-bearing mice. FIZ revealed that lung lesions, but not nontumor parenchyma of the lung, expressed gelatinolytic activity and that treatment with ONO-4817 abrogated the gelatinolytic activity in lung lesions. These results suggest that the combined use of MMPIs with cytotoxic anticancer drugs may be helpful in the control of established lung micrometastasis by tumor cells expressing MMPs. PMID:12516105

  5. 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.

  6. The effect of combining recombinant human tumor necrosis factor-alpha with local radiation on tumor control probability of a human glioblastoma multiforme xenograft in nude mice

    International Nuclear Information System (INIS)

    Purpose: To evaluate the antitumor activity of recombinant human tumor necrosis factor-alpha (rHuTNF-α) on a human glioblastoma multiforme (U87) xenograft in nude mice, and to study the effect of combining rHuTNF-α with local radiation on the tumor control probability of this tumor model. Methods and Materials: U87 xenograft was transplanted SC into the right hindleg of NCr/Sed nude mice (7-8 weeks old, male). When tumors reached a volume of about 110 mm3, mice were randomly assigned to treatment: rHuTNF-α alone compared with normal saline control; or local radiation plus rHuTNF-α vs. local radiation plus normal saline. Parameters of growth delay, volume doubling time, percentage of necrosis, and cell loss factor were used to assess the antitumor effects of rHuTNF-α on this tumor. The TCD50 (tumor control dose 50%) was used as an endpoint to determine the effect of combining rHuTNF-α with local radiation. Results: Tumor growth in mice treated with a dose of 150 μg/kg body weight rHuTNF-α, IP injection daily for 7 consecutive days, was delayed about 8 days compared to that in controls. Tumors in the treatment group had a significantly longer volume doubling time, and were smaller in volume and more necrotic than matched tumors in control group. rHuTNF-α also induced a 2.3 times increase of cell loss factor. The administration of the above-mentioned dose of rHuTNF-α starting 24 h after single doses of localized irradiation under hypoxic condition, resulted in a significant reduction in TCD50 from the control value of 60.9 Gy to 50.5 Gy (p 50 value in the treatment vs. the control groups

  7. 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.

  8. 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.

  9. 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.

  10. 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...

  11. 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

  12. Reversal of multidrug resistance with KR-30035: evaluated with biodistribution of Tc-99m MIBI in nude mice bearing human tumor xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Kyun; Lee, Jae Tae; Lee, Byung Ho [Kyungpook National Univ. Hospital, Taegu (Korea, Republic of)] [and others

    2001-06-01

    KR-30035 (KR), a new MDR reversing agent, has been found to produce a similar degree of increased Tc-99m MIBI uptake in cultured tumor cells over-expressing mdr1 mRNA compared to verapamil (VP), with less cardiovascular effects. We assessed the MDR-reversing ability of KR in vivo, and effects of various doses of KR on MIBI uptake in nude mice bearing P-glycoprotein (P-gp) positive (+) and P-gp negative (-) human tumor xenografts. P-gp (+) HCT15/CLO2 colorectal and P-gp (-) A549 non-small cell cancer cells were inoculated in each flank of 120 nude mice (20 mice x 6 groups). Group 1 (Gr1) mice received 10mg/kg Kr i.p. 3 times (x3); Gr2, 10mg/kg VP i.p. x3; Gr3, 10mg/kg KR i.p. x2 + 25mg/kg KR i.p. x1; Gr4, 10mg/kg KR i.p. x 2 + 50mg/kg i.p. x1; Gr5, 10mg/kg Kr i.p. x2 + 25mg/kg KR i.v. x1, GrC, controls. The mice were then injected with Tc-99m MIBI and sacrificed after 10 min, 30 min, 90 min and 240 min. Tumor uptake of MIBI (TU) in each group was compared. Tu in P-gp (+) and (-)tumors were both higher in Gr1 than Gr2. Washout rate between the 10 min and 4 hours was lower in Gr5 of P-gp (+) cell (0.93) than the control. Percentage increases in Tu were higher in P-gp (+) than P-gp (-) tumors with all KR doses. Pgp (+) TU were highest at 10 min (173% of GrC) and persisted up to 240 min (144%) in Gr3. Larger doses of KR resulted in a lesser degree of increase in P-gp (+) TU at 10 min (130% in Gr4 and 117% in Gr5) and 30 min (178%, 129%), but TU increased by time up to 240 min (177%, 196%). Heart and lung uptakes were markedly increased in Gr4 and Gr5 at 10 and 3C min, likely due to cardiovascular effects. No mice died. These data further suggest that KR that has significantly lower cardiovascular toxicity than verapamil can be used as an active inhibitor of MDR. Even a relatively low dose of KR significantly increased Tc-99m MIBI uptake in P-gp (+) tumors in vivo.

  13. In vivo 31P magnetic resonance spectroscopy and 1H magnetic resonance imaging of human bladder carcinoma on nude mice: effects of tumour growth and treatment with cis-dichloro-diamine platinum

    DEFF Research Database (Denmark)

    De Certaines, J D; Albrectsen, J; Larsen, V A;

    1992-01-01

    In vivo 31P NMR spectroscopy and 1H NMR imaging were used to examine the bladder T24B carcinoma in nude mice during untreated growth and in response to chemotherapy by Cis-dichloro-diammine-platinum (CDDP) at a dose of 8 mg/kg i.p. Untreated growth was associated with an increase of inorganic pho...

  14. The effect of the overall treatment time of fractionated irradiation on the tumor control probability of a human soft tissue sarcoma xenograft in nude mice

    International Nuclear Information System (INIS)

    Purpose: To study the impact of the overall treatment time of fractionated irradiation on the tumor control probability (TCP) of a human soft tissue sarcoma xenograft growing in nude mice, as well as to compare the pretreatment potential doubling time (Tpot) of this tumor to the effective doubling time (Teff) derived from three different schedules of irradiation using the same total number of fractions with different overall treatment times. Methods and Materials: The TCP was assessed using the TCD50 value (the 50% tumor control dose) as an end point. A total of 240 male nude mice, 7-8 weeks old were used in three experimental groups that received the same total number of fractions (30 fractions) with different overall treatment times. In group 1, the animals received three equal fractions/day for 10 consecutive days, in group 2 they received two equal fractions/day for 15 consecutive days, and in group 3 one fraction/day for 30 consecutive days. All irradiations were given under normal blood flow conditions to air breathing animals. The mean tumor diameter at the start of irradiation was 7-8 mm. The mean interfraction intervals were from 8-24 h. The Tpot was measured using Iododeoxyuridine (IudR) labeling and flow cytometry and was compared to Teff. Results: The TCD50 values of the three different treatment schedules were 58.8 Gy, 63.2 Gy, and 75.6 Gy for groups 1, 2, and 3, respectively. This difference in TCD50 values was significant (p pot (2.4 days) was longer than the calculated Teff in groups 2 and 3 (1.35 days). Conclusion: Our data show a significant loss in TCP with prolongation of the overall treatment time. This is most probably due to an accelerated repopulation of tumor clonogens. The pretreatment Tpot of this tumor model does not reflect the actual doubling of the clonogens in a protracted regimen

  15. Therapeutic effect of intratumoral injection of 188Re labeled stannic sulfur suspension in liver cancer. A comparative study with chemical agents in nude mice

    International Nuclear Information System (INIS)

    Objectives: Hepatoma is a common disease in some countries. The intervention therapy was used often for non-resectable tumor. The aim of our study was to compare the therapeutic effect of 188Re labeled stannic sulfur suspension to ethanol, acetic acid and the mixture of mitomycin and lipiodol for hepatoma in an animal model by intermittently injection. Methods: Forty-nine nude mice bearing hepatic cell carcinoma were divided into six groups. Group 1 (n=14) was intratumoral y injected with 0.1 ml saline. There were 5 experimental groups (group 2 to 6). Each group consisted of 7 mice. The mice in group 2 was intratumoral y injected with 18.5 MBq/0.1 ml 188Re labeled stannic sulfur suspension each, the mice in group 3 was injected intratumorally with 9.25 MBq/0.1 ml 188Re labeled stannic sulfur suspension each, group 4 was injected intratumorally with 0.1 ml ethanol, the mice in group 5 was injected with 0.1 ml 30% acetic acid and group 6 was injected intratumorally with 30 μg mitomycin in 0.1 ml lipiodol respectively. The mice were sacrificed 7 days post injection and the specimen were collected for pathological analysis. Results: The average tumor weight were 1.75±0.29 g (mean±S.D.), 0.26±0.03 g, 0.44±0.17 g, 1.38±0.25 g, 0.91±0.28 g, 1.38±0.28 g for group 1 to 6 respectively. Tumors in all experimental groups were significantly smaller than group 1 (control group, P88Re labeled stannic sulfur suspension injection had the smallest tumor weight among all the experimental groups (P188Re labeled stannic sulfur suspension shows better therapeutic effect. (authors)

  16. 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

  17. 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

  18. Bcl-2反义核酸治疗Burkitt'S淋巴瘤裸鼠模型的研究%Bcl-2 antisense therapy in athymic nude mice models of human burkitt's lymphoma

    Institute of Scientific and Technical Information of China (English)

    兰小鹏; 吕联煌; 林景娟; 陈英玉; 陈振兴; 张昭秀

    2002-01-01

    目的探讨Bcl-2反义核酸治疗Burkitt's淋巴瘤的疗效.方法将不含EB病毒的人类BL的细胞株-cA46移植到BAB/C裸鼠体内,采用体内体外交替传代的方式,建立BL裸鼠模型,并将荷瘤裸鼠随机分为反义治疗(A组)、无义对照(B组)和空白对照(C组)三个组,每组5只.A组注射Bcl-2反义核酸,B组注射无义寡核苷酸,C组不注射任何制剂;治疗剂量为5mg/kg/d,给药方式为瘤内局部注射,每天注射一次,连续给药15天.结果A组肿瘤的生长明显受到抑制,其中一只裸鼠的肿瘤消失,其余4只的瘤块明显小于B组和c组.A组对C组的肿瘤抑制率为89.5%;A组对B组的肿瘤抑制率为83.3%,二者无显著差异(P>0.05);而B组对C组的抑制率为36.9%与前二者差异非常显著(P<0.01).结论Bcl-2反义核酸对具有Bcl-2高表达的Burkitt's淋巴瘤具有明显的疗效,具有潜在的临床应用价值.

  19. 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.

  20. 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.

  1. 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.

  2. 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

    International Nuclear Information System (INIS)

    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

  3. 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.

  4. 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

  5. Preliminary study of MR diffusion weighted imaging in nude mice models of hepatic Bel7402 tumors after adenovirus-mediated cytosine diaminase-thymidine kinase gene therapy

    International Nuclear Information System (INIS)

    Objective: To study the characteristics of DWI in nude mice models of hepatic Bel7402 tumors after treatment with adenovirus-mediated cytosine diaminase-thymidine kinase (Ad. CD-TK) double suicide gene therapy, and then to identify whether DWI can be used for assessing curative effect of postoperative tumors. Methods: Thirty nude mice models of hepatic Bel7402 tumors were successfully created using cell suspension method, after the tumor grew to more than 1 cm in diameter, 20 tumor models were treated by intratumoral administration of Ad. CD-TK for 3 days plus intraperitonea (i.p.) treatment with 5-Fc and GCV for the duration of the study.Then they were randomly divided into three groups during 5-Fc and GCV treatment. The remaining 10 tumor models were used as controls. MR scanning were performed in 10th day before and after tumor implantation in all models by using EPI-SE series and SENSE technology for treatment group. Tumor volumes and ADC values were calculated pretreatment and posttreatment. Cell apoptosis were determined by using TUNEL method. Analyze the change of ADC and apoptosis index (AI) in different times, t test was used for comparison the difference of AI and ADC values respectively. Results: After 10 days,the tumor volumes of the treatment groups and controls were respectively (724.16 ±57.45) mm3, (754.57 ± 66.84) mm3, with no significant difference (t=0.488, P >0.05). The ADC values of the treatment groups were (0.98 ±0.11) × 10-3 mm2/s,the ones of the control groups were (0.68 ±0.04) × 10-3 mm2/s; AI of the treatment groups were (23.25 ±6.57)%, the ones of the control groups were (2.57 ± 0.58)%. There were difference in both groups (t=4.473, 5.874; P<0.01). Conclusion: DWI can be effectively to monitor the early pathological changes of hepatic Bel7402 tumors after Ad. CD-TK double suicide gene therapy, and provide experimental evidences for clinical application. (authors)

  6. Effects of 125I-Labeled Peptide Nuclear Acid Targeting Ki67 on the Growth of Implanted Human Renal Cell Carcinoma in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    JiacunChen; JunnianZheng; SongWu; HaibiaoLai; XiaoqingSun; JunjieLiu

    2004-01-01

    OBJECTIVE To investigate the potential of 125I-labeled anti-sense peptide nucleic acids (125I-AS-PNAs) to inhibit the expression of the Ki-67 gene and growth of implanted human renal carcinoma cells in nude mice.METHODS Anti-sense peptide nucleic acids (AS-PNAs) targeting the Ki67 gene were synthesized and labeled with 125I by the Chloraseptine-T method. Drugs including PNAs and 125I-AS-PNAs capsulated by cationic lipid were directly injected into tumors in nude mice. The Ki67 expression in tumors was detected by an immunohistochemical technique and Western blot. The apoptosis of tumor cells was detected by a TUNEL assay. Tumor volumes were measured every 3 days and tumor suppression rates were calculated at 12 days after treatment. Control groups were treated with AS-PNA, MMPNAs (mismatch PNAs) and 125I-Na.RESULTS The Ki67 expression rate of tumors treated by 125I-AS-PNAs [(15.3±1.8)%] was lower than that treated by AS-PNAs [(23.0±2.4)%] (P<0.01). The Ki67 protein production rate of tumors treated by 125I-AS-PNAs [(43.6±3.5)%] was lower than that treated by AS-PNAs [(59.7±2.3)%] (P<0.01 ). The apoptosis rate of tumors treated by 125I-AS-PNAs [(40.3±2.4)%] was higher than that treated by AS-PNAs [(31.1 ±2.0)%] (P<0.01). The volume of tumors treated by 125I-AS-PNAs [(330.4±57.8) mm3 ]was smallerthan that treated by AS- PNAs [(513.2±64.2 ) mm3] (P<0.01 ).CONCLUSION 125I-AS-PNAs targeted against the Ki67 gene have a greater inhibitory effect on the expression of the Ki67 gene and a larger apoptotic action on human renal carcinoma cells and can more efficiently inhibit tumor growth than AS-PNAs. 125I-AS-PNAs targeting the Ki67 gene may be a promising anti-sense/anti-gene radiotherapy method for treating renal cell carcinoma.

  7. Superparamagnetic iron oxide nanoparticles mediated 131I-hVEGF siRNA inhibits hepatocellular carcinoma tumor growth in nude mice

    International Nuclear Information System (INIS)

    Hepatocellular carcinoma (HCC) is a primary liver tumor and is the most difficult human malignancy to treat. In this study, we sought to develop an integrative approach in which real-time tumor monitoring, gene therapy, and internal radiotherapy can be performed simultaneously. This was achieved through targeting HCC with superparamagnetic iron oxide nanoparticles (SPIOs) carrying small interfering RNA with radiolabled iodine 131 (131I) against the human vascular endothelial growth factor (hVEGF). hVEGF siRNA was labeled with 131I by the Bolton-Hunter method and conjugated to SilenceMag, a type of SPIOs. 131I-hVEGF siRNA/SilenceMag was then subcutaneously injected into nude mice with HCC tumors exposed to an external magnetic field (EMF). The biodistribution and cytotoxicity of 131I-hVEGF siRNA/SilenceMag was assessed by SPECT (Single-Photon Emission Computed Tomography) and MRI (Magnetic Resonance Imaging) studies and blood kinetics analysis. The body weight and tumor size of nude mice bearing HCC were measured daily for the 4-week duration of the experiment. 131I-hVEGF siRNA/SilenceMag was successfully labeled; with a satisfactory radiochemical purity (>80%) and biological activity in vitro. External application of an EMF successfully attracted and retained more 131I-hVEGF siRNA/SilenceMag in HCC tumors as shown by SPECT, MRI and biodistribution studies. The tumors treated with 131I-hVEGF siRNA/SilenceMag grew nearly 50% slower in the presence of EMF than those without EMF and the control. Immunohistochemical assay confirmed that the tumor targeted by 131I-hVEGF siRNA/SilenceMag guided by an EMF had a lower VEGF protein level compared to that without EMF exposure and the control. EMF-guided 131I-hVEGF siRNA/SilenceMag exhibited an antitumor effect. The synergic therapy of 131I-hVEGF siRNA/SilenceMag might be a promising future treatment option against HCC with the dual functional properties of tumor therapy and imaging

  8. 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.

  9. 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...

  10. 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.

  11. 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

    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......Besides bone marrow, the kidneys are often dose-limiting organs in internal radiotherapy. The effects of high-linear energy transfer (LET) radiation on the kidneys after alpha-radioimmunotherapy (alpha-RIT) with the alpha-particle emitter, (211)At, were studied in nude mice by serial measurements...... 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...

  12. ABCG2-overexpressing S1-M1-80 cell xenografts in nude mice keep original biochemistry and cell biological properties

    Institute of Scientific and Technical Information of China (English)

    Fang Wang; Yong-Ju Liang; Xing-Ping Wu; Xiao-Dong Su; Li-Wu Fu

    2012-01-01

    S1-M1-80 cells,derived from human colon carcinoma S1 cells,are mitoxantrone-selected ABCG2-overexpressing cells and are widely used in in vitro studies of multidrug resistance (MDR).In this study,S1-M1-80 cell xenografts were established to investigate whether the MDR phenotype and cell biological properties were maintained in vivo.Our results showed that the proliferation,cell cycle,and ABCG2 expression level in S1-M1-80 cells were similar to those in cells isolated from S1-M1-80 cell xenografts (named xS1-M1-80 cells).Consistently,xS1-M1-80 cells exhibited high levels of resistance to ABCG2 substrates such as mitoxantrone and topotecan,but remained sensitive to the non-ABCG2 substrate cisplatin.Furthermore,the specific ABCG2 inhibitor Ko143 potently sensitized xS1-M1-80 cells to mitoxantrone and topotecan.These results suggest that S1-M1-80 cell xenografts in nude mice retain their original cytological characteristics at 9 weeks.Thus,this model could serve as a good system for further investigation of ABCG2-mediated MDR.

  13. Topical administration of Tetrasodium-Mesotetraphenyl-Porphinesulfonate (TPPS): correlations between drug penetration and depth of necrosis in skin of nude mice following red light irradiation

    International Nuclear Information System (INIS)

    The main side effect in photodynamic therapy is photosensitization of the patient's skin following systemic administration of the photosensitizing agent. In the case of superficial lesions, this problem can be avoided by topically applying the drug: in this way a local treatment can be performed. The photosensitizing properties of a 2% solution of TPPS (Tetrasodium-Tetraphenylpophinesulfonate) in a vehicle containing a penetration enhancer, Azone, on skin of nude mice has been tested. An aliquot of 0.1 ml/cm2 of the solution was painted on the skin overlying an s.c. implanted NMU-1 tumor. Subsequently, animals were sacrificed at different times after applications. Fluorescence microscopy revealed that TPPS penetration depth was related to time elapsed after application and to painting modalities. Solution penetration was enhanced by wiping with ether immediately before painting. Irradiation at 80 mW/cm2 for 20 min with a dye laser emitting at 640 nm, 4 h after TPPS applications, produced necrosis of the upper skin layers, up to 0.2 mm in depth. These findings suggest that topical TPPS administration, followed by laser irradiation, may be a suitable treatment modality for skin lesions involving epithelial layers, even though several aspects of this methodology need further investigation

  14. Biodistribution and γ imaging of 125I-labeled goat anti-human IgG polyclonal antibody in nude mice bearing human colon cancer xenografts

    International Nuclear Information System (INIS)

    The possibility of IgG secreted from tumor cells as a target for radioimmunoimaging and targeted therapy of cancers were investigated. Goat anti-human IgG polyclonal anti- body (GAHG) was radioiodinated using Iodogen method, and the in vitro stability and pharmacokinetics were evaluated. The biodistribution and γ imaging of 125I-GAHG were performed in nude mice bearing HT-29 human colon cancer xenografts. 125I-GAHG showed good in vitro stability, and its blood clearance was defined as a two-compartment model, with T1/2α and T1/2β were 1.19 h and 43.99 h, respectively. The tumor uptake of 125I-GAHG was higher than that of 125I-labeled normal goat IgG control (125I-GIgG). 125I-GAHG showed good tumor retention when injecting via intra-tumor. In the biodistribution study, the highest tumor uptake of 125I-GAHG was 6.71±2.19%ID/g at 72 h postinjection and the T/NT increased along with the postinjection time. The results show that 125I-GAHG have good tumor-specific uptake which may provide a novel idea for radioimmunoimaging and targeted therapy of cancers. (authors)

  15. Somatostatin receptor subtype 2-mediated scintigraphy and localization using 99mTc-HYNIC-Tyr3-octreotide in human hepatocellular carcinoma-bearing nude mice

    Institute of Scientific and Technical Information of China (English)

    Yong Li; Jian-Ming Si; Jun Zhang; Jin Du; Fan Wang; Bing Jia

    2005-01-01

    AIM: To investigate the uptake of 99mTc-HYNIC-Tyr3-octreotide (99mTc-HYNIC-TOC) in human hepatocellular carcinoma (HCC), which can provide the localizable diagnosis in hepatic carcinoma.METHODS: The expression of somatostatin receptor 2(SSTR2) messenger RNA (mRNA) in human HCC cell line HepG2 was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). Uptake of 99mTc-HYNIC-TOC was evaluated in the human HCC implanted into BALB/c nude mice. ANMIS2000 nuclear medicine analysis system was used to calculate the ratio of 99mTC uptake between tumor tissue and vital organs.RESULTS: We demonstrated the expression of SSTR2mRNA in human HCC cell line HepG2 by RT-PCR. The size of the RT-PCR products was 364 bp detected by sequence analysis of the human SSTR2 mRNA. Scintigraphy proved that 99mTc-HYNIC-TOC was uptaken in the tumor tissue,liver and kidney of the tumor-bearing mice.CONCLUSION: Based on expression of the SSTR2 mRNA in human NCC, 99mTc-NYNIC-TOC can markedly bind with and be uptaken by human HCC tissues as compared with normal liver tissue. The significant retention of radionuclide in kidney and bladder is probably related to non-specific peptide uptake in the tubulus cells of kidney and possibly due to excretion by kidney. Our results show that localizable diagnosis and targeting radiotherapy with radionuclidelabeled somatostatin analog for HCC are of great value to be further studied.

  16. 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

  17. 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.

  18. Luciferase bioluminescence imaging monitoring gene therapeutic effect of apoptosis-inducing ligand for lung cancer A549 cells nude mice transplantation tumor in vivo

    International Nuclear Information System (INIS)

    Objective: To detect the expression and effect of human tumor necrosis factor related apoptosis-inducing ligand (hTRAIL) in vivo,by using a novel double expressing adenoviral vector encoding hTRAIL and firefly luciferase (luc) gene (ad-luc-hTRAIL), in which luc was used as reporter gene. Methods: Lung cancer A549 cell xenografts in 16 nude mice models were established in subcutaneous inoculation way, the adenovirus vectors (ad-luc-hTRAIL, ad-hTRAIL, ad-luc) and phosphate buffer saline (PBS) (n=4) as control were injected into tumor respectively. The size of the tumor was measured at different time points (4, 7, 10, 14, 21, 28 d) after injection. The activity of luciferase in surface of the tumor was detected in vivo by using high-sensitivity cooled-charged coupled device (CCD) camera. The expression of hTRAIL was demonstrated by immunohistochemistry staining after sacrificing the animals at different time points, and immunohistochemical scores (IHS) were measured. The apoptosis rate of tumor cells was detected by using TUNEL and calculated. Analysis of variance, the paired t test and linear correlation analysis was used for the statistics. Results: The growing speed of tumour xenografts was more slowly in ad-luc-hTRAIL and ad-hTRAIL groups than PBS group (t=2.71, 2.72, P<0.05). The tumor volumes of ad-luc-hTRAIL, ad-hTRAIL, ad-luc and PBS groups 28 days after injection were (208.4 ± 42.3), (181.5 ±23.9), (403.1 ± 54.0) and (427.0 ± 59.3) mm3, respectively. There was no significant difference between ad-luc group and PBS group (t=2.07, P>0.05). The expression of luciferase in ad-luc-hTRAIL group reached its peak at 7th day (1.37 ± 1.04), and then decreased quickly. The IHS and apoptosis rate in ad-luc-hTRAIL and ad-hTRAIL groups reached their peaks at 7th day, the peak values of IHS were 6.25 ±2.06 and 6.5 ± 2.89, the peak values of apoptosis rate were (60.75 ± 8.06)% and (61.50 ± 8.47)%,respectively. The amount of luciferase expression (absolute number of

  19. 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.

  20. 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.

  1. 蜂毒素对裸鼠骨肉瘤治疗作用及安全性的实验研究%Experimental Study of Treatment and Safety of Melittin on Xenotransplanted Models of Nude Mice

    Institute of Scientific and Technical Information of China (English)

    高启龙; 杨峰; 姚亚民; 王怀章; 刘怀民; 陈永强

    2011-01-01

    目的:观察蜂毒素对骨肉瘤裸鼠移植瘤生长抑制作用及毒副反应.方法:建立裸鼠骨肉瘤原位移植瘤模型,随机分4组:生理盐水组,蜂毒素低、高剂量组,顺铂组.观察各组裸鼠骨肉瘤的体积和体质量抑制率;放射免疫法测定血清碱性磷酸酶活性;测定外周血常规、骨髓有核细胞数目;光镜观察心肝脾肺肾及肿瘤的病理组织学情况;电镜观察肿瘤细胞的微细结构.结果:蜂毒素低剂量组肿瘤体积和体质量抑制率分别为42.98%、39.03%,高剂量组分别为67.54%、48.66%,蜂毒素能明显降低血清AKP水平;光镜与电镜下蜂毒素能诱导骨肉瘤细胞凋亡或坏死;高剂量蜂毒素给药后可见扭体动作、精神不振、萎靡少动等毒性反应,肾脏病理切片可见肾小管间质扩张充血,肾细胞间隙炎性细胞集聚.蜂毒素各组骨髓及心肺肝脾等脏器未造成明显毒副反应.结论:蜂毒素具有抑制骨肉瘤裸鼠移植瘤生长的作用,并能促使肿瘤细胞凋亡或坏死,无明显的毒副作用.%Objective; To study the antitumor effects and toxic and side effects of Melittin on xenotransplanted models of nude mice. Methods: Xenotransplanted models of SD rat osteosarcoma cell UMR - 106 in the laevo - hind tibia of nude mice were established. Inoculated mice were randomly divided into normal saline group,positive controlgroup,low and high dose Melittin group. All the nude mice were sacrificed after treatment,the size and weight of tumor were measured and the tumor volumes and the inhibition rates of tumor were calculated,and peripheral blood cells,alkaline phosphatase and medullary karyote in one femur of nude mice were counted by hematology analyzer. Tumor tissues, myocardium, lung, liver, spleen, kidney and brain were sectioned, stained with hematoxylin and eosin.and then observed by light and electron microscope. Results-.The mice treated with high dose Melittin groups showed significantly smaller volume

  2. 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

  3. Preparation of 99Tcm labeled survivin mRNA antisense PNA and gene imaging in nude mice bearing lung carcinoma A549 xenografts

    International Nuclear Information System (INIS)

    Objective: To prepare the 99Tcm-survivin mRNA antisense peptide nucleic acid (PNA)and investigate its value as a gene imaging agent in tumor bearing mice and early diagnosis in tumor. Methods: Survivin mRNA antisense PNA and mismatch PNA were synthesized. Four amino acids (Gly- (D)Ala-Gly-Gly) and Aba (4-aminobutyric acid) were linked to the 5' end of PNA. Gly- (D)Ala-Gly-Gly served as a chelating moiety for strong chelation of 99Tcm and Aba acted as a spacer to minimize the steric hindrance. PNAs were labeled with 99Tcm by the ligand-exchange method. The labeling efficiency and radiochemical purity were measured by HPLC and ITLC methods. There were five BALB/c nude mice bearing human lung carcinoma (A549) in each of antisense PNA and mismatch PNA groups. Gene imaging of 99Tcm-survivin mRNA antisense and mismatch PNAs were performed at 1, 2 and 4 h post the injection, respectively, and the T/NT ratio was measured by the method of ROI. The statistical comparisons of average values were performed with the two-group t-test for independent sample by SPSS 13.0. Results: The product kept stable in vitro. The labeling efficiency of 99Tcm-survivin mRNA antisense PNA was (95.48 ±1.92)% and more than 85% after the incubation for 24 h in serum. The radiochemical purity was >95%. The labeling efficiency of mismatch PNA was similar to the antisense PNA. 99Tcm-survivin mRNA antisense PNA was especially uptaken by tumor lesion, and its accumulation reached the top at 4 h post the injection. T/NT ratios at 1, 2, and 4 h were 2.70 ± 0.28, 3.44 ± 0.35,4.21 ± 0.63, respectively. In the comparison, the T/NT ratio of 99Tcm-survivin mRNA mismatch PNA at 4 h (3.12 ±0.50) was significantly lower (t=2.918, P=0.019). Conclusions: 99Tcm-survivin mRNA antisense PNA has high labeling efficiency,good stability and no need of purification. Its characteristic of especial uptake by tumor lesion provides the potential value in early diagnosis of tumor. (authors)

  4. 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

    International Nuclear Information System (INIS)

    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). 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). 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. Application of an unrestricted ketogenic diet enriched with omega-3 fatty acids and MCT delayed tumour growth in a mouse xenograft model. Further

  5. Differentiation and functional maturation of bone marrow-derived intestinal epithelial T cells expressing membrane T cell receptor in athymic radiation chimeras

    International Nuclear Information System (INIS)

    The thymus dependency of murine intestinal intraepithelial lymphocytes (IEL) was studied in an athymic F1----parent radiation chimera model. IEL, although not splenic or lymph node lymphocytes, from athymic chimeras displayed normal levels of cells bearing the class-specific T cell Ag, CD4 and CD8; the TCR-associated molecule, CD3; and the Thy-1 Ag. Moreover, two-color flow cytometric analyses of IEL from athymic mice demonstrated regulated expression of T cell Ag characteristic of IEL subset populations from thymus-bearing mice. In immunoprecipitation experiments, surface TCR-alpha beta or TCR-gamma delta were expressed on IEL, although not on splenic lymphocytes, from athymic chimeras. That IEL from athymic chimeras constituted a population of functionally mature effector cells activated in situ, similar to IEL from thymus-bearing mice, was demonstrated by the presence of CD3-mediated lytic activity of athymic lethally irradiated bone marrow reconstituted IEL. These data provide compelling evidence that intestinal T cells do not require thymic influence for maturation and development, and demonstrate that the microenvironment of the intestinal epithelium is uniquely adapted to regulate IEL differentiation

  6. 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

  7. 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

  8. Imaging targeted at tumor with {sup 188}Re-labeled VEGF{sub 189} exon 6-encoded peptide and effects of the transfecting truncated KDR gene in tumor-bearing nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Qin Zhexue; Li Qianwei; Liu Guangyuan; Luo Chaoxue; Xie Ganfeng; Zheng Lei [Department of Nuclear Medicine, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Huang Dingde [Department of Nuclear Medicine, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China)], E-mail: huangdde@tmmu.edu.cn

    2009-07-15

    Introduction: Planar imaging of {sup 188}Re-labeled vascular endothelial growth factor (VEGF){sub 189} exon 6-encoded peptide (QKRKRKKSRYKS) with single photon emission computed tomography (SPECT) in tumor-bearing nude mice and effects of the transfecting truncated KDR gene on its imaging were investigated, so as to provide a basis for further applying the peptide to tumor-targeted radionuclide treatment. Methods: QKRKRKKSRYKS, coupling with mercaptoacetyltriglycine (MAG{sub 3}) chelator was labeled with {sup 188}Re; then in vivo distribution, planar imaging with SPECT and blocking experiment in tumor-bearing nude mice were analyzed. Recombinant adenovirus vectors carrying the truncated KDR gene were constructed to transfect tumor tissues to evaluate the effects of truncated KDR on the in vivo distribution and tumor planar imaging of {sup 188}Re-MAG{sub 3}-QKRKRKKSRYKS in tumor-bearing nude mice. Results: The labeled peptide exhibited a sound receptor binding activity. Planar imaging with SPECT demonstrated significant radioactivity accumulation in tumor 1 h after injection of the labeled peptide and disappearance of radioactivity 3 h later. Significant radioactivity accumulation was also observed in the liver, intestines and kidneys but was not obvious in other tissues. An hour after injection of the labeled peptide, the percentage of the injected radioactive dose per gram (%ID/g) of tumor and tumor/contralateral muscle tissues ratio were 1.98{+-}0.38 and 2.53{+-}0.33, respectively, and increased to 3.08{+-}0.84 and 3.61{+-}0.59 in the group transfected with the truncated KDR gene, respectively, and radioactivity accumulation in tumor with planar imaging also increased significantly in the transfection group. Conclusion: {sup 188}Re-MAG{sub 3}-QKRKRKKSRYKS can accumulate in tumor tissues, which could be increased by the transfection of truncated KDR gene. This study provides a basis for further applying the peptide to tumor targeted radionuclide imaging and

  9. Enhancement of bone marrow allografts from nude mice into mismatched recipients by T cells void of graft-versus-host activity.

    OpenAIRE

    Lapidot, T; Lubin, I; Terenzi, A; Faktorowich, Y; Erlich, P; Reisner, Y

    1990-01-01

    Transplantation of 8 x 10(6) C57BL/6-Nu+/Nu+ (nude) bone marrow cells into C3H/HeJ recipients after conditioning with 8 Gy of total body irradiation has resulted in a markedly higher rate of graft rejection or graft failure compared to that found in recipients of normal C57BL/6 or C57BL/6-Bg+/Bg+ (beige) T-cell-depleted bone marrow. Mixing experiments using different numbers of nude bone marrow cells with or without mature thymocytes (unagglutinated by peanut agglutinin) revealed that engraft...

  10. In vivo imaging and specific targeting of P-glycoprotein expression in multidrug resistant nude mice xenografts with [{sup 125}I]MRK-16 monoclonal antibody

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Andrew M.; Rosa, Eddie; Mehta, Bippin M.; Divgi, Chaitanya R.; Finn, Ronald D.; Biedler, June L.; Tsuruo, Takashi; Kalaigian, Hovannes; Larson, Steven M

    1995-05-01

    Multidrug resistance (MDR) in tumors is associated with P-glycoprotein (Pgp) expression. In vivo quantitation of Pgp may allow MDR to be evaluated noninvasively prior to treatment planning. The purpose of this study was to radiolabel MRK-16, a monoclonal antibody that targets an external epitope of P-glycoprotein, and perform in vivo quantitation of P-glycoprotein in a MDR xenograft nude mouse model. MRK-16 was labeled with {sup 125}I by the iodogen method, with subsequent purification by size exclusion chromatography. Groups of 10 Balb/c mice were each xenografted with colchicine-resistant or -sensitive neuroblastoma cell lines, respectively. Whole body clearance and tumor uptake over time was quantitated by gamma camera imaging, and biodistribution studies were performed with [{sup 125}]MRK-16 and an isotype matched control antibody, A33. Quantitative autoradiography and immunohistochemistry analysis of tumors was also evaluated to confirm specific targeting of [{sup 125}I]MRK-16. Peak tumor uptake was at 2-3 days post-injection, and was significantly greater in resistance compared to sensitive tumors (mean % injected dose/g {+-} SD) (18.76 {+-} 2.94 vs 10.93 {+-} 0.96; p < 0.05). Quantitative autoradiography verified these findings (19.13 {+-} 0.622 vs 12.08 {+-} 0.38, p < 0.05). Specific binding of [{sup 125}I]MRK-16 was confirmed by comparison to [{sup 131}I]A33 in biodistribution studies, and localized to cellular components of tissue stroma by comparison of histologic and autoradiographic sections of sensitive and resistant tumors. Immunoblot analysis demonstrated a 4.5-fold difference in P-glycoprotein expression between sensitive and resistant cell lines without colchicine selective pressure. We conclude that in vivo quantitation of P-glycoprotein in MDR tumors can be performed with [{sup 125}I]MRK-16. These findings suggest a potential clinical application for radiolabeled MRK-16 in the in vivo evaluation of multidrug resistance in tumors.

  11. 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.

  12. Inhibition of metastasis to lung of a human nasopharyngeal carcinoma cell line CNE-2L2 transfected with pRc/CMV-antisense 6A8 cDNA in nude mice

    Institute of Scientific and Technical Information of China (English)

    张立新; 刘玉琴; 马凤蓉; 顾蓓; 史耕先; 赵雪梅; 李波; 高进; 赵方萄; 张淑珍; 李国燕; 王讯; 朱立平

    1999-01-01

    The growth of CNE-2L2 cell, a cloned line of human nasopharyngeal carcinoma with a high potentiality of metastasis to lung was inhibited to a certain extent after transfection with a recombinant antisense expression vector of a cDNA encoding a human α-mannosidase (pRc/CMV-antisense 6A8 cDNA)( the Genbank accession number of 6A8 cDNA is U37248) in comparison with that of the cell transfected with the Mock and of the wild cell. Two months after a subcutaneous inoculation of CNE-2L2 cell into the axilla of nude mice metastatic lesions in the lung were observed in 9/10 mice (90%) with grade Ⅲ in 8 mice and grade Ⅱ in one mouse in the wild cell group, in 6/8 mice (75%) with grade Ⅲ in one mouse, grade Ⅱ in 2 mice and grade Ⅰ in 3 mice in the Mock-transfection group, in only 3/10 mice (30%) with all grade Ⅰ in pRc/CMV-antisense 6A8 cDNA-transfection group.

  13. 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

  14. Dose-dependent effect of 17 beta-estradiol determined by growth curves and flow cytometric DNA analysis of a human breast carcinoma (T61) grown in nude mice

    DEFF Research Database (Denmark)

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

    1985-01-01

    An estrogen and progesterone receptor-positive human breast carcinoma (T61) grown in nude mice was exposed to 1.0, 0.1, 0.01, and 0.001 mg 17 beta-estradiol. These doses resulted in serum peak concentrations (day 1) of estradiol ranging from 3.5 X 10(-8) to 6.9 X 10(-10) M. The effect of the trea...... are a reflection of the estradiol-induced cell destruction. Since no tumor growth stimulation could be observed even at very low serum estradiol concentrations, the T61 human breast carcinoma may represent a new aspect in the study of human breast cancer....... fraction of polyploid cells. The results suggest that estradiol induces a dose-dependent cell killing effect in the T61 human breast carcinoma. The correlation between the treatment-induced growth delay and the effect on the cell cycle distribution indicates that the changes in the cell cycle......An estrogen and progesterone receptor-positive human breast carcinoma (T61) grown in nude mice was exposed to 1.0, 0.1, 0.01, and 0.001 mg 17 beta-estradiol. These doses resulted in serum peak concentrations (day 1) of estradiol ranging from 3.5 X 10(-8) to 6.9 X 10(-10) M. The effect...

  15. Establishment of lung metastasis model of human primary malignant melanoma in the small intestine in nude mice%人原发性小肠恶性黑色素瘤裸鼠肺转移模型的建立

    Institute of Scientific and Technical Information of China (English)

    张宁; 脱帅; 杨波; 刘秋珍

    2009-01-01

    目的 建立原发性小肠恶性黑色素瘤肺转移动物模型.方法 采用人原发性小肠恶性黑色素瘤肺转移瘤的新鲜瘤组织块植入裸鼠小肠黏膜层内,当裸鼠体内形成肺转移瘤后重复筛选4次,再将肺转移瘤植入另一只裸鼠小肠黏膜行鼠问连续传代.观察原位移植成瘤率和转移率,进行形态学、染色体核型和流式细胞仪分析.结果 建成的人原发性小肠恶性黑色素瘤裸鼠肺转移模型命名为HSIM-0601,瘤细胞胞质内可见大量黑色素颗粒及黑色素复合体,S-100、HMB-45呈阳性表达.染色体数57~59条;流式细胞DNA指数值1.49,均为异倍体.HSIM-0601已传至26代,共移植裸鼠173只,成瘤率和液氮冻存复苏成活率均为100%.肺转移率为100%(173/173),淋巴结转移率为61.3%(106/173).结论 首次成功地建立了人原发性小肠恶性黑色素瘤裸鼠原位移植肺转移模型HSIM-0601.完整地模拟了人小肠恶性黑色素瘤患者的自然临床病理过程,为研究原发性小肠恶性黑色素瘤肺转移机制和抗转移治疗提供了理想的动物模型.%Objective To provide an ideal animal model for exploring the pathogenesis and experimental treatment of malignant melanoma in the small intestine.Methods Fresh tissue of lung metastatic lesions from patients with malignant melanoma of the smallintestine were transplanted into mucosa of the small intestine in nude mice.After 4 times of screening.the tissue of the lung metastatic lesions from the nude mice were transplanted into the small intestine of additionat nude mice.Tumorgenecity and metastasis of transplanted tumors were observed,and were analyzed by morphology,karyotype and flow cytometry.Results A lung metastatic model of human primary malignant melanoma of the small intestine in nude mice was successfully constructed and named HSIM-0601.Massive melanin granules and melanin complex were seen in cytoplasm of tumor cells.Immunohistochemical straining of S-100 and

  16. 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

  17. A dominated and resistant subpopulation causes regrowth after response to 1,3-bis(2-chloroethyl)-1-nitrosourea treatment of a heterogeneous small cell lung cancer xenograft in nude mice

    DEFF Research Database (Denmark)

    Aabo, K; Roed, H; Vindeløv, L L;

    1994-01-01

    ) and a resistant (NYH) tumor were used to produce mixed solid tumors in nude mice. Mixtures of 592/NYH (9:1 and 1:1) were inoculated s.c. After 3-4 weeks of tumor growth, the mice were stratified according to tumor size and randomized to treatment with BCNU 40 mg/kg i.p. (10% of lethal dose) or no treatment. Tumor...... growth curves were used to calculate the effect of the treatment, and changes in the relative proportions of 592 and NYH in the mixed tumors were monitored by flow cytometric DNA analysis by which the two cell lines were distinguishable due to differences in DNA content. A significant response...... was eradicated. These results indicate that resistant and undetectable (dominated) subpopulations in heterogeneous tumors may be responsible for relapse and that the fractional size and the growth characteristics of the resistant subpopulation may determine the magnitude of the clinical response to cytotoxic...

  18. 蜂毒素对人肝癌细胞裸鼠移植瘤生长的影响及其部分机制%Effect and partial mechanisms of melittin on human hepatocellular carcinoma cells xenograft in nude mice

    Institute of Scientific and Technical Information of China (English)

    王朋景; 李俊; 黄艳; 吴宝明

    2011-01-01

    Objective To study the effects of melittin on the growth of human hepatocellular carcinoma HepG-2 cells xenograft in BALB/c nude mice and explore its possible mechanism of antitumor action in vivo. Methods The nude mice with HepG-2 cell xenografts were randomly divided into control group, melittin group(1 ,2,4 mg/ kg ), 5-FU group( 2 mg/kg ), administered for 10 days. The mice were killed 2 days after treatment. The xenograft tumor growth in mice was measured after injection of melittin. Tumor volume , tumor weight and spleen index were calculated. The levels of interlukin-l( IL-1 ) and tumor necrosis factor-a( TNF-α ) in serum of nude mice were detected by enzyme-linked immunosorbent assay( ELISA ). The apoptosis index of tumor tissue was measured by TUNEL method. Results While injected with l,2 and 4 mg/kg of melittin, the inhibitory rate of tumor growth were 41. 2% . 60. 9% and 71. 0% , respectively. The tumor volume of xenograft in nude mice was significantly smaller in melittin groups than that in control group( P <0. 01 ). Levels of IL-I and TNF-a. the apoptosis index in the melittin groups were significantly higher than those in the control group( P <0. 05 .P <0. 01 ) . Conclusion Melittin could inhibit the growth of tumor in vivo. which might be related to reinforcement of the immunity of mice and the apoptosis of tumor cells.%目的 探讨蜂毒素对人肝癌HepG-2细胞株裸鼠移植瘤的抑制作用.方法 建立人肝癌HepG-2细胞裸鼠皮下移植瘤模型,随机分为模型组、蜂毒素组(1、2、4 mg/kg)和氟尿嘧啶 (5-FU,2 mg/kg) 组,各组腹腔注射给药10 d,用药结束后隔天处死动物.观察蜂毒素腹腔注射对人肝癌细胞在裸鼠体内生长的的影响,计算各组裸鼠肿瘤的大小、瘤重及脾指数.ELISA法检测裸鼠血清白介素-1(IL-1)及肿瘤坏死因子-α(TNF-α).TUNEL法检测裸鼠移植瘤细胞凋亡情况.结果 蜂毒素(1、2、4 mg/kg)组的抑瘤率分别为41.2%、60.9%、71.0%,蜂

  19. Thymus-dependent sensitizing processes involved in the induction of CNS disease in mice by parainfluenza type 1 virus

    International Nuclear Information System (INIS)

    Parainfluenza type 1 virus injected intracerebrally into adult mice induced a mononuclear cell infiltration in the subarchnoidal and perivascular spaces, exudation of inflammatory cells into parenchymal tissue and preferential chronic degeneration of white matter. No correlation was found between the severity of the central nervous system (CNS)2 lesions and the levels of circulating hemagglutination inhibition antibody. Inactivation of the virus by ultraviolet light (uv) did not affect the ability of the virus to produce the CNS lesions in these mice. As part of an inquiry into the mechanisms involved in the production of CNS lesions, the present study reports the response of athymic nude mice and sensitization through prior CNS exposure to virus antigen in immunocompetent mice. (U.S.)

  20. Effects of Melittin on Angiogenesis of Human Hepatocellular Carcinoma BEL-7402 Cell Xenografts in Nude Mice%蜂毒素对人肝癌裸鼠移植瘤的抗血管生成作用

    Institute of Scientific and Technical Information of China (English)

    宋长城; 吕祥; 程彬彬; 李柏; 凌昌全

    2011-01-01

    Objective To study the effects of Melittin on the growth and angiogenesis of human hepatocellular carcinoma BEL-7402 cells xenograft in BALB/C nude mice. Methods The xenografts derived from BEL-7402 cells were established in BALB/C nude mice. The xenograft tumor growth in mice was measured after introtumoral injection of Melittin. SABC method of immunohistochemistry was used to measure microvessel density ( MVD ) and the expression of basic fibroblast growth factor ( Bfgf ),Hypoxia inducible factor-lct( HIF-lct ) and nuclear factor Kb ( NF-Kb ). Results When injected introtumorally with 40、60 and 80 μg/kg of Melittin, the relative tumor proliferation rate were 48. 78% 、38. 33% and 33. 82% respectively. The tumor volume of xenograft of nude mice was significantly smaller in Melittin groups than in normal saline ( NS ) control group ( P <0.01 ). MVD of Melittin-treated groups was significantly lower than that of NS control group ( P < 0.01 ). Immunohistochemical technique showed the expression of Bfgf,HIF-1α and NF-Kb of Melittin-treated groups was down-regulated significantly as compared with NS control group ( P <0.01 ). Conclusion Melittin could inhibit the growth of human hepatocellular carcinoma BEL-7402 cell xenografts in Nude Mice. The inhibition of angiogenesis by the down-regulation of b-FGF, HIF-1α and NF-Kb expression might play a key role in the anti-neoplastic effect of Melittin.%目的 探讨蜂毒素对人肝癌裸鼠移植瘤生长的影响及其抗血管生成作用.方法 建立人肝癌裸鼠皮下移植瘤模型,观察蜂毒素对肿瘤生长的影响.采用免疫组织化学法,检测肿瘤组织微血管密度 (microvessel density,MVD) 及碱性成纤维细胞生长因子 (basic fibroblast growth factor,bFGF)、缺氧诱导因子-1α (hypoxia inducible factor-1α,HIF-1α) 和核转录因子κB (nuclear factor κB,NF-κB) 的水平.结果 蜂毒素低、中、高剂量组相对肿瘤增殖率分别为 48.78%、38.33% 和33.82%.与生理

  1. 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...

  2. Influences of androgen on the growth of human prostate cancer PC-3M model in nude mice and the changes of the androgen receptor levels and protein kinase C activity

    International Nuclear Information System (INIS)

    Nude mice bearing transplanted human prostate cancer cell line PC-3M were treated with male sex hormone. Results demonstrated that low dose of testosterone propionate (TP) (50 mg/kg wt.) stimulated the tumor growth, and the androgen receptor (AR) levels and protein kinase C (PKC) activity were elevated in the tumor tissue. On the contrary higher dose of TP (400 mg/kg wt.) inhibited the tumor growth, and the AR level and PKC activity in tumor tissue were reduced significantly. These results showed that TP has a biphasic effect on the growth of human prostate cancer PC-3M cell line. The mechanism of the biphasic effect and its relationship between AR and PKC levels are also discussed

  3. 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

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

    International Nuclear Information System (INIS)

    Introduction: The aim of the study was to evaluate the uptake of [18F]-1-deoxy-1-fluoro-scyllo-inositol ([18F]-scyllo-inositol) in human breast cancer (BC) and glioma xenografts, as well as in inflammatory tissue, in immunocompromised mice. Studies of [18F]-2-fluoro-2-deoxy-D-glucose ([18F]-FDG) under the same conditions were also performed. Methods: Radiosynthesis of [18F]-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 [18F]-scyllo-inositol and [18F]-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 [18F]-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/μmol at end of synthesis). Uptake of [18F]-scyllo-inositol was greatest in MDA-MB-231 BC tumours and was comparable to that of [18F]-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 [18F]-scyllo-inositol in inflammation was lower than [18F]-FDG. While uptake of [18F]-scyllo-inositol in intracranial U-87 MG xenografts was significantly lower than [18F]-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 [18F]-scyllo-inositol was successfully visualized by PET imaging in human BC and glioma xenografts, with lower accumulation in inflammatory tissue than [18F]-FDG. The tumour-to-brain ratio of [18F]-scyllo-inositol was also significantly higher than that of [18F]-FDG for visualizing intracranial glioma xenografts in NOD SCID mice, giving a better contrast. -- Graphical Abstract: Display Omitted

  5. 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

  6. 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.

  7. 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...... lymphocyte counts in the thoracic duct lymph. Finally, the inguinal lymph nodes contained germinal centres. Xenogeneic and allogeneic thymus transplants did not induce constant changes in the parameters observed compared with the untreated nudes. No clear difference was observed between the adrenalectomized...

  8. Reversible control of oestradiol-stimulated growth of MCF-7 tumours by tamoxifen in the athymic mouse.

    OpenAIRE

    Iino, Y.; Wolf, D. M.; Langan-Fahey, S. M.; Johnson, D.A.; Ricchio, M.; Thompson, M E; Jordan, V C

    1991-01-01

    We investigated the ability of high concentrations of oestradiol to reverse the growth inhibitory action of tamoxifen on MCF-7 breast cancer cells in vivo. Tamoxifen inhibits the oestradiol stimulated growth of MCF-7 cells in athymic mice. Using a sustained release preparation of tamoxifen we consistently achieved serum concentrations of the drug in the 40 to 50 ng ml-1 range and much higher levels in tissues. These serum levels are sufficient to inhibit the oestrogen stimulated growth of MCF...

  9. 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 changes......, and antibody responses. The rats challenged with P. aeruginosa alginate beads experienced a generally more severe lung pathology and the antibody responses were more homogeneous with less dispersion as compared to the rats having free live P. aeruginosa bacteria. In general, manifestations were more severe...... in the athymic rats compared to the normal rats. It is, however, notable that the athymic rats developed similar microscopic lung manifestations as the normal rats when given a large number of P. aeruginosa in the beads, with dense accumulation of neutrophil granulocytes and microcolonies comparable...

  10. Inhibition and SAHA combined with DDP on cervical cancer xenografts in nude mice%SAHA联合顺铂对裸鼠宫颈癌抑瘤作用及其机制

    Institute of Scientific and Technical Information of China (English)

    田志华; 郝钢华; 侯晓静; 邢军

    2015-01-01

    目的:观察组蛋白去乙酰化酶抑制药SAHA联合顺铂(cis-diamminedichloroplatinum,DDP)抑瘤作用及机制。方法饲养40只Balb/c-nu/nu雌性裸鼠,细胞悬液皮下注射法构建人宫颈癌SiHa细胞株裸鼠移植瘤模型,当移植瘤8~10 mm大小时,36只荷瘤裸鼠被随机分为6组(对照组、25 mg/kg SAHA组、50 mg/kg SAHA组、5 mg/kg DDP组、25 mg/kg SAHA+DDP组、50 mg/kg SAHA+DDP组),给药第17天拉颈处死裸鼠。对移植瘤的湿重、瘤体积、肿瘤生长抑制率输入SPSS 19.0软件进行统计学分析。结果与各对照组比,联合组显示出最大程度的肿瘤体积的缩小及肿瘤生长抑制率增加(P<0.05)。结论 SAHA与DDP联合治疗宫颈癌,其作用机制可能与组蛋白去乙酰化酶1(histone deacetylase 1,HDAC1)蛋白水平下调有关。%[Absrract]ObjectiveTo study the effect of histone deacetylase inhibitor SAHA (N-Hydroxy-N-phenyloctanediamide) combined with cis-diamminedichloroplatinum (DDP) on cervical cancer cells (SiHa) in nude mice.MethodsCervical cancer cell suspension was subcutaneously injected into 40 nude mice to establish cervical cancer model. When the transplanted tumor was about 8 mm in length, 36 mice with tumor in similar size were selected and divided into six groups (control group, 25 mg/kg SAHA group, 50 mg/kg SAHA group, 5 mg/kg DDP group, 25 mg/kg SAHA+DDP group) , and 50 mg/kg SAHA+DDP group. Nude mice were killed on the 17th day. Wet weight of tumor, inhibitory rate and tumor volume were collected. SPSS 19.0 software was used for statistical analysis.ResultsCompared with the control group, the DDP plus SAHA group showed superiority in inhibiting tumor growth (P<0.05).ConclusionThe effects from SAHA and DDP might be associated with down-regulating expressions of HDAC1 protein.

  11. 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.

  12. Inhibition of rhabdomyosarcoma in nude mice by TNF related apoptosis inducing ligant combined with diamminedichloroplatinum%TRAIL蛋白联合顺铂抑制裸鼠横纹肌肉瘤生长的实验研究

    Institute of Scientific and Technical Information of China (English)

    苗金红; 徐玉生; 王家祥

    2009-01-01

    目的 探讨肿瘤坏死因子相关凋亡诱导配体(TRAIL)蛋白及联合顺铂对RD人横纹肌肉瘤裸鼠移植瘤生长的影响及其可能的作用机制.方法 将RD人横纹肌肉瘤细胞制成细胞悬液后接种于裸鼠皮下,成瘤后将裸鼠随机分4组:生理盐水组、TRAIL组、顺铂组及两药联合组.检测裸鼠的重量和体积;测定裸鼠肝功能、尿素氮及肌酐;另取肝肾组织进行切片,HE染色观察;用FCM方法检测肿瘤组织Fas表达;用RT-PCR检测DR4和DR5mRNA的表达.结果 各组裸鼠实验前后的体重变化无明显差异;DDP组和TRAIL+DDP组裸鼠的血清丙氨酸转氨酶高于生理盐水组,DDP组与TRAIL+DDP组裸鼠尿素氮和肌酐值比较,无明显差异;TRAIL组、DDP组和TRAIL+DDP组移植瘤的重量均明显降低;各组肝肾组织切片观察未见明显改变;TRAIL+DDP组Fas表达水平高于DDP组和TRAIL组;DDP组和TRAIL+DDP组裸鼠移植瘤细胞的DR5mRNA、DR4mRNA表达水平明显升高,而TRAIL组没有明显改变.结论 TRAIL和顺铂对裸鼠移植瘤的生长有抑制作用,联用有协同作用.%Objective To observe the effect of inhibition of rhabdomyosareoma in nude mice treated by TNF related apoptosis inducing ligant (TRAIL) combined with diamminedichloroplatinum (DDP), and try to explore the mechanism. Methods Human rhabdomyosareoma cells were inoculated in nude mice subcutaneouly. The nude mice were randomly divided into 4 groups: mice in the TRAIL groups accepted TRAIL injection with the dose of 10μg/Kg; mice in the DDP group accepted DDP in-jection with the dose of 3 mg/kg; mice in the TRAIL + DDP group accepted TRAIL and DDP injection with the abovementioned doses; mice in the control group accepted normal saline injection. The chan-ges of tumor weight and size and the tumor growth inhibition rate were recorded. The functions of liv-er and kidney were evaluated. HE staining was utilized to observe the morphologic changes of livers and kidneys. The expression

  13. 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.

  14. Rab25基因对乳腺癌裸鼠移植瘤生长的影响%Effects of Rab25 gene on the growth of implanted tumor of breast cancer in nude mice

    Institute of Scientific and Technical Information of China (English)

    张小彬; 陆云飞; 沈桂鑫; 吴非

    2014-01-01

    目的:建立一系列Rab25表达水平不同的乳腺癌细胞裸鼠移植瘤模型,观察不同水平Rab25表达对乳腺癌裸鼠移植瘤的影响。方法:通过分别上调及沉默Rab25基因在乳腺癌细胞中的表达,建立Rab25表达水平不同的乳腺癌细胞的裸鼠移植瘤模型,测量肿瘤体积,绘制肿瘤生长曲线,检测肿瘤组织中Rab25表达差异。结果:Rab25转染组较干扰组、原株细胞组及空质粒组对裸鼠细胞致瘤能力明显增强。转染组裸鼠瘤体中Rab25 mRNA表达明显增强,而干扰组瘤体Rab25 mRNA表达明显减弱。结论:Rab25为促癌基因,其高表达可直接增强乳腺癌细胞的增殖侵袭能力,而RNA干扰技术有可能为乳腺癌的肿瘤靶向和基因治疗提供新的思路。%Objective To establish nude mice models with implanted tumor of breast cancer cells with different expressing levels of Rab25 gene , and to observe the effects of Rab25 gene on the growth of implanted tumor. Methods Nude mice models with implanted tumor of breast cancer cells with different expressing levels of Rab25 gene were constructed through up-regulating or silencing the expression of Rab25 gene in breast cancer cells. The size of implanted tumor was measured, the growth curve of tumor was portrayed, and the expression of Rab25 gene in tumor tissues was detected. Results The tumorigenic effect on nude mice was the strongest and the highest in Rab25 up-regulating group , as compared to those in Rab25 interference group , original cells group, and Rab25 empty plasmid group. The expression of Rab25 mRNA in interference group was significantly reduced. Conclusions Rab25 is a cancer-promoting gene , its high expression could directly enhance the proliferation of breast cancer cells. RNA interference technology had the potential to provide new ideas for tumor targeting and gene therapy for breast cancer.

  15. 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

  16. 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

  17. 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

  18. 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

  19. STAT1基因转染对人肺腺癌裸鼠移植瘤生长的影响%Effect of STAT1 gene transfection on human lung carcinoma xenograft growth in nude mice

    Institute of Scientific and Technical Information of China (English)

    马源; 陈俊杰; 陈成水; 王梦怡; 李晓丹; 陈超蕾; 陈乐夫; 余静; 周伶俐

    2013-01-01

    Objective:To investigate the effects of signal transduction and activators of transcription 1 in the progression of lung cancer in vivo.Methods:STAT1 gene or empty vectors were transfected into NCL-H 1299 cells with plasmids constructed as previous.Nude mice were transplanted subcutaneously with H 1299 cells,H1299 cells transfected with empty vectors,H1299 stably transfected with STAT1,respectively.The size of tumor was examined by caliper every two days.Five weeks after inoculation,the tumors were resected and weighed.Western blot was used to detect the level of STAT1 protein in tumor tissues.Results:Both volume and weight of the tumor in the STAT1 transfected group were less than those in the other groups (P<0.05).Western blot revealed that the protein level of STAT1 and phosphorylated-STAT1 in STAT1 transfected group were rises notably.Conclusion:The recombinant plasmid STAT1 can significantly suppress the tumor growth of human lung cancer cell NCL-H1299 subcutaneous xenografts in nude mice through up-regulate of STAT1 expression.%目的:探讨信号转导和转录活化因子1 (signal transduction and activators of transcription 1,STAT1)基因转染对肺癌移植瘤生长的影响.方法:构建稳定转染STAT1基因(转染组)及空载体(空载体组)的肺腺癌NCL-H1299细胞,使用未转染的细胞及上述两种转染细胞分别建立裸鼠皮下移植瘤模型,连续观察并测量肿瘤生长情况,Western blot法检测肿瘤组织内STAT1活化情况.结果:STAT1基因转染组裸鼠移植瘤接种33 d后瘤体积及瘤重小于未转染组及空载体组(均P<0.05).Western blot检测结果提示STAT1转染组的肿瘤组织STAT1表达及磷酸化水平均明显升高.结论:STAT1基因转染可提高移植瘤组织内STAT1活化水平,并对肿瘤生长起抑制作用.

  20. 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.

  1. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, R.E.; Lefkovits, I.; Soeederberg, 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.

  3. 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.

  4. 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.

  5. The effect of circulating antigen on the biodistribution of the engineered human antibody hCTM01 in a nude mice model

    International Nuclear Information System (INIS)

    Clinical studies are currently underway to assess the biodistribution and therapeutic potential of the genetically engineered human antibody hCTM01 directed against polymorphic epithelial mucin (PEM) in patients with ovarian carcinoma. The present study was undertaken to assess the effect of circulating PEM antigen on the biodistribution of the anti-PEM antibody in mice bearing MUC-1 transfected adenocarcinoma cell lines. Tumour xenografts were established from three cell lines: 413-BCR, which expressed antigen on the cell surface and also shed antigen into the circulation, E3P23, which expressed the antigen but did not shed into the circulation, and a negative control (410.4 MUCI). Groups of five mice were injected with 1.0 mg/kg antibody, imaged after 72 h and then sacrificed, followed by assay of tissue uptake. The results showed a clear difference in the tumour and liver uptake, with the non-secreting cell line showing almost twice the tumour uptake and approximately 20% of the liver uptake of the secreting cell line. (orig.). With 4 figs., 1 tab

  6. Herbal compound 'Songyou Yin' reinforced the ability of interferon-alfa to inhibit the enhanced metastatic potential induced by palliative resection of hepatocellular carcinoma in nude mice

    International Nuclear Information System (INIS)

    Liver resection is a widely accepted treatment for hepatocellular carcinoma (HCC). Our previous clinical study showed that the rate of palliative resection was 34.0% (1958-2008, 2754 of 8107). However, the influence of palliative resection on tumor metastasis remains controversial. The present study was conducted to evaluate the effect of palliative resection on residual HCC and to explore interventional approaches. Palliative resection was done in an orthotopic nude mice model of HCC (MHCC97H) with high metastatic potential. Tumor growth, invasion, metastasis, lifespan, and some molecular alterations were examined in vivo and in vitro. Mice that underwent palliative resection were treated with the Chinese herbal compound 'Songyou Yin,' interferon-alfa-1b (IFN-α), or their combination to assess their effects. In the palliative resection group, the number of lung metastatic nodules increased markedly as compared to the sham operation group (14.3 ± 4.7 versus 8.7 ± 3.6, P < 0.05); tumor matrix metalloproteinase 2 (MMP2) activity was elevated by 1.4-fold, with up-regulation of vascular endothelial growth factor (VEGF) and down-regulation of tissue inhibitor of metalloproteinase 2 (TIMP2). The sera of mice undergoing palliative resection significantly enhanced cell invasiveness by 1.3-fold. After treatment, tumor volume was 1205.2 ± 581.3 mm3, 724.9 ± 337.6 mm3, 507.6 ± 367.0 mm3, and 245.3 ± 181.2 mm3 in the control, 'Songyou Yin,' IFN-α, and combination groups, respectively. The combined therapy noticeably decreased the MMP2/TIMP2 ratio and prolonged the lifespan by 42.2%. Moreover, a significant (P < 0.001) reduction of microvessel density was found: 43.6 ± 8.5, 34.5 ± 5.9, 23.5 ± 5.6, and 18.2 ± 8.0 in the control and treatment groups, respectively. Palliative resection-stimulated HCC metastasis may occur, in part, by up-regulation of VEGF and MMP2/TIMP2. 'Songyou Yin' reinforced the ability of IFN-α to inhibit the

  7. 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-

  8. Pathomorphology observation on nude mice immunized and challenged with third-stage infective hook worm (Ancylostoma caninum) larvae%犬钩虫第三期钩蚴免疫裸鼠再感染AcL3的组织病理学观察

    Institute of Scientific and Technical Information of China (English)

    郭俭; 吴嘉形; 杨元清; 薛剑; 强慧琴; 肖树华

    2009-01-01

    Objective To observe the inflammatory responses and morphology changes in the lung and skin of nude mice immunized and challenged with third stage hookworm larvae of Ancylostoma caninum (AcL3),and then,to investigate the feasibility of nude mice as vaccine screening animal model.Methods Nude mice BALB/c-nu/nu were immunized subcutaneously with three doses of 500 AcL3 at 2-week intervals,and then challenged percutaneously with 500 AcL3.Lungs and skins were excised from post-challenged nude mice after 6,24,72 h and 7 d,and then examined by light microscopy.Non-immunized nude mice served as negative controls.Results In both non-immunized mice and majority of immunized mice,the AcL3 exhibited no structural damage and infiltrating inflammatory cells were absent at the surrounding tissues.There were no changes in the architecture of skin and lung tissues.However.about 0.5%-2.2% AcL3 in the skin of immunized mice exhibited euticular swelling,damage and even death,and the surrounding tissue was infihrated by polymorphonuclear inflammatory cells.From 24 h to 72 h post-challenge,granulomata were observed surrounding the dead AcL3.ConchLsion Weak post-vaccination host immune response against challenged AcL3 was seen in nude mice,indicating that it was unsuitable to be used as vaccine screening animal model.%目的 观察裸鼠经犬钩虫第三期钩蚴(AcL3)免疫后,其皮肤和肺内AcL3的形态变化及宿主的组织细胞反应,评价其作为疫苗筛选动物模型的可能性. 方法取BALB/c-nu/nu 小鼠,每两周由皮下免疫接种活的AcL3 500条,共3次,并丁末次免疫后1周由皮肤攻击感染AcL3 500条.用未免疫的感染AcL3 裸鼠作对照,攻击感染后不同时间取感染部位皮肤和肺脏,观察宿卡皮肤和肺内AcL3的组织病理学变化. 结果攻击感染后6、24、72 h及7 d,皮肤内的绝人部分虫体切面形态和组织结构与感染对照裸鼠皮肤内的相似,仪0.5%~2.2%的虫体切而示有变性、死亡,偶见

  9. Pharmacokinetics of internally labeled monoclonal antibodies as a gold standard: comparison of biodistribution of /sup 75/Se-, /sup 111/In-, and /sup 125/I-labeled monoclonal antibodies in osteogenic sarcoma xenografts in nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Koizumi, M.; Endo, K.; Watanabe, Y.; Saga, T.; Sakahara, H.; Konishi, J.; Yamamuro, T.; Toyama, S.

    1989-04-01

    In order to know the true biodistribution of anti-tumor monoclonal antibodies, three monoclonal antibodies (OST6, OST7, and OST15) against human osteosarcoma and control antibody were internally labeled with 75Se by incubating (75Se)methionine and hybridoma cells. 75Se-labeled monoclonal antibodies were evaluated both in vitro and in vivo using the human osteogenic sarcoma cell line KT005, and the results were compared with those of 125I- and 111In-labeled antibodies. 75Se-, 125I- and 111In-labeled monoclonal antibodies had identical binding activities to KT005 cells, and the immunoreactivity was in the decreasing order of OST6, OST7, and OST15. On the contrary, in vivo tumor uptake (% injected dose/g) of 75Se- and 125I-labeled antibodies assessed using nude mice bearing human osteosarcoma KT005 was in the order of OST7, OST6, and OST15. In the case of 111In, the order was OST6, OST7, and OST15. High liver uptake was similarly seen with 75Se- and 111In-labeled antibodies, whereas 125I-labeled antibodies showed the lowest tumor and liver uptake. These data indicate that tumor targeting of antibody conjugates are not always predictable from cell binding studies due to the difference of blood clearance of labeled antibodies. Furthermore, biodistribution of both 111In- and 125I-labeled antibodies are not identical with internally labeled antibody. Admitting that internally labeled antibody is a ''gold standard'' of biodistribution of monoclonal antibody, high liver uptake of 111In-radiolabeled antibodies may be inherent to antibodies. Little, if any, increase in tumor-to-normal tissue ratios of antibody conjugates will be expected compared to those of 111In-labeled antibodies if stably coupled conjugates are administered i.v.

  10. 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.

  11. No evidence for a different magnitude of the time factor for continuously fractionated irradiation and protocols including gaps in two human squamous cell carcinoma in nude mice

    International Nuclear Information System (INIS)

    Background and purpose: To study whether the magnitude of the time factor is different for continuously fractionated irradiation and for fractionation protocols including gaps. Materials and methods: Two human head and neck squamous cell carcinomas (SCCs), FaDu and GL, were transplanted subcutaneously into the right hindleg of NMRI (nu/nu) mice and irradiated with 30 fractions under ambient conditions within 2, 6 and 10 weeks. Irradiations within 6 and 10 weeks were given either as a continuous course or with a mid-course gap of 3 weeks. The end-point of the experiments was local tumor control at day 120 (FaDu) or day 180 (GL) after the end of treatment. Results: In FaDu tumors, two experimental cohorts (A, B) yielded significantly different results and were analyzed separately. In cohort A, the tumor control dose 50% (TCD50) increased from 37 to 89 Gy when the treatment time of continuous fractionated irradiation was extended from 2 to 10 weeks. The recovered dose/day (Dr) was 0.98 Gy (95% confidence interval, 0.72; 1.27). In cohort B, the TCD50 increased from 35 to 63 Gy, and the Dr was 0.51 Gy (0.24; 0.75). In GL tumors, the TCD50 for continuously fractionated irradiation increased from 41 to 48 Gy. This increase was not significant, and the Dr was 0.15 Gy (0; 0.30). None of the TCD50 and Dr values obtained in both tumor models for continuous irradiation vs. irradiation with a gap were significantly different. Conclusions: Prolongation of the overall treatment time of fractionated irradiation resulted in a pronounced decrease of local control in human FaDu SCC and little decrease of local control in human GL SCC. No evidence was found that the magnitude of the time factor in these tumors is different for continuous fractionation or fractionation protocols including gaps

  12. Influence of melittin on growth of human K562 cell xenografts in nude mice%蜂毒素对人K562细胞裸鼠皮下移植瘤生长的影响

    Institute of Scientific and Technical Information of China (English)

    秦进; 王春光

    2011-01-01

    Objective To investigate the growth inhibitory effect of melittin on xenografted human K562 cells in nude mice and its relation with the expression change of Bax and Bcl-2. Methods Human K562 cells were inoculated BALB/C nude mice, and then the tumor-bearing were classified randomly into 5 groups, including low concentration (30μg/kg), middle concentration (60μg/kg) and high concentration (120 μg/kg) melittin groups, negative crontrol group and hydroxy urine group. The growth of xenografted tumors was observed. Apoptosis morphological transformation of K562 cells induced by melittin was detected by HE staining and transmission electronic scan microscope. Apoptosisrelated protein levels of Bax and Bcl-2 were determined by Western Blot. The levels of Bax and Bcl-2 mRNA were determined by reverse transcription polymerase chain reaction (RT-PCR). Results Compared to negative control group, all the melittin treatment groups showed having statistical significance ( P < 0.05 ). The high concentration melittin group showed similar inhibition ratio as the hydroxy urine negative control group ( P > 0.05). Apoptosis and necrosis of tumor cells were found in all melittin groups under the light and electronic sean microscope, and the high concentration melittin group had the strongest effect. The tumor cells in hydroxy urine group were mainly necrosis. The results of Western Blot indicated that the expression of Bax protein was up-regulated by melittin, while Bcl-2 protein was down-regulated in K562 cell tumor tissue. The results of RT-PCR indicated the expression of Bax mRNA was upregulated by melittin, while Bcl-2 mRNA was down-regnlated in K562 cell tumor tissue. Conclusions Melittin suppresses significantly the growth of K562 cells in nude mice. Melittin increases the expression of Box and decreases the expression of Bcl-2 to induce the apoptosis of K562 cells. This is one of the possible mechanisms of antitumor.%目的 探讨蜂毒素对K562细胞裸鼠移植瘤的

  13. 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

  14. Human epidermal stem cells combined with acellular dermal scaffold in nude mice for skin transplantation%人表皮干细胞复合裸鼠脱细胞真皮支架制备的人工皮肤

    Institute of Scientific and Technical Information of China (English)

    赵跃华; 张永红; 林凯

    2016-01-01

    背景:多种原因会导致皮肤大面积缺损的出现,临床可采用组织工程人工皮肤进行移植修复,而构建组织人工皮肤需要种子细胞和支架材料。目的:观察人表皮干细胞复合裸鼠脱细胞真皮构建的组织工程人工皮肤的应用效果。方法:①取幼儿包皮分离培养人表皮干细胞,取裸鼠皮肤制备脱细胞真皮支架,将两者复合构建人工皮肤。②10只 SD 大鼠随机等分为组织工程皮肤组和脱细胞真皮支架组,均制备皮肤缺损模型,分别采用移植脱细胞真皮支架与人表皮干细胞复合物与单纯脱细胞真皮支架进行修复。结果和结论:①人工皮肤均呈乳白色,质地柔软且富有弹性,柔韧性好,不易断裂,并具有良好的随形性,可加工为不同的形状。②2组大鼠修复后创面均未出现明显渗出。造模后2周,组织工程皮肤组裸鼠移植皮肤均呈现出良好的生长状态,创面逐渐愈合。脱细胞真皮支架组出现瘢痕愈合,且2只动物移植失败。③结果表明,以人表皮干细胞为种子细胞,以裸鼠脱细胞真皮材料为支架,可复合获得组织工程皮肤,并对皮肤缺损动物具有良好的修复效果。%BACKGROUND: Many factors can lead to a large area of skin defects, and tissue-engineered artificial skil transplantation composed by seeding cel s and scaffold materials can be used for skin defect repair. OBJECTIVE: To construct the skin implantation scaffold based on human epidermal stem cel s combined with acel ular dermal matrix in nude mice. METHODS: Human epidermal stem cel s from children’s foreskin were isolated and cultured, and the skin of nude mice was obtained to prepare acel ular dermal matrix scaffold. Then, the human epidermal stem cel s were cultured on the acel ular dermal matrix scaffold to construct artificial skin. Ten Sprague-Dawley rats were equivalently randomly divided into two groups: rats

  15. 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

  16. 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

  17. Adenovirus mediated angiostatin gene therapy for ovarian cancer: experiment with nude mice%重组腺病毒载体介导血管抑素基因治疗裸鼠卵巢癌的实验研究

    Institute of Scientific and Technical Information of China (English)

    贾长茹; 杨树艳; 韩世愈; 孙蕾

    2008-01-01

    Objective To built an expression vector of angiostatin (AG) gene with recombinated replication defective adenovirus and investigate the therapeutic effect of human AG gene on ovarian cancer. Methods (1) Human AG K ( 1-3 ) cDNA was inserted into the vector pShuttle to build the recombinant plasmid pShttle-AG ( K1-3 ). pAdeno-X-AG (K1-3) was built by double-cut and recombinated pShttle-AG (K1-3) to vector pAdeno-X, and then recombinant adenovirus was finally prepared by transinfection of pAdeno-X-AG (K1-3) into to the human embryo kidney cells of the line 293. (2) Human ovarian cancer cells of the line SKOV3 were inoculated subcutaneously into nude mice of the line BALB/c nu/nu to establish model of human ovarian cancer. Then the mice were randomly divided into 3 groups to be injected with Ad = AG (K1-3), Ad-LacZ, or phosphate buffered saline (PBS) around the cancer every 5 days. The tumor size was measured every 5 days to calculate the tumor volume and tumor inhibition rate. Three days after the last injection the mice were killed. The tumor tissues, livers, and kidneys of the mice underwent imunohistochemistry to calculate the microvessel density (MVD) and expression of vessel endothelial growth factor (VEGF) and AG. Results The tumor volume and weight of the Ad-AG ( K1-3 ) group were significantly less than those of the PBS and Ad-LacZ groups ( all P 0. 05). The expression levels of CD34 and VEGF of the Ad-AG( K1-3 ) group were both significantly lower than those of the PBS and Ad-LacZ groups (all P 0. 05 ). Conclusion Human angiostatin mediated by adenovirus suppresses the angiogenesis and the growth of human ovarian cancer in the nude mice model, which suggests that it is promising in clinical application.%目的 构建携带血管抑素(AG)基因K(1-3)重组复制缺陷型腺病毒表达载体,研究腺病毒介导的人血管抑素基因对卵巢癌的治疗作用.方法 (1)将人血管抑素K(1-3)cDNA插入穿梭载体pShuttle产生重组质粒pShttle-AG(K1

  18. 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

  19. 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

  20. 18F-FDG对于乳腺癌模型小鼠治疗作用的研究%Therapeutic effect of positron emission tomography agent 18F-FDG on MCF-7 in nude mice

    Institute of Scientific and Technical Information of China (English)

    许秦风; 郭万华; 李爱梅; 林夏雯; 贾支俊

    2012-01-01

    To study the therapeutic potential of PET agent [ 18F] labeled 2 - deoxy - 2 - fluoro - D - glucose (18F - FDG) to MCF - 7 in nude mice and its molecular mechanism. [ Methods] The breast cancer cell line MCF -7 was cultured with 18F - FDG in different doses (0 -7.4 × 106 Bq/mL). The y - ray high energy counting machine was used to detect uptake of -γ - ray by MCF - 7 cells. The MCF - 7 cells were inoculated in nude mice. The tumor - bearing mice were treated with normal saline, 3.7 MBq, 11. 1 MBq and 37 MBq 18F-FDG, respectively. Dynamic changes of xenogafts volume were calculated. Then these mice were imaged by microPET with I8F - FDG. Tumors were analyzed for expression of cleaved CASPASE - 3 and BCL - 2 by western blot. [ Results] In vitro uptake of l8 F - FDG by MCF - 7 cells was linear dose dependence. All treatment groups showed significant reduction of tumor growth rate compared with the control group ( P 0. 05 ) , but the expression levels of BCL-2 in the two groups were both lower than that in 3.7 MBq group(P <0. 05) , and the expression levels of cleaved CASPASE - 3 were higher than that in 3. 7 MBq group (P < 0.05 ). [ Conclusions ] The study suggested that 18 F - FDG had a therapeutic effect in breast cancer by decreasing of BCL - 2 expression and increasing of cleaved CASPASE - 3 expression.%[目的]探讨18氟-氟代脱氧葡萄糖(18F-FDG)诱导乳腺癌细胞的凋亡作用及分子机制.[方法]使用0~7.4 × 106 Bq/mL18F-FDG作用于体外培养乳腺癌细胞MCF-7,应用γ高能计数仪测定细胞摄取射线量;接种MCF-7细胞至24只雌性裸鼠腋下构建小鼠乳腺癌模型,成瘤后分别由尾静脉注射生理盐水、3.7 MBq、11.1 MBq和37 MBq18F-FDG,观察肿瘤生长情况,Micro-animal PET进行瘤体显像;Western Blot方法检测肿瘤瘤体凋亡相关蛋白BCL-2及cleaved CASPASE-3表达情况.[结果]体外MCF-7细胞摄取实验表明,在一定剂量范围内,随着射线剂量的增加,对数生长期的MCF-7细胞

  1. Establishment of whole-body visualization models of ovarian cancer orthotopic and metastatic model in nude mice.%整体可视化卵巢癌原位及转移动物模型的建立

    Institute of Scientific and Technical Information of China (English)

    黎静; 王雪飞; 钟梅

    2012-01-01

    Objective To establish visualization model of orthotopic growth and metastasis of ovarian cancer. Methods The pEGFP - N1 plasmid was transfected into human ovarian carcinoma cell line HO -8910 for construction of enhanced green fluorescent protein (EGFP) consistent expression pEGFP - N1/H0 -8910 cells. pEGFP - N1/HO -8910 cells were inoculated subcutaneously in nude mice, and the orthotopic tumor growth was evaluated in real time using fluorescence stereo microscope. Whole - body visualization model of ovarian carcinoma was established surgically, and evaluated by conventional pathological methods. Results EGFP was consistently expressed at high level in pEGFP - N1/ HO -8910 cells. Subcutaneous injection of pEGFP - N1/HO - 8910 cells resulted in tumor growth in nude mice, assessed with fluorescence stereo microscope producing visualized real - time tumor growth. Visualization animal model was established successfully with surgical orthotopic implantation (SOI) of the tumor. Two weeks after surgery, all the mice developed ovarian carcinoma without metastasis. Six weeks after surgery, peritoneal metastasis was observed in 2 mice, in which liver metastasis was also presented. The whole - body visualization animal model was validated by pathological detection. Conclusion Whole - body visualization model of orthotopic and metastatic tumor growths provides a reliable model for observing the pathogenic behavior of human ovarian carcinoma.%目的 建立整体可视化卵巢癌原位及转移动物模型,实时观察卵巢癌发展、转移的规律.方法 将pEGFP-N1表达质粒转染入人卵巢癌细胞株HO-8910中,建立稳定表达绿色荧光蛋白(EGFP) 的卵巢癌细胞株 pEGFP-N1/HO-8910,裸鼠皮下接种pEGFP-N1/HO-8910细胞,利用肿瘤细胞表达EGFP的特点,借助整体荧光成像系统,并利用IPP5.0软件采集、分析卵巢癌细胞发出的荧光信号,实时观察卵巢癌细胞在裸鼠皮下的生长情况,利用卵巢癌外科原位手术移

  2. 具有摄锝功能甲状腺乳头状癌移植瘤裸鼠模型的建立%Establishment of nude mice xenograft model of papillary thyroid carcinoma with the ability of 99mTc-intake

    Institute of Scientific and Technical Information of China (English)

    张蓉; 俞立波; 李梅芳; 郭明高; 李连喜; 陆汉魁; 陆俊茜; 包玉倩; 贾伟平

    2014-01-01

    目的 建立具有摄锝功能甲状腺乳头状癌皮下移植瘤裸鼠模型,为研究甲状腺乳头状癌的发病机制及放射性碘治疗提供工具.方法 取人甲状腺乳头状癌细胞系IHH-4,以1×107细胞数制成200μl细胞悬液接种于9只裸鼠(5周龄雌性裸鼠,品系BALB/c-nu/nu)皮下,观察成瘤时间,并用PET-CT观察肿瘤大小及形态,用放射性核素发射式计算机断层(ECT)观察移植瘤的摄锝功能.结果 裸鼠皮下成瘤率为100.0% (9/9),细胞接种后1周裸鼠皮下可以形成肉眼可见的肿瘤,4周时PET-CT检测肿瘤大小约1.8cm×2.4cm,ECT显示腹腔注射放射性99m锝后15 min移植瘤可以显像.结论 应用人甲状腺乳头状癌细胞系IHH4成功建立甲状腺乳头状癌皮下移植瘤裸鼠模型,移植瘤具有良好的摄锝功能,为甲状腺乳头状癌发病机制及放射性碘治疗等的研究提供了良好的动物模型.%Objective To establish the nude mice xenograft model of papillary thyroid carcinoma with the ability to accumulate 99mTc,and to provide a tool for further study in both pathogenesis and radioactive iodine treatment of papillary thyroid carcinoma.Methods 1 × 107 cells in 200 μl suspension liquids of the human papillary thyroid carcinoma cell lines IHH-4 were inoculated into nine nude mice (five week-old female nude mice,BALB/c-nu/ nu).Tumor formation was recorded,and the size and morphology of tumor were observed by PET-CT.Emission computed tomography (ECT) was used to observe the function of 99mTc intake by xenografts.Results The percentage of the formation of xenografts in nude mice was 100.0% (9/9).One week after the cells were injected into nude mice,visible tumors were formed.PET-CT performed by the fourth week demonstrated that tumor size was about 1.8 cm × 2.4 cm.Xenograft' image was displayed by ECT after 15 minutes of intraperitoneal injection of 99mTc.Conclusion The nude mice xenograft model of papillary thyroid carcinoma was successfully

  3. Effects of simvastatin on human breast cancer osteolytic bone metastasis in a nude mice model%辛伐他汀在裸鼠模型中对乳腺癌骨转移的影响

    Institute of Scientific and Technical Information of China (English)

    陈明霞; 张蔚; 曲建力; 李强; 王海

    2015-01-01

    目的 观察辛伐他汀在裸鼠模型中对乳腺癌骨转移的作用.方法采用完全随机分组方法 将60只裸鼠分为3组,每组20只,裸鼠左心腔注射乳腺癌骨转移细胞株(MDA-MB-231),7d后,分别皮下注射辛伐他汀、生理盐水及无任何处理(2次/周,19 d).应用图像分析软件评估骨转移瘤的面积.随后处死裸鼠,用放射免疫法检测骨转移癌髓腔内甲状旁腺素相关蛋白(PTHrP)浓度;应用骨密度检测软件进行组织形态学分析,计数骨转移灶每毫米癌组织与临近骨小梁之间破骨细胞的数量.计量资料比较采用方差分析,P<0.05为差异有统计学意义.结果 与生理盐水组和无处理组相比,注射辛伐他汀的裸鼠骨转移癌面积明显减小(0.51±0.18 mm2 vs 2.13±1.24 mm2 vs 2.29±1.22 mm2;F=15.600,P=0.002; F=15.673,P=0.001),骨转移癌周围髓腔内PTHrP浓度明显降低(0.98±0.20 pmol/L vs 2.11±0.31 pmol/L vs 1.99±0.29 pmol/L;F=61.469,P<0.001;F=58.274,P<0.001),并且其转移灶破骨细胞的数量明显减少(4.00±1.73个/mm vs 11.40 ±4.93个/mm vs 10.91±3.87个/mm;F=17.820,P=0.001,F=17.184,P=0.002).结论 辛伐他汀能够降低乳腺癌细胞PTHrP的分泌,从而抑制乳腺癌细胞在骨内生长及其对骨质的破坏.%Objective To observe the effect of simvastatin on bone metastasis of breast cancer in nude mice model.Methods Sixty mice were divided into three groups randomly with 20 in each group.Mice were inoculated with MDA-MB-231 cells into the left cardiac ventricle.After 7 days,mice were treated with either simvastatin,saline,or nothing twice per week for 19 days.The area of osteolytic metastases was subsequently measured in long bones of all mice using an image analysis system.After sacrifice,parathyroid hormone-related protein (PTHrP) concentrations in bone marrow from all mice were determined using a two-site immunoradiometric assay.Osteoclast number expressed per millimeter of tumor/bone interface was assessed

  4. Radiosensitizing effect of artesunate on nude mice transplanted with HeLa cells of cervical cancer%青蒿琥酯对子宫颈癌裸鼠移植瘤放射增敏作用的研究

    Institute of Scientific and Technical Information of China (English)

    周媛媛; 曹建平; 封阳; 张旭光; 朱巍; 倪倩影; 耿冲; 陈光烈; 罗居东; 樊赛军

    2011-01-01

    Objective To investigate the radiosensitization of artesunate on nude mouse transplanted with HeLa cells,and to explore its possible mechanisms.Methods HeLa cells were inoculated into the nude mice to establish tumor model.Mice were randomly divided into 4 groups as blank control,artesunate group,radiation group and artesunate + radiation group when average volume of tumor were about 5 mm × 5 mm× 5 mm.During the term of treatment,the volume of tumors were measured every 2days.After 14 days treatment,the mice were killed and tumor tissues were harvested for flow cytometry to detect the alteration of cell cycle.Meanwhile,the pathological change of the tumor tissue was observed with HE staining method,and the change of expression of cycle regulatory protein Cyclin B1,Cdc2 and Wee1 were detected by Western blot.Results The growth of tumor was significantly inhibited by artesunate combined with radiation and its inhibition rate was 72.34%.Flow cytometry results showed that the percent of cells in G1 phase increased and G2 phase decreased in the artesunate + radiation group compared with those in irradiation group ( t =4.41,4.12,P < 0.05 ).The expression level of Cyclin B1 was obviously increased while that of Wee1 decreased in the artesunate + radiation compared with irradiation group.There was no difference in the expression of Cdc2 among the four groups.Conclusions Artesunate can dramatically increase the radiosensitivity of transplanted tumor of HeLa cells.The possible mechanism might be related to the decreasing G2 phase by regulating the expression of Cyclin B1 and Wee1.%目的 探讨青蒿琥酯对子宫颈癌HeLa细胞裸鼠移植瘤的放射增敏效应及其作用机制.方法 建立子宫颈癌HeLa细胞裸鼠移植瘤模型.待移植瘤平均体积增至5 mmx5 mmx5mm时,采用随机数字表法将裸鼠分为对照组、单纯药物组(青蒿琥酯)、单纯照射组( 10 Gy)及药物+照射组(青蒿琥酯+ 10 Gy).测量移植瘤体积,计算肿瘤体

  5. 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.

  6. 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.

  7. 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

  8. Tumor uptake of radioiodinated anti-human pulmonary surfactant-associated protein monoclonal antibody PE 10 in nude mice bearing human pulmonary adenocarcinoma in combination with an unlabeled preload

    International Nuclear Information System (INIS)

    This study assessed the potential use of radioimmunoscintigraphy of pulmonary alveolar Type II cells tumor with the radiolabeled anti-human surfactant-associated protein (SP) monoclonal antibody (MAb) PE 10 in combination with preloads of unlabeled MAb. The in vitro binding of iodine-125 (125I)-labeled MAb PE 10 (1 μg), which had a specific radioactivity of 400 MBq/mg, on human pulmonary papillary adenocarcinoma NCI-H441 cells that produced SP was investigated. In NCI-H441 tumor-bearing nude mice, the tumor uptake of 125I-MAb PE 10 (5 μg) was examined in combination with preloads of unlabeled MAb PE 10 (0, 5, 10, and 50 μg). An isotype-matched unassociated murine MAb was used as a control both in vitro and in vivo. 125I-MAb PE 10 showed specific cell binding compared with 125I-control MAb. Tumor uptake of 125I-MAb PE 10 in vivo reached a peak of 4.97±0.33% injected dose per gram (%ID/g) at 48 h postinjection. Preloads of 5 and 10 μg unlabeled MAb PE 10 significantly enhanced tumor uptake at 48 h postinjection ( 5.94±0.29% ID/g and 5.72±0.29% ID/g, respectively), whereas preload of 50 μg unlabeled MAb PE 10 significantly decreased tumor uptake ( 2.75±0.32% ID/g) at 48 h. Preload of 5 μg unlabeled MAb PE 10 significantly increased the tumor-to-blood radioactivity ratio at 48 h ( 2.39±0.16). Preloads of unlabeled control MAb did not cause any significant change in tumor uptake. Immunohistochemistry showed the intracellular and pericellular patterns of SP expression in tumor cells. In conclusion, radioimmunoscintigraphy with MAb PE 10 labeled with a γ-emitting radioiodine such as 123I might be a useful means of targeting pulmonary alveolar Type II tumor cells in combination with preloading with an optimal dose of the unlabeled MAb

  9. 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.

  10. 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

  11. 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.

  12. Transgenic nude mouse with ubiquitous green fluorescent protein expression as a host for human tumors.

    Science.gov (United States)

    Yang, Meng; Reynoso, Jose; Jiang, Ping; Li, Lingna; Moossa, Abdool R; Hoffman, Robert M

    2004-12-01

    We report here the development of the transgenic green fluorescent protein (GFP) nude mouse with ubiquitous GFP expression. The GFP nude mouse was obtained by crossing nontransgenic nude mice with the transgenic C57/B6 mouse in which the beta-actin promoter drives GFP expression in essentially all tissues. In crosses between nu/nu GFP male mice and nu/+ GFP female mice, the embryos fluoresced green. Approximately 50% of the offspring of these mice were GFP nude mice. Newborn mice and adult mice fluoresced very bright green and could be detected with a simple blue-light-emitting diode flashlight with a central peak of 470 nm and a bypass emission filter. In the adult mice, the organs all brightly expressed GFP, including the heart, lungs, spleen, pancreas, esophagus, stomach, and duodenum. The following systems were dissected out and shown to have brilliant GFP fluorescence: the entire digestive system from tongue to anus; the male and female reproductive systems; brain and spinal cord; and the circulatory system, including the heart and major arteries and veins. The skinned skeleton highly expressed GFP. Pancreatic islets showed GFP fluorescence. The spleen cells were also GFP positive. Red fluorescent protein (RFP)-expressing human cancer cell lines, including PC-3-RFP prostate cancer, HCT-116-RFP colon cancer, MDA-MB-435-RFP breast cancer, and HT1080-RFP fibrosarcoma were transplanted to the transgenic GFP nude mice. All of these human tumors grew extensively in the transgenic GFP nude mouse. Dual-color fluorescence imaging enabled visualization of human tumor-host interaction by whole-body imaging and at the cellular level in fresh and frozen tissues. The GFP mouse model should greatly expand our knowledge of human tumor-host interaction. PMID:15574773

  13. 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

  14. Pathogenicity and genetic variation of 3 strains of Corynebacterium bovis in immunodeficient mice.

    Science.gov (United States)

    Dole, Vandana S; Henderson, Kenneth S; Fister, Richard D; Pietrowski, Michael T; Maldonado, Geomaris; Clifford, Charles B

    2013-07-01

    Corynebacterium bovis has been associated with hyperkeratotic dermatitis and acanthosis in mice. We studied 3 different strains of C. bovis: one previously described to cause hyperkeratotic dermatitis (HAC), one that infected athymic nude mice without leading to the classic clinical signs, and one of bovine origin (ATCC 7715). The 3 strains showed a few biochemical and genetic differences. Immunodeficient nude mice were housed in 3 independent isolators and inoculated with pure cultures of the 3 strains. We studied the transmission of these C. bovis studies to isolator-bedding and contact sentinels housed for 5 to 12 wk in filter-top or wire-top cages in the respective isolators. Using a 16S rRNA-based qPCR assay, we did not find consistent differences in growth and transmission among the 3 C. bovis strains, and neither the incidence nor severity of hyperkeratosis or acanthosis differed between strains. Housing in filter-top compared with wire-top cages did not alter the morbidity associated with any of the strains. Our findings confirmed the variability in the gross and histologic changes associated with C. bovis infection of mice. Although bacteriology was a sensitive method for the detection of Corynebacterium spp., standard algorithms occasionally misidentified C. bovis and several related species. Our study demonstrates that PCR of skin swabs or feces is a sensitive and specific method for the detection of C. bovis infection in mice. An rpoB-based screen of samples from North American vivaria revealed that HAC is the predominant C. bovis strain in laboratory mice. PMID:23849444

  15. 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, xenogeneic...... skin rejection, and antibody titers were also measured in the same groups of animals. The experiments showed that both allogeneic and isogeneic thymus grafting cause a significant amplification of cells in the different T lymphocyte subpopulations. The functional tests, however, indicate that the T...... cell response is far better following isografting. We, therefore, conclude that isogeneic thymus grafting is an easy method of reconstituting the nude rat immunologically....

  16. Curcumin reverses multidrug resistance in HCT-8/VCR nude mice xenograft%姜黄素逆转结肠癌裸鼠移植瘤多药耐药的研究

    Institute of Scientific and Technical Information of China (English)

    卢伟东; 傅仲学; 覃勇; 李雷; 杨闯

    2011-01-01

    Objective To investigate the multi-drug resistance reversal effects of curcumin on xenografts derived from multi-drug resistant human colon carcinoma cell line HCT-8/VCR, and to explore the possible mechanism. Methods The models of HCT-8/VCR xenograft ( 100 mm3 ) in nude mice were established through implanting 0.1 ml cells at 4 × 107 cells/mi. Twenty nude mice bearing HCT-8/VCR tumors were randomized into 4 groups according to different treatments, that is, group A: control group, group B: VCR group (2 mg/kg injected around the tumor mass, once per 2 d, for 7 times), group C: curcumin group(50 mg/kg,injected around the tumor mass, once per 2 d, for 7 times), group D: curcumin plus VCR group ( as combined the treatment of groups B and C). Tumor volume was calculated with L × D2/2 which were measured once per 2 d, for 14 d. Tumor weight was measured and specimens were collected from the mice in each group in 2weeks after the interventions. Morphology of xenografts were investigated by HE staining. The expressions of MDR1, P-glycoprotein (P-gP) and survivin were observed with reverse transcriptase PCR and Western blot assay respectively. Effects of curcumin on reversing multi-drug resistance of tumor in different treatments were evaluated. ResuIts Curcumin plus VCR significantly inhibited the growth of xenografts, with the tumor weight of group D (0.42 ±0.23 g) significantly lower than those of the other 3 groups ( group A 1.21 ±0. 25 g, group B 1.13 ±0.27 g and group C 0.75 ±0.27 g, P <0.05). RT-PCR and Western blotting results showed that the expressions of MDRI mRNA (0.39 ± 0. 11 ), P-gp (0.34 ± 0.07 ) , survivin mRNA (0.80 ± 0.12) and pro tein (0.40 ± 0.11 ) in group C and those of MDRI mRNA (0.18 ± 0.05 ), P-gp (0.15 ± 0.02 ), survivin mR NA (0.63 ± 0.04 ) and protein (0.40 ± 0. 11 ) in group D were significantly lower than those in group A ( MDR1 mRNA 0.99 ±0.23, P-gp 0.71 ±0.23, survivin mRNA 1.19 ±0.32 and protein 0.88 ±0. 15, P < 0. 05

  17. 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

  18. 腺病毒介导CDglyTK双自杀基因系统对裸鼠皮下移植瘢痕疙瘩的治疗作用%Effects of recombinant adenovirus-mediated double suicide genes on implanted human keloid: experiment with athymic mice

    Institute of Scientific and Technical Information of China (English)

    徐斌; 刘振中; 张敬; 宗宪磊; 蔡景龙

    2008-01-01

    目的 探讨由大肠杆菌胞嘧啶脱氨酶(CD)基因/5-氟胞嘧啶(5-Fc)和单纯疱疹病毒胸苷激酶(HSV-TK)基因/丙氧鸟苷(GCV)基因治疗系统整合形成的腺病毒介导CDgly/TK双自杀基因系统对瘢痕疙瘩的治疗作用及其机制.方法 采用皮下移植保留表皮的入瘢痕疙瘩组织块的方法建立瘢痕疙瘩裸鼠模型,术后第7天将20只模型裸鼠分4组,每组5只.A组瘢痕内注射生理盐水;B组瘢痕内注射生理盐水+腹腔注射5-Fc和GCV;C组瘢痕内注射自行构建的莆组CDglyTK双自杀基因腺病毒(CDgly/TK);D组瘢痕内注射CDgly/TK+腹腔注射5-Fc和GCV;用药持续18 d.术后2、7(用药前)、14、21、28、35、42 d测量各组瘢痕疙瘩组织块体积;术后42 d取出瘢痕疙瘩组织块,HE染色进行组织学检查,末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法检测成纤维细胞凋亡情况,免疫组织化学染色检测Bcl-2、Bax蛋白质的表达.结果 用药前和用药后7、14、21、28、35 d,D组瘢痕疙瘩组织块体积(mm3)分别为173±5、172±5、147±5、125±6、112±7和84±9,从用药后14 d开始明显缩小(均P<0.05);而其他3组瘢痕疙瘩组织块体积均明显增大,从用约后7 d开始各时点测得的体积均明显大于D组(均P<0.05).D组瘢痕疙瘩组织中有大量小鼠组织细胞浸润,胶原结构破坏和成纤维细胞凋亡明显重于其他3组,Bcl-2蛋门质表达明显弱于而Bax蛋白质表达明显强于其他3组.结论 腺病毒介导的CDglyTK双自杀基因系统在瘢痕疙瘩裸鼠模型中对瘢痕疙瘩产生治疗作用,诱导成纤维细胞凋亡足其主要作用机制.%Objective To detect the effects of the recombinant adenovirus-mediated double suicide genes constructed by Escherichia coli cytosine deaminase (CD)/5-fluorocytosine (5-Fc) and herpes simplex virus-thymidine kinase (HSV-TK)/ganiclovir (GCV)-CDglyTK on implanted human keloids and mechanisms thereof.Methods Twenty nude mice were

  19. Evaluation of meta-[211At]astatobenzylguanidine in an athymic mouse human neuroblastoma xenograft model

    International Nuclear Information System (INIS)

    A paired-label biodistribution was performed in athymic mice bearing SK-N-SH human neuroblastoma xenografts to compare the tissue uptake of meta-[211At]astatobenzylguanidine ([211At]MABG) and [131I]MIBG. Significantly higher (p 211At]MABG was seen in tumor (3.8 ± 0.8% ID/g vs. 3.1 ± 0.7% ID/g at 8 h) compared to [131I]MIBG. Desipramine reduced tumor uptake of [211At] MABG by 43%, suggesting that its accumulation was related to the specific uptake-1 mechanism. Higher uptake of [211At]MABG was also seen in normal tissue targets such as heart (6.0 ± 0.9% ID/g vs. 4.5 ± 0.8% ID/g at 8 h; p 211At]MABG by 1.5-fold while reducing uptake in heart and several other normal tissues. The vesicular uptake inhibitor tetrabenazine reduced heart uptake by 30% without reducing the tumor uptake. These results suggest such strategies might be useful for improving [211At]MABG tumor-to-normal tissue ratios

  20. Experimental Study of the Relation of Inhibiting Vasculogenic Mimicry and Inducing Cell Apoptosis of Melittin on Osteosarcoma Xenotransplanted Models of Nude Mice%蜂毒素抑制骨肉瘤血管生成拟态与影响肿瘤细胞增殖、调亡的关系

    Institute of Scientific and Technical Information of China (English)

    高启龙; 姚亚民; 杨峰; 田同德; 陈永强

    2011-01-01

    目的:探讨蜂毒素抑制骨肉瘤裸鼠移植瘤的作用及机制.方法:建立裸鼠骨肉瘤原位移植瘤模型,裸鼠18只,随机分3组:生理盐水组,蜂毒素组,顺铂组.观察各组裸鼠骨肉瘤体积和瘤体质量抑制率;应用免疫组化CD34与PAS双重染色法检测各组裸鼠瘤体血管生成拟态密度;免疫组织化学法检测增值细胞核抗原(PCNA)蛋白表达;TUNEL法检测肿瘤细胞凋亡;运用相关性分析法研究蜂毒素抑制骨肉瘤血管生成拟态与影响肿瘤细胞增殖、凋亡的关系.结果:蜂毒素组瘤体积和瘤体质量抑制率分别为42.98%、39.03%,蜂毒素能明显抑制CD34与PAS双重染色法标记的肿瘤血管生成拟态密度,能明显抑制肿瘤细胞增殖、促进细胞凋亡,且蜂毒素抑制肿瘤血管生成拟态密度与肿瘤细胞增殖呈正相关、与细胞凋亡呈负相关.结论:蜂毒素具有抑制骨肉瘤裸鼠移植瘤生长的作用,其作用机制可能与其能够抑制肿瘤血管生成拟态、诱导肿瘤细胞凋亡、抑制细胞增殖有关.%Objective:To study the antitumor effects and mechanism of Melittin on osteosarcoma xenotransplanted models of nude mice. Methods ; Xenotransplanted models of nude mice osteosarcoma cell UMR - 106 in the laevo - hind tibia of nude mice were established. Inoculated mice were randomly divided into normal saline group, positive control group, Melittin group. All the nude mice were sacrificed after treatment, the size and weight of tumor were measured and the tumor volumes and the inhibition rates of tumor were calculated, Expression of PCNA was deteced by immunohistochemical method. The VM density in tumor tissues was detected by CD34 and PAS double staining in vivo. TUNEL semi - quantitative assay was used to study the melittin - induced apoptosis in OS cell line. To study mainly the relation of inhibiting vasculogenic mimicry and inducing cell apoptosis. Results : Inhibiting rate ofmelittin in tumor

  1. Comparison of tumorigenic effect between inoculating method of slicing subaxillary skin and suturing and method of adopting paracentesis trocar of human nasopharyngeal carcinoma on nude mice%裸鼠腋下皮肤切开缝合和穿刺套针注射接种人鼻咽癌细胞成瘤效果比较

    Institute of Scientific and Technical Information of China (English)

    吴媛; 周训钊; 钟昌桃; 颜魁; 韦正波; 谢莹

    2015-01-01

    目的:比较裸鼠腋下皮肤切开缝合和穿刺套针注射接种人鼻咽癌细胞成瘤效果。方法制备鼻咽癌HONE-1细胞裸鼠皮下移植瘤块样本。将8只BALB/c裸鼠随机分为A、B组,各4只。 A、B组分别使用皮肤切开缝合接种和穿刺套针接种方法于裸鼠右侧腋下接种细胞株移植瘤组织块,比较两组裸鼠肿瘤出现时间、体积、质量。结果 A、B组肿瘤出现时间均为接种后第3天。与B组相比,A组裸鼠较早出现精神萎靡、皮肤粗糙、毛发光泽不良、食欲不振、活动量减低、脊椎明显、弓背等状况。两组裸鼠体质量均有所下降,A组比B组肿瘤生长迅速,但差异无统计学意义。 A、B组肿瘤质量分别为(0.85±0.39)、(0.75±0.30) g,两组比较,P>0.05。结论裸鼠腋下皮肤切开缝合和穿刺套针注射接种人鼻咽癌细胞均能达到好的成瘤效果。%Objective To compare the tumorigenic effect between the inoculating method of slicing the subaxillary skin and suturing and the method of adopting the paracentesis trocar of human nasopharyngeal carcinoma on the nude mice. Methods The samples of subcutaneous transplanted tumors in nude mice were established with nasopharyngeal carcinoma HONE-1 cells.Eight BALB/c nude mice were randomly divided into two groups:group A and B, 4 mice in each group. The right subaxillary skin of each mouse was subcutaneously inoculated with the tissue masses through slicing the skin, or adopting the paracentesis trocar in the two groups, respectively.The occurrence time, volume and mass of tumor in each group were compared.Results The occurrence time of tumor in each group was 3 days after being inoculated.Compared with group B, the occurrence time of dispirited mind, coarse skin, shineless hair, loss of appetite, low activity, distinct spinal column, hunched backs and other conditions were earlier in the group A.The weight of mice was decreased in both

  2. 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

  3. 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.

  4. Inhibition of growth of human liver carcinoma xenograft tumor by 6, 8-ditrifluoromethy-7-acetoychrysin in nude mice%6,8-二-三氟甲基-7-乙酰氧基白杨素抑制人肝癌裸鼠移植瘤生长

    Institute of Scientific and Technical Information of China (English)

    谭翔文; 夏红; 许金华; 曹建国

    2011-01-01

    Objective: To investigate the inhibitory effects of 6, 8-ditrifluoromethy-7-acetoychrysin (dFMAChR) on the growth of human liver carcinoma xenograft tumor in nude mice. Methods: The nude mice model was established by inoculation of human liver carcinoma HepG2 cells, and randomly divided into six groups, NS group (0.1 ml/10 g), 5-FLJ (20 mg/kg) group, ChR (100 mg/kg) group, low dose dFMAChR (20 mg/kg) group, media dose dFMAChR (40 mg/kg) group and high dose dFMAChR (80 mg/kg) group. The body weight and tumor volume and weight were investigated. The histomorphology change of the xenografts were observed by HE staining. TLJNEL staining was utilized to observe the apoptosis of human liver cancer xenograft cells in nude mice. Results: The inhibition rate of tumor weight in mice treated with dFMAChR at a dose of 20, 40, 80 mg/kg was 40.17%, 47.41% and 66.81%, respectively. The results of HE staining and TLJNEL staining showed that dFMAChR induces the apoptosis of xenograft cells in nude mice after treatment. Conclusion: dFMAChR posseses therapeutic action in human liver cancer.%目的:研究6,8-二-三氟甲基-7-乙酰氧基白杨素(dFMAChR)对人肝癌裸鼠移植瘤生长的抑制作用.方法:建立人肝癌HepG2细胞裸鼠移植瘤模型,随机分为6组,生理盐水(0.1 ml/10 g)组、氟尿嘧啶(5-Fu,20 mg/kg)组、白杨素(100 mg/kg)组、低剂量dFMAChR(20 mg/kg)组、中剂量dFMAChR(40 mg/kg)组和高剂量dFMAChR(80 mg/kg)组.测定移植瘤大小和重量;HE染色,光镜下观察移植瘤组织形态学特征;TUNEL法检测移植瘤细胞凋亡作用.结果:20、40、80 mg/kg dFMAChR 诱导的移植瘤的瘤重抑制率分别为40.17%、47.41%和66.81%.HE染色与TUNEL法检测结果表明,dFMAChR能明显诱导移植瘤细胞凋亡.结论:dFMAChR具有抗人肝癌治疗作用.

  5. 蜂毒素对胃癌SGC-7901细胞裸鼠移植瘤的抑制作用及其部分机制%Study of melittin on tumor inhibition and partial mechanism of human gastric cancer SGC-7901 cell xenografts in nude mice

    Institute of Scientific and Technical Information of China (English)

    楼蓉; 李俊; 吕雄文; 金涌; 赵斌; 吴宝明; 任丹阳; 王亚丽

    2011-01-01

    目的 研究蜂毒素对人胃癌SGC-7901细胞裸鼠移植瘤的抑制作用,并初步探讨其作用机制.方法 建立人胃癌SGC-7901细胞裸鼠移植瘤模型,采用抑瘤率指标评价蜂毒素对荷瘤小鼠的抑瘤作用,采用脏器指数、中性红法测定腹腔巨噬细胞吞噬功能,改良的四甲基偶氮唑盐(MTT)比色法检测自然杀伤(NK)细胞活性,ELISA法测定血清白介素2(IL-2)的含量,观察机体免疫变化情况.结果 蜂毒素(2、4 mg/kg)能抑制荷瘤小鼠的肿瘤生长,提高脾脏指数,增强腹腔巨噬细胞吞噬功能和NK细胞的活性,蜂毒素(4 mg/kg)能增加血清中IL-2的含量.结论 蜂毒素对荷瘤小鼠具有较强的抑瘤作用,可能与其提高机体免疫功能有关.%Objective To explore the effects and mechanism of melittin on tumor growth of human gastric cancer SGC-7901 cell xenografts in nude mice. Methods The xenografts derived from SGC-7901 cells were established in nude mice. The effect of melittin on tumor-bearing mice was evaluated by inhibition rate. Phagocytosis of peritoneal macrophage was measured by neutral red method. NK cell activity was detected by improved MTT assay. Concent of interleukin-2 ( IL-2 ) in serum was determined by ELISA method. The changes of immunity of tumor-bearing mice were observed by above-mentioned and organ index. Results Melittin ( 2, 4 mg/kg) could inhibit the tumor growth, while improve the index of spleen, enhance phagocytosis of peritoneal macrophage and NK cell activity, and melittin ( 4 mg/kg ) could increase IL-2 level in serum. Conclusion Melittin has significant inhibition on tumor-bearing mice, which is related to reinforcing the immunity of mice.

  6. 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

  7. 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

  8. FXR激动剂GW4064对裸鼠肝癌细胞移植瘤增殖及血管生成的影响%Effect of FXR Agonist GW4064 on the Proliferation and Angiogenesis of HCC Cells in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    位全芳; 路菊; 陶忠芬; 黄文琪; 糜建红

    2015-01-01

    目的:探讨研究法尼酯x受体(FXR)激动剂GW4064对裸鼠肝癌细胞移植瘤增殖及血管生成的影响.方法:选取人肝癌细胞系HepG2进行体外培养,将细胞悬液接种于BALB/c裸鼠皮下.裸鼠成瘤后,随机分为两组,分别腹腔注射DMSO和GW4064.一周后,处死动物取肿瘤组织,通过免疫组织化学法检测肿瘤组织中Ki-67和CD31的表达,同时计数肿瘤组织中的微血管密度(CD31-MVD); Western blot法检测其FXR和白介素-8(IL-8)的蛋白表达.结果:与对照组相比,FXR激动剂GW4064处理组的肿瘤组织中FXR的蛋白表达量明显增高,微血管密度CD31-MVD值显著降低,同时Ki-67、IL-8及CD31的表达水平均显著降低.结论:FXR激动剂GW4064能显著增加FXR的表达,抑制裸鼠肝癌细胞移植瘤的增殖及新生血管的形成.%Objective:To investigate the effect of FXR agonist GW4064 on the proliferation and angiogenesis of hepatocellular carcinoma (HCC)cells in BALB/c nude mice.Methods:Human hepatocellular carcinoma cell line HepG2 were cultured in vitro,then implanted subcutaneously in nude mice.When the subcutaneous xenograft was formed,the nude mice were randomly divided into a control group and an experimental group,which were injected with DMSO and GW4064 respectively.After one week,the tumor was separated,the expression of Ki67 and CD31 were detected by immunohistochemical(IHC) method,the microvessel density (CD31-MVD) of tumors were calculated,and the expression of FXR and IL-8 were detected by Western blot assays.Results:Compared with control group,the expression of FXR increased significantly,the microvessel density CD31-MVD value decreased significantly,while the expression level ofKi-67,IL-8 and CD3 1were significantly inhibited in GW4064 group.Conclusion:FXR agonist GW4064 may stimulate the expression of FXR thereby inhibiting the cell proliferation and tumor angiogenesis of hepatocellular carcinoma cell xenografts in nude mice.

  9. 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

  10. PI-103增强顺铂对CI3K细胞裸鼠移植瘤生长的抑制作用%PI-103 Enhances Cisplatin-Caused Growth Inhibition of C13K Cell Xenografts in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    刘勇; 孔繁飞; 方勇; 李智敏; 孙淑华

    2013-01-01

    Objective To examine the effect of PI-103 in combination with cisplatin on the proliferation and apoptosis of C13K cells and growth of xenografts of nude mice. Methods The proliferation of C13K cells was assessed by MTT assay after exposure to PI 403, cisplatin or both. Apoptosis was evaluated by flow cytometry. Immunoblot analysis was performed to detect the ex -pression of phosphorylation of AKT and S6 kinase 1. C13K cells was subcutaneously transplanted into nude mice ( n = 16) , which were randomly divided into control group , PI-103 group, cisplatin group and combined treatment group. After treatment for 4 consecutive weeks, the tumor inhibition rate was evaluated. Results PI-103 in combination with cisplatin inhibited the proliferation of C13 K cells in a time-dependent manner. The inhibitory effect of combination therapy was superior to PI 403 or cisplatin treatment alone. PI403 increased cisplatin induced apoptosis in C13K cells. PI403 inhibited the expression of phosphorylation of AKT and S6 kinase 1 in C13K cells. PI-103 plus cisplatin significantly inhibited the growth of xenografts in nude mice and there was significant difference between combined treatment group and cisplatin group. Conclusion PI-103 may enhance growth inhibition of C13K cell xenografts by cisplatin in nude mice.%目的 通过评价PI-103联用顺铂对C13K细胞体外增殖、凋亡及裸鼠移植瘤生长的影响为卵巢癌的靶向治疗寻找新的药物.方法 C13K细胞经PI-103和/或顺铂处理后,以MTT法检测细胞的增殖情况,以流式细胞仪检测细胞凋亡,Western印迹检测p-AKT和p-S6K1的表达情况.建立C13K细胞皮下裸鼠移植瘤模型,随机分成对照组、PI-103组、顺铂组、合并组4组,连续用药4周.观察肿瘤生长情况,计算抑瘤率.结果 PI-103联合顺铂抑制C13K细胞增殖,且随时间延长抑制作用越显著,抑制效果优于单独用药.PI-103可增强顺铂在C13K细胞中引起的凋亡.经PI-103作用后的C13K

  11. c-FLIP antisense oligonucleotide-loaded nanoparticles inhibit growth of human orbital rhabdomyosarcoma xenograft in nude mice%c-FLIP反义寡核苷酸纳米粒抑制人眼眶横纹肌肉瘤裸鼠移植瘤的生长

    Institute of Scientific and Technical Information of China (English)

    梁莉; 魏锐利

    2013-01-01

    Objective To investigate the effect of cellular Fas-associated death domain-like interleukin-1β-converting enzyme-inhibitory protein (c-FLIP) antisense oligonucleotide (ASODN)-loaded nanoparticles (NP) on the human orbital rhabdomyosarcoma xenograft in nude mice,so as to assess the feasibility of nanoparticles as a gene vector.Methods The model of human orbital rhabdomyosarcoma xenograft was established in nude mice,and the tumors were injected with c-FLIP ASODN NP,c-FLIP ASODN or normal saline (NS).The tumor volume and histopathological changes of tumor were observed.Western blotting analysis and immunohistochemical analysis were used to examine the expression of c-FLIP in tumor tissues of each group.Apoptosis of tumor cells was detected using TUNEL method.Results The growth of human orbital rhabdomyosarcoma in nude mice was significantly inhibited in ASODN NP group compared with the other two groups.Western blotting analysis showed that c-FLIP protein expression in ASODN NP and ASODN groups was significantly decreased compared with NS group (P<0.05).Immunohistochemical study showed that c-FLIP expression was found in the endochylema,and the c-FLIP positive cells in ASODN NP group was significantly less than those in the other two groups (P<0.05).Tumor cell apoptosis was observed in both ASODN NP and ASODN groups,with more found in the former,and only a few apoptotic cells were found in the NS group.Conclusion c-FLIP ASODN NP can effectively inhibit the growth of human orbital rhabdomyosarcoma xenograft in nude mice,indicating that nanoparticles may serve as a safe and effective vector for ASODN.%目的 探讨c-FLIP反义寡核苷酸(c-FLIP ASODN)纳米粒(NP)对裸鼠体内人眼眶横纹肌肉瘤移植瘤生长的影响,评估纳米粒作为基因载体的可行性.方法 皮下种植法建立裸鼠人眼眶横纹肌肉瘤动物模型,瘤体内分别注射c-FLIP反义寡核苷酸纳米粒(ASODN NP组)、未包裹的c-FLIP反义寡核苷酸(ASODN组)及生

  12. 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

  13. RGD修饰的葫芦素B纳米脂质载体对乳腺癌荷瘤裸鼠的抑瘤作用%Inhibitory Effect of RGD Modified B Nano Lipid Carrier on Breast Cancer Bearing Nude Mice

    Institute of Scientific and Technical Information of China (English)

    唐淑洁; 赵旭伟; 张佳琦; 刘洋; 王梓丞

    2016-01-01

    Objective:To prepare RGD conjugated cucurbitacin B loaded liposome(RGD-CuB-NLC) and observe RGD-CuB-NLC’s anti-cancer effect on the treatment with the cells of breast cancer in vitro and RGD-CuB-NLC’s anti-cancer effect on nude mice of human breast cancer.Method:The liposomes were prepared by thin film hydration method,a single cell suspension liquid of the MCF-7 cells of breast cancer was made according to the cultivation of the adherent cell method,then it was inoculated into 96 hole cell culture plate,the group of RGD-CuB-NLC was designed,the control groups were CuB-NLC,RGD-NLC and the blank group of NLC were designed,the rate of suppression in different condition were calculated.Nude mouse transplantation tumor were established,30 qualified nude mice models of human breast cancer xenograft were randomly divided into 5 groups, each group was 6,the mice of 5 groups were respectively treated by CuB,CuB-NLC,RGD-NLC,RGD-CuB-NLC and 0.9% sodium chloride solution every 24 hours per time,7 times in total.The body weight of nude mice and the weight of the transplanted tumor growth were recorded,and the inhibition rate of tumor growth were calculated. Result:For RGD-CuB-NLC group,the form was the circular,the encapsulation rate>80%,partical size was less than 150 nm,the average particle size was (115.6±2.1)nm,polydispersity index was (0.217±0.033),the electric potential was(-12.31±0.76)mV.The inhibition ratio of different liposome on breast cancer cells in the group of NLC was 0,the group of CuB-NLC was (46.3±2.21)%,the group of RGD-NLC was (55.7±3.22)%, the group of RGD-CuB-NLC was (75.6±5.67)%,the differences were statistically significant(P80%,粒径<150 nm,平均为(115.6±2.1)nm,多分散系数为(0.217±0.033),电位为(-12.31±0.76)mV。不同脂质体对乳腺癌细胞体外抑制率分别为:NLC组为0,CuB-NLC组为(46.3±2.21)%,RGD-NLC组为(55.7±3.22)%, RGD-CuB-NLC组为(75.6±5.67)%,比较

  14. 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

  15. 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

  16. 量子点-RGD探针光动力疗法联合吉西他滨治疗胰腺癌荷瘤裸鼠初探%Efficacy of Quantum Dots-RGD Based Photodynamic Therapy Combined with Gemcitabine for Treatment of Pancreatic Cancer Xenograft in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    高双; 倪倩雯; 周敏; 徐雷鸣

    2014-01-01

    Background:Pancreatic cancer is obscure in onset and progresses rapidly with very poor prognosis. Photodynamic therapy( PDT)has been developed as a novel anti-tumor treatment modality since 1980s. At present,there are only limited researches on pancreatic cancer treated with PDT in vivo. Aims:To investigate the efficacy of quantum dots-RGD ( QDs-RGD)based PDT combined with gemcitabine for treatment of pancreatic cancer xenograft in nude mice. Methods:QDs-RGD probe was synthesized and nude mice bearing pancreatic cancer xenograft was established. Nude mice were imaged at 1,5,10 and 24 hours after injection of QDs-RGD and QDs by in vivo imaging system. Forty model nude mice were randomly divided into five groups:control group( without any treatment),simple illumination group( laser 630 nm, 120 J/cm2,20 min),PDT group(QDs-RGD 0. 5 nmol+laser irradiation),gemcitabine group(gemcitabine 50 mg/kg)and combination group(QDs-RGD 0. 5 nmol+laser irradiation+gemcitabine 50 mg/kg). All the nude mice were sacrificed 18 days later. Tumor weight and volume were measured and tumor inhibition rate was calculated. Results:Fluorescence of tumor was shown 1 hour after injection and became clearest at the 5th hour,then showing a decrescendo trend. Density of QDs surrounding tumor was significantly less than that of QDs-RGD and faded away at the 10th hour. Tumor weight and volume in PDT group,gemcitabine group and combination group were all significantly lower than those in control group and simple illumination group(P0. 05),as well as between PDT group and gemcitabine group(P >0. 05). Tumor inhibition rate in combination group,gemcitabine group and PDT group was 70. 5%,43. 5% and 37. 1%, respectively. Conclusions:QDs-RGD based PDT combined with gemcitabine can inhibit the growth of pancreatic cancer xenograft in nude mice,which introduces a new idea to the treatment of pancreatic cancer.%背景:胰腺癌发病隐匿,进展迅速,预后极差。光动力疗法( PDT)是20

  17. Learning from nudity: lessons from the nude phenotype.

    Science.gov (United States)

    Mecklenburg, Lars; Tychsen, Birte; Paus, Ralf

    2005-11-01

    In mice, rats, and humans, loss of function of Foxn1, a member of the winged helix/forkhead family of transcription factors, leads to macroscopic nudity and an inborn dysgenesis of the thymus. Nude (Foxn1(nu)/Foxn1(nu)) mice develop largely normal hair follicles and produce hair shafts. However, presumably because of a lack of certain hair keratins, the hair shafts that are generated twist and coil in the hair follicle infundibulum, which becomes dilated. Since hair shafts fail to penetrate the epidermis, macroscopic nudity results and generates the - grossly misleading - impression that nude mice are hairless. Here, we provide an overview of what is known on the role of Foxn1 in mammalian skin biology, its expression patterns in the hair follicle, its influence on hair follicle function, and onychocyte differentiation. We focus on the mechanisms and signaling pathways by which Foxn1 modulates keratinocyte differentiation in the hair follicle and nail apparatus and summarize the current knowledge on the molecular and functional consequences of a loss of function of the Foxn1 protein in skin. Foxn1 target genes, gene regulation of Foxn, and pharmacological manipulation of the nude phenotype (e.g. by cyclosporine A, KGF, and vitamin D3) are discussed, and important open questions as well as promising research strategies in Foxn1 biology are defined. Taken together, this review aims at delineating why enhanced research efforts in this comparatively neglected field of investigative dermatology promise important new insights into the controls of epithelial differentiation in mammalian skin. PMID:16232301

  18. 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"

  19. 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. PMID:27356059

  20. 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

  1. 蜂毒素(Mel)对裸鼠骨肉瘤的抑制作用与影响肿瘤血管生成、细胞增殖和凋亡的关系%The relation of inhibiting angiogenesis and inducing cell apoptosis of melittin ( Mel) on xenotransplanted models of nude mice

    Institute of Scientific and Technical Information of China (English)

    高启龙; 李寒冰; 姚亚民; 陈永强; 杨峰

    2012-01-01

    目的 探讨蜂毒素(melittin,Mel)抑制骨肉瘤裸鼠移植瘤的作用机制.方法 用SD大鼠成骨肉瘤UMR- 106细胞株建立骨肉瘤原位移植瘤裸鼠模型,将18只裸鼠随机等分为3组,生理盐水组、Mel组和顺铂组.观察各组裸鼠骨肉瘤的体积和体质量抑制率;应用免疫组织化学法检测各组裸鼠瘤体CD31、CD105、PCNA蛋白表达;应用TUNEL法检测肿瘤细胞凋亡;运用相关性分析法研究Mel抑制骨肉瘤血管生成与细胞增殖、凋亡的关系.结果 Mel组肿瘤体积和体质量抑制率分别为42.98%和39.03%,Mel能明显抑制CD31、CD105标记的血管生成密度,能明显抑制肿瘤细胞增殖,促进细胞凋亡,且Mel抑制肿瘤血管生成与细胞增殖呈正相关及与细胞凋亡呈负相关.结论 Mel具有抑制骨肉瘤裸鼠移植瘤生长的作用,其作用机制可能与其能够抑制肿瘤血管生成、诱导肿瘤细胞凋亡及抑制细胞增殖有关.%Objective To study the antitumor effects and mechanism of melittin (Mel) on xenotransplanted models of nude mice. Methods Xenotransplanted models of SD rat osteosarcoma (OS) cell UMR-106 in the laevo-hind tibia of nude mice were established. Eighteen inoculated mice were randomly divided into normal saline group, positive control group and Mel group. All the nude mice were sacrificed after treatment. The size and weight of tumor were measured and the tumor volumes, and the inhibition rates of tumor were calculated. The expressions of CD31.CD1D5 and PCNA were deteced by immunohistochemical method. TUNEL semi-quantitative assay was used to study the melittin-induced apoptosis in OS cell line. The relation of inhibiting angiogenesis and inducing cell apoptosis was analyzed by correlation test . Results The mice treated with Mel showed significantly smaller in tumor volume and weight than those of NS group after treatment. Microvessel densities and the protein expressions of CD31 ,CD1()5 and PCNA in Mel group were

  2. 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...

  3. 组蛋白去乙酰化酶抑制剂联合化疗对乳腺癌细胞增殖影响的动物实验研究%The Effect of Histone Deacetylase Inhibitor Combined with Chemotherapy on Breast Cancer Cells in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    聂建云; 陈杨萍; 黄云超

    2011-01-01

    Objective: To study the effect of histone deacetylase inhibitor SAHA (N-Hydroxy-N- phenyloctanediamide)combined with chemotherapy on breast cancer cells in nude mice.Methods: Breast cancer cell suspension was subcutaneously injected into 80 nude mice to establish breast cancer model When the transplanted tumor was about 10mm in length, 60 mice with tumor in similar size were selected and divided into six groups, with 10 in each group.The six groups were the control group, SAHA group,taxol group, adriamycin group, taxol plus SAHA group, and adriamycin plus SAHA group.Data including blood cell count, serum level of cholesterol, liver function ( serum glutamic-pyruvic transaminase and bilirubin ), kidney function ( serum urea nitrogen and creatinine ), body weight, wet weight of tumor, inhibitory rate and tumor volume were collected.SPSS 12.0 software was used for statistical analysis.Results: Compared with the control group, the treatment groups had higher inhibitory rate and lower tumor volume ( P< 0.05).The taxol plus SAHA group showed superiority in inhibiting tumor growth ( P< 0.05).Compared with the control group,the groups treated with taxol or adriamycin had lower body weigh, lower level of white blood cell count, lower level of serum glutamic-pyruvic transaminase and higher level of bilirubin ( P < 0.05 ).No differences were foumd in the above indices between chemotherapy groups and SAHA plus chemotherapy groups ( P > 0.05 ).Conclusion: SAHA combined with chemotherapy (taxol or adriamycin ) has synergistic inhibitory ettect on the growth of breast cancer in nude mice without increasing side effects, suggesting its possible application in breast cancer treatment in the future.%目的:通过动物模型研究组蛋白去乙酰化酶抑制剂联合化疗对乳腺癌细胞株增殖周期的影响.方法:饲养Balb/c-nu/nu雌性裸鼠,细胞悬液皮下注射法构建人乳腺癌细胞株MCF-7裸鼠移植瘤模型,随机分为6组(对照组、组蛋白去

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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.

  9. CXCR4单克隆抗体抑制乳腺癌MCF-7细胞裸鼠移植瘤的实验研究%CXCR4 monoclonal antibody inhibits the growth of MCF-7 breast cancer xenograft in nude mice

    Institute of Scientific and Technical Information of China (English)

    杜成; 谢晓冬

    2012-01-01

    Objective:To investigate the effect of CXCR4 monoclonal antibody( CXCR4 mAb )on the growth of human MCF - 7 breast cancer xenograft subcutaneously implanted in nude mice and to explore the antitumor mechanism of CXCR4 mAb. Methods: 8 - week - old Balb/c femal nude mice were adopted to establish a subcutaneously tumor- bearing model. Treating animals with CXCR4 mAb. The inhibitory effects of CXCR4 mAb on tumor growth were assessed after treatment. Immunohistochemical staining was performed to examine the expressions of PCNA,Caspase- 3 and VEGF. Results: CXCR4 mAb significantly inhibited the growth of breast cancer xenograft in nude mice. Inhibition ratio of tumor volum reached 71. 4% . After treatment, CXCR4 mAb markedly downregulated the expressions of PCNA and VEGF while upregulated the expression of Caspase - 3. Conclusion: CXCR4 mAb might inhibit breast cancer growth in vivo via the induction of cancer cell apoptosis and inhibition of cancer cell proliferation and tumor angiogenesis.%目的 研究CXC趋化因子受体4(CXC chemokine receptor 4,CXCR4)单克隆抗体(CXCR4 mAb)对人乳腺癌MCF-7细胞裸鼠皮下移植瘤生长的影响,并初步探讨CXCR4 mAb抗肿瘤的作用机制.方法 采用8周龄Balb/c雌性裸鼠,建立乳腺癌MCF-7细胞裸鼠皮下移植瘤模型.运用CXCR4 mAb进行干预,从整体水平观察CXCR4 mAb对肿瘤生长的影响,采用免疫组织化学法检测肿瘤组织中增殖细胞核抗原(PCNA)、半胱氨酸天冬氨酸酶3(Caspase-3)和血管内皮细胞生长因子(VEGF)的表达情况.结果 CXCR4 mAb可明显抑制移植瘤的生长,瘤体抑制率达到71.4%;CXCR4 mAb治疗后的肿瘤组织中PCNA和VEGF表达明显下降,而Caspase-3表达上升.结论 CXCR4 mAb可能是通过抑制肿瘤细胞增殖、促进肿瘤细胞凋亡及抑制肿瘤血管形成而发挥抗肿瘤生长的作用.

  10. 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

  11. 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

  12. Research on the mechanism of period2 on the growth inhibition of human ovarian cancer ;xenografts in nude mice%生物钟基因Period2对卵巢癌裸鼠移植瘤生长抑制作用的机制研究

    Institute of Scientific and Technical Information of China (English)

    王朝霞; 李莉; 李风艳; 张三元

    2016-01-01

    Objective:To investigate the mechanism of biological clock gene Period2 on the growth inhibition of human ovarian cancer xenografts in nude mice. Methods:Construction of ovarian cancer xenograft in nude mice with ovarian cancer SKVO3 cell. By using gene trans-fection technique,the recombinant gene Period2 was introduced into the tumor tissue. The ex-pression of Period2 was detected by Real-time PCR and Western blot methods. The animals were sacrificed in two weeks after treatment and measured the weight of the tumor. The volume and weight of the tumor were measured during intervention. Real-time PCR and Western blot methods were used to detect the expressions changes of B cell lymphoma-2 gene ( Bcl-2 ) and Bcl-2 related X protein ( Bax ) gene in tumor tissues. Results:Period2 gene was successfully transfected and expressed in the tumor tissues of nude mice. Compared with the other two groups,the tumor growth rate of Period2 overexpression group was slowed, tumor volume and weight was reduced,tumor inhibition rate was increased,the expression of apoptosis gene Bax was increased,and the expression of apoptosis inhibition gene Bcl-2 was decreased. The differ-ence was statistically significant compared with the other two groups(P<0. 05). Conclusions:Period2 may promote tumor cell apoptosis by inhibiting the expression of apoptosis inhibition gene Bcl-2 and promoting the expression of apoptosis related gene Bax. So it can inhibit the growth and metastasis of ovarian cancer,and play a role in tumor suppression.%目的:探讨生物钟基因Period2对卵巢癌裸鼠移植瘤生长抑制的作用机制。方法:采用卵巢癌SKVO3细胞株构建裸鼠卵巢癌移植瘤,利用基因转染技术外源性导入重组基因质粒Period2。采用Real-time PCR法和Western bolt法检测移植瘤中Period2表达,治疗期间测量移植瘤体积。治疗后2周处死裸鼠,称取瘤重,采用Real-time PCR和Western blot法检测肿瘤组织中Bcl-2和Bax基因的表达

  13. 雷帕霉素抑制子宫内膜癌裸鼠移植瘤生长活体成像的观察%Bioluminescence imaging evaluation of the inhibitory effect of rapamycin in nude mice bearing endometrial cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    李田; 杨越波; 孟丽荣; 李小毛; 许成芳; 李征然

    2011-01-01

    目的:观察雷帕霉素(RAPA)对不同PTEN表达子宫内膜癌裸鼠移植瘤的抑制作用.方法:通过慢病毒转染构建稳定表达绿色荧光蛋白(GFP)的HEC-1A(PTEN阳性)和Ishikawa( PTEN阴性)细胞抹,建立裸鼠移植瘤模型.活体成像系统观察肿瘤的生长情况.观察RAPA治疗后肿瘤的体积及重量的变化.HE染色观察肿瘤的病理形态学变化.结果:建立稳定表达GFP的子宫内膜癌细胞系及裸鼠移植瘤模型,活体荧光成像显示,治疗组裸鼠荧光强度较对照组明显减弱.治疗组肿瘤体积及重量明显小于对照组(P<0.05),Ishikawa细胞纽的抑瘤率(67.1%)较高于HEC-1A细胞组的抑瘤率(48.1%).治疗组的肿瘤组织可见大片肿瘤细胞坏死,对照组肿瘤细胞坏死少.结论:RAPA对PTEN阳性及阴性的子宫内膜癌生长均有明显的抑制作用,PTEN的丢失可增加RAPA抗子宫内膜癌的敏感性.%OBJECTIVE: To investigate the inhibilpry effect of ra-pamycin (RAPA) in nude mice bearing endometrial cancer cell lines with different PTEN status. METHODS: HEC-1A (PTEN positive) and Ish-ikawa (PTEN negative) cell lines with stable expression of green fluorescent protein (GPP) were established by transfection via lentiviral vec-lor. The HEC-1A-GFP and IshikawaGFP cells were inoculated into the nude mice to prepare the subcutaneously xenografted tumor model. The dynamic growth of xenografted tumor was observed using fluorescence imaging system in vivo. After treated with RAPA, the volume and weight of transplanted tumors in nude mice were measured. Morphology of transplanted tumor tissues was observed by HE staining. RESULTS; The stable GFP-expressing endometrial cancer cell lines and xenografted tumor model were obtained. Optical imaging showed that the fluorescent intensity of treated group was apparently lower than that of the control. As compare with control group,the tumor volume and weight of treated group were signicandy decreased ( P< 0-05). The

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. Local tumor control following single dose irradiation of human melanoma xenografts: Relationship to cellular radiosensitivity and influence of an immune response by the athymic mouse

    International Nuclear Information System (INIS)

    The potential usefulness of untreated congenitally athymic adult mice as hosts for human tumors in radiocurability studies was investigated using five human melanoma xenograft lines (E.E., E.F., G.E., M.F., V.N.). The tumor radiocurability was found to differ considerably among the lines; the radiation doses required to achieve local control of 50% of the tumors irradiated (TCD50 values) ranged from 29.6 +/- 2.1 (SE) to 67.9 +/- 3.5 Gy. Since the clinical relevance of experimentally determined TCD50 values depends on to what extent they are modified by a host immune response, a possible immune reactivity against the melanomas was investigated by comparing the radiocurability data with cell survival data measured in vitro after irradiation in vivo and by performing quantitative tumor transplantability studies. The radiocurability and the cell survival data were found to agree well for the E.F., G.E., and M.F. melanomas. Moreover, the number of tumor cells required to achieve tumors in 50% of the inoculation sites (TD50 values) in untreated and in whole-body irradiated mice were similar, suggesting that the TCD50 values measured for these lines were not significantly influenced by a host immune response. On the other hand, the E.E. and V.N. melanomas showed significantly lower TCD50 values in vivo than predicted theoretically from the in vitro cell survival data and a significantly lower number of tumor cells required to achieve tumors in 50% of the inoculation sites in whole-body irradiated than in untreated mice, suggesting that the radiocurability of these two lines was enhanced due to an immune response by the host. Athymic mice may thus express a significant immune reactivity against some human tumor xenograft lines but not against others

  20. 转基因细胞毒性T淋巴细胞的生物学特性及其对荷瘤裸鼠的抗肿瘤作用%Biological characters of cytotoxic T lymphocytes transfected with tumor necrosis factor-alpha gene and its antitumor effects on transplanted carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    罗意革; 陆云飞; 邱庆明

    2004-01-01

    肿瘤过继免疫治疗提供新型的效应细胞,对防治肿瘤转移和复发,促进肿瘤康复具有积极的意义.%BACKGROUND: Antitumor immunity is suppressed in patients with tumor. It is an effective way to improve the efficacy of adoptive immunity therapy and promote rehabilitation by enhancing the cytokine activity of cytotoxic T lymphocyte (CTL).OBJECTIVE: To study the biological characters and antitumor effects of cytotoxic CTL transfected with tumor necrosis factor-α(TNF-α) gene, and seek a new way of immunegene therapy and adoptive immunity therapy for the treatment of tumor.DESIGN: Block randomizaed experiment.SETTING and MATERIALS: The experiment was done in the Center of Laboratory of Guangxi Medical University. CTL was obtained from lymphocytes isolated from human hepatocellular carcinoma tissue, and stimulated by BEL7404 cells and interferon γ(IFN-γ) . A total of 28 male BALB/c nude mice(aged 4 -6 weeks and weighing 18 -20 g) obtained from the Department of Experimental Animal Sciences of Peking University Health Sciences Center(SPF grade; certificate number: 01-3048).INTERVENTION: CTL was transfected with TNF-α gene by gene recombinant retrovirus vector. The models of tumor nude mice were established by injecting BEL7404 in the armpit of the right forelimb of these nude mice.Twenty-eight nude mice were divided into 4 groups according to their weights, with 7 mice in each group. The efficacy of transgene CTL on tumor in situ(armpit of right forelimb) and ex situ(armpit of left forelimb) were observed. Mice injected with normal saline were taken as the control group.phenotype of CTL and the secretion of TNF-α before or after TNF-α gene rate and tumor generation rate.RESULTS: The morphology, proliferation activity, and cell phenotype of the transgene CTL were similar to CTL. However, the transgene CTL could continuously and efficiently secret TNF-α, with an expression dose as high as 410 ng/L in 72 hours. The transgene CTL had a strong

  1. Suppression of the growth of subcutaneous transplanted human liver cancer and lung metastasis in nude mice treated by sorafenib combined with fluorouracil%索拉非尼联合氟尿嘧啶抑制荷人肝癌裸鼠肿瘤生长和肺转移

    Institute of Scientific and Technical Information of China (English)

    沈沪佳; 王艳红; 徐建

    2013-01-01

    Objective The aim of this study was to explore the inhibitory effect of sorafenib and 5-Fu on transplanted human liver cancer in nude mice,and to investigate the synergistic effect and mechanism between sorafenib and 5-Fu.Methods The nude mouse model of human liver cancer was made by transplantation of human highly metastatic liver cancer cell line HCCLM3 cells,and the tumor-bearing nude mice were treated with sorafenib,5-Fu or both,respectively,and mock-treated tumor-beating nude mice as negative control.To assess the anti-tumor effect of sorafenib and the synergistic effect of sorafenib combined with 5-Fu by measuring the tumor weight and number of lung metastases.Moreover,the expressions of phosphorylated extracellular signal-regulated kinase (p-ERK),P-glycoprotein (P-gp) and topoisomerase 2-alpha (Topo Ⅱa) in the nude mice were assayed by immunocytochemistry and Western blot.Results The tumor weights and numbers of lung metastases were: (2.7 ± 0.825) g and 12.714 ± 6.317 in the negative control group,(0.933 ± 0.333) g and 4.333 ± 3.983 in the sorafenib group,(0.786 ± 0.212) g and 5.429 ±4.315 in the Sorafenib +5-Fu combination group,and (2.438 ± 0.793)g and 10.429 ± 6.241 in the 5-Fu group.Statistically,the tumor weights and numbers of lung metastases in the sorafenib group and combination group were significantly decreased,compared with that in the control group (P < 0.05).There was no significant difference in the tumor weight and number of lung metastases between the sorafenib group and the combination treatment group (P > 0.05).The expression levels of p-ERK,P-gp and Topo Ⅱ a proteins in the tumors after normalization were: negative control (0.017 ±0.010,0.085 ± 0.012,0.103 ± 0.093),sorafenib group (0.010 ±0.008,0.044 ±0.020,0.020 ±0.018),combination group (0.011 ±0.007,0.043 ±0.023,0.062 ±0.026),and 5-Fu group (0.018 ±0.009,0.063 ±0.032,0.065 ± 0.034),respectively.Statistically,the expression of p-ERK,P-gp and Topo Ⅱ a in the

  2. 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

  3. Synthesis of 2'-deoxy-2'-[{sup 18}F]-fluoro-5-ethyl-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FEAU) and micro-PET imaging of HSV-tk gene expression in tumor-bearing nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Alauddin, M.M.; Shahinian, A.; Park, R.; Tohme, M.; Fissekis, J.D.; Conti, P.S. [Univ. of Southern California, Los Angeles, CA (United States). PET Imaging Science Center

    2004-07-01

    Herpes simplex virus type-1 thymidine kinase (HSV1-tk) is being used as a suicide gene for gene therapy of cancer. An in vivo method to assess the HSV1-tk enzyme activity after gene transfer is desirable to monitor gene expression as an indicator of gene delivery. Imaging of the HSV1-tk reporter gene along with various reporter probes is of current interest. We originally developed [{sup 18}F]-FHPG and [{sup 18}F]-FHBG for PET imaging of HSV1-tk gene expression and demonstrated that [{sup 18}F]-FHBG is more useful than [{sup 18}F]-FHPG for this purpose. [{sup 124}I]-FIAU has been shown to be a potential PET imaging agent for HSV1-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. We also demonstrated that radiolabeled FMAU can be used as a marker for HSV-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. Earlier we reported a synthesis for 2'-deoxy-2'-[{sup 18}F]fluoro-5-methyl-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FMAU) and some other 5-substituted nucleosides. We have synthesized now [{sup 18}F]-FEAU, used the tracer for micro-PET imaging of suicide gene expression in tumor-bearing nude mice, and compared the results with earlier studies using [{sup 14}C]-FMAU. (orig.)

  4. Synthesis of 2'-deoxy-2'-[{sup 18}F]-fluoro-5-iodo-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FIAU) and micro-PET imaging of suicide gene expression in tumor-bearing nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Alauddin, M.M.; Shahinian, A.; Park, R.; Tohme, M.; Fissekis, J.D.; Conti, P.S. [Univ. of Southern California, Los Angeles, CA (United States). PET Imaging Science Center

    2004-07-01

    Herpes simplex virus type-1 thymidine kinase (HSV1-tk) is being used as a suicide gene for gene therapy of cancer. An in vivo method to assess the HSV1-tk enzyme activity after gene transfer is desirable to monitor gene expression as an indicator of gene delivery. Imaging of the HSV1-tk reporter gene along with various reporter probes is of current interest. We originally developed [{sup 18}F]-FHPG and [{sup 18}F]-FHBG for PET imaging of HSV1-tk gene expression and demonstrated that [{sup 18}F]-FHBG is more useful than [{sup 18}F]-FHPG for this purpose. [{sup 124}I]-FIAU has been shown to be a potential PET imaging agent for HSV1-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. We also demonstrated that radiolabeled FMAU can be used as a marker for HSV-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. Earlier we reported a synthesis for 2'-deoxy-2'-[{sup 18}F]fluoro-5-methyl-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FMAU) and some other 5-substituted nucleosides. We have synthesized now [{sup 18}F]-FIAU, used the tracer for micro-PET imaging of suicide gene expression in tumor-bearing nude mice, and compared the results with earlier studies using [{sup 14}C]-FMAU. (orig.)

  5. 脐带间充质干细胞对裸鼠胸腺发育的作用及机制%Effects and mechanisms of human umbilical cord-derived mesenchymal stem cells on the thymus development in nude mice

    Institute of Scientific and Technical Information of China (English)

    王黎明; 王立华; 李铭; 王倩云; 杨洁; 刘广洋; 丛秀丽; 刘拥军

    2014-01-01

    背景:自身免疫性疾病的传统治疗方法很难有效解决患者免疫耐受机制缺失的问题。间充质干细胞具有再生修复实质组织器官和免疫调节的生物学特性。目的:探讨人脐带源间充质干细胞对裸鼠胸腺发育的影响及作用机制。方法:采用腹腔注射的方式向Foxn1-/-的BABL/c裸鼠体内注射人脐带源间充质干细胞,2×106/只,分析治疗后裸鼠胸腺残基的组织结构变化、胸腺上皮细胞的分布及成熟度,以及发育后的胸腺成熟淋巴细胞输出功能,并探讨人脐带源间充质干细胞发挥治疗作用的机制。结果与结论:胸腺残基出现了清晰的皮髓质结构,胸腺上皮细胞数量增加并且胸腺输出功能增强,外周血中调节性T细胞增多。其作用机制可能是由于人脐带源间充质干细胞能够定植在胸腺组织内并且表达多种促进胸腺发育的细胞因子,尤其是对胸腺发育非常重要的角质形成细胞生长因子。结果表明人脐带源间充质干细胞能够为裸鼠胸腺的结构发育和功能成熟提供合适的微环境,促进裸鼠胸腺残基的发育和功能成熟,为间充质干细胞治疗免疫性疾病的作用机制提出了新的理论观点。%BACKGROUND:For autoimmune diseases, it is difficult to effectively solve the lack of immunological tolerance in patients by traditional treatments. Mesenchymal stem cells have the biological functions of tissue and organ regeneration and immune regulation. OBJECTIVE:To explore the effects and mechanisms of human umbilical cord-derived mesenchymal stem cells on the development of thymus in nude mice. METHODS:Human umbilical cord-derived mesenchymal stem cells were intraperitoneal y injected into BABL/c nude mice at a dose of 2×106 per mouse. We analyzed the maturation and distribution of thymic epithelial cells in the thymus rudiment of nude mice and the thymopoiesis of this newly developed thymus rudiment

  6. RhoA基因沉默抑制卵巢癌腹腔移植瘤恶性生物学行为的研究%Inhibitory effects of RhoA gene silence on malignant biological behaviors of human ovarian cancer in nude mice intraperitoneal xenograft

    Institute of Scientific and Technical Information of China (English)

    蒋文燕; 康佳丽; 王小霞; 杨文娟; 聂妙玲; 周聪

    2013-01-01

    Objective:To investigate the effects of RhoA gene silence on the malignant biological behaviors of ovarian xenograft in nude mice in vivo.Methods:Twenty one female nude mice were randomly assigned to three groups:HO8910-RhoA-shRNA group,HO8910-RhoA-NC group and HO8910 group.The stable knockdown of RhoA cell line,negative control cell line and ovarian cancer cell line HO8910 were inoculated respectively into abdominal cavity of each group to establish intraperitoneal xenograft model of human ovarian cancer.Abdominal circumference were recorded every two days,the nude mice were sacrificed four weeks after-inoculation.The ascitic volume,dissemination position number,disseminated tumor number,tumor weight and tumor growth inhibition rate were recorded.Histopathological analysis for xenograft tissues were observed by HE staining.The expression of RhoA mRNA and protein of xenograft tissues were detected by real-time qPCR and Western blot.Cell apoptosis in tumor tissues was observed by TUNEL method and apoptotic index (AI) were counted.Results:Abdominal circumference in HO8910-RhoA-shRNA group growth delay were statistically significant (P < 0.05).The HO8910-RhoA-shR-NA group had decreased in ascitic volume (P =0.01),dissemination position number (P < 0.001),disseminated tumor number (P < 0.001) and tumor weight(P < 0.001),with tumor growth inhibition rate of 70.62%.The relative expression of RhoA mRNA and protein were both significantly decreased in HO8910-RhoA-shRNA group (P< 0.001).AI was significantly increased in HO8910-RhoA-shRNA group (P < 0.001).Conclusion:RhoA gene silenced by Lentivirus-mediated RNAi can significantly suppress the malignant biological behaviors of human ovarian cancer in nude mice xenograft.%目的:研究慢病毒介导RhoA基因沉默对人卵巢癌裸鼠腹腔移植瘤生长、侵袭及转移等恶性生物学行为的影响.方法:21只裸鼠随机分为HO8910-RhoA-shRNA组、HO8910-RhoA-NC组和HO8910组,每组7

  7. 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

  8. 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

  9. Peloruside A Inhibits Growth of Human Lung and Breast Tumor Xenografts in an Athymic nu/nu Mouse Model.

    Science.gov (United States)

    Meyer, Colin J; Krauth, Melissa; Wick, Michael J; Shay, Jerry W; Gellert, Ginelle; De Brabander, Jef K; Northcote, Peter T; Miller, John H

    2015-08-01

    Peloruside A is a microtubule-stabilizing agent isolated from a New Zealand marine sponge. Peloruside prevents growth of a panel of cancer cell lines at low nanomolar concentrations, including cell lines that are resistant to paclitaxel. Three xenograft studies in athymic nu/nu mice were performed to assess the efficacy of peloruside compared with standard anticancer agents such as paclitaxel, docetaxel, and doxorubicin. The first study examined the effect of 5 and 10 mg/kg peloruside (QD×5) on the growth of H460 non-small cell lung cancer xenografts. Peloruside caused tumor growth inhibition (%TGI) of 84% and 95%, respectively, whereas standard treatments with paclitaxel (8 mg/kg, QD×5) and docetaxel (6.3 mg/kg, Q2D×3) were much less effective (%TGI of 50% and 18%, respectively). In a second xenograft study using A549 lung cancer cells and varied schedules of dosing, activity of peloruside was again superior compared with the taxanes with inhibitions ranging from 51% to 74%, compared with 44% and 50% for the two taxanes. A third xenograft study in a P-glycoprotein-overexpressing NCI/ADR-RES breast tumor model showed that peloruside was better tolerated than either doxorubicin or paclitaxel. We conclude that peloruside is highly effective in preventing the growth of lung and P-glycoprotein-overexpressing breast tumors in vivo and that further therapeutic development is warranted. Mol Cancer Ther; 14(8); 1816-23. ©2015 AACR. PMID:26056149

  10. 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

  11. 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

  12. 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

  13. 下调ATM表达对裸鼠喉鳞状细胞癌移植瘤放射感性影响的研究%Effect of Down-regulated ATM Expression on Radiosensitivity for Laryngeal Squamous Cell Carcinoma in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    李丽; 冯俊; 王朝莉; 敬保迁

    2013-01-01

    Objective To investigate the effect of antisense oligodeoxynucleotides (AS-Lipo) targeting ATM on radiosensitivity for laryngeal squamous cell carcinoma (Hep-2).Methods Clonogenic survival assay was carried out to detect the survival ability of Hep-2 cells after irradiation,and flow cytometry was used to analyze the cell apoptosis.TUNEL assay was used to analyze cell apoptosis expression in Hep-2 cells transplantation tumor in nude mice.Results After the same dose radiotherapy,the survival fraction (SF) of cells treated with ATM AS-Lipo was lower than that of other groups (P < 0.05).After 4 Gy radiation,the apoptotic rate of the group irradiated with ATM AS-Lipo was (30.7 ± 1.31)%,which was significantly higher than that of others (P < 0.05).There were many apoptotic cells detected by TUNEL analysis in tumors treated with irradiation in combination with ATM AS-Lipo,which was notably more than that of irradiation alone.The AI (Apoptotic Index) for mice tumors treated with irradiation in combination with ATM AS-Lipo was (17.12 ±4.2)%,significantly higher than that of other groups.Conclusion ATM AS-Lipo strengthens radiosensitivity for laryngeal squamous cell carcinoma in nude mice.%目的 探讨反义ATM多核苷酸(AS-Lipo)作用于裸鼠移植瘤对喉鳞状细胞癌(Hep-2)放射治疗敏感性的影响.方法 用克隆生存率来检测喉鳞状细胞癌放射治疗后的生存能力;用流式细胞仪来分析喉癌细胞的凋亡情况;用Tunel染色法检测各组瘤体中细胞凋亡情况.结果 在同等剂量的放射治疗下,AS-Lipo组的生存分数最低.接受4 Gy放射治疗后,行流式细胞仪检测,结果发现AS-Lipo组的凋亡率为(30.7±1.31)%,远高于转染Sen-Lipo、Mis-Lipo、Lipo组.ATM AS-Lipo+放疗组的细胞凋亡数显著高于单独放射治疗组;ATM AS-Lipo+放射治疗组裸鼠瘤体内的凋亡指数为(17.12±4.2)%,与其他组比较差异有统计学意义.结论 反义ATM多核苷酸增强了裸鼠喉

  14. 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

  15. An athymic mouse model to mimic cobalt-60 cutaneous radiation injury

    Energy Technology Data Exchange (ETDEWEB)

    Mosca, Rodrigo Crespo; Ferreira, Danilo Cardenuto; Napolitano, Celia Marina; Santin, Stefany Plumeri; Dornelles, Leonardo Dalla Porta; Alvarenga, Eluara Ortigoso; Mathor, Monica Beatriz, E-mail: rcmosca@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Propose: Cutaneous wound from irradiation is the most common complication in radiotherapy treatment, and can be lead to mortality. We describe an athymic mouse model to mimic cutaneous radiation injury by Cobalt-60. Methods: A protocol was including dosimetry with silicon diodes,10x10x5 cm arrangement made by four lead bricks and PVC pipe designed to immobilize the athymic mouse in order to irradiate one clamped back skin point that was subdivided in four parts. To get the measurements of dose rates on the arrangement in Panoramic Irradiator, it was used a silicon diode encased in an opaque protection for ambient light and connected to an electric cable, forming a dosing probe. The currents generated in diode sensitive volume as a function of time of exposure to gamma radiation coming from the radiator, with dose rate of 0,015 Gy/min in positions 1, 0,021 Gy/min in position 2, 0,55 Gy/min in position 3 and 1,45 Gy/min in position four. After the dosimetry, each athymic mouse was anesthetized using Xylazine and Ketamine dilution and entered into a PVC pipe and a small portion of skin (1 cm{sup 3}) was clamped. This tube was then fixed to arrangement and the athymic mouse was irradiate for 60 min, than it was being returned to its cage. Results: The wound was visualized in all animals and photographed after 5 days of irradiation, with the emergence of ulceration after 9 days. No systemic or lethal sequelae occurred or visualized in any animals. Late clinical signs included a wound healing after 22 days. Conclusion: While still being a baseline study, we created a new functional preclinical animal model that can be used for new therapies and may improve radiotherapy management. (author)

  16. 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

  17. The effect of Fe3O4 nanometer magnetic fluid induced hyperthermia on implanted liver cancer in nude mice%交变磁场下Fe3O4纳米磁流体对裸鼠移植性肝癌的杀伤作用

    Institute of Scientific and Technical Information of China (English)

    彭健; 唐琦; 潘一峰; 陈伟; 黄远飞; 张阳德

    2011-01-01

    Objective To study the therapeutic effect of Fe3O4 nanometer magnetic fluid-induced hyperthermia on implanted liver cancer in nude mice under alternating magnetic field. Methods Nude mice model bearing implanted HepG2 was established. Mice were then randomly divided into 3 groups: the blank control group; the magnetic field group; nanometer magnetic fluid group. The magnetic field group were just put under the magnetic field; Nanometer magnetic fluid group received injection of PEG-PEI/Fe3O4 nanometer magnetic fluid under the alternating magnetic field. At the frequency of 40 kHz, and magnetic field of 5 kA/m, 15 minutes one day in the next 14 days. On the 7th day and the 15th day, the changes of tumor volume and weight were recorded, cell apoptosis were observed and recorded and pathological examination was done. Results On the 7th and the 15th day, in the nanometer magnetic fluid group, tumors' volume was smaller and the weight was lighter than other groups, and the tumor inhibitory rate of 54. 20% (t = 14. 506,P <0. 01 ) was significantly higher than the control group and the magnetic field group 22. 66% ( t = 7.497, P < 0. 05 ). In the control group, tumor cells grew well, high density, the nucleus engrained, the shape irregular, the nuclear fission clear; compared with the control group, in the magnetic field group, tumor cells scatter thinly, intercellular substance increases, and necrosis area formed;in the nanometer magnetic fluid group, many of tumor cells died, their cell nucleus broke up and vanished,the blood vessel reduced obviously, and the tumor cell spread thinly. Conclusions Under the alternating magnetic field, PEG-PEI/Fe3O4 nanometer magnetic fluid inhibits liver cancer growth in nude mice model of HepG2.%目的 研究交变磁场作用下Fe3O4纳米磁流体对HepG2裸鼠移植性肝癌细胞的杀伤作用.方法 建立HepG2裸鼠肝癌移植模型,将荷瘤裸鼠随机分成空白对照组、磁场空白组、Fe3O4纳米磁流体组3组.

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 人小细胞肺癌NCI-H446裸鼠模型的99mTc-octreotide受体显像研究%99mTc-octreotide Receptor Scintigraphy in NCI-H446 Small Cell Lung Cancer Nude Mice Model

    Institute of Scientific and Technical Information of China (English)

    李超; 左书耀; 王叙馥; 刘新峰; 王国明; 武风玉

    2015-01-01

    分布高峰。结论运用99mTc-octreotide作显像剂,人小细胞肺癌NCI-H446裸鼠模型具有极高的显像阳性率,且3h肿瘤显像最清楚。%Background and objective For highly aggressive small cell lung cancer (SCLC), early diagnosis is im-portant for its prognosis, but the current inspection methods are more limited, with poor specificity of the traditional imaging methods, and the high cost of PET/CT, difcult to popularization and application. SCLC is kind of neuroendocrine tumors, high expression of somatostatin receptors, which is the cornerstone of its early molecular imaging diagnosis. Te aim of this study is to observe the biodistribution and metabolism of 99mTc-octreotide in normal and the human SCLC bearing nude mice. Methods Dynamic and static scintigraphy at 0.5 h, 2 h, 3 h, 4 h were performed in both normal and tumor bearing nude mice afer intravenous injection of 99mTc-octreotide. Te technique of drawing region of interest (ROI) was used to obtain the aver-aged pixel counts and the activity-time (A-T) curve of brain, heart, lung, liver, kidney, tumor, respectively. Results ① Te biodistribution study in normal nude mice showed highest uptake in kidney and liver, lower in lung and heart, lowest in brain. Most 99mTc-octreotide was excreted via kidney. ② All tumors were displayed clearly at 3 h postinjection of 99mTc-octreotide. Te averaged T/N ratio at 0.5 h, 2 h, 3 h, 4 h postinjection of 99mTc-octreotide was 1.163±0.03, 2.08±0.12, 3.03±0.23, 2.689±0.31, respectively (F=51.69, P<0.000,1). Te radioactivity of tumor was lower than liver, and similar with the lung. Te curve of tu-mor showed a radioactivity peak at 2 min-3 min postinjection. Conclusion 99mTc-octreotide receptor imaging on nude mice bearing SCLC shares high positive rate, especially at 3 h postinjection.

  3. Observation of cetuximab treatment effect in colorectal cancer xenografted nude mice by 18F-FDG PET/CT%18F-FDG PET/CT成像观察西妥昔单抗对结直肠癌裸鼠移植肿瘤影响的实验研究

    Institute of Scientific and Technical Information of China (English)

    李雯雯; 赵广银; 张兆; 龙成露; 黄颖; 苏乔

    2015-01-01

    目的建立结直肠癌裸鼠移植肿瘤模型,用小动物18F-FDG PET/CT技术评价西妥昔单抗对人结直肠癌移植肿瘤的影响。方法 BALB/c 裸鼠皮下分别接种人结直肠癌细胞HCT116、LIM1215,建立HCT116与LIM1215两种荷瘤裸鼠模型。将成瘤后的模型分为对照组和西妥昔单抗治疗组(n=5),并且全程观察肿瘤体积变化情况。给药1周后采用小动物18F-FDG PET/CT技术评价实体肿瘤模型,并测量各组织与器官的18F-FDG最大每克组织摄取率。结果小动物18F-FDG PET/CT成像显示裸鼠接种部位肿瘤内放射性摄取值增高,LIM1215与HCT116肿瘤模型的治疗组与对照组相比,肿瘤/组织或器官18F-FDG摄取比率均普遍降低,其中肿瘤/颈肌、肿瘤/心脏与肿瘤/肝脏比值差异有统计学意义(P=0.047、0.008、0.024),但两种肿瘤模型的肿瘤体积测量结果均显示,治疗组与对照组的肿瘤生长趋势差异无统计学意义。结论在西妥昔单抗对结直肠癌裸鼠移植肿瘤模型的治疗实验中,西妥昔单抗对肿瘤生长尚未有明显抑制作用时,小动物18F-FDG PET/CT可监测到肿瘤葡萄糖代谢的变化。%Objective To observe the effect of cetuximab in tumor with small animal PET/CT by establishing the xenogenous implant model of colorectal cancer in nude mice. Methods HCT116 and LIM1215 tumor-bearing nude mouse models were developed by subcutaneous implantation of HCT116 and LIM1215 cells into BALB/c-nu mice. The tumor models were divided into the control group and cetux-imab treatment group (n=5), and to observe the growth of tumor. Then the tumor models were evaluated by small animal 18F-FDG PET/CT after one week, and we measured the maximum percentage injected dose per gram from tissue and organ at the same time. Results The uptake of 18F-FDG in tumor tissues was significantly higher than that in normal tissues. Compared with control group, the 18F-FDG uptake rates of tumors/tissue or organ were generally

  4. A multifunctional drug combination shows highly potent therapeutic efficacy against human cancer xenografts in athymic mice.

    Directory of Open Access Journals (Sweden)

    Xiu-Jun Liu

    Full Text Available The tumor microenvironment plays a crucial role during tumor development. Integrated combination of drugs that target tumor microenvironment is a promising approach to anticancer therapy. Here, we report a multifunctional combination of low-cytotoxic drugs composed of dipyridamole, bestatin and dexamethasone (DBDx which mainly acts on the tumor microenvironment shows highly potent antitumor efficacy in vivo. In mouse hepatoma H22 model, the triple drug combination showed synergistic and highly potent antitumor efficacy. The combination indices of various combinations of the triple drugs were between 0.2 and 0.5. DBDx inhibited the growth of a panel of human tumor xenografts and showed no obvious systemic toxicity. At tolerated doses, DBDx suppressed the growth of human hepatocellular carcinoma BEL-7402, HepG2, and lung adenocarcinoma A549 xenografts by 94.5%, 93.7% and 96.9%, respectively. Clonogenic assay demonstrated that DBDx showed weak cytotoxicity. Western blot showed that Flk1 and Nos3 were down-regulated in the DBDx-treated group. Proteomic analysis showed that DBDx mainly affected the metabolic process and immune system process; in addition, the angiogenesis and VEGF signaling pathway were also affected. Conclusively, DBDx, a multifunctional drug combination of three low-cytotoxic drugs, shows synergistic and highly potent antitumor efficacy evidently mediated by the modulation of tumor microenvironment. Based on its low-cytotoxic attributes and its broad-spectrum antitumor therapeutic efficacy, this multifunctional combination might be useful in the treatment of cancers, especially those refractory to conventional chemotherapeutics.

  5. Effect of Cnidium Lactone on Serum Mutant P53 and BCL-2/BAX Expression in Human Prostate Cancer Cells PC-3 Tumor-Bearing BALB/C Nude Mouse Model

    OpenAIRE

    Bi, Dongbin; Yang, Mingshan; Zhao, Xia; Huang, Shiming

    2015-01-01

    Background Cnidium lactone is a natural coumarin compound that can inhibit a variety of cancer cell proliferation and induce cancer cell apoptosis. This experiment investigated the effect of cnidium lactone on molecular marker expression in prostate cancer nude mice to study its effect in inducing apoptosis. Material/Methods We randomly and equally divided 30 male BALB/C nude mice inoculated with human prostate cancer cells PC-3 into a negative control group, a cyclophosphamide group (500 mg/...

  6. 人弥漫性大B细胞淋巴瘤移植瘤模型的建立及生长特性观察%Establishment and characterization of a nude mice model of human diffuse large B-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    于宝华; 周晓燕; 张铁成; 张太明; 施达仁

    2011-01-01

    Objective To establish a diffuse large B-cell lymphoma (DLBCL)-mice model using human DLBCL cell line LY8, to investigate its characteristics of growth and to provide a model for in vivo study of DLBCL pathogenesis and treatment. Methods LY8 cells were injected subcutaneously into the right flank of nude mice. Harvested tumor tissues were cut into small pieces of 1.5 mm × 1.5 mm × 1.5 mm and implanted subcutaneously into nude mice. Tumor growth was visualized and the histologic characteristics were documented. Expression of LCA, CD20, CD79α, Ki-67, CD3, CD45RO, bcl-6, MUM-1, CD1O and bcl-2 were examined by using immunohistochemistry. IgH clonal rearrangement and status of three microsatellite loci (D14S68, D18S69, D20S199) in the xenografted tumor samples and the parental cell line LY8 were detected using PCR amplification followed by PAGE. Results The subcutaneous xenograft DLBCL model was successfully established by using cell line LY8, and a stable growth was achieved up to the 9th generation. The tumor in each generation showed similar growth characteristics and the rate of subcutaneous tumor formation was 91.9% (114/124). The tumor growth was observed from the 2nd week after implantation, reaching 1.3 cm in major diameter at the 3rd week and 2. 0 cm at the 4th week. The tumor had identical morphological characteristics with those of human DLBCL, and expressed LCA, CE0,CD79α, bcl-6, MUM-1, CD1O and bcl-2. The tumor of xenograft mice and cell line LY8 showed identical IgH rearrangement and microsatellite length. Conclusions A human DLBCL bearing mouse model was successfully established. The mice model is similar to human counterpart with high stability and repeatability. Therefore, it provides an ideal animal model for in vivo studies of the biological characteristics and treatment of DLBCL.%目的 建立人弥漫性大B细胞淋巴瘤(DLBCL)细胞株LY8裸鼠皮下移植瘤模型并观察其生长特性,为探讨淋巴瘤发病机制及治

  7. 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

  8. Quantitative studies of lymphoid organs, blood and lymph in inbred athymic and euthymic LEW rats under germfree and specified-pathogen-free conditions

    DEFF Research Database (Denmark)

    Klausen, B; Hougen, H P

    1987-01-01

    Four groups of inbred male LEW rats were examined: A, germfree athymic; B, specified pathogen free (SPF) athymic; C, germfree euthymic; D, SPF euthymic. All animals were killed at 18 weeks and compared with respect to body weight, histological appearance and cell density of the lymphoid organs......, haematological values and differential counts of bone marrow, peripheral blood and lymph. Athymic rats had a lower body weight, less densely populated lymphoid organs, and fewer lymphocytes in the blood and lymph compared with euthymic animals. No difference was seen between athymic rats under germfree and SPF...

  9. 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

  10. Evaluation of Nonacog Beta Pegol Long-term Safety in the Immune-deficient Rowett Nude Rat (Crl:NIH-Foxn1rnu).

    Science.gov (United States)

    Rasmussen, Caroline E; Nowak, Jette; Larsen, Julie M; Bottomley, Anna; Rowles, Alison; Offenberg, Hanne

    2016-07-01

    Nonacog beta pegol is a 40-kDa polyethylene glycosylated (PEGylated) human recombinant coagulation factor IX, intended for the treatment of hemophilia B. Human coagulation factors are immunogenic in animals; therefore, to evaluate the long-term toxicity of nonacog beta pegol, an immune-deficient, athymic rat (Rowett nude; Crl:NIH-Foxn1(rnu)) was used. Rats (n = 216) were given intravenous nonacog beta pegol 0, 40, 150, 600, or 1,200 IU/kg every 5th day for 26 weeks. To avoid infections, the animals were housed in a full-barrier environment with sterilized food and bedding. Standard toxicity end points were unaffected by treatment. All treated animals were exposed to nonacog beta pegol throughout the study, and no animals developed antidrug antibodies. Immunohistochemical staining revealed PEG in choroid plexus epithelial cells in a dose-dependent manner. Transmission electron microscopy showed that PEG was distributed in cytoplasmic vesicles of these cells, with no apparent effect on cellular organelle structures. Fourteen (6.5%) animals were euthanized or died prematurely due to nontreatment-related infections in the urogenital system and skin. In conclusion, the athymic rat is a suitable model for testing chronic toxicity of human proteins that are immunogenic in animals. Nonacog beta pegol was generally well tolerated, with no adverse effect of PEG on choroid plexus epithelial cells. PMID:26940713

  11. The nude beach as a liminal homoerotic place

    OpenAIRE

    Monterrubio, J. Carlos

    2013-01-01

    As a socially, culturally and sexually constructed space, the nude beach has been the focus of academic research. Some studies have analysed the nude beach as a place where erotic relations and meanings among men are performed, constructed, negotiated and transformed. These studies however have seldom acknowledged the multiple dimensions of sexualised practices and subjectivities taking place at the nude beach among men. By adopting a homoerotic framework, this study analyses a number of sexu...

  12. 三羟异黄酮对HER-2/neu过度表达乳腺癌裸鼠移植瘤血管生成的抑制作用%Inhibitory effect of genistein on the angiogenesis in HER-2/neu-overexpressing breast cancer xenograft in nude mice

    Institute of Scientific and Technical Information of China (English)

    朱俊东; 余小平; 糜漫天

    2005-01-01

    乳腺癌的预后.%BACKGROUND: Angiogenesis is an important prognostic indicator for malignant tumors. Breast cancer overexpressing oncogene HER-2/neu often denotes a poor prognosis. Many studies have demonstrated the antitumor effect of genistein against breast cancer.OBJECTIVE: To study the relationship between HER-2/neu expression and angiogenesis in breast cancer as well as the effect of genistein on the angiogenesis in HER-2/neu-overexpressing breast cancer.DESIGN: A randomized controlled observatory experiment with nude mice.SETTING: Department of nutrition and food hygiene of a military medical university.MATERIALS: Twenty specific pathogen-free(SPF) normal female BALB/c nude mice weighing (10 ± 2) g, aged 3 to 4 weeks, were purchased from the Experimental Animal Center of the Third Military Medical University.METHODS: This study was carried out in the Department of Nutrition and Food Hygiene, Third Military Medical University from June 2001 to March 2002. HER-2/neu-overexpressing breast cancer cell line MCF-7/HER-2 was generated by transfecting MCF-7 cells with human HER-2/neu cDNA. MCF-7/HER-2 and MCF-7 cells were inoculated in female BALB/c nude mice to establish tumor-bearing mouse models. Four weeks after the inoculation, the mice with MCF-7/HER-2 xenografts were randomly divided into control,genistein treatment, and anti-HER-2/neu antibody treatment groups to receive corresponding treatments every other day for two weeks, at the end of which the tumor volume, microvessel density(MVD) and vascular endothelial growth factor(VEGF) expression in the xenografts were measured.MAIN OUTCOME MEASURES: MVD and VEGF expression in the xenograft tumor. Secondary outcome measures: Identification of HER-2/neu-transfected from MCF-7-transfected cells and the tumor volume.RESULTS: The MVD was 16 ±6, 98 ±21, 56± 18, and 52 ± 19 in each visual field in the MCF-7 xenografts group, control group, genstein treatment group and anti-HER-2/neu antibody treatment group recpectively. MVD and VEGF expression in MCF-7

  13. Preparation of 99Tcm-(HYNIC-BMS-200261) (tricine) (TPPTS) and its biodistribution and preliminary imaging study in nude mice bearing human breast cancer%99Tcm-(HYNIC-BMS-200261)(tricine)-(TPPTS)的制备及对荷乳腺癌裸鼠的显像研究

    Institute of Scientific and Technical Information of China (English)

    李环; 刘晓建; 刘杰; 金超岭; 王猛; 方纬; 戴皓洁; 颜珏; 郑玉民

    2016-01-01

    Objective To synthesize 99Tcm-(HYNIC-BMS-200261) (tricine) (trisodium triphenylphosphine-3,3',3"-trisulfonate) (99Tcm-(HYNIC-BMS-200261) (tricine) (TPPTS)) and evaluate its biodistribution and feasibility of imaging in nude mice bearing human breast cancer xenografts.Methods HYNIC was conjugated to BMS-200261,then tricine and TPPTS were used as coligands for 99Tcm-labeling.The radiochemical purity and stability of 99Tcm-(HYNIC-BMS-200261) (tricine) (TPPTS) were measured with HPLC.Biodistribution in normal mice and imaging in nude mice bearing MDA-MB-435 breast cancer xenografts were performed respectively.Results The radiochemical purity of 99Tcm-(HYNIC-BMS-200261)(tricine) (TPPTS) was over 90%,and remained over 85% after 4 h at room temperature.The biodistribution data in normal mice showed a rapid clearance from blood.The tracer uptake of blood was (0.08±0.02) %ID/g at 2 h postinjection.99Tcm-(HYNIC-BMS-200261)(tricine) (TPPTS) was excreted mainly via the liver and kidneys.There was little radioactivity accumulation in gastrointestinal tract.The tracer uptake of spleen,stomach and small intestine were (0.35±0.13),(0.27±0.11) and (0.25±0.07) %ID/g at 2 h postinjection.Gamma imaging showed the tumor tissue uptake was remarkable at 30 min postinjection,with the maximum T/NT ratio of 3.40±0.30 at 1 h postinjection.Conclusions 99Tcm-(HYNIC-BMS-200261) (tricine) (TPPTS) may be easily prepared with high radiochemical purity and stability.The imaging results and biodistribution characteristics sug,gest it may be promising for the detection of breast cancer.%目的 制备99Tcm-(HYNIC-BMS-200261)(N-三羟甲基甘氨酸)(三苯基膦三间磺酸钠盐)[99Tcm-(HYNIC-BMS-200261)(tricine) (TPPTS)]三重配位化合物,评价其在正常小鼠及荷乳腺癌裸鼠体内的生物分布,并对荷乳腺癌裸鼠进行初步显像研究.方法 先用双功能螯合剂HYNIC与BMS-200261耦联,再以tricine和TPPTS为协同配体,进行99Tcm标

  14. Effects of tissue specific cytosine deaminase/5-fluorocytosine thermotherapy on hepatic metastasis of colonic carcinoma in nude mice%组织特异性胞嘧啶脱氨酶和5-氟胞嘧啶热化疗对裸鼠结肠癌肝脏转移的影响

    Institute of Scientific and Technical Information of China (English)

    黎成金; 王羊; 王烈; 涂小煌; 王瑜; 张宝明

    2009-01-01

    目的 探讨组织特异性胞嘧啶脱氨酶/5-氟胞嘧啶(CD/5-FC)系统热化疗对裸鼠结肠癌肝脏转移的影响.方法 将45只裸鼠按随机数字表法分为3组:对照组、非热疗组、热疗组,每组15只.门静脉注射法建立结肠癌肝脏转移动物模型,3组分别给予不同的治疗方法.采用χ2检验和单因素方差分析3组肝脏肿瘤转移率、转移数目;观察各组病理学变化、肿瘤细胞凋亡指数;荧光定量RT-PCR和Westernblot检测肿瘤组织中CD基因的表达情况.结果 对照组、非热疗组、热疗组肝脏平均转移癌结节数目和转移率分别为(4.6±1.3)、(2.2±1.0)、(0.5±0.8)个和100.0%、60.0%、13.3%,3组比较差异有统计学意义(F=25.898,χ2=5.208,19.548,5.168,P<0.05);肿瘤细胞凋亡指数平均为4.6%、9.9%和17.4%.热疗组可见大量细胞空泡变性、坏死、溶解现象,有较多的凋亡小体形成.3组均可以检测到CD基因的表达.结论 组织特异性CD/5-FC系统热化疗对转CD基因结肠癌LoVo细胞裸鼠肝脏转移有明显的抑制作用.%Objective To investigate the effects of tissue specific cytosine deaminase/5-fluorocytosine (CD/5-FC) thermotherapy on hepatic metastasis of colonic carcinoma in nude mice. Methods Forty-five nude mice were randomly divided into control group, 5-FC group and 5-FC thermotherapy group according to the random number table (15 mice in each group). Mice models of hepatic metastasis of colonic carcinoma were established by portal vein injection of LoVo/CEACD cells. The hepatic metastasis rate and number of metastatic nodules of the 3 groups were compared by ehi-square test and one-way ANOVA. The pathological changes in tumor tissues and apoptotic index of tumor cells were observed. The expression of the CD gene in tumor tissues was detected by fluorescent quantitative RT-PCR and Western blot. Results The number of metastatic nodules and liver metas-tasis rate were 4.6±1.3 and 100.0% in control group, 2.2±1

  15. 液质联用法同时测定埃罗替尼及其活性代谢产物OSI-420在BALB/c裸鼠体内的浓度及其药代动力学研究%A sensitive LC-MS/MS method to determine the concentrations of erlotinib and its active metabolite OSI-420 in BALB/c nude mice plasma simultaneously and its application to a pharmacokinetic study

    Institute of Scientific and Technical Information of China (English)

    李梦瑶; 吴琼; 李汉青; 宁妙然; 陈烨; 李良; 周田彦; 卢炜

    2012-01-01

    A simple,rapid and sensitive LC-MS/MS method was developed to quantify erlotinib and its active metabolite,OSI-420,simultaneously in BALB/c nude mice plasma.Erlotinib,OSI-420 and propranolol (internal standard) were extracted from nude mice plasma samples by liquid-liquid extraction.Separation was achieved on a reversed phase CIR column with a mobile phase of acetonitrile-water (35∶65,v/v) containing 5 mM ammonium formate (pH =3.0).All compounds were monitored by mass spectrometry with electrospray positive ionization.The lower limit of quantification was 0.5 ng/mL for both erlotinib and OSI-420; accuracy was estimated by relative error,which was in the range from 0.07% to 8.00% for erlotinib and -2.83% to 6.67%for OSI-420; precision was validated by relative standard deviation,which was from 2.28% to 15.12% for erlotinib and from 1.96% to 11.50% for OSI-420.This method was applied to a pharmacokinetic study of BALB/c nude mice following oral administration of erlotinib at 12.5 mg/kg.A 2-compartment model was used to fit the pharmacokinetics of erlotinib and l-compartment model for the pharmacokinetics of OSI-420.The ratio of the active metabolite to parent drug in mice was greater than previously reported in humans and probably reflects interspecies difference in the rate of conversion of erlotinib to OSI-420.%本试验建立了一种简单快速灵敏的液质联用方法,用以同时测定裸鼠血浆内埃罗替尼及其活性代谢物OSI-420的浓度.采用液液萃取法从血浆中提取埃罗替尼,OSI-420和内标普萘洛,用C18反相柱进行分离,流动相为乙腈-5 mM甲酸铵(35∶65,v/v,pH=3.0).所有化合物均采用电喷雾电离源,正离子方式检测.埃罗替尼和OSI-420的最低定量下限均为0.5 ng/mL.埃罗替尼的准确度在0.07%-8.00%范围内,OSI-420准确度在-2.83%-6.67%范围内:埃罗替尼精密度在2.28%-15.12%范围内,OSI-420精密度在1.96%-11.50%范围内.此

  16. Molecular studies of growth inhibition by 3-bromopyruvic acid in human gastric tumors implanted in nude mice%3-溴丙酮酸对人胃癌细胞裸小鼠皮下种植瘤的作用机制

    Institute of Scientific and Technical Information of China (English)

    曹卫; 张晓东; 陆云飞

    2013-01-01

      目的探讨3-溴丙酮酸(3-Bromopyruvic acid,3-BrPA)对人胃癌细胞株 SGC-7901裸鼠皮下种植瘤的抑制作用及其机制。方法建立人胃癌裸鼠皮下种植瘤模型,将成瘤后的裸鼠随机分为实验组:3-BrPA 低剂量、3-BrPA 中剂量、3-BrPA 高剂量组;PBS(磷酸盐缓冲液)阴性对照组1(pH7.4),PBS 阴性对照组2(pH6.8~7.8);阳性对照5-FU 组。每天于瘤体周围皮下注射给药,连续4周,停药24 h 后取出瘤体并检测瘤体细胞中己糖激酶的活性,分别用免疫组化 SP 法和Western blot 法检测 cleaved caspase-3、bax、bcl-2和 p53蛋白的表达。结果随着3-BrPA 剂量的增加,瘤体细胞中己糖激酶的活性逐渐下降,并呈剂量依赖性。3-BrPA 给药组的 p53、bcl-2蛋白表达下降,而 bax、caspase-3(P17KD)蛋白表达升高,与 PBS 阴性对照组相比差异均有统计学意义(P<0.05)。结论3-BrPA 诱导人胃癌细胞株 SGC-7901裸鼠皮下种植瘤细胞凋亡的机制可能是通过抑制细胞内的己糖激酶活性,上调 bax 蛋白的表达,下调 p53、bcl-2蛋白的表达,最终活化caspase-3而引起的。%Objective To investigate the effects of 3-Bromopyruvic acid(3-BrPA)on the growth of gastric cancer in vivo and to explore how it exerts these effects. Methods Human gastric carcinoma SGC-7901 cells were subcutaneously implanted in nude mice,which were randomly divided into six groups(each n=10)that received subcutaneous injections of 1.85,2.23,or 2.67 mg/kg 3-BrPA;5-FU;or PBS(two groups).After 28 days of treatment,the expression of apoptosis-associated proteins p53,bcl-2,bax and active caspase-3 was examined by immunohistochemistry and Western blotting.Hexokinase activity was assessed using a commercial kit. Results Hexokinase activity gradually declined with increasing 3-BrPA dose. Mice in the 3-BrPA groups showed lower expression of p53 and bcl-2 and higher expression of bax and active caspase-3

  17. Solanine inhibits prostate cancer Du145 xenograft growth in nude mice by inducing cell cycle arrest in G1/S phase%龙葵素通过诱导细胞周期G1/S阻滞抑制裸鼠前列腺癌细胞Du145移植瘤生长

    Institute of Scientific and Technical Information of China (English)

    钟伟枫; 刘思平; 潘斌; 唐兆烽; 钟锦光; 周芳坚

    2016-01-01

    Objective To investigate the effect of solanine on the growth of human prostate cancer cell xenograft in nude mice. Methods Human prostate cancer Du145 cells were injected into the subcutaneous layers on the back of nude mice. After a week, the mice bearing subcutaneous tumor graft were randomly divided into solanine treatment group and saline control group for treatment for 3 weeks. The tumor grafts were then harvested to evaluate the inhibition rate. The mRNA and protein expressions of cell cycle-related genes in the tumors were detected by qRT-PCR and Western blotting, respectively, and tumor cell apoptosis was detected using TUNEL method. Results The tumor growth rate in solanine-treated group was significantly slower than that in the control group (P<0.01). The mRNA and protein expressions of C-myc, cyclin D1, cyclin E1, CDK2, CDK4 and CDK6 were significantly inhibited by solanine. Solanine significantly up-regulated p21 mRNA and protein expression in the tumors and induced a higher apoptosis rate of the tumor cells than saline (P<0.01). Conclusion The tumor-inhibition effect of solanine is probably mediated by regulating the expressions of genes related with G1/S cell cycle arrest and cell apoptosis.%目的:探讨龙葵素对前列腺癌细胞Du145裸鼠移植瘤生长的影响及分子机制。方法采用高度恶性的转移前列腺癌细胞株Du145作为动物体内实验的模型,裸鼠皮下接种Du145细胞建立裸鼠皮下瘤模型。1周后将接种的裸鼠随机分为2组:龙葵素实验组和生理盐水空白对照组,每3 d分别向实体瘤中间部位注射0.2 mL龙葵素(50μg/mL)和生理盐水,观察裸鼠体内肿瘤生长,3周后颈椎脱臼处死裸鼠,剥离肿瘤组织,测量肿瘤的重量并根据肿瘤重量计算抑瘤率。实时荧光定量PCR和Western blotting技术检测各组裸鼠瘤体细胞周期相关基因mRNA和蛋白表达。Tunel原位检测各组裸鼠瘤体组织凋亡情况。结果龙葵素

  18. 消痰散结方对裸鼠人胃癌MKN-45皮下移植瘤模型血清蛋白质组表达的影响%Comparative Serum Proteomic Study of Xiaotan Sanjie Recipe Intervened MKN-45 Human Gastric Tumor-bearing Nude Mice

    Institute of Scientific and Technical Information of China (English)

    陈天池; 魏品康; 贾占民; 魏振

    2012-01-01

    目的 观察消痰散结方对裸鼠人胃癌MKN-45皮下移植瘤模型血清蛋白质组表达的影响.方法 30只BALB/c-nu/nu裸鼠随机分为正常组、模型组、干预组,采用瘤块接种方法造模.正常组自由饮食,模型组、干预组分别给予生理盐水、消痰散结方灌胃.运用蛋白质组学的双向凝胶电泳技术,观察3组之间的血清蛋白质组表达差异,筛选出与消痰散结方作用相关的差异表达蛋白质,并对其进行质谱鉴定,确认差异表达蛋白质的身份.结果 去除血清中高丰度蛋白质后获得分辨率高、重复性稳定性好的血清2-DE图谱.与正常组比较,模型组中找到25个差异表达蛋白点,其中12个表达上调,13个表达下调.与模型组比较,干预组中找到19个差异表达蛋白点,其中14个表达上调,5个表达下调.3组间比较共找到差异表达蛋白点9个,与正常组比较,在模型组中表达上调、在干预组表达回调至正常组水平的3个,最终鉴定为结合珠蛋白、泛素蛋白连接酶、组蛋白甲基转移酶;与正常组比较,在模型组中表达下调、在干预组表达回复至正常组水平的有6个,其中3个鉴定为载脂蛋白A1、过氧化物酶1、超氧化物歧化酶.结论 消痰散结方对载脂蛋白A1、过氧化物酶1等功能蛋白表达的综合性调节可能是其发挥抗胃癌作用的重要机制.%Objective To observe the serum protein spectrum changes of MKN-45 gastric cancer cell bearing nude mice intervened by Xiaotan Sanjie Recipe on the platform of proteomics. Methods Thirty BALB/c-nu/nu mice were randomly divided into normal group, model group and intervention group. MKN45 gastric cancer cells were subcutaneously implanted into immune-incompetent nude mice in model group and intervention group to establish tumor bearing model. The control group was fed freely. The model group and the intervention group was separately administrated with saline and Xiaotan Sanjie Recipe, which

  19. 白花蛇舌草对人肝癌 HepG2细胞裸鼠皮下移植瘤 PI3K/Akt 信号通路的影响%Effect of Hedyotis Diffusa Willd on PI3K/Akt Pathway in Nude Mice Implanted Hepatoma HepG2 Cells

    Institute of Scientific and Technical Information of China (English)

    章尤权; 王清泰; 陈旭征; 魏建威

    2015-01-01

    目的:探讨白花蛇舌草对人肝癌 HepG2细胞裸鼠皮下移植瘤组织磷酸酰肌醇3激酶(PI3K)、总蛋白激酶 B(Akt)和磷酸化 Akt(p-Akt)蛋白表达的影响。方法建立肝癌裸鼠皮下移植瘤模型,随机分为药物组(6 g·kg -1·d -1白花蛇舌草灌胃)和模型组(同等体积生理盐水灌胃),连续给药4周后处死,观察抑瘤率;免疫组织化学染色检测肿瘤组织 PI3K、总 Akt 和 p-Akt 蛋白的表达。结果与模型组比较,药物组瘤体质量明显下降(t =4.270,P =0.006),抑瘤率达61.29%;PI3K 蛋白表达灰度值从82.00±2.72升高至118.67±8.44(t =0.209,P =0.049);Akt 蛋白表达灰度值从72.37±2.89升高至105.19±4.718(t =2.050, P <0.001),p-Akt 蛋白表达灰度值从87.99±4.16升高至96.34±5.72(t =4.123,P =0.002),提示 PI3K、Akt 和 p-Akt 的蛋白表达水平均较模型组明显减低。结论白花蛇舌草通过可调控 PI3K/ Akt 信号通路的相关蛋白抑制肿瘤血管新生。%Objective To evaluate the effect of hedyotis diffusa willd on phosphoinositide 3 kinase(PI3K),pro-tein kinase B(Akt)protein and phosphorylated Akt(p-Akt)protein expressions in nude mice with hepatic carci-noma transplanted subcutaneously. Methods Nude mice xenografts were established. The mice were randomly divid-ed into 2 groups:the hedyotis diffusa willd group and the vehicle group,which received hedyotis diffusa willd(6 g·kg -1 ·d -1 ,intragastric administration)and normal saline( intragastric administration),respectively. After 4 weeks of treatment,the tumors were harvested and weighed. The levels of PI3K,Akt and p-Akt proteins were ob-served with immunohistochemical staining. Results The tumor weight of the hedyotis diffusa willd group were high-er than that of the vehicle group(t = 4. 270,P = 0. 006). The gray levels of PI3K,Akt and p-Akt in the hedyotis dif-fusa willd group(118. 67 ± 8. 44,105. 19 ± 4. 718,96. 34 ± 5. 72)were

  20. The inhibiting effect of endostatin on transplant tumor of breast carcinoma MCF-7 cell in nude mice%内皮抑素对乳腺癌MCF-7细胞裸鼠移植瘤的抑制作用

    Institute of Scientific and Technical Information of China (English)

    招敏仪; 徐波; 夏金堂; 蔡文松; 肖焕擎

    2009-01-01

    Objective To observe inhibiting effect of endostatin on subcutaneous transplant tumor of breast carcinoma, and to illuminate the therapeutic effect of endostatin in the cancer. Methods The effect of en-dostatin on MCF-7 cell proliferation was studied by MTr. The model of MCF-7 cell transplant tumor on nude mice was constructed. Endostatin was injected intradermally around the transplant tumor. Inhibition effect on the tumor was observed. Results Endostatin with the concentration of 10 μ/mL and 15 μg/mL can inhibitMCF-7 cell proliferation effectively (P < 0. 05 ). After endostatin injection, tumor weight, volume and mi-crovessel density decreased significantly(P < 0.05 ). Conclusion Endostatin can inhibit breast carcinoma proliferation through inhibiting angiogenesis and the tumor cell itself.%目的 观察内皮抑素对乳腺癌裸鼠皮下移植瘤的影响,探讨内皮抑素用于乳腺癌治疗的应用前景.方法 MTT法测定内皮抑素对MCF-7细胞生长的抑制率.构建乳腺癌细胞MCF-7裸鼠皮下移植瘤模型,瘤体周边注射内皮抑素,观察其对乳腺癌细胞的抑制作用.结果 10μg/mL和15 μg/mL浓度的内皮抑素能有效抑制MCF-7细胞生长(P<0.05).皮下注射内皮抑素后,移植瘤的瘤重和瘤体积及肿瘤微血管密度均较对照组下降(P<0.05).结论 内皮抑素具有良好的生物学活性,通过抑制血管生成及直接抑制肿瘤细胞生长而发挥抗乳腺癌的作用.

  1. CHANGES IN MOUSE CIRULATING LEUKOCYTE NUMBERS IN C57BL/6 MICE IMMUNOSUPPRESSED FOR CRYPTOSPORIDIUM PARVUM OOCYST PRODUCTION

    Science.gov (United States)

    The Iowa strain of Cryptosporidium parvum will not propagate in immunocompetent mice, but will successfully infect genetically immunocompromised Nude or SCID mice as well as immunocompetent mice which have been immunosuppressed with glucocorticoids. Using dexamethasone - tetracy...

  2. PI-88对TE-13细胞及裸鼠移植瘤中乙酰肝素酶表达的影响%The influence of PI-88 on heparanase protein expression of human esophageal cancer cell and xenograft of nude mice

    Institute of Scientific and Technical Information of China (English)

    朱辉; 何明; 陈新; 李宝重; 徐新建; 李飞

    2015-01-01

    目的:探讨硫酸化寡聚多糖(PI-88)对食管鳞癌细胞株TE-13乙酰肝素酶(Hpa)表达的影响,以及对裸鼠人食管癌移植瘤生长、血管生成及Hpa蛋白表达的影响。方法体外培养TE-13细胞,实验分为A组(对照组)、B组(15 mg/L PI-88干预组)和C组(30 mg/L PI-88干预组)。培养36 h后Western blot检测各组细胞Hpa蛋白表达。选取10只BALB/c/nu裸鼠,皮下接种TE-13细胞建立食管癌裸鼠移植瘤模型,建模成功后随机均分为观察组及对照组。观察组腹腔注射PI-8840 mg/(kg·d),对照组给予等剂量生理盐水,连续注射14 d。每2 d测量移植瘤体积,注射第14天处死动物,剥除移植瘤行CD34染色,检测微血管密度(MVD)。Western blot及免疫组化染色检测Hpa蛋白表达。结果与A组相比,B、C组细胞Hpa蛋白表达量明显降低(P<0.001),且存在药物浓度依赖性。观察组裸鼠移植瘤体积、MVD值、Hpa蛋白表达水平及阳性细胞数均低于对照组(均P<0.05)。结论 PI-88可抑制TE-13细胞及食管癌裸鼠皮下移植瘤中Hpa表达,并抑制肿瘤生长和血管生成。%Objective To explore the inhibitory effects of sulfated oligosaccharides PI-88 on the heparanase protein expression of human esophageal squamous cancer cell (ESCC) line TE-13, and to explore the effects of growth, angiogenesis and heparanase protein expression on ESCC xenografts of nude mice. Methods TE-13 cells were cultured and divided into three groups:group A (control group), group B (15 mg/L PI-88) and group C (30 mg/L PI-88). Heparanase protein expression of TE-13 cells was measured by Western blot assay after being cultured for 36 h. The ESCC suspension was injected subcutaneously in 10 BALB/c/nu mice to build up ESCC xenograft model. The model mice were divided randomly into observation group and control group (5 mice per group). The mice in observation group received 40 mg/(kg·d) PI-88. The mice

  3. Roles of MAPK/ERK signaling pathway in the growth inhibition of an established A431 xenograft tumor in nude mice by resveratrol%MAPK/ERK信号转导通路在白藜芦醇抑制A431细胞株裸鼠移植瘤生长中的作用机制研究

    Institute of Scientific and Technical Information of China (English)

    郝玉琴; 黄维星; 宁晓洪; 冯红霞; 张国惠; 李衡贵; 郝春光

    2013-01-01

    evaluate the effect of resveratrol on the growth of an established A431 xenogratt tumor in nude mice.Methods The model of human skin squamous cell carcinoma was established by inoculating A431 cells in log-phase growth into the left axillary fossa of Balb/c (nu/nu) nude mice.After 7-8 days,60 mice bearing human A431 skin squamous cell carcinoma xenografts were randomly and equally divided into 6 groups:blank control group receiving no treatment,negative control group treated with intraperitoneal sodium chloride physiological solution,positive control group treated with intraperitoneal cyclophosphamide,high-,medium-and low-dose resveratrol groups treated with intraperitoneal resveratrol of 40,20 and 10 μg per gram body weight per day,respectively.Tumor size was measured at a 4-day interval during the treatment course.After 14-day treatment,the mice were sacrificed.Xenograft tumors were removed from these mice and subjected to weight measurement,pathological examination by hematoxylin and eosin (HE) staining and apoptosis detection by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL).Western blot was conducted to quantify the protein expression of apoptosis-related factors,including phosphorylated extracellular signal-regulated protein kinase (p-ERK),p53 and caspase 3.Data were processed by SPSS 13.0 software,and statistical analysis was carried out by analysis of variance and Pearson correlation analysis.Results By the end of treatment,the xenograft tumor volume was (1153.56 ± 255.41) mm3,(1001.69 ± 115.08) mm3,(1206.80 ± 175.88) mm3,(1342.28 ± 211.12) mm3,(1642.34 ± 225.85) mm3 and (1564.32 ± 156.49) mm3,and the weight was (1.84 ±0.30) g,(1.72 ± 0.39) g,(1.96 ± 0.40) g,(2.67 ± 0.73) g,(3.16 ± 0.52) g,and (3.33 ± 0.59) g,respectively in the positive control group,high-,medium-and low-dose resveratrol group,negative control group and blank control group.Significant differences were observed in the xenograft tumor volume (F =16.00,P

  4. Looking at Nude Artwork in a Museum Context

    Science.gov (United States)

    Decker, Greg

    2004-01-01

    In an increasingly religious culture, and with museum audiences with large populations of children, nude artworks continue to be cultural lightning rods, generating controversy--sometimes disliked, feared or misunderstood. As a figurative painter who paints nudes, and more importantly as a Teaching Artist who deals with nudity in classroom or…

  5. 131Ⅰ-酪氨酸-奥曲肽对荷人非小细胞肺癌小鼠的抑瘤效果%The experimental study on anti-tumor effect of 131Ⅰ-Tyr-octreotide in nude mice bearing human non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    苏燕; 王峰; 张乐乐; 郑玉民; 孟庆乐; 蒋娥; 李少华; 王自正

    2009-01-01

    目的 探讨131Ⅰ标记酪氨酸-奥曲肽(131Ⅰ-Tyr-octreotide)对荷人非小细胞肺癌(NSCLC)小鼠的抑瘤效果.方法 经氯胺T法标记Tyr-octreotide,测其放化纯及其在小鼠体内的生物分布;建立荷人NSCLC小鼠模型,分为尾静脉注射131Ⅰ-Tyr-octreotide组、肿瘤间质注射131Ⅰ-Tyr-octreotide组、肿瘤间质单纯注射131Ⅰ组和间质注射生理盐水组,观察肿瘤部位的放射性摄取,勾画感兴趣区(ROI),计算肿瘤与对侧正常组织(T/NT)放射性比值,并对肿瘤进行细胞周期检测和免疫组织化学检测,观察癌细胞的凋亡.采用SPSS 11.0软件进行统计学处理,组间两两比较行单因素方差分析.结果 标记产物放化纯为(95.23±1.67)%,比活度为3.5×106Bq/ug.小鼠体内放射性分布示肾摄取最高,肝、脾摄取较少;荷瘤鼠显像示:间质注射131Ⅰ-Tyr-octreotide组肿瘤放射性浓聚较尾静脉注射和间质单纯注射131Ⅰ明显,放射性滞留较久;其24 h的T/NT比值最高,为52.74±0.13,明显高于其他2组(8.90±0.23,6.42±0.02,q=628.81和664.33,P均<0.05);流式细胞检测可见经间质给药组较尾静脉给药组和单纯注射131Ⅰ组G1期细胞阻滞明显[各组G1期肿瘤细胞占总细胞的百分比分别为(83.17±6.86)%、(57.02±18.81)%、(49.29±7.80)%,q=1.56~6.86,P均<0.05],免疫组织化学检查结果示肿瘤细胞大量凋亡,可见凋亡小体形成.结论 131Ⅰ-Tyr-octreotide易于标记且与生长抑素受体(SSTR)表达阳性的NSCLC有较高的亲和力,对肿瘤组织有较强的促凋亡和抑瘤作用.%Objective Radionuclide-labeled low molecular weight polypeptide is reeently advocated for the diagnosis and treatment of malignant tumor. The purpose of this study was to evaluate the anti-tumor effect of 131Ⅰ-Tyr-octreotide in nude mice bearing human non-small cell lung cancer (NSCLC). Methods 131Ⅰ-Tyr-octreotide was prepared by Ch-T method. The radiochemical purity was measured and biodistribution

  6. 寡脱氧核苷酸致敏树突状细胞对SKOV -3卵巢癌移植瘤抑瘤作用的研究%Study on the immunosuppressive action of dendritic cells sensitized by CpG ODN on human SKOV -3 ovarian carcinoma xenografts in nude mice

    Institute of Scientific and Technical Information of China (English)

    叶明殊; 李娜; 黄秀敏

    2011-01-01

    Objective: To investigate the immunosuppressive action of dendritic cells (DCs) sensitized by oligonucleotides containing " un - methylated cytimidine - phosphodiester bond - guanylie acid" motif (CpG ODN) on human ovarian carcinoma xenografts in nude mice. Methods: Human peripheral blood -derived dendritic cells were isolated and co - incubated with CpG ODN2006, CA125, or CPG OND + CA125. T cells were obtained from DCs, and the suspensions of different groups of pulsed DCs were co - incubated with T cells. The cytotoxic T lymphocyte ( CTL) reaction were used to detect the proliferating activity of T cells. Ovarian carcinoma cells of the line SKOV - 3 were added into the culture fluid of T cells induced by different groups of DCs. MTT colorimetry were performed to calculate the killing activity. Then nude mice bearing SKOV - 3 transplanting tumor were immuned with the activated T cells by intraperitoneal injection, and tumor growth was observed. Results: Human peripheral blood - derived dendritic cells were activated significantly by CpG ODN2006 associated with CA125 in vitro. The activated DCs promoted the proliferation of T cells, and there was significant difference with impulsed DC and CA125 - pulsed DC (all P <0.01) . CTLs induced by CpG ODN + CA125 - pulsed DC appeared stronger specific cytotoxicity on SKOV3 cells than those by CpG ODN - pulsed DC, CA125 - pulsed DC and impulsed DC at the same effectors: target ratios ( all P < 0. 01). More marked growth inhibition of SKOV -3 transplanting tumor was observed in CpG OND + CA125 - pulsed group than CpG ODN - pulsed and CA125 -pulsed groups (PCpGODN <0. 05, PCA125 <0. 01) in vivo. Conclusion: DCs sensitized by CpG ODN + CA125 can inhibit the growth of ovarian carcinoma. It may provide a new alternative for the immunotherapy of ovarian carcinoma.%目的:探讨含未甲基化胞嘧啶-磷酸二酯键-鸟嘌呤(CpG)基序的寡脱氧核苷酸(CpG ODN)致敏树突状细胞(DCs)对裸鼠人卵巢癌移植瘤生长

  7. Imaging and biodistribution of ~(99)Tc~m labeled peptide high-binding VEGF receptor 3 in nude mice with ovarian cancer%~(99)Tc~m标记VEGFR-3高亲和融合多肽在荷人卵巢癌裸鼠体内的分布和显像研究

    Institute of Scientific and Technical Information of China (English)

    王玲; 梁志清; 侍立峰; 杨明福; 刘广元

    2009-01-01

    目的 研究~(99)Tc~m标记VEGFR-3高亲和融合肽(phage-SHSWHWLPNLRHYAS)在荷人卵巢癌裸鼠体内分布和放射免疫定位显像.方法 用NHS-MAG3为双功能鳌合剂,固相法合成多肽.~(99)Tc~m预亚锡直接标记法进行标记,纸层析法测定标记率.经尾静脉注射于荷瘤鼠体内,取不同时相进行SPECT显像,测定标记物在体内的分布情况并进行分析.结果 融合多肽的~(99)Tc~m标记率为95.27%,放射化学纯度为96%,放射性浓度24.6 MBq/ml.经鼠尾静脉注射后1 h,植瘤部位开始出现放射性浓集,肾脏、肝脏及膀胱组织也可见显像;注射后3 h肿瘤显像最清晰,每克组织注射百分剂量率(%ID/g)为(30.20±6.89).其余大部分脏器的T/NT值均达最高,最高为肌肉(13.13);注射后4 h肿瘤部位显像逐渐消退.对照组裸鼠的肿瘤部位始终未见显像.结论 筛选获得的VEGFR-3高亲和融合肽能够靶向荷瘤鼠体内肿瘤组织,实现肿瘤的靶向受体显像.%Objective To investigate the imaging and biodistribution of ~(99)Tc~m labeled peptide (phage-SHSWHWLPNLRHYAS) high-binding VEGF receptor 3 in nude mice with ovarian cancer. Methods We used NHS-MAG3 as the bifunctional chelating agent and synthesized the peptide above. It was completed with pre-stannous direct labeling by ~(99)Tc~m and then the labeling efficiency was determined by paper chromatography. The tumor bearing mice were injected via tail veins with radiolabeled peptide. The tumors were imaged with single photon emission computed tomography (SPECT). We measured and calculated the biodistribution of the radiolabeled peptide. Results The labeled rate was 95. 27% and the radiochemical purity was 96%. Under a SPECT apparatus, we observed tumor location image at 1 h post injection and the tumor images was the clearest at 3 h post injection, with the injected dose per gram of tissue (%ID/g) of (30. 20±6. 89) at the tumor sites. The tumor/muscle ratio was 13.13. Conclusion Our peptide can

  8. 荷人结肠癌裸鼠注射负载超顺磁性氧化铁聚合物纳米囊泡后的MRI表现%The MRI study of supraparamagnetic ironic oxide loaded polymeric nano-vesicles in human colonic carcinoma xenograft in nude mice

    Institute of Scientific and Technical Information of China (English)

    冯仕庭; 李皓; 孙灿辉; 蔡华崧; 周健; 帅心涛; 李子平; 孟悛非

    2011-01-01

    Objective To synthesize the hydrophobic supraparamagnetic ironic oxide(SPIO) loaded and hydrophilic SPIO loaded polymeric nano-vesicles and to investigate the feasibility of using hydrophobic SPIO loaded and hydrophilic SPIO loaded polymeric nano-vesicles to display the tumor in MRI in vivo through animal experiments. Methods The polymeric nano-vesicles were prepared from poly (D, L-lactic acid) (PDLLA) and poly (ethylene glycol) (PEG) by a multiple emulsion/solvent evaporation method.The hydrophobic SPIO and hydrophilic SPIO were loaded in the polymeric nano-vesicles respectively.Eighteen nude mice models with human colorectal carcinoma xenograft were established. They were divided equally into three groups (n = 6). The three groups of nude mice models were injected with water-soluble SPIO, hydrophobic SPIO loaded and hydrophilic SPIO loaded vesicle via the mice caudal vein respectively.Dynamic MRI scan were performed in all the mice models. T2WI signal intensity and T2 relaxation time were measured in the tumor, liver and muscle by using T2 mapping software. ANOVA of repeated measurement was used to analyze if there were significant differences of signal intensity changes among the three groups, while Bonferroni method was used for pair-wise comparison. Results On T2 WI, tumors showed decrease in signal intensity after hydrophobic or hydrophilic SPIO loaded polymeric nano-vesicle injection, while no signal intensity decrease was found in the tumor after water-soluble SPIO administration. The maximum percentage of signal intensity decrease in tumor caused by hydrophobic SPIO loaded and hydrophilic SPIO loaded vesicle were 11.00%, 11.40%, respectively. There was statistical significant difference of signal intensity changes among these three groups (F = 10. 96, P < 0. 01). The decrease in signal intensity in the groups with hydrophilic or hydrophobic SPIO loaded polymeric nano-vesicles injection were more pronounced as compared with that of water-soluble SPIO (P

  9. OB glue paste technique for establishing nude mouse human gastric cancer orthotopic transplantation models

    Institute of Scientific and Technical Information of China (English)

    Jun Shi; Guo-Jing Zheng; Xiao-Mei Su; Ya-Lin Chen; Yan-Fang Liu; Ling Xu; Pin-Kang Wei; Shen Zhang; Zhi-Feng Qin; Jun Li; Da-Zhi Sun; Yan Xiao; Zhi-Hong Yu; Hui-Ming Lin

    2008-01-01

    AIM: To establish nude mouse human gastric cancer orthotopic transplantation models using OB glue paste technique.METHODS: Using OB glue paste technique,orthtopic transplantation models were established by implanting SGC-7901 and MKN-45 human gastric cancer cell strains into the gastric wall of nude mice.Biological features,growth of the implanted tumors,the success rate of transplantation and the rate of auto-metastasis of the two models were observed.RESULTS: The success rates of orthotopic transplantation of the two models were 94.20% and 96%.The rates of hepatic metastasis,pulmonary metastasis,peritoneal metastasis,lymphocytic metastasis and splenic metastasis were 42.13% and 94.20%,48.43% and 57.97%,30.83% and 36.96%,67.30% and 84.06%,and 59.75% and 10.53%,respectively.The occurrence of ascites was 47.80% and 36.96%.CONCLUSION: OB glue paste technique is easy to follow.The biological behaviors of the nude mouse human gastric cancer orthotopic transplantation models established with this technique are similar to the natural processes of growth and metastasis of human gastric cancer,and,therefore,can be used as an ideal model for experimental research of proliferative metastasis of tumors.

  10. Lack of transmission of murine norovirus to mice via in vitro fertilization, intracytoplasmic sperm injection, and ovary transplantation.

    Science.gov (United States)

    Raspa, Marcello; Mahabir, Esther; Fray, Martin; Volland, Ruth; Scavizzi, Ferdinando

    2016-07-15

    Since its discovery in 2003, murine norovirus (MNV) is still endemic in many rodent animal facilities. Our aim was to determine the risk of transmission of MNV (91% homology to MNV3) to embryo recipients and pups via assisted reproductive technologies, especially those which compromise the integrity of the zona pellucida. In vitro fertilization (IVF), assisted in vitro fertilization (AIVF) with reduced glutathione, intracytoplasmic sperm injection, and ovary transplantation were performed. Murine norovirus was detected by qualitative and quantitative reverse transcription polymerase chain reaction. After natural infection of immunocompetent C57BL/6NTacCnrm and immunodeficient athymic nude mice with MNV, the mesenteric lymph nodes, small intestine, spleen, liver, lung, brain, ovary, and testis were infected at specific intervals for more than a 1-year period. At Week 12, the number of viral genomes per milligram of gonad from both strains was 20 to 50. Murine norovirus strictly adhered to spermatozoa collected from infected mice because three washes did not remove MNV from the sperm. After using MNV-positive sperm for IVF, AIVF, and intracytoplasmic sperm injection, 27 to 30 genomes were detected in IVF (n = 100) and AIVF (n = 100) embryos from both mouse strains. Approximately 87% of MNV detected in these embryos was found in the zona pellucida. However, all embryo transfer recipients, pups, and ovary recipients were MNV-negative. The results indicate that manipulation of the germplasm through assisted reproductive technologies did not lead to transmission of MNV to mice. This may be because of the absence of an infectious dose or failure of the MNV strain to replicate effectively in developing embryos and the reproductive tract. PMID:26972226

  11. Targeting surface nucleolin with a multivalent pseudopeptide delays development of spontaneous melanoma in RET transgenic mice

    Directory of Open Access Journals (Sweden)

    Briand Jean-Paul

    2010-06-01

    Full Text Available Abstract Background The importance of cell-surface nucleolin in cancer biology was recently highlighted by studies showing that ligands of nucleolin play critical role in tumorigenesis and angiogenesis. By using a specific antagonist that binds the C-terminal tail of nucleolin, the HB-19 pseudopeptide, we recently reported that HB-19 treatment markedly suppressed the progression of established human breast tumor cell xenografts in the athymic nude mice without apparent toxicity. Methods The in vivo antitumoral action of HB-19 treatment was assessed on the spontaneous development of melanoma in the RET transgenic mouse model. Ten days old RET mice were treated with HB-19 in a prophylactic setting that extended 300 days. In parallel, the molecular basis for the action of HB-19 was investigated on a melanoma cell line (called TIII derived from a cutaneous nodule of a RET mouse. Results HB-19 treatment of RET mice caused a significant delay in the onset of cutaneous tumors, several-months delay in the incidence of large tumors, a lower frequency of cutaneous nodules, and a reduction of visceral metastatic nodules while displaying no toxicity to normal tissue. Moreover, microvessel density was significantly reduced in tumors recovered from HB-19 treated mice compared to corresponding controls. Studies on the melanoma-derived tumor cells demonstrated that HB-19 treatment of TIII cells could restore contact inhibition, impair anchorage-independent growth, and reduce their tumorigenic potential in mice. Moreover, HB-19 treatment caused selective down regulation of transcripts coding matrix metalloproteinase 2 and 9, and tumor necrosis factor-α in the TIII cells and in melanoma tumors of RET mice. Conclusions Although HB-19 treatment failed to prevent the development of spontaneous melanoma in the RET mice, it delayed for several months the onset and frequency of cutaneous tumors, and exerted a significant inhibitory effect on visceral metastasis

  12. Suppression of the expression of multidrug resistance protein in liver cancer cells by sorafenib and the growth of subcutaneous tumor in nude mice model treated by a combination of sorafenib and fluorouracil%索拉非尼抑制人肝癌细胞耐药蛋白表达及其与氟尿嘧啶联用抑制裸鼠移植瘤生长的研究

    Institute of Scientific and Technical Information of China (English)

    沈沪佳; 王艳红; 徐建

    2012-01-01

    目的 观察索拉非尼对人肝癌高转移细胞HCCLM3多药耐药蛋白表达的抑制作用及其与5-氟尿嘧啶(5-Fu)联用的协同效应.方法 使用索拉非尼和/或5-Fu对HCCLM3细胞进行干预后,应用免疫细胞化学方法、Western blot法分别检测细胞中磷酸化细胞外信号调节激酶(pERK)及耐药蛋白渗透性糖蛋白(P-gp)和拓扑异构酶2A(TOP-2α)的表达;将HCCLM3细胞接种于裸鼠皮下,并进行药物干预治疗,通过观察肿瘤体积的变化,评估药物对肿瘤生长的抑制作用.细胞实验及裸鼠实验均设置对照组(C)、索拉非尼组(S)、5-Fu组(F)、索拉非尼与5-Fu联用组(SF).结果 各组细胞的pERK、P-gp及TOP-2α表达分别为:C组(0.061 ±0.026、0.076±0.033、0.075±0.022)、S组(0.024±0.011、0.027±0.006、0.025±0.024)、F组(0.080±0.036、0.047±0.005、0.059±0.025)、SF组(0.027±0.015、0.022±0.019、0.038±0.020).与C组比较,S组和SF组的pERK、P-gp、TOP-2α的表达明显下降(P<0.05).各组裸鼠皮下瘤体积(cm3)分别为:C组(5.292±1.523)、S组(1.620 ±0.784)、SF组(1.1100.402)、F组(4.327±1.709).与C组比较,S组和SF组裸鼠的肿瘤体积明显缩小(P<0.05).结论 索拉非尼单独或与5-Fu联用能明显抑制HCCLM3细胞中pERK、P-gp、TOP-2α蛋白的表达及裸鼠皮下瘤的生长.%Objective To explore the inhibitory effect of sorafenib on the expression of multidrug resistance proteins in HCCLM3,a human hepatocellular carcinoma cell line with high metastatic potential,and to investigate the synergistic effects of sorafenib and fluorouracil (5-Fu).Methods The HCCLM3 cells were treated with sorafenib plus 5-Fu or alone,respectively,and mock-treated as negative control.The expression of phosphorylated extracellular signal-regulated kinase ( pERK),P-glycoprotein (P-gp) and topoisomerase 2α(TOP-2α) in these cells was analyzed by immunocytochemistry and Western blotting.Moreover,nude mice were subcutaneously inoculated with HCCLM3

  13. 二甲双胍联合奥沙利铂对肺癌裸鼠移植瘤 VEGF-C、VEGFR-3、CD44 v6和β-catenin 表达的影响%Effects of metformin combined with oxaliplatin on VEGF-C, VEGFR-3, CD44v6 andβ-catenin expression of lung cancer xenograft in nude mice

    Institute of Scientific and Technical Information of China (English)

    陈玉琴; 陈刚

    2015-01-01

    目的:探讨二甲双胍联合奥沙利铂对肺癌裸鼠移植瘤血管内皮生长因子-C( VEGF-C)、血管内皮生长因子受体-3(VEGFR-3)、CD44变异体蛋白6(CD44v6)和β-链蛋白(β-catenin)分子表达水平的影响。方法建立肺癌裸鼠移植瘤模型,将裸鼠随机分为二甲双胍组、奥沙利铂组、联合用药组及对照组,每组分别给予二甲双胍、奥沙利铂、二甲双胍+奥沙利铂及灭菌蒸馏水等干预,42 d后处死动物,留取肿瘤组织,分别采用免疫组织化学法及实时荧光定量PCR法检测肿瘤组织中VEGF-C、VEGFR-3、CD44v6和β-catenin蛋白及mRNA的表达。结果二甲双胍组、奥沙利铂组和联合用药组的抑瘤率分别为28.97%、34.37%和50.27%。与对照组相比,奥沙利铂组、联合用药组VEGF-C、VEGFR-3、CD44v6和β-catenin蛋白及mRNA表达水平均降低(P均<0.05);与二甲双胍组、奥沙利铂组比较,联合用药组VEGF-C、VEGFR-3、CD44v6和β-catenin 蛋白及mRNA表达水平均降低(P 均<0.05), VEGF-C、VEGFR-3、CD44v6和 β-catenin 蛋白组间比较有统计学差异( F 值分别为79.281、151.275、171.294、164.149,P均<0.01);VEGF-C、VEGFR-3、CD44v6和β-catenin mRNA组间比较差异均有统计学意义(F值分别为78.897、81.029、64.100、83.892,P均<0.01)。结论奥沙利铂及二甲双胍均可抑制VEGF-C、VEGFR-3、CD44v6和β-catenin的表达,联合应用抑制效果更强。%Objective To investigate the effects of metformin combined with oxaliplatin on the expression levels of vascular endothelial growth factor-C (VEGF-C), vascular endothelial growth factor receptor-3 (VEGFR-3), CD44v6 andβ-catenin of lung cancer xenograft in nude mice .Methods We established human lung cancer xenograft models in the nude mice.The nude mice were randomly divided into metformin-treated, oxaliplatin-treated, metformin combined with ox

  14. Tumor penetration with intact MAb and fragments demonstrated in vitro on tumor spheroids and in vivo in the nude mouse model

    International Nuclear Information System (INIS)

    Tumor spheroids grown in culture represent a good in vitro model for the study of tumor penetration phenomena of potential radiotherapeutics. Using this system, it was found that Fab-fragments penetrate tumors more quickly and deeply than complete antibodies. These results were confirmed in tumor bearing nephrectomized nude mice

  15. 99Tcm标记RGD环肽四聚体在神经胶质瘤裸鼠模型中的显像研究%Imaging of 99Tcm-cycllc RGD tetramer in nude mice bearing U87MG human glioma xenografts

    Institute of Scientific and Technical Information of China (English)

    余子璘; 贾兵; 刘昭飞; 史继云; 赵慧云; 杨志; 王凡

    2009-01-01

    Objective Multimeric cyclic RGD (Arg-Gly-Asp) peptides are capable of improving the integrin αvβ3-binding affinity due to the polyvalence effect.In this study,the authors prepare 99Tcm-la-bearing cyclic RGD tetramer E{E[c(RGDfK)]2}2,and evaluate its biodistribution and imaging in nude mice beating U87 MG human glioma xenografts with integrinαvβ3-positive.Methods 99Tcm-hydrazino-nictinamide (HYNIC)-E{E[c(RGDfK)]2}2 was prepared by two-step method,while HYNIC wag chosen as bifunctional chelator,and tricine and trisodium triphenylphosphine-3,3,3-trisuifonate (TPPTS) as coligands.The af-finity of c (RGDyK) monomer,HYNIC-E[c(RGDfK)]2 dimer and HYNIC-E{E[c(RGDfK)]2}2 tetramer to integrin αvβ3 was compared by in vitro competitive assay against binding of 125I-c(RGDyK)to integrin αvβ3.positive U87 MG human glioma cells.The biodistribution [the percentage of injection dose per gram of tissue(%ID/g)] and imaging were performed in nude mice bearing UB7MG human glioma xenografts.Re-suits The labeling yield of 99Tcm-HYNIC-E{E[c(RGDfK)2}2 was over 95%,and the radiochemical purity was more than 99%after purification with Sop-Pak C18 cartridge.The 50%inhibiting concentration (IC30) val-ues of c(RGDyk),HYNIC-E[c(RGDfK)]2 and HYNIC-E{E[c(RGDfK)]2}2 were 85.9,9.5 and 4.5 nmol/L, respectively.The result indicated that RGD tetramer possessed a significantly higher affinity to in-tegrinαvβ3.The biodistribution data showed that 99Tcm-HYNIC-E{E[c(RGDfK)]2}2 was excreted mainly through kidneys.The tumor uptake of 99Tcm-HYNIC-E{E[c(RGDfK)]2}2 was two times higher than 99Tcm- HYNIC-E[c(RGDfK)]2,at 1h postinjection,with the uptake of(10.32±0.07)%ID/g and(5.15±0.52)%ID/g,respectively,which was consistent with the in vitro competitive binding data.The tumor up-tale of 99Tcm-HYNIC.E{E[c(RGDfK)]2}2 was still as higher as(9.35±1.35)%ID/g at 4 h postinjec-tion, which demonstrated that the retention time of radiotracer in tumor was long enough.The imaging showed that tumor was clearly

  16. 斑蝥素酸镁对人肝癌细胞SMMC-7721及其裸鼠皮下移植瘤的影响%Effect of magnesium cantharidate on hepatocellular carcinoma SMMC-7721 cells and subcutaneous hepatocellular SMMC-7721 carcinoma transplantation tumors in nude mice

    Institute of Scientific and Technical Information of China (English)

    晏容; 刘云; 朱欣婷; 易小飞; 刘流; 李晓飞

    2015-01-01

    [Objectives] To investigate the effect of magnesium cantharidate on hepatocellular carcinoma SMMC-7721 cells and subcutaneous SMMC-7721 transplantation tumors in nude mice.[Methods] 1. The sulforhodamine B(SRB) assay was employed to evaluate the effect of magnesium cantharidate on the inhibition of hepatocellular carcinoma cellsin vitro. 2. Flow cytometry(FCM)was used to measure the effect of magnesium cantharidate on cell-cycle arrest and cell apoptosis of hepatocellular carcinoma cells. 3. Hoechst 33342 staining was used to observe the effect of magnesium cantharidate on morphological changes in hepatocellular carcinoma cells. 4. Transmission electron microscopy (TEM) was used to observe the effect of magnesium cantharidate on the ultra-structure of hepatocellular carcinoma cells. 5. A model system using subcutaneous transplantation tumors composed of hepatocellular carcinoma cells was set up in nude mice. The experimental group was injected with magnesium cantharidate (6.26×10-5mmol) around the tumor and the control group was given the same volume of sterile saline. The inhibition rates of the tumor in the two groups were calculated and compared. 6. Apoptosis in the experimental group was observed with the TUNEL staining method.[Results] 1. The results show that magnesium cantharidate had an obvious inhibitory effect on the proliferation of hepatocellular carcinoma cells, and that this increased gradually with dosage. The IC50 value was 1.79μmol/L.2.FCM at which point the cell-cycle of SMMC-7721 changed. The ratio of cultured cells declined in the G0/G1 phase, whereas cells increased dramatically in the G2/M phase. The cell-cycle arrested in the G2/M phase. Cell apoptosis increased gradually with concentration of magnesium cantharidate. 3. Hoechst 33342 staining showed that hepatocellular carcinoma cells displayed morphological features typical of apoptotic cells. 4. TEM revealed nuclear abnormities, including concentrations of chromatin on the nuclear edge

  17. 磁性纳米氧化铁颗粒在人肝癌Bel7402细胞裸鼠模型中的定向浓集及其生物学效应%Investigation on the migration and biologic effects of nano FeOx powders under the exposure of extremely low frequency altering electric magnetic fiek in human heptoma-bearing nude mice in vivo

    Institute of Scientific and Technical Information of China (English)

    居会祥; 戴真煜; 孙明忠

    2011-01-01

    Objective To investigate the mechanism and biologic effects of 37 nm magnetic nano FeOx powders (MNPs) on human hepatoma-bearing nude mice. Methods 37 nm MNPs were prepared by coprecipitation methods and then injected into human hepatoma (Bel-7402) bearing-nude mice through the tail vein. After injection of MNPs, the mice were first exposed under static magnetic field and then treated under extremely low frequency altering-electric magnetic field directing to the tumor area. The migration and trafficking of MNPs were determined by MMR. Tumor growth was monitored with calipers every 5 days and rumor volume was calculated on the basis of three-dimensioned measurements. The apoptosis of tumor cells was analyzed by flow cytometry analysis. The expressions of apoptosis-associated proteins Bcl-2, Bax and HSP27 were determined using western-blot analysis. Results Static magnetic field could direct the migration and trafficking of MNPs to the tumor site with a higher ratio of 98.9%. Extremely Low Frequency Electric-Magnetic Field (EMF) treatment could inhibit the proliferation of tumor cells and prolong the survive time of tumor-bearing mice injected with MNPs. In addition, the survival time of tumor-bearing mice and percentages of prohibition on tumor cell growth were 27.4 ± 0.7 days and 37.5 ± 0.8%( F = 0.005, P < 0.05), respectively.The results of flow cytometry analyses showed that about 18. 1士 0.6% ( F = 0.030, P < 0.05) of tumor cells were induced into early apoptosis. Furthermore, expressions of apoptosis-associated proteins Bcl-2 and Bax were significantly induced by MNPs under EMF treatment. The ratio of Bcl/Bax in both MNPs and EMF treatment 0.05). Heat shock protein-27 (Hsp-27) was not significantly induced in different treatment groups. Conclusion Injection of MNPs with EMF exposure on human hepatoma-bearing nude mice could significantly prolong the survival time, inhibit the tumor proliferation and growth. and induce tumor cells into apoptosis.%目的

  18. Regulation of estrogen receptors α and β in human breast carcinoma by exogenous leptin in nude mouse xenograft model

    Institute of Scientific and Technical Information of China (English)

    YU Wei; GU Jun-chao; LIU Jian-zhong; WANG Shao-hong; WANG Yu; ZHANG Zhong-tao; MA Xue-mei; SONG Mao-min

    2010-01-01

    Background It is essential to clarify the interactions of hormones during the progression of human breast cancer. This study examined the effects of exogenous human leptin on estrogen receptor (ER) α and β in human breast tumor tissue in a nude mouse xenograft model.Methods We created nude mice xenografts of MCF-7 human breast cancer cells, and randomly divided them into an experimental group and a control group. The mice in experimental group were injected subcutaneously around tumors with human leptin, while the control group were injected with the same dose of normal saline. A real-time RT-PCR assay was developed to quantify the mRNA of Erα,β in the tumor tissues. Western blotting analyses were used to assess the relative quantities of the Erα,β proteins.Results Leptin-treated xenografted nude mice were successfully established. The amount of Era mRNA was significantly higher in the leptin group than in the control group (P<0.01), while the amount of Erβ mRNA was significantly lower in the leptin group than in the control group (P<0.01). Western blotting analyses revealed that the Erα protein level was significantly higher in the leptin group than in the control group (P<0.01), while the Erβ protein level was significantly lower in the leptin group than in the control group (P <0.01).Conclusions Nude mouse xenograft model can be safely and serviceably treated with human leptin by subcutaneous injections around tumor. Erα,β were both targets of leptin in breast cancer. Leptin can up-regulate the expression of Erα and down-regulate the expression of the Erβ in human breast tumor.

  19. Effects of microporous porcine acellular dermal matrix combined with bone marrow mesenchymal cells of rats on the regeneration of cutaneous appendages cells in nude mice%微孔化猪脱细胞真皮基质与大鼠骨髓间充质细胞对裸鼠皮肤附件细胞再生的作用

    Institute of Scientific and Technical Information of China (English)

    罗旭; 辛国华; 曾逃方; 林才; 曾元临; 李郁葱; 邱泽亮

    2013-01-01

    色清亮渗液;A、D组均未见明显脓性分泌物.B、C组皮片外观与周围皮肤颜色接近.(5)移植术后5、7 d,A、B、C组真皮基质的微孔结构中已见血管化,其内可见有形红细胞;D组移植皮片部分干燥坏死.移植术后14 d,A、B、C组真皮基质的微孔结构中已完全血管化,其内可见大量的红细胞.纵切片中,A组微孔真皮基质成活,但与其上所覆盖的无孔猪ADM未紧密结合;B、C组皮片与真皮基质间连接紧密,皮片中均未见皮肤附属器,C组创面皮片与真皮基质交接处可见特殊的单层细胞.(6)D组移植皮片末能成活,故放弃电镜观察.移植术后7d,A、B、C组透射电镜图片未见明显差别.移植术后14 d,A、B组移植物中未见皮脂腺样及汗腺样细胞,也未见新生神经末梢,仅见Fb迁入.C组创面刃厚皮与真皮基质交接处可见大量新生毛细血管增生,Fb粗面内质网分裂增殖旺盛,可见新生的无髓神经末梢;在真皮基质浅层,出现单个游离的皮脂腺样及汗腺样细胞 结论 LPADM为骨髓间充质细胞群的迁移和分化提供了“干细胞龛”样微环境,联合刃厚皮片移植可在体诱导外源性BMSC分化,实现部分皮肤附件的重建.%Objective To observe the effects of microporous porcine acellular dermal matrix (ADM) combined with bone marrow mesenchymal cells (BMMCs) population containing bone mesenchymal stem cells (BMSCs) of rats on the regeneration of cutaneous appendages cells in nude mice.Methods Split-thickness dermal grafts,20 cm × 10 cm in size and 0.3 mm in thickness,were prepared from a healthy pig which was sacrificed under sanitary condition.Laser microporous porcine ADM (LPADM) was produced by laser punching,hypertonic saline solution acellular method,and crosslinking treatment,and nonporous porcine ADM (NPADM) was produced by the latter two procedures.Then the appearance observation,histological examination and scanning electron microscope observation were

  20. Effects of siRNA targeting androgen receptor gene by electroporation on human bladder cancer xenografts in nude mice%电穿孔法介导雄激素受体基因沉默抑制裸鼠膀胱癌移植瘤生长的研究

    Institute of Scientific and Technical Information of China (English)

    韩邦旻; 吴吉涛; 崔迪; 荆翌峰; 赵福军; 洪艳; 夏术阶

    2011-01-01

    目的 观察电穿孔法转染靶向雄激素受体(AR)的小干扰RNA(siRNA)对裸鼠人膀胱癌移植瘤生长的影响.方法 建立人膀胱癌细胞124的荷瘤裸鼠模型,于肿瘤直径0.5 cm大小时,瘤体接受AR-siRNA的电转染治疗,转染无效序列siRNA为阴性对照组,瘤体未受电穿击为空白对照组.观察裸鼠肿瘤生长;4周后处死,绘制肿瘤生长曲线;肿瘤组织石蜡包埋,常规切片,TUNEL法检测移植瘤凋亡.结果 电转染AR-siRNA后瘤体组织AR基因的表达显著被抑制,也能明显抑制裸鼠移植瘤的生长;TUNEL检测凋亡率为(13.1±6.9)%,显著高于阴性对照组(P<0.01).结论 电穿孔法靶向AR的siRNA可有效阻断种植瘤内AR表达,阻断雄激素受体途经信号传导,进而诱导细胞凋亡,能明显抑制人膀胱癌裸鼠皮下移植瘤的生长.%Objective To investigate the antitumor efficacy of small interfering RNA (siRNA)mediated inhibition of androgen receptor (AR) gene expression in T24 bladder tumor xenografts using electroporation. Methods Athymic mouse human bladder cancer transplantation tumor model was established by injecting T24 cells subcutaneously. When tumor diameter was exceeded 0. 5 cm, AR-siRNA was deliered into tumor xenografts by electroporation. The cells with nonspecific siRNA delivery and un-treatment served as control groups. Tumor volumes were measured weekly. The animals were sacrificed after the treatments, and the histological changes of xenografts were observed by Hematoxylin and Eosin ( HE) staining and TUNEL assay. Results The athymic mouse exnograft tumor model was established successfully.After AR-siRNA treatment, tumor growth was inhibited as compared with the controls. The number of TUNEL-positive cells was significantly increased in AR-siRNA group as compared with the nonspecific siRNA group ( P < 0. 01). Conclusion siRNA targeting AR gene could inhibit obviously the growth of athymic mouse human T24 bladder carcinoma transplantation