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Sample records for protects athymic nude

  1. Neuromuscular transmission in the athymic nude mouse.

    PubMed

    Schofield, G G; Marshall, I G

    1980-10-01

    No major differences were observed in the mechanical properties of diaphragm, extensor digitorum longus and soleus muscles from athymic nude and control mice. Denervated soleus muscles from nudes and controls showed no significant differences in their sensitivities to the cholinoceptor agonists acetylcholine and carbachol, either in the absence or presence of the anticholinesterase, physostigmine, suggesting that postjunctional receptor function is essentially normal. Phrenic nerve-diaphragm preparations from nudes were less sensitive to the twitch-augmenting effects of neostigmine. No difference in the time course of endplate potentials (epps) between nudes and controls was seen either in the absence or presence of neostigmine. Hence the observed differences in twitch augmentation are unlikely to be due to differences in acetylcholinesterase activity in the two muscles. In normal mice miniature endplate potential (mepp) amplitude decreased and mepp frequency increased with age. These changes were associated with an increase in muscle fibre diameter and a concomitant decrease in membrane resistance. Such changes did not occur in nude mice; thus mepp amplitude remained, high as in young normal muscle. It is suggested that the thymus may play a role in muscle development and that the effects on neuromuscular transmission are secondary to changes in development. In cut diaphragm muscles transmitter reversal potentials in nudes and controls were not different. Although there was no difference in the amplitude of the first epp of a train, or in the immediately releasable acetylcholine store, the quantal content of the first epp, the probability of transmitter release, the total nerve terminal acetylcholine store and the transmitter mobilization rate were all reduced. It is considered probable that all the measurable differences in transmitter release can be explained in terms of the nude muscle fibre diameter being small and being associated with a small nerve terminal

  2. Heterotransplantation of human craniopharyngiomas in athymic "nude" mice.

    PubMed

    Bullard, D E; Bigner, D D

    1979-04-01

    Surgical biopsies from 2 human craniopharyngiomas were transplanted subcutaneously into 6 athymic "nude" mice. Morphologically characteristic craniopharyngiomas grew in 5 of these animals. In 4 animals growth was sufficient to allow transplantation into a second generation of animals. In all, 11 craniopharyngiomas were present at autopsy in the 14 animals into which the tumors had been transplanted. The tumors that grew in the animals had the same adamantinomatous architecture, epithelial nests, and keratinized nodules that were present in the original surgical sample and that are characteristic of human craniopharyngiomas. It may be possible to study growth characteristics and therapeutic sensitivities of human craniopharygniomas growing in "nude" mice.

  3. Infections of Brugia pahangi in conventional and nude (athymic) mice.

    PubMed

    Suswillo, R R; Owen, D G; Denham, D A

    1980-12-01

    AKR, BALB/c and CBA/Ca and T.O. mice were completely resistant to infection with third stage infective larvae of Brugia pahangi. Third, fourth and fifth stage worms transplanted from the peritoneal cavity of jirds into the peritoneal cavity of mice continued to develop. BALB/c mice were the most susceptible of the strains tested and adult worms were obtained after each type of transplanted infection. Congenitally athymic nude mice were much less resistant to transplanted worms and infective larvae developed to full maturity in most of them. Ten of 14 athymic mice infected by the intraperitoneal (ip) inoculation of infective larvae had microfilariae in their blood or peritoneal cavities. At autopsy a percentage recovery of adult worms of 0-38% (mean 11.1%) was obtained. Microfilariae were only found in the blood of 2 of 6 athymic mice infected by subcutaneous (sc) infection and at autopsy 0-19.1% (mean 6.1%) recoveries were obtained. The thymic littermates of the nudes were more resistant than those most of the other strains used.

  4. Study of Camelpox Virus Pathogenesis in Athymic Nude Mice

    PubMed Central

    Duraffour, Sophie; Matthys, Patrick; van den Oord, Joost J.; De Schutter, Tim; Mitera, Tania; Snoeck, Robert; Andrei, Graciela

    2011-01-01

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

  5. Spontaneous hyperglycemia and impaired glucose tolerance in athymic nude BALB/c mice.

    PubMed

    Zeidler, A; Tosco, C; Kumar, D; Slavin, B; Parker, J

    1982-09-01

    Basal plasma glucose, glucose tolerance, and insulin secretion were investigated in young and mature athymic nude BALB/c mice and in age-matched controls. Basal plasma glucose levels in male athymic nude mice were similar to those of controls at 1, 3, and 4 wk of age. At 6, 8, and 12 wk of age, male athymic nudes had significantly higher basal plasma glucose levels when compared with controls (P less than 0.01). Plasma immunoreactive insulin concentrations were similar in athymic nudes and controls at 1 wk of age, but at 3 wk of age and subsequently at 6, 8, and 12 wk athymic nude mice had significantly decreased insulin levels when compared with their age-matched controls (P less than 0.05). We found impaired glucose tolerance in male athymic nude mice at all age groups when compared with both female athymic nudes and control BALB/c mice. The discovery of a spontaneous diabetic syndrome (hyperglycemia, impaired glucose tolerance, and decreased insulin secretion) in a colony of athymic nude mice may provide an excellent model for studying the genetics and interactions between the immune and endocrine systems.

  6. Diffuse scaling dermatitis in an athymic nude mouse.

    PubMed

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

    2013-07-01

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

  7. Effect of immune reconstitution on resistance to Brugia pahangi in congenitally athymic nude mice.

    PubMed

    Vickery, A C; Vincent, A L; Sodeman, W A

    1983-06-01

    The dichotomy of resistance to Brugia pahangi (Nematoda: Filarioidea) between nonsusceptible, euthymic C3H/HeN mice, heterozygotic for the "nu" gene (+/nu), and susceptible, congenitally-athymic "nude" (nu/nu) C3H/HeN mice, suggests that resistance is thymus-dependent. To test this hypothesis, the effect of syngeneic neonatal thymus grafts and neonatal thymus cell suspensions on recovery of worms at day 40 PI, and responses to Concanavalin A (Con A) were examined in reconstituted nudes. Nude recipients of a thymus graft 7 or 14 wk before subcutaneous inoculation with 50 infective larvae (L3) yielded no worms and responded strongly to Con A. Serum from these mice reacted in two lines of identity with serum from similarly-infected heterozygotes by double radial immunodiffusion against an adult worm saline extract. Nude recipients of a thymus 2 days or 3 wk before inoculation harbored an average of three or two worms, respectively. Intravenous injection of nude recipients with 10(7) or 10(8) neonatal thymus cells seven weeks before inoculation was less effective in conferring resistance to B. pahangi and responsiveness to Con A. Complete resistance to B. pahangi could be adoptively transferred to nude mice by 10(8) spleen cells obtained from infection-primed heterozygotes and injected intravenously on the day of larval inoculation. The same numbers of worms were significantly reduced. less effective when injected 3 wk before inoculation, although numbers of worms were significantly reduced. Passive transfer of primed heterozygote serum, containing high titers of antibodies to adult worm and larval antigens, failed to protect nude recipients against a larval inoculum in the absence of cellular reconstitution.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Comparative patterns of serum immunoglobulin levels in specific-pathogen-free congenitally athymic (nude), hereditarily asplenic (Dh/+), congenitally athymic-asplenic (lasat) and splenectomized athymic mice.

    PubMed Central

    Eckels, D D; Gershwin, M E; Drago, J; Faulkin, L

    1979-01-01

    Serial determinations of serum immunoglobulin levels were assessed in congenitally athymic (nude), hereditarily asplenic (Dh/+) and congenitally athymic-asplenic (lasat) mice and the results compared to normal intact littermate controls (nu/+), neonatally splenectomized nu/+ and neonatally splenectomized nude mice. Quantification of Ig levels was accomplished by radial immunodiffusion, for IgM, IgG1, IgG2a, IgG2b and IgA antibody isotypes. Intact spleen and/or thymus function was shown to have marked effects on the age-dependent development of serum IgM, IgG2b and IgA production. Furthermore, because of higher levels of IgA in congenitally athymic-asplenic mice and neonatally splenectomized nude mice v. sham splenectomized nude mice, it is suggested that an IgA-specific suppressor population resides in the spleen. Finally, because of frequent problems in the literature in interpretation of immunoglobulin values, the criteria for the statistical evaluation of such data in establishing normal serum Ig values and ascertaining real differences between treatment groups are emphasized. PMID:159256

  9. Immunity to Brugia pahangi in athymic nude and normal mice: eosinophilia, antibody and hypersensitivity responses.

    PubMed

    Vickery, A C; Vincent, A L

    1984-11-01

    Congenitally athymic nude (nu/nu) mice, immunologically reconstituted by thymus grafting before inoculation with infective larvae, and mice heterozygous for the nu gene (nu/+), mounted potent protective humoral and cellular immune responses to Brugia pahangi. Although responses were not identical, both groups of mice produced IgM, IgG and IgE antibodies specific for adult worm antigen (S-Ag) present in a crude aqueous extract, made immediate and delayed hypersensitivity footpad swelling responses when challenged with S-Ag and eliminated their infection in the early larval stages. Heterozygotes also exhibited a marked eosinophilia which peaked coincident with larval killing. In contrast, thymus grafting of patent nudes had no effect upon microfilaraemias or adult worm burdens and did not completely protect against a challenge larval inoculum although antibodies specific for S-Ag were produced. With the occasional exceptions of moderate immediate footpad swelling and very low titres of IgM specific for S-Ag, no specific immune responses to B. pahangi were found in ungrafted nude mice which allowed full development of adult worms and supported patent infections.

  10. Studies on the immune response of congenitally athymic (nude) mice.

    PubMed

    Jutila, J W; Reed, N D; Isaak, D D

    1975-01-01

    The central role of the thymus in immunity was assessed in nude mice. Nudes failed to reject allografts and xenografts and to respond to foreign erythrocytes but responded normally to endotoxin and pneumococcal polysaccharide. Thymus reconstitution was demonstrated in vivo and in vitro whereas reconstitution with thymic humoral factors or polyanions was not detected. Coliform overgrowth and depressed IgA levels in nudes appeared to contribute to wasting. These data emphasize the need for thymus participation in many immune phenomena.

  11. Strategies to prevent, treat, and provoke Corynebacterium-associated hyperkeratosis in athymic nude mice.

    PubMed

    Burr, Holly N; Lipman, Neil S; White, Julie R; Zheng, Junting; Wolf, Felix R

    2011-05-01

    Athymic nude mice infected with Corynebacterium bovis typically exhibit transient hyperkeratotic dermatitis. Our vivarium experienced an increased incidence of disease characterized by persistent skin lesions and increased mortality, leading to this study. For detection of infection, skin and buccal swab methods showed comparable sensitivities in nude mice. Various prevention, treatment, and eradication strategies were evaluated through clinical assessment, microbiology, and histopathology. In experimentally naïve athymic nude mice, a 2-wk course of prophylactic amoxicillin-containing diet (1200 ppm amoxicillin; effective dose, 200 mg/kg) was ineffective at preventing infection or disease. There was also no significant difference in disease duration or severity in athymic nude mice that received amoxicillin diet or penicillin-streptomycin topical spray (penicillin, 2500 U/mL; streptomycin, 2500 μg/mL). Prolonged treatment with 4 or 8 wk of amoxicillin diet cleared only a small number of athymic nude mice that had subclinical C. bovis infections. Antibiotic sensitivity of C. bovis isolates demonstrated a small colony isolate with less susceptibility to all antibiotics compared with a large colony isolate. Resistance did not appear to develop after prolonged treatment with amoxicillin. Provocation testing by administration of cyclophosphamide (50 mg/kg i.p. every 48 to 72 h for 90 d) to subclinically infected athymic nude mice resulted in prolonged clinical disease that waxed and waned without progression to severe disease. Our findings suggest that antibiotic prophylaxis and treatment of clinical disease in experimentally naïve mice is unrewarding, eradication of bacterial infection is difficult, and severe disease associated with C. bovis is likely multifactorial.

  12. Strategies to Prevent, Treat, and Provoke Corynebacterium-Associated Hyperkeratosis in Athymic Nude Mice

    PubMed Central

    Burr, Holly N; Lipman, Neil S; White, Julie R; Zheng, Junting; Wolf, Felix R

    2011-01-01

    Athymic nude mice infected with Corynebacterium bovis typically exhibit transient hyperkeratotic dermatitis. Our vivarium experienced an increased incidence of disease characterized by persistent skin lesions and increased mortality, leading to this study. For detection of infection, skin and buccal swab methods showed comparable sensitivities in nude mice. Various prevention, treatment, and eradication strategies were evaluated through clinical assessment, microbiology, and histopathology. In experimentally naïve athymic nude mice, a 2-wk course of prophylactic amoxicillin-containing diet (1200 ppm amoxicillin; effective dose, 200 mg/kg) was ineffective at preventing infection or disease. There was also no significant difference in disease duration or severity in athymic nude mice that received amoxicillin diet or penicillin–streptomycin topical spray (penicillin, 2500 U/mL; streptomycin, 2500 µg/mL). Prolonged treatment with 4 or 8 wk of amoxicillin diet cleared only a small number of athymic nude mice that had subclinical C. bovis infections. Antibiotic sensitivity of C. bovis isolates demonstrated a small colony isolate with less susceptibility to all antibiotics compared with a large colony isolate. Resistance did not appear to develop after prolonged treatment with amoxicillin. Provocation testing by administration of cyclophosphamide (50 mg/kg IP every 48 to 72 h for 90 d) to subclinically infected athymic nude mice resulted in prolonged clinical disease that waxed and waned without progression to severe disease. Our findings suggest that antibiotic prophylaxis and treatment of clinical disease in experimentally naïve mice is unrewarding, eradication of bacterial infection is difficult, and severe disease associated with C. bovis is likely multifactorial. PMID:21640035

  13. Tumor development after polyoma infection in athymic nude mice.

    PubMed

    Stutman

    1975-04-01

    Nude (nu/nu) mice in a CBA/H background show an age-dependent ssuceptibility to tumor development after polyoma virus infection (strain LID-1) when compared with nu/ + or CBA/H mice, which is apparent when 15- or 30-day-old mice are used: tumor incidence was 83 to 90% in nudes and 0 to 10% in controls. Latent perids for tumor development were also shortened in nudes. However, with increasing age nude mice become partially resistant and only 25% develop tumors when infected at 120 days of age. This partial resistance could be transferred with spleen cells to newborn mice. The cells in spleen responsible for this transfer can be eliminated by lysis with anti-Ig and complement or by pre-treatment of the donor with 100 mg/kg of cyclophosphamide and were not affected by treatment in vitro with anti-Thy.1.2 or procedures that remove adherent cells and/or macrophages. When the cells in 15-day-old nu/ + spleen were studied, both anti-Ig or anti-Thy.1.2 treatment eliminated tranfer of resistance to newborn. Virus replication in tissues of nude mice was increased 5 days after infection when compared with nu/ + but became comparable by day 15 after infection. Hemagglutination-inhibition antibodies in serum of nude and nu/ + had comparable titers when measured early after infection but higher titers were observed in nu/ + later after infection.

  14. Ovarian development in athymic nude mice. II. The growth of the oocyte and follicle.

    PubMed

    Lintern-Moore, S; Pantelouris, E M

    1975-01-01

    Congenitally athymic mice homozygous for the Mendelian recessive mutation "nude" develop well defined morphological and quantitative changes in the ovarian follicle population. A decline in follicle numbers at 2 months of age is preceded by a retardation in follicle growth at 1 month of age. The growth of the oocyte and its nucleus are not affected by the nude mutation. However, the rate of growth and maximum size of the oocyte nucleolus are reduced in nudes. These developmental events are discussed in relation to the genetic activity of the oocyte, the role of pituitary gonadotrophins in follicular and oocyte growth and the possible role of the thymus gland in these processes.

  15. Athymic (nude) mice fail to delete functional self-reactive helper T cells.

    PubMed

    Caulfield, M J; Stanko, D; Isaak, D D

    1993-09-01

    We have examined the thymic requirement for the antibody response to a foreign antigen coupled to self erythrocytes. We find that self erythrocytes mediate thymus-independent, carrier specific help for the antibody response to the pneumococcal cell wall polysaccharide antigen, PnC. Thus, athymic nude mice gave a high primary antibody plaque-forming cell (PFC) response to PnC-mouse RBC but a low response to PnC coupled to sheep or burro RBC. The meager response to PnC coupled to foreign RBCs could not be attributed to antigenic competition since the response to the carrier (burro RBC) was < 100 PFC per spleen. Reconstitution of nude mice with splenic T cells from euthymic mice enhanced rather than suppressed the antibody response to PnC-mouse RBC. The results document that in the absence of thymic deletion, functional self-reactive helper cells persist in the nude mouse.

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

    PubMed

    Ito, A; Kamiyama, T

    1987-06-01

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

  17. Accretion of biopsy specimens of vaginal adenosis from patients exposed in utero to diethylstilbestrol, when transplanted to athymic nude mice.

    PubMed

    Pienkowski, M M; Mann, L C; Rosloniec, E F; Welsch, C W

    1979-03-01

    Vaginal adenosis biopsy specimens from 10 patients exposed in utero to diethylstilbestrol were transplanted for 30 days into athymic (nude) mice. Almost all grafts were recovered, and they had morphologic features closely resembling those of the original biopsy specimens, i.e., cystic, complex, and simple occult glands covered mainly with an endocervical type of epithelium showing extensive squamous metaplasia. Autoradiographic analysis of these grafts after pulse administration of [3H]thymidine into the mice revealed extensive labeling of epithelial cells. These results imply that female athymic (nude) mice are compatible hosts for accretion of the human adenosis.

  18. T-cell lymphoma induction by radiation leukemia virus in athymic nude mice

    PubMed Central

    1978-01-01

    We report the development of extrathymic lymphoblastic lymphomas in RadLV-inoculated congenitally athymic nude mice. Thus, a leukemogenic virus which appears to require the presence of a thymus for its replication in normothymic mice can infect and transform target cells in the absence of this organ in the athymic host. The cells of one of these lymphomas have been established in vitro as a permanent cell line, BALB/Nu1. This cell line as well as a lymphoma induced in NIH/Swiss nude mice exhibit several T-cell markers, including terminal deoxynucleotidyl transferase activity, Thy-1.2, and Ly-2.2, but not Ly- 1.2 nor TL. Ig determinants were not detected. The characteristics of the tumor cells support the view that cells with T-cell markers may normally exist in nude mice and undergo neoplastic transformation and clonal expansion after infection with a leukemogenic virus. The alternative possibility that virus-induced differentiation of prothymocytes may lead to the expression of Thy-1.2 and Ly-2.2 antigens is also considered. BALB/Nu1 cells release large numbers of type C viral particles. The virus, designated radiation leukemia virus (RadLV)/Nu1, has RTase activity and the protein profile characteristic of murine leukemia virus (MuLV). In radioimmunoassays, it cross-reacts completely with RadLV/VL3, a virus obtained from RadLV-induced C57BL/Ka thymic lymphoma cells in culture, and slightly with a xenotropic virus (BALB:virus-2) and with AKR MuLV. On inoculation into C57BL/Ka mice it has thymotropic and leukemogenic activity. In vitro it is B-tropic, poorly fibrotropic, and has limited xenotropic activity. Thus, RadLV/Nu1 appears to be biologically and serologically similar or identical to its parent virus, RadLV. PMID:214507

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

    PubMed

    Ito, A

    1985-04-01

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

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

    PubMed Central

    Ito, A

    1985-01-01

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

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

    PubMed

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

    2014-03-23

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

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

    PubMed

    Ito, A; Kamiyama, T

    1984-10-01

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

  3. Phenotypic characterization of collagen gel embedded primary human breast epithelial cells in athymic nude mice.

    PubMed

    Yang, J; Guzman, R C; Popnikolov, N; Bandyopadhyay, G K; Christov, K; Collins, G; Nandi, S

    1994-06-30

    We have developed a method to characterize the phenotypes and tumorigenicity of dissociated human breast epithelial cells. The dissociated cells were first embedded in collagen gels and subsequently transplanted subcutaneously in vivo in athymic nude mice. The transplantation of dissociated epithelial cells from reduction mammoplasties, presumed to be normal, always resulted in normal histomorphology. Epithelial cells were arranged as short tubular structures consisting of lumina surrounded by epithelial cells with an occasional more complex branching structure. These outgrowths were surrounded by intact basement membrane and were embedded in collagen gel that, at termination, contained collagenous stroma with fibroblasts and blood vessels. In contrast, transplantation of dissociated breast epithelial cells from breast cancer specimens resulted in outgrowths with an invasive pattern infiltrating the collagen gel as well as frank invasion into vascular space, nerves and muscles. These observations were made long before the subsequent palpable stage which resulted if left in the mouse for a long enough time. The dissociated human breast epithelial cells thus retained their intrinsic property to undergo morphogenesis to reflect their original phenotype when placed in a suitable environment, the collagen gel.

  4. A Novel Dietary Flavonoid Fisetin Inhibits Androgen Receptor Signaling and Tumor Growth in Athymic Nude Mice

    PubMed Central

    Khan, Naghma; Asim, Mohammad; Afaq, Farrukh; Zaid, Mohammad Abu; Mukhtar, Hasan

    2010-01-01

    Androgen receptor (AR)–mediated signaling plays an important role in the development and progression of prostate cancer (PCa). Hormonal therapies, mainly with combinations of antiandrogens and androgen deprivation, are the mainstay treatment for advanced disease. However, emergence of androgen resistance largely due to inefficient antihormone action limits their therapeutic usefulness. Here, we report that fisetin, a novel dietary flavonoid, acts as a novel AR ligand by competing with the high-affinity androgen to interact with the ligand binding domain of AR. We show that this physical interaction results in substantial decrease in AR stability and decrease in amino-terminal/carboxyl-terminal (N-C) interaction of AR. This results in blunting of AR-mediated transactivation of target genes including prostate-specific antigen (PSA). In addition, treatment of LNCaP cells with fisetin decreased AR protein levels, in part, by decreasing its promoter activity and by accelerating its degradation. Fisetin also synergized with Casodex in inducing apoptosis in LNCaP cells. Treatment with fisetin in athymic nude mice implanted with AR-positive CWR22Rυ1 human PCa cells resulted in inhibition of tumor growth and reduction in serum PSA levels. These data identify fisetin as an inhibitor of AR signaling axis and suggest that it could be a useful chemopreventive and chemotherapeutic agent to delay progression of PCa. PMID:18922931

  5. The origin of T cells in permanently reconstituted old athymic nude rats. Analysis using chromosome or allotype markers.

    PubMed Central

    Bell, E B; Sparshott, S M; Drayson, M T; Hunt, S V

    1989-01-01

    Athymic PVG-rnu/rnu rats receiving a single intravenous injection of syngeneic euthymic thoracic duct lymphocytes (TDL) develop normal levels of CD4+ T lymphocytes and survive for more than 2 years in a conventional animal house. We investigated the origin of the T cells (and B cells) in reconstituted nude recipients by transferring TDL carrying either the 3T chromosome marker or the RT6b + Igk-1b allotype or the RT7b (leucocyte-common) allotype markers. Karyotype analysis of spleen and lymph node (LN) cells from 1- to 2-year-old PVG-3T/3T-reconstituted nude recipients, stimulated in vitro with phytohaemagglutinin (PHA), unexpectedly revealed that a majority (79-97%) of dividing cells were of nude origin. However, extensive nude cell division was also recorded in PHA-stimulated cultures using mixtures of euthymic (PVG-3T/3T) and unreconstituted nude spleen cells; the assumption that only T cells divide in PHA-stimulated cultures thus appears to be erroneous. In contrast to the karyotype analysis, sIg- RT6b+ LN cells obtained from nude recipients reconstituted 2 years earlier with PVG-RT6b allotype-marked TDL, were all of donor origin with no indication of a nude-derived sIg- RT6a+ population. Igk-1b+ donor B cells were not found in these same recipients. Dual fluorescence analysis of TDL from 18- to 20-month RT7b-reconstituted nudes showed that 91-100% of CD4+ cells were donor-derived. When tested functionally, sIg- RT7b+ (donor) cells, but not sIg- RT7b- (nude-derived) cells, were able to reject skin allografts and induce local graft-versus-host (GVH) responses. Donor T cells, in contrast to CD4+ cells of nude origin, divided extensively in nude recipients; FACS-purified RT7b+ (donor) TDL retransferred from 17-month primary reconstituted nude rats, expanded further (60-100-fold) in secondary nude recipients. In conclusion, only the donor-derived CD4+ cells in reconstituted nude rats displayed T-cell function; evidence to the contrary from karyotype analysis was

  6. The origin of T cells in permanently reconstituted old athymic nude rats. Analysis using chromosome or allotype markers.

    PubMed

    Bell, E B; Sparshott, S M; Drayson, M T; Hunt, S V

    1989-12-01

    Athymic PVG-rnu/rnu rats receiving a single intravenous injection of syngeneic euthymic thoracic duct lymphocytes (TDL) develop normal levels of CD4+ T lymphocytes and survive for more than 2 years in a conventional animal house. We investigated the origin of the T cells (and B cells) in reconstituted nude recipients by transferring TDL carrying either the 3T chromosome marker or the RT6b + Igk-1b allotype or the RT7b (leucocyte-common) allotype markers. Karyotype analysis of spleen and lymph node (LN) cells from 1- to 2-year-old PVG-3T/3T-reconstituted nude recipients, stimulated in vitro with phytohaemagglutinin (PHA), unexpectedly revealed that a majority (79-97%) of dividing cells were of nude origin. However, extensive nude cell division was also recorded in PHA-stimulated cultures using mixtures of euthymic (PVG-3T/3T) and unreconstituted nude spleen cells; the assumption that only T cells divide in PHA-stimulated cultures thus appears to be erroneous. In contrast to the karyotype analysis, sIg- RT6b+ LN cells obtained from nude recipients reconstituted 2 years earlier with PVG-RT6b allotype-marked TDL, were all of donor origin with no indication of a nude-derived sIg- RT6a+ population. Igk-1b+ donor B cells were not found in these same recipients. Dual fluorescence analysis of TDL from 18- to 20-month RT7b-reconstituted nudes showed that 91-100% of CD4+ cells were donor-derived. When tested functionally, sIg- RT7b+ (donor) cells, but not sIg- RT7b- (nude-derived) cells, were able to reject skin allografts and induce local graft-versus-host (GVH) responses. Donor T cells, in contrast to CD4+ cells of nude origin, divided extensively in nude recipients; FACS-purified RT7b+ (donor) TDL retransferred from 17-month primary reconstituted nude rats, expanded further (60-100-fold) in secondary nude recipients. In conclusion, only the donor-derived CD4+ cells in reconstituted nude rats displayed T-cell function; evidence to the contrary from karyotype analysis was

  7. Tumorigenesis in athymic nude mouse skin by chemical carcinogens and ultraviolet light

    SciTech Connect

    Anderson, L.M.; Rice, J.M.

    1987-01-01

    A variety of established skin tumorigenesis protocols were tested for efficacy on athymic nu/nu mice (BALB/c background) and compared on euthymic nu/+ counterparts. Chemical carcinogens and UV light were applied to the ears of 10 mice of each sex and genotype for each group. Treatments were: 0.5 mg 7,12-dimethylbenz(a)anthracene ((DMBA) CAS: 57-97-6) to each ear; 0.125 mg DMBA to each ear, followed by 0.1 microgram 12-O-tetradecanoylphorbol-13-acetate ((TPA) CAS: 16561-29-8) twice weekly for 56 weeks; 0.2 mg N-nitroso-N-methylurea ((NMU) CAS: 684-93-5; 1% in acetone, 20 microliter) to each ear; 0.1 mg NMU to each ear weekly for 30 weeks; 0.2 mg NMU to each ear, followed by TPA twice weekly for 56 weeks; two ip doses of N-nitroso-N-ethylurea ((NEU) CAS: 759-73-9; 25 mg/kg each), followed by TPA twice weekly topically for 56 weeks; and exposure to sunlamps (250- to 400-nm emission) two or three times per week for 20 weeks, for a total dose of 3.7 X 10(5) J/m2. The chemical treatments caused mainly squamous papillomas and carcinomas, sebaceous adenomas and adenocarcinomas, and basal cell tumors, which appeared both on the skin of the ears and elsewhere. UV light caused squamous tumors, basal cell tumors, and sarcomas. Ear skin of the nu/nu mice developed significantly more squamous tumors than those of nu/+ mice after DMBA-TPA, NMU-TPA, NEU-TPA, repeated NMU, or UV light. Similar results were obtained for the skin of the heads and bodies. Even a single dose of NMU caused a few tumors on the nude, but not the euthymic, mice. A single dose of DMBA caused primarily sebaceous adenomas, distributed at random over the entire bodies. These results show that, contrary to previous reports, nude mice are sensitive to skin tumorigenesis, more so than euthymic nu/+ mice similarly exposed to diverse types of carcinogen and treatment protocols.

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

    PubMed

    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

    2014-12-01

    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, this is the first report of C. bovis infection in nude mice from Korea.

  9. Ovarian development in athymic nude mice. III. The effect of PMSG and oestradiol upon the size and composition of the ovarian follicle population.

    PubMed

    Lintern-Moore, S; Pantelouris, E M

    1976-01-01

    The response of 1 month old congenitally athymic nude mice and their phenotypically normal littermates to exogenous pregnant mare serum gonadotrophin (PMSG) and oestradiol-17beta has been tested. An equal increase in the number of growing follicles was detected in both nudes and controls in response to PMSG. A specific increase occurred in the number of unilaminar follicles in the initial growth stages in addition to the increase in the number of multilaminar and vesicular follicles. Oestradiol depressed follicular growth equally in both nudes and controls. The contracted appearance of growing follicles in nudes disappeared under the influence of PMSG and was induced in ovaries of control mice treated with oestradiol. We conclude that the ability of the mouse ovary to respond to exogenous PMSG and the oestradiol is not impaired by congenital athymia as expressed in the nude genotype. The data suggest that the retardation of follicular growth already reported in 1 month old nudes arises from a deficiency of gonadotrophin.

  10. Dermal penetration and systemic distribution of sup 14 C-labeled vitamin E human skin grafted athymic nude mice

    SciTech Connect

    Klain, G.J.

    1989-03-13

    In vivo percutaneous penetration and tissue distribution of 14C-labeled vitamin E applied to human skin grafted onto athymic nude mice were determined. At 1 hr, mouse skin contained the highest level of radioactivity, followed by the muscle, blood, liver, lung, adipose tissue, spleen, kidney, brain, heart, and eyes. A linear increase with time in tissue radioactivity was observed throughout the 24 hr experimental period. At 4 and 24 hrs skin grafts were highly radioactive. At 4 hrs the epidermis and the upper portion of the dermis contained more radioactivity than the remaining portion of the dermis. In contrast, at 24 hrs the highest level of radioactivity was detected in the lower dermis. No radioactivity was detected in expired air while 0.2% of the dose was found in the urine. The data show that vitamin E does penetrate skin and that the dermis acts as a barrier or reservoir for this highly lipophilic compound.

  11. Adoptive transfer of nontransgenic mesenteric lymph node cells induces colitis in athymic HLA-B27 transgenic nude rats

    PubMed Central

    Hoentjen, F; Tonkonogy, S L; Liu, B; Sartor, R B; Taurog, J D; Dieleman, L A

    2006-01-01

    HLA-B27 transgenic (TG) rats develop spontaneous colitis when colonized with intestinal bacteria, whereas athymic nude (rnu/rnu) HLA-B27 TG rats remain disease free. The present study was designed to determine whether or not HLA-B27 expression on T cells is required for development of colitis after transfer of mesenteric lymph node (MLN) cells into rnu/rnu HLA-B27 recipients. Athymic nontransgenic (non-TG) and HLA-B27 TG recipients received MLN cells from either TG or non-TG rnu/+ heterozygous donor rats that contain T cells. HLA-B27 TG rnu/rnu recipients receiving either non-TG or TG MLN cells developed severe colitis and had higher caecal MPO and IL-1β levels, and their MLN cells produced more IFN-γ and less IL-10 after in vitro stimulation with caecal bacterial lysate compared to rnu/rnu non-TG recipients that remained disease free after receiving either TG or non-TG cells. Interestingly, proliferating donor TG T cells were detectable one week after adoptive transfer into rnu/rnu TG recipients but not after transfer into non-TG recipients. T cells from either non-TG or TG donors induce colitis in rnu/rnu TG but not in non-TG rats, suggesting that activation of effector T cells by other cell types that express HLA-B27 is pivotal for the pathogenesis of colitis in this model. PMID:16487247

  12. Ovarian development in athymic nude mice. IV. The effect of PMSG and oestradiol on the growth of the oocyte and follicle.

    PubMed

    Lintern-Moore, S; Pantelouris, E M

    1976-01-01

    Retarded follicular and oocyte nucleolar growth rates in ovaries of 1 month old congenitally athymic nude mice are restored by pregnant mare serum gonadotrophin (PMSG). By contrast oestradiol-17beta depresses follicular growth rate in phenotypically normal (control) mice to levels found in nude littermates. Paradoxically, oestradiol-17beta stimulates nucleolar growth rate in control mice, but not nudes, to levels found in PMSG treated groups. These results are discussed in relation to the position of the thymus gland in the pituitary/ovarian axis and the mode of action gonadotrophin upon oocyte and follicular growth in the pre-puberal mouse ovary.

  13. NSG Mice Provide a Better Spontaneous Model of Breast Cancer Metastasis than Athymic (Nude) Mice

    PubMed Central

    Puchalapalli, Madhavi; Zeng, Xianke; Mu, Liang; Anderson, Aubree; Hix Glickman, Laura; Zhang, Ming; Sayyad, Megan R.; Mosticone Wangensteen, Sierra; Clevenger, Charles V.; Koblinski, Jennifer E.

    2016-01-01

    Metastasis is the most common cause of mortality in breast cancer patients worldwide. To identify improved mouse models for breast cancer growth and spontaneous metastasis, we examined growth and metastasis of both estrogen receptor positive (T47D) and negative (MDA-MB-231, SUM1315, and CN34BrM) human breast cancer cells in nude and NSG mice. Both primary tumor growth and spontaneous metastases were increased in NSG mice compared to nude mice. In addition, a pattern of metastasis similar to that observed in human breast cancer patients (metastases to the lungs, liver, bones, brain, and lymph nodes) was found in NSG mice. Furthermore, there was an increase in the metastatic burden in NSG compared to nude mice that were injected with MDA-MB-231 breast cancer cells in an intracardiac experimental metastasis model. This data demonstrates that NSG mice provide a better model for studying human breast cancer metastasis compared to the current nude mouse model. PMID:27662655

  14. Relationship between age of allogeneic thymus donor and immunological restoration of athymic ('nude") mice.

    PubMed

    Radov, L A; Sussdorf, D H; McCann, R L

    1975-12-01

    In nude mice back-crossed a minimum of five times to BALB/c, solid thymus grafts from C57Bl donors 3 days of age or younger restored both the humoral immune response against sheep erythrocytes and cellular immunity as tested by rejection of CBA skin grafts. Donor thymus placed under the renal capsule at a dose of 0-5 mg/g of recipient resulted in normal humoral immunity, while a minimum dose of 1-5 mg/g was required to reconstitute cellular competence. None of the various amounts of allogeneic thymus tissue transplanted affected the immunological status of nude recipients when grafts were obtained from donors 4 days of age or older. Histological findings correlated with the humoral and cellular responses observed. In nudes grafted with neonatal tissue, the thymus implant proliferated and developed normal architecture. The density of lymphocytes in thymus-dependent regions of peripheral lymphoid organs was near normal. On the other hand, most grafts from older (3-week-old) donors were resorbed by 90 days after implantation. In a number of cases, however, Russell bodies and numerous blast and plasma cells were seen in the graft site. Our observations suggest a possible cytotoxic rejection of implants from older allogeneic donors, while the survival and restorative capacity of transplants from 3-day-old or younger donors may have been due to a tolerogenic effect of the graft on the nude recipient.

  15. Relationship between age of allogeneic thymus donor and immunological restoration of athymic ('nude") mice.

    PubMed Central

    Radov, L A; Sussdorf, D H; McCann, R L

    1975-01-01

    In nude mice back-crossed a minimum of five times to BALB/c, solid thymus grafts from C57Bl donors 3 days of age or younger restored both the humoral immune response against sheep erythrocytes and cellular immunity as tested by rejection of CBA skin grafts. Donor thymus placed under the renal capsule at a dose of 0-5 mg/g of recipient resulted in normal humoral immunity, while a minimum dose of 1-5 mg/g was required to reconstitute cellular competence. None of the various amounts of allogeneic thymus tissue transplanted affected the immunological status of nude recipients when grafts were obtained from donors 4 days of age or older. Histological findings correlated with the humoral and cellular responses observed. In nudes grafted with neonatal tissue, the thymus implant proliferated and developed normal architecture. The density of lymphocytes in thymus-dependent regions of peripheral lymphoid organs was near normal. On the other hand, most grafts from older (3-week-old) donors were resorbed by 90 days after implantation. In a number of cases, however, Russell bodies and numerous blast and plasma cells were seen in the graft site. Our observations suggest a possible cytotoxic rejection of implants from older allogeneic donors, while the survival and restorative capacity of transplants from 3-day-old or younger donors may have been due to a tolerogenic effect of the graft on the nude recipient. PMID:1193689

  16. Immunofluorescence studies of a possible prethymic T-cell differentiation in congenitally athymic (nude) mice.

    PubMed

    Loor, F; Roelants, G E

    1975-06-30

    A rabbit antimouse brain theta reagent was made specific for cells of the T lineage by absorption in vivo in nude mice. When used in double fluorescence together with an antimouse immunoglobulin reagent, four types of cells were found in spleen and lymph nodes of both normal and nude mice: Ig+thetaBr-, Ig-thetaBr+, Ig-thetaBr-, and Ig+thetaBr+. The data show that about 20% of nude mouse spleen lymphocytes are definitely of T lineage (Ig-thetaBr+). On these cells, the detection of the "thetaBr" determinant, which is identical or very close to the "theta" determinant, depends on the large amplification produced by indirect immunofluorescence, which suggests a low density of theta antigen. Similar experiments suggest the presence of cells that express some TL antigen in the spleen of nudes made congenic to a TL+ strain (BALB/c). It is proposed that the T-cell precursor that will further differentiate in the thymus already expresses a low density of theta and, in TL+ strains, TL antigen.

  17. Tumor grafting induces changes of gut microbiota in athymic nude mice in the presence and absence of medicinal Gynostemma saponins.

    PubMed

    Chen, Lei; Tai, William C S; Brar, Manreetpal S; Leung, Frederick C C; Hsiao, W L Wendy

    2015-01-01

    Recent findings have revealed that gut microbiota plays a substantial role in modulating diseases such as autism, rheumatoid arthritis, allergies, and cancer that occur at sites distant to the gut. Athymic nude mice have been employed for tumorigenic research for decades; however, the relationships between the gut microbiome and host's response in drug treatment to the grafted tumors have not been explored. In this study, we analyzed the fecal microbiome of nonxenograft and xenograft nude mice treated with phytosaponins from a popular medicinal plant, Gynostemma pentaphyllum (Gp). Analysis of enterobacterial repetitive intergenic consensus (ERIC)-PCR data showed that the microbiota profile of xenograft mice departed from that of the nonxenograft mice. After ten days of treatment with Gp saponins (GpS), the microbiota of the treated mice was closer to the microbiota at Day 0 before the implantation of the tumor. Data obtained from 16S pyrosequencing of fecal samples reiterates the differences in microbiome between the nonxenograft and xenograft mice. GpS markedly increased the relative abundance of Clostridium cocleatum and Bacteroides acidifaciens, for which the beneficial effects on the host have been well documented. This study, for the first time, characterizes the properties of gut microbiome in nude mice responding to tumor implant and drug treatment. We also demonstrate that dietary saponins such as GpS can potentially regulate the gut microbial ecosystem by increasing the number of symbionts. Interestingly, this regulation of the gut ecosystem might, at least in part, be responsible for or contribute to the anticancer effect of GpS.

  18. Tumor Grafting Induces Changes of Gut Microbiota in Athymic Nude Mice in the Presence and Absence of Medicinal Gynostemma Saponins

    PubMed Central

    Chen, Lei; Tai, William C. S.; Brar, Manreetpal S.; Leung, Frederick C. C.; Hsiao, W. L. Wendy

    2015-01-01

    Recent findings have revealed that gut microbiota plays a substantial role in modulating diseases such as autism, rheumatoid arthritis, allergies, and cancer that occur at sites distant to the gut. Athymic nude mice have been employed for tumorigenic research for decades; however, the relationships between the gut microbiome and host’s response in drug treatment to the grafted tumors have not been explored. In this study, we analyzed the fecal microbiome of nonxenograft and xenograft nude mice treated with phytosaponins from a popular medicinal plant, Gynostemma pentaphyllum (Gp). Analysis of enterobacterial repetitive intergenic consensus (ERIC)-PCR data showed that the microbiota profile of xenograft mice departed from that of the nonxenograft mice. After ten days of treatment with Gp saponins (GpS), the microbiota of the treated mice was closer to the microbiota at Day 0 before the implantation of the tumor. Data obtained from 16S pyrosequencing of fecal samples reiterates the differences in microbiome between the nonxenograft and xenograft mice. GpS markedly increased the relative abundance of Clostridium cocleatum and Bacteroides acidifaciens, for which the beneficial effects on the host have been well documented. This study, for the first time, characterizes the properties of gut microbiome in nude mice responding to tumor implant and drug treatment. We also demonstrate that dietary saponins such as GpS can potentially regulate the gut microbial ecosystem by increasing the number of symbionts. Interestingly, this regulation of the gut ecosystem might, at least in part, be responsible for or contribute to the anticancer effect of GpS. PMID:25992551

  19. [Microsurgical transplantation of bone tumors of uncertain prognosis in athymic nude mice].

    PubMed

    Duprez, A; Féry, A; Sommelet, J

    1986-01-01

    Eight cases of human bone or soft tissue tumours were transplanted to nude mice. After such transplants to nude mice which are immunologically deficient, the malignant tumors developed like benign tumours, but maintaining malignant cytological characteristics. The transplants of normal human tissues or of benign tumours decreased in size or remained stable. The technique allowed a change of an original diagnosis of osteosarcoma to a final diagnosis of chondrosarcoma. It made it possible to diagnose a benign osteoblastoma, the diagnosis of which was doubtful before the transplant between osteosarcoma and chondroblastoma. It was possible to diagnose the malignancy of a haemangiopericytoma of muscle. Two aggressive tumours--a non-ossifying fibroma and a giant-cell tumour--were rated as benign after transplantation. This technique also allowed a more precise diagnosis of the grade of one chondrosarcoma and one osteosarcoma. Finally, transplantation also made it possible to test the efficacy of chemotherapy. In a patient so treated, the extreme cell proliferation after transplantation to the nude mouse led to a change in the drugs administered.

  20. Effect of ambient temperature on phenotype and functions of professional phagocytes of athymic nude mice.

    PubMed

    Vetvicka, V; Holub, M; Houstek, J

    1993-02-01

    Cytofluorometric analysis of surface marker expression was performed on myeloid cells isolated from bone marrow, spleen and lymph nodes of nude mice and nu/+ and +/+ mice (haired controls) exposed for various time periods to ambient temperature of 22 degrees C or 28 degrees C. A rise in the proportion of cells bearing macrophage markers (MAC-1, MAC-3 and F4/80) in the spleen and of FcR+ cells in all tissues tested was found in 22 degrees C-exposed nudes with high nonshivering thermogenesis. Numbers of MAC-1+ macrophages and actively phagocytic cells increased also in peritoneal exudates. There was a conspicuous predominance of large macrophages in the exudates and the specific markers decreased in density on their surface. Ia expression declined in all tissues tested with the length of exposure to cold. In the granulocytic series (BP-2+ cells), there was a decrease in the bone marrow and lymph nodes and an increase in the spleen and circulation, which suggested an enhanced mobilization and increased production at extramedullary sites in cold-exposed nude mice. The changes in haired mice were negligible.

  1. Relative potencies of different anti-herpes agents in the topical treatment of cutaneous herpes simplex virus infection of athymic nude mice.

    PubMed Central

    Descamps, J; De Clercq, E; Barr, P J; Jones, A S; Walker, R T; Torrence, P F; Shugar, D

    1979-01-01

    Thirteen established anti-herpes compounds have been directly compared in a single assay system for their effects on the development of herpetic skin lesions, and mortality associated therewith, in athymic nude (nu/nu) mice inoculated intracutaneously with herpes simplex virus type 1 (KOS). When applied topically (at 1% in a water-soluble ointment), phosphonoacetic acid, E-5-(2-bromovinyl)-2'-deoxyuridine, acycloguanosine, and trisodium phosphonoformate emerged as the most active agents. PMID:526011

  2. ABCG2-overexpressing H460/MX20 cell xenografts in athymic nude mice maintained original biochemical and cytological characteristics

    PubMed Central

    Zhang, Wei; Chen, Zhen; Chen, Likun; Wang, Fang; Li, Furong; Wang, Xiaokun; Fu, Liwu

    2017-01-01

    H460/MX20 are derived from large cell lung cancer H460 cell line and then transformed into ABCG2-overexpressing cells by mitoxantrone’s induction, which are widely used in study of multidrug resistance (MDR) in vitro. To establish and spread the model of H460/MX20 cell xenografts, we investigated whether cell biological characteristics and the MDR phenotype were maintained in vivo model. Our results demonstrated that the cell proliferation, cell cycle, and ABCG2 expression level in xH460/MX20 cells isolated from H460/MX20 cell xenografts were similar to H460/MX20 cells in vitro. Importantly, xH460/MX20 cells exhibited high levels of resistance to ABCG2 substrates such as mitoxantrone and topotecan as H460/MX20 cells did. Furthermore, lapatinib, the inhibitor of ABCG2, potently reversed mitoxantrone- and topotecan-resistance of xH460/MX20 cells. Taken together, these results suggest that H460/MX20 cell xenografts in athymic nude mice still retain their original cytological characteristics and MDR phenotype. Thus, the H460/MX20 cell xenografts model could serve as a sound model in vivo for study on reversal MDR. PMID:28059154

  3. ABCG2-overexpressing H460/MX20 cell xenografts in athymic nude mice maintained original biochemical and cytological characteristics.

    PubMed

    Zhang, Wei; Chen, Zhen; Chen, Likun; Wang, Fang; Li, Furong; Wang, Xiaokun; Fu, Liwu

    2017-01-06

    H460/MX20 are derived from large cell lung cancer H460 cell line and then transformed into ABCG2-overexpressing cells by mitoxantrone's induction, which are widely used in study of multidrug resistance (MDR) in vitro. To establish and spread the model of H460/MX20 cell xenografts, we investigated whether cell biological characteristics and the MDR phenotype were maintained in vivo model. Our results demonstrated that the cell proliferation, cell cycle, and ABCG2 expression level in xH460/MX20 cells isolated from H460/MX20 cell xenografts were similar to H460/MX20 cells in vitro. Importantly, xH460/MX20 cells exhibited high levels of resistance to ABCG2 substrates such as mitoxantrone and topotecan as H460/MX20 cells did. Furthermore, lapatinib, the inhibitor of ABCG2, potently reversed mitoxantrone- and topotecan-resistance of xH460/MX20 cells. Taken together, these results suggest that H460/MX20 cell xenografts in athymic nude mice still retain their original cytological characteristics and MDR phenotype. Thus, the H460/MX20 cell xenografts model could serve as a sound model in vivo for study on reversal MDR.

  4. Low-dose dietary genistein negates the therapeutic effect of tamoxifen in athymic nude mice

    PubMed Central

    Yang, Xujuan; Hartman, James A.; Cooke, Paul S.; Doerge, Daniel R.; Ju, Young H.; Helferich, William G.

    2012-01-01

    The present study examined the effect of dietary genistein, a soy isoflavone, on breast cancer patients who take tamoxifen, an antiestrogen treatment, using a preclinical model. The interaction of various doses of genistein with tamoxifen on the growth of estrogen receptor-positive breast cancer MCF-7 cells was investigated by subcutaneously injecting MCF-7 cells into the flank of ovariectomized athymic mice. Animals were randomized into eight experimental groups with 10–13 mice per group: control (C), estrogen (E) (0.08 mg E implant), tamoxifen (T) (3 mg T implant), estrogen + tamoxifen (E + T), tamoxifen + 500 p.p.m. genistein (T + G500), estrogen + tamoxifen + 250 p.p.m. genistein (E + T + G250), estrogen + tamoxifen + 500 p.p.m. genistein (E + T + G500) and estrogen + tamoxifen + 1000 p.p.m. genistein (E + T + G1000). Treatment of tamoxifen significantly reduced the estrogen-induced MCF-7 tumor prevalence and tumor size. This inhibitory effect of tamoxifen was significantly negated by the low doses of dietary genistein (250 and 500 p.p.m.), whereas the 1000 p.p.m. genistein did not have the same effect. Cells harvested from tamoxifen-treated tumors retained estrogen responsiveness of their progenitor MCF-7 cells, indicating that the abrogating effect of genistein on tamoxifen-treated tumor growth was not caused by a diminished tamoxifen response but directly by genistein. The low doses of dietary genistein abrogated the inhibitory effect of tamoxifen potentially by acting on the tumor cell proliferation/apoptosis ratio and the messenger RNA (mRNA) expression of cyclin D1 in addition to regulating the mRNA expression of progesterone receptor. Therefore, data from the current study suggest that caution is warranted regarding the consumption of dietary genistein by breast cancer patients while on tamoxifen therapy. PMID:22266527

  5. Phellinus Linteus Extract Sensitizes Advanced Prostate Cancer Cells to Apoptosis in Athymic Nude Mice

    PubMed Central

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

    2010-01-01

    Phellinus linteus (PL) mushroom possesses anti-tumor property. We previously reported that the treatment with PL caused cultured human prostate cancer cells to undergo apoptosis. To further studying the mechanisms of PL-mediated apoptosis, we performed xenograft assay, together with in vitro assays, to evaluate the effect of PL on the genesis and progression of the tumors formed from the inoculation of prostate cancer PC3 or DU145 cells. After the inoculation, nude mice were injected with PL every two days for 12 days. Although PL treatment did not prevent the formation of the inoculated tumors, the growth rate of the tumors after PL treatment was dramatically attenuated. We then tested the effect of PL on the tumors 12 days after the inoculation. After inoculated tumors reached a certain size, PL was administrated to the mice by subcutaneous injection. The histochemistry or immunochemistry analysis showed that apoptosis occurred with the activation of caspase 3 in the tumors formed by inoculating prostate cancer DU145 or PC3 cells. The data was in a good agreement with that from cultured cells. Thus, our in vivo study suggests that PL not only is able to attenuate tumor growth, but also to cause tumor regression by inducing apoptosis. PMID:20360989

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

    PubMed

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

    2010-03-31

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

  7. Novel intrapulmonary model for orthotopic propagation of human lung cancers in athymic nude mice.

    PubMed

    McLemore, T L; Liu, M C; Blacker, P C; Gregg, M; Alley, M C; Abbott, B J; Shoemaker, R H; Bohlman, M E; Litterst, C C; Hubbard, W C

    1987-10-01

    A major impediment to the study of human lung cancer pathophysiology, as well as to the discovery and development of new specific antitumor agents for the treatment of lung cancer, has been the lack of appropriate experimental animal models. This paper describes a new model for the propagation of human lung tumor cells in the bronchioalveolar regions of the right lungs of athymic NCr-nu/nu mice via an intrabronchial (i.b.) implantation procedure. Over 1000 i.b. implantations have been performed to date, each requiring 3 to 5 min for completion and having a surgery-related mortality of approximately 5%. The model was used successfully for the orthotopic propagation of four established human lung cancer cell lines including: an adenosquamous cell carcinoma (NCI-H125); an adenocarcinoma (A549); a large cell undifferentiated carcinoma (NCI-H460), and a bronchioloalveolar cell carcinoma (NCI-H358). When each of the four cell lines was implanted i.b. using a 1.0 X 10(6) tumor cell inoculum, 100 +/- 0% (SD) tumor-related mortality was observed within 9 to 61 days. In contrast, when the conventional s.c. method for implantation was used at the same tumor cell inoculum, only minimal (2.5 +/- 5%) tumor-related mortality was observed within 140 days (P less than 0.001). Similarly, when a 1.0 X 10(5) or 1.0 X 10(4) cell inoculum was used, a dose-dependent, tumor-related mortality was observed when cells were implanted i.b. (56 +/- 24% or 25 +/- 17%) as compared with the s.c. method (5 +/- 5.7% or 0.0 +/- 0%) (P less than 0.02 and P less than 0.05, respectively). Most (greater than 90%) of the lung tumors propagated by i.b. implantation were localized to the right lung fields as documented by necropsy and/or high-resolution chest roentgenography techniques which were developed for these studies. The intrapulmonary model was also used for establishment and propagation of xenografts derived directly from enzymatically digested, fresh human lung tumor specimens obtained at the

  8. Pomegranate fruit extract inhibits prosurvival pathways in human A549 lung carcinoma cells and tumor growth in athymic nude mice.

    PubMed

    Khan, Naghma; Hadi, Naghma; Afaq, Farrukh; Syed, Deeba N; Kweon, Mee-Hyang; Mukhtar, Hasan

    2007-01-01

    Developing novel mechanism-based chemopreventive approaches for lung cancer through the use of dietary substances which humans can accept has become an important goal. In the present study, employing normal human bronchial epithelial cells (NHBE) and human lung carcinoma A549 cells, we first compared the growth inhibitory effects of pomegranate fruit extract (PFE). Treatment of PFE (50-150 microg/ml) for 72 h was found to result in a decrease in the viability of A549 cells but had only minimal effects on NHBE cells as assessed by the MTT and Trypan blue assays. PFE treatment of A549 cells also resulted in dose-dependent arrest of cells in G0-G1 phase of the cell cycle (as assessed by DNA cell cycle analysis). We further found that PFE treatment also resulted in (i) induction of WAF1/p21 and KIP1/p27, (ii) decrease in the protein expressions of cyclins D1, D2 and E, and (iii) decrease in cyclin-dependent kinase (cdk) 2, cdk4 and cdk6 expression. The treatment of cells with PFE inhibited (i) phosphorylation of MAPK proteins, (ii) inhibition of PI3K, (iii) phosphorylation of Akt at Thr308, (iv) NF-kappaB and IKKalpha, (v) degradation and phosphorylation of IkappaBalpha, and (vi) Ki-67 and PCNA. We also found that PFE treatment to A549 cells resulted in inhibition of NF-kappaB DNA-binding activity. Oral administration of PFE (0.1 and 0.2%, wt/vol) to athymic nude mice implanted with A549 cells resulted in a significant inhibition in tumor growth. Our results provide a suggestion that PFE can be a useful chemopreventive/chemotherapeutic agent against human lung cancer.

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

    NASA Astrophysics Data System (ADS)

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

    2007-02-01

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

  10. Ovarian development in athymic nude mice V. The effects of PMSG upon the numbers and growth of follicles in the early juvenile ovary.

    PubMed

    Lintern-Moore, S; Pantelouris, E M

    1976-01-01

    The composition and growth patterns of the ovarian follicle population have been determined in early juvenile athymic nude mice and their phenotypically normal littermates. Nude ovaries contained significantly more primordial follicles and fewer trilaminar follicles at 10 days of age. The rate of growth of the oocyte nucleolus was significantly less than in control ovaries. Treatment with PMSG from days 7 to 9 restored the rate of oocyte nucleolar growth in nudes to control levels. PMSG also increased the number of follicles commencing growth in both nudes and controls and the differences in the numbers of primordial and trilaminar follicles were no longer detectable. The data demonstrate that abnormalities in the ovarian follicle population of the nude are detectable as early as the 10th day of life and can be reversed by treatment with exogenous gonadotrophin. These results are discussed in relation to the role of the thymus gland in ovarian development and the competence of the early juvenile ovary to respond to gonadotrophin.

  11. Influence of Anti-Mouse Interferon Serum on the Growth and Metastasis of Tumor Cells Persistently Infected with Virus and of Human Prostatic Tumors in Athymic Nude Mice

    NASA Astrophysics Data System (ADS)

    Reid, Lola M.; Minato, Nagahiro; Gresser, Ion; Holland, John; Kadish, Anna; Bloom, Barry R.

    1981-02-01

    Baby hamster kidney or HeLa cells form tumors in 100% of athymic nude mice. When such cells are persistently infected (PI) with RNA viruses, such as mumps or measles virus, the tumor cells either fail to grow or form circumscribed benign nodules. Neither the parental nor the virus PI tumor cells form invasive or metastatic lesions in nude mice. Previous studies have indicated a correlation between the susceptibility of virus-PI tumor cells in vitro and the cytolytic activity of natural killer (NK) cells and their failure to grow in vivo. Because interferon (IF) is the principal regulatory molecule governing the differentiation of NK cells, it was possible to test the relevance of the IF--NK cell system in vivo to restriction of tumor growth by treatment of nude mice with anti-IF globulin. This treatment was shown to reduce both IF production and NK activity in spleen cells. Both parental and virus-PI tumor cells grew and formed larger tumors in nude mice treated with anti-IF globulin than in control nude mice. The viral-PI tumor cells and the uninfected parental cells formed tumors in treated mice that were highly invasive and often metastatic. Some human tumor types have been notoriously difficult to establish as tumor lines in nude mice (e.g., primary human prostatic carcinomas). When transplanted into nude mice treated either with anti-IF globulin or anti-lymphocyte serum, two prostatic carcinomas grew and produced neoplasms with local invasiveness and some metastases. The results are consistent with the view that interferon may be important in restricting the growth, invasiveness, and metastases of tumor cells by acting indirectly through components of the immune system, such as NK cells.

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2007-02-01

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

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

    PubMed

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

    2014-09-01

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

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

    PubMed

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

    2008-04-01

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

  16. Antiproliferative effect of methyl-beta-cyclodextrin in vitro and in human tumour xenografted athymic nude mice.

    PubMed Central

    Grosse, P. Y.; Bressolle, F.; Pinguet, F.

    1998-01-01

    The anti-tumour activity of methyl-beta-cyclodextrin (MEBCD), a cyclic oligosaccharide known for its interaction with the plasma membrane, was investigated in vitro and in vivo and compared with that of doxorubicin (DOX) in the human tumour models MCF7 breast carcinoma and A2780 ovarian carcinoma. In vitro proliferation was assessed using the MTT assay. In vivo studies were carried out using xenografted Swiss nude mice injected weekly i.p. with MEBCD at 300 or 800 mg kg(-1) or DOX at 2 mg kg(-1), during 2 months. Under these conditions, MEBCD was active against MCF7 and A2780 cell lines and tumour xenografts. For each tumour model, the tumoral volume of the xenografted mice treated with MEBCD was at least twofold reduced compared with the control group. In the MCF7 model, MEBCD (800 mg kg(-1)) was more active than DOX (2 mg kg(-1)). After 56 days of treatment with MEBCD, no toxicologically meaningful differences were observed in macroscopic and microscopic parameters compared with controls. The accumulation of MEBCD in normal and tumour tissues was also assessed using a chromatographic method. Results indicated that after a single injection of MEBCD, tumour, liver and kidneys accumulated the highest concentrations of MEBCD. These results provided a basis for the potential therapeutic application of MEBCD in cancer therapy. PMID:9820174

  17. A polysaccharide from Lentinus edodes inhibits human colon cancer cell proliferation and suppresses tumor growth in athymic nude mice

    PubMed Central

    Wang, Jinglin; Li, Weiyong; Huang, Xiao; Liu, Ying; Li, Qiang; Zheng, Ziming; Wang, Kaiping

    2017-01-01

    The antitumor effect of Lentinan is thought rely on the activation of immune responses; however, little is known about whether Lentinan also directly attacks cancer cells. We therefore investigated the direct antitumor activity of SLNT (a water-extracted polysaccharide from Lentinus edodes) and its probable mechanism. We showed that SLNT significantly inhibited proliferation of HT-29 colon cancer cells and suppressed tumor growth in nude mice. Annxein V-FITC/PI, DAPI, AO/EB and H&E staining assays all showed that SLNT induced cell apoptosis both in vitro and in vivo. SLNT induced apoptosis by activating Caspase-3 via both intrinsic and extrinsic pathways, which presented as the activation of Caspases-9 and -8, upregulation of cytochrome c and the Bax/Bcl-2 ratio, downregulation of NF-κB, and overproduction of ROS and TNF-α in vitro and in vivo. Pretreatment with the caspase-3 inhibitor Ac-DEVD-CHO or antioxidant NAC blocked SLNT-induced apoptosis. These findings suggest that SLNT exerts direct antitumor effects by inducing cell apoptosis via ROS-mediated intrinsic and TNF-α-mediated extrinsic pathways. SLNT may thus represent a useful candidate for colon cancer prevention and treatment. PMID:27888812

  18. Brugia pahangi in nude mice: protective immunity to infective larvae is Thy 1.2+ cell dependent and cyclosporin A resistant.

    PubMed

    Vickery, A C; Nayar, J K

    1987-03-01

    Mechanisms of protective immunity to larvae of Brugia pahangi were studied in congenitally athymic nude C3H/HeN mice and their syngeneic heterozygous littermates. An average 11% of subcutaneous larval inocula was recovered from control nudes 28 days after inoculation. No worms were recovered from nude recipients of viable splenic Thy 1.2+ T lymphocytes from heterozygotes which had killed a priming dose of B. pahangi larvae. Primed T lymphocytes, depleted of either Lyt 1.1+ or Lyt 2.1+ cells or incubated with anti-Thy 1.2 monoclonal antibody and complement, failed to protect nude mice against a larval challenge. Nor were primed B lymphocytes depleted by Thy 1.2+ T cell contaminants protective. Treatment with cyclosporin A (CsA) did not increase the numbers of worms recovered from heterozygotes nor did CsA treatment of heterozygous cell donors abolish the ability of primed Thy 1.2+ T lymphocytes to transfer protection to nude mice. IgG but not IgM antibody titres to B. pahangi antigens were depressed in all CsA-treated mice. CsA treatment of nude mice had no direct effect upon development of B. pahangi larvae. These results show that protective immunity to larvae of B. pahangi in mice depends upon small numbers of Thy 1.2+ T cells which are CsA-resistant.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26299806

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2008-02-01

    Post-operative verification of the specificity and sensitivity of photodynamic therapy (PDT) is most pressing for deeply placed lesions such as brain tumors. We wish to determine whether Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) can provide a non-invasive and unambiguous quantitative measure of the specificity and sensitivity of brain tumor PDT. Methods: 2.5 x 10 5 U87 cells were injected into the brains of six athymic nude rats. After 5-6 days, the animals received 0.5 mg/kg b.w. of the phthalocyanine photosensitizer Pc 4 via tail-vein injection. On day 7 peri-tumor DCE-MRI images were acquired on a 7T microMRI scanner before and after tail-vein administration of 100 μL gadolinium and 400 μL saline. After this scan the animals received a 30 J/cm2 dose of 672-nm light from a diode laser (i.e., PDT). The DCE-MRI scan protocol was repeated on day 13. Next, the animals were euthanized and their brains were explanted for Hematoxylin and Eosin (H&E) histology. Results: No tumor was found in one animal. The DCE-MRI images of the other five animals demonstrated significant tumor enhancement increase (p < 0.053 two-sided t-test and p < 0.026 one-sided t-test) following PDT. H&E histology presented moderate to severe tumor necrosis. Discussion: The change in signal detected by DCE-MRI appears to be due to PDT-induced tumor necrosis. This DCE-MRI signal appears to provide a quantitative, non-invasive measure of the outcome of PDT in this animal model and may be useful for determining the safety and effectiveness of PDT in deeply placed tumors (e.g., glioma).

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

    NASA Astrophysics Data System (ADS)

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

    2007-02-01

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

  3. Optimal gadolinium dose level for magnetic resonance imaging (MRI) contrast enhancement of U87-derived tumors in athymic nude rats for the assessment of photodynamic therapy

    NASA Astrophysics Data System (ADS)

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

    2009-02-01

    This study aims to determine the effect of varying gadopentetate dimeglumine (Gd-DTPA) dose on Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) tracking of brain tumor photodynamic therapy (PDT) outcome. Methods: We injected 2.5 x 105 U87 cells (derived from human malignant glioma) into the brains of six athymic nude rats. After 9, 12, and 13 days DCE-MRI images were acquired on a 9.4 T micro-MRI scanner before and after administration of 100, 150, or 200 μL of Gd-DTPA. Results: Tumor region normalized DCE-MRI scan enhancement at peak was: 1.217 over baseline (0.018 Standard Error [SE]) at the 100 μL dose, 1.339 (0.013 SE) at the 150 μL dose, and 1.287 (0.014 SE) at the 200 μL dose. DCE-MRI peak tumor enhancement at the 150 μL dose was significantly greater than both the 100 μL dose (p < 3.323E-08) and 200 μL dose (p < 0.0007396). Discussion: In this preliminary study, the 150 μL Gd-DTPA dose provided the greatest T1 weighted contrast enhancement, while minimizing negative T2* effects, in DCE-MRI scans of U87-derived tumors. Maximizing Gd-DTPA enhancement in DCE-MRI scans may assist development of a clinically robust (i.e., unambiguous) technique for PDT outcome assessment.

  4. 1,1-Bis(3'-indolyl)-1-(p-biphenyl)methane inhibits basal-like breast cancer growth in athymic nude mice

    PubMed Central

    Su, Yunpeng; Vanderlaag, Kathryn; Ireland, Courtney; Ortiz, Janelle; Grage, Henry; Safe, Stephen; Frankel, Arthur E

    2007-01-01

    Introduction 1,1-Bis (3'-indolyl)-1-(p-biphenyl) methane (CDIM9) has been identified as a new peroxisome proliferator-activated receptor (PPAR)-γ agonist that exhibits both receptor dependent and independent antitumor activities. CDIM9 has not previously been studied with respect to its effects against basal-like breast cancer. Our goal in the present study was to investigate the anti-basal-like breast tumor activity of CDIM9 in vitro and in vivo. Methods The effects of CDIM9 on cell protein and DNA syntheses were determined in basal-like breast cancer MDA-MB231 and BT549 cells in vitro. Maximum tolerated dose and dose-limited toxicity were determined in BalB/c mice, and antitumor growth activities were assessed in MDA-MB231 basal-like breast tumor xenografts in athymic nude mice. Results CDIM9 exhibited selective cell cytotoxicity and anti-proliferation effects on basal-like breast cancer lines. In MDA-MB231 cell, CDIM9 induced caveolin-1 and p27 expression, which was significantly downregulated by co-treatment with the PPAR-γ antagonist GW9662. Nonsteroidal anti-inflammatory drug-activated gene-1 and activating transcription factor-3 were upregulated by CDIM9 through a PPAR-γ independent pathway. CDIM9 (40 mg/kg daily, intraperitoneally, for 35 days) inhibited the growth of subcutaneous MDA-MB231 tumor xenografts by 87%, and produced a corresponding decrease in proliferation index. Nearly half of the treated mice (46%) had complete durable remissions, confirmed by histology. The growth of an established tumor was inhibited by CDIM9 treatment (64 mg/kg daily, intraperitoneally, for 10 days), with a mean tumor growth inhibition of 67% as compared with controls. CDIM9 induced increases in tumor caveolin-1 and p27 in vivo, which may contribute to its antitumor activity in basal-like breast cancer. Conclusion CDIM9 showed potent antiproliferative effects on basal-like breast cancer cell in tissue culture and dramatic growth inhibition in animal models at safe doses

  5. Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) for the assessment of Pc 4-sensitized photodynamic therapy of a U87-derived glioma model in the athymic nude rat

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

    Introduction: Dynamic Contrast-Enhanced-Magnetic Resonance Imaging (DCE-MRI) may provide a means of tracking the outcome of Pc 4-sensitized photodynamic therapy (PDT) in deeply placed lesions (e.g., brain tumors). We previously determined that 150 μL of gadolinium (Gd-DTPA) produces optimal enhancement of U87-derived intracerebral tumors in an athymic nude rat glioma model. We wish to determine how consistently DCE-MRI enhancement will detect an increase in Gd-enhancement of these tumors following Pc 4-PDT. Methods: We injected 2.5 x 105 U87 cells into the brains of 6 athymic nude rats. After 7-8 days pre-Pc 4 PDT peri-tumor DCE-MRI images were acquired on a 7.0T microMRI scanner before and after administration of 150 μL Gd. DCE-MRI scans were repeated on Days 11, 12, and 13 following Pc 4-PDT (Day 8 or 9). Results: Useful DCE-MRI data were obtained for these animals before and after Pc 4- PDT. In the pre-Pc 4-PDT DCE-MRI scans an average normalized peak Gd enhancement was observed in tumor tissue that was 1.297 times greater than baseline (0.035 Standard Error [SE]). The average normalized peak Gd enhancement in the tumor tissue in the scan following PDT (Day 11) was 1.537 times greater than baseline (0.036 SE), a statistically significant increase in enhancement (p = 0.00584) over the pre-PDT level. Discussion: A 150 μL Gd dose appears to provide an unambiguous increase in signal indicating Pc 4-PDT-induced necrosis of the U87-derived tumor. Our DCEMRI protocol may allow the development of a clinically robust, unambiguous, non-invasive technique for the assessment of PDT outcome.

  6. Antrodia salmonea induces G2 cell-cycle arrest in human triple-negative breast cancer (MDA-MB-231) cells and suppresses tumor growth in athymic nude mice.

    PubMed

    Chang, Chia-Ting; Hseu, You-Cheng; Thiyagarajan, Varadharajan; Huang, Hui-Chi; Hsu, Li-Sung; Huang, Pei-Jane; Liu, Jer-Yuh; Liao, Jiunn-Wang; Yang, Hsin-Ling

    2017-01-20

    Antrodia salmonea (AS), is a well-known folk medicinal mushroom in Taiwan, has been reported to exhibit anti-oxidant, anti-angiogenic, and anti-inflammatory effects. In the present study, we examined the effects of AS on cell-cycle arrest in vitro in MDA-MB-231 cells and on tumor regression in vivo using an athymic nude mice model. AS (0-200μg/mL) treatment significantly induced G2 cell-cycle arrest in MDA-MB-231 cells by reducing the levels of cyclin B1, cyclin A, cyclin E, and CDC2 proteins. In addition, N-acetylcysteine (NAC) pretreatment prevented AS induced G2 cell-cycle arrest, indicating that ROS accumulation and subsequent cell cycle arrest might be a major mechanism of AS-induced cytotoxicity. Further, AS treatment decreased COX-2 expression and induced PARP cleavage was significantly reversed by NAC pretreatment in MDA-MB-231 cells. The in vivo study results revealed that AS treatment was effective in terms of delaying the tumor incidence and reducing the tumor growth in MDA-MB-231-xenografted nude mice. TUNEL assay, immunohistochemical staining and Western blotting confirmed that AS significantly modulated the xenografted tumor progression as demonstrated by induction of apoptosis, autophagy, and cell-cycle arrest. Our data strongly suggest that Antrodia salmonea could be an anti-cancer agent for human breast cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. AMPKα1 deletion in fibroblasts promotes tumorigenesis in athymic nude mice by p52-mediated elevation of erythropoietin and CDK2

    PubMed Central

    Ding, Ye; Lu, Qiulun; Zou, Ming-Hui; Song, Ping

    2016-01-01

    Angiogenesis is essential for tumor development. Accumulating evidence suggests that adenosine monophosphate-activated protein kinase (AMPK), an energy sensor and redox modulator, is associated with cancer development. However, the effect of AMPK on tumor development is controversial, and whether AMPK affects tumor angiogenesis has not been resolved. We show that deletion of AMPKα1, but not AMPKα2, upregulates non-canonical nuclear factor kappa B2 (NF-κB2)/p52-mediated cyclin-dependent kinase 2 (CDK2), which is responsible for the anchorage-independent cell growth of immortalized mouse embryo fibroblasts (MEFs). Co-culture with AMPKα1 knockout MEFs (or their conditioned medium) enhances the migration and network formation of human microvascular endothelial cells, which is dependent on p52-upregulated erythropoietin (Epo). AMPKα1 deletion stimulates cellular proliferation of allograft MEFs, angiogenesis, and tumor development in athymic nu/nu mice, which is partly ameliorated by antibody-mediated Epo neutralization. Therefore, the AMPKα1-p52-Epo pathway may be involved in stromal fibroblast-mediated angiogenesis and tumorigenesis. PMID:27449088

  8. Combined inhibition of mTORC1 and mTORC2 signaling pathways is a promising therapeutic option in inhibiting pheochromocytoma tumor growth: in vitro and in vivo studies in female athymic nude mice.

    PubMed

    Giubellino, Alessio; Bullova, Petra; Nölting, Svenja; Turkova, Hana; Powers, James F; Liu, Qingsong; Guichard, Sylvie; Tischler, Arthur S; Grossman, Ashley B; Pacak, Karel

    2013-02-01

    Several lines of evidence, including the recent discovery of novel susceptibility genes, point out an important role for the mammalian target of rapamycin (mTOR) signaling pathway in the development of pheochromocytoma. Analyzing a set of pheochromocytomas from patients with different genetic backgrounds, we observed and confirmed a significant overexpression of key mTOR complex (mTORC) signaling mediators. Using selective ATP-competitive inhibitors targeting both mTORC1 and mTORC2, we significantly arrested the in vitro cell proliferation and blocked migration of pheochromocytoma cells as a result of the pharmacological suppression of the Akt/mTOR signaling pathway. Moreover, AZD8055, a selective ATP-competitive dual mTORC1/2 small molecular inhibitor, significantly reduced the tumor burden in a model of metastatic pheochromocytoma using female athymic nude mice. This study suggests that targeting both mTORC1 and mTORC2 is a potentially rewarding strategy and supports the application of selective inhibitors in combinatorial drug regimens for metastatic pheochromocytoma.

  9. Combined Inhibition of mTORC1 and mTORC2 Signaling Pathways Is a Promising Therapeutic Option in Inhibiting Pheochromocytoma Tumor Growth: In Vitro and In Vivo Studies in Female Athymic Nude Mice

    PubMed Central

    Bullova, Petra; Nölting, Svenja; Turkova, Hana; Powers, James F.; Liu, Qingsong; Guichard, Sylvie; Tischler, Arthur S.; Grossman, Ashley B.

    2013-01-01

    Several lines of evidence, including the recent discovery of novel susceptibility genes, point out an important role for the mammalian target of rapamycin (mTOR) signaling pathway in the development of pheochromocytoma. Analyzing a set of pheochromocytomas from patients with different genetic backgrounds, we observed and confirmed a significant overexpression of key mTOR complex (mTORC) signaling mediators. Using selective ATP-competitive inhibitors targeting both mTORC1 and mTORC2, we significantly arrested the in vitro cell proliferation and blocked migration of pheochromocytoma cells as a result of the pharmacological suppression of the Akt/mTOR signaling pathway. Moreover, AZD8055, a selective ATP-competitive dual mTORC1/2 small molecular inhibitor, significantly reduced the tumor burden in a model of metastatic pheochromocytoma using female athymic nude mice. This study suggests that targeting both mTORC1 and mTORC2 is a potentially rewarding strategy and supports the application of selective inhibitors in combinatorial drug regimens for metastatic pheochromocytoma. PMID:23307788

  10. Combination of 13-Cis Retinoic Acid and Lovastatin: Marked Antitumor Potential In Vivo in a Pheochromocytoma Allograft Model in Female Athymic Nude Mice

    PubMed Central

    Nölting, Svenja; Giubellino, Alessio; Tayem, Yasin; Young, Karen; Lauseker, Michael; Bullova, Petra; Schovanek, Jan; Anver, Miriam; Fliedner, Stephanie; Korbonits, Márta; Göke, Burkhard; Vlotides, George

    2014-01-01

    Currently, there are no reliably effective therapeutic options for metastatic pheochromocytoma (PCC) and paraganglioma. Moreover, there are no therapies that may prevent the onset or progression of tumors in patients with succinate dehydrogenase type B mutations, which are associated with very aggressive tumors. Therefore, we tested the approved and well-tolerated drugs lovastatin and 13-cis-retinoic acid (13cRA) in vitro in an aggressive PCC mouse cell line, mouse tumor tissue-derived (MTT) cells, and in vivo in a PCC allograft nude mouse model, in therapeutically relevant doses. Treatment was started 24 hours before sc tumor cell injection and continued for 30 more days. Tumor sizes were measured from outside by caliper and sizes of viable tumor mass by bioluminescence imaging. Lovastatin showed antiproliferative effects in vitro and led to significantly smaller tumor sizes in vivo compared with vehicle treatment. 13cRA promoted tumor cell growth in vitro and led to significantly larger viable tumor mass and significantly faster increase of viable tumor mass in vivo over time compared with vehicle, lovastatin, and combination treatment. However, when combined with lovastatin, 13cRA enhanced the antiproliferative effect of lovastatin in vivo. The combination-treated mice showed slowest tumor growth of all groups with significantly slower tumor growth compared with the vehicle-treated mice and significantly smaller tumor sizes. Moreover, the combination-treated group displayed the smallest size of viable tumor mass and the slowest increase in viable tumor mass over time of all groups, with a significant difference compared with the vehicle- and 13cRA-treated group. The combination-treated tumors showed highest extent of necrosis, lowest median microvessel density and highest expression of α-smooth muscle actin. The combination of high microvessel density and low α-smooth muscle actin is a predictor of poor prognosis in other tumor entities. Therefore, this drug

  11. Combination of 13-Cis retinoic acid and lovastatin: marked antitumor potential in vivo in a pheochromocytoma allograft model in female athymic nude mice.

    PubMed

    Nölting, Svenja; Giubellino, Alessio; Tayem, Yasin; Young, Karen; Lauseker, Michael; Bullova, Petra; Schovanek, Jan; Anver, Miriam; Fliedner, Stephanie; Korbonits, Márta; Göke, Burkhard; Vlotides, George; Grossman, Ashley; Pacak, Karel

    2014-07-01

    Currently, there are no reliably effective therapeutic options for metastatic pheochromocytoma (PCC) and paraganglioma. Moreover, there are no therapies that may prevent the onset or progression of tumors in patients with succinate dehydrogenase type B mutations, which are associated with very aggressive tumors. Therefore, we tested the approved and well-tolerated drugs lovastatin and 13-cis-retinoic acid (13cRA) in vitro in an aggressive PCC mouse cell line, mouse tumor tissue-derived (MTT) cells, and in vivo in a PCC allograft nude mouse model, in therapeutically relevant doses. Treatment was started 24 hours before sc tumor cell injection and continued for 30 more days. Tumor sizes were measured from outside by caliper and sizes of viable tumor mass by bioluminescence imaging. Lovastatin showed antiproliferative effects in vitro and led to significantly smaller tumor sizes in vivo compared with vehicle treatment. 13cRA promoted tumor cell growth in vitro and led to significantly larger viable tumor mass and significantly faster increase of viable tumor mass in vivo over time compared with vehicle, lovastatin, and combination treatment. However, when combined with lovastatin, 13cRA enhanced the antiproliferative effect of lovastatin in vivo. The combination-treated mice showed slowest tumor growth of all groups with significantly slower tumor growth compared with the vehicle-treated mice and significantly smaller tumor sizes. Moreover, the combination-treated group displayed the smallest size of viable tumor mass and the slowest increase in viable tumor mass over time of all groups, with a significant difference compared with the vehicle- and 13cRA-treated group. The combination-treated tumors showed highest extent of necrosis, lowest median microvessel density and highest expression of α-smooth muscle actin. The combination of high microvessel density and low α-smooth muscle actin is a predictor of poor prognosis in other tumor entities. Therefore, this drug

  12. 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

    NASA Astrophysics Data System (ADS)

    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.

  13. CpG oligodeoxynucleotide stimulates protective innate immunity against human renal cell carcinoma xenografted in nude mice.

    PubMed

    Zhou, Pei-jun; Ma, Bin-bin; He, Wei; Xu, Da; Wang, Xiang-hui

    2011-09-01

    Renal cell carcinoma easily develops metastasis, which is highly resistant to a variety of therapies. Oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN) are potent activators of innate and adaptive immunity. CpG ODN is inclined to be used as vaccine adjuvant or in combination with other therapies to exert antitumor effect mediated by the adaptive immunity. Herein, we examined the antitumor effect of CpG ODN monotherapy and the role of innate immunity on human RCC Caki-1 cells xenografted in nude mice. Our results indicated that the peritumoral subcutaneous injections of CpG ODN1826 once a week resulted in significant inhibition of the growth of Caki-1 xenografts compared with the control groups, and the survival of tumor-bearing mice were also prolonged significantly. When cytotoxicity of splenic cells from host mice was assessed, it was found that CpG ODN1826 significantly promoted the cytotoxicities of splenocytes targeting primary Caki-1 cells or YAC-1 cells, indicating that the activity of natural killer cells in tumor-bearing nude mice was enhanced by CpG ODN1826 monotherapy. The serum concentrations of interleukin-12 were increased in mice treated with CpG ODN1826. Thus, CpG ODN1826 monotherapy induces significant inhibitory effects on the growth of human RCC xenografted in athymic immunodeficient mice, and the tumor-bearing mice achieves long-term survival, which might be attributed to enhanced innate immunity.

  14. Altered thyrotropic and somatotropic responses to environmental challenges in congenitally athymic mice.

    PubMed

    Goya, R G; Sosa, Y E; Cónsole, G M; Dardenne, M

    1995-06-01

    Neonatal thymectomy or congenital absence of the thymus induces morphologic alterations in pituitary somatotrophs as well as in thyroid epithelium. It was therefore of interest to assess somatotropic and thyrotropic cell morphology and the corresponding serum hormone levels in athymic nude mice under basal and stressful conditions, taking as a reference their haired counterparts. Normal (+/+), heterozygous nude (nul+) and homozygous (nu/nu) CD-1 mice were subjected to either 1-h immobilization stress or 2-h cold stress. Serum levels of growth hormone (GH), thyrotropin (TSH), thyroxine (T4), and triiodothyronine (T3) were assessed by RIA at 0, 30, and 60 min poststress. Athymic animals showed lower basal levels of serum TSH, GH, and T3, but not T4, than their heterozygous littermates. Immunohistochemical assessment of somatotropic and thyrotropic cell populations revealed a normal morphology in the athymic animals. Immobilization stress induced a marked reduction in GH and TSH levels in normal mice but had only a weak effect in athymic animals. Two hours of cold exposure caused a comparable increase in serum TSH in normal and athymic animals, whereas the serum T4 and T3 response to cold was greater in the athymic nudes. Cold exposure drastically reduced serum GH levels in normal animals but had only a weak effect in the athymic mice. We conclude that congenital athymia in the mouse is associated with decreased basal levels of serum TSH and GH in the presence of a normal somatotroph and thyrotroph morphology. The anomalous responses of athymic mice to stress do not appear to be due to primary hypopituitarism but rather, to an altered modulation of pituitary hormone secretion.

  15. Role of neutralizing antibodies and T-cells in pathogenesis of herpes simplex virus infection in congenitally athymic mice.

    PubMed

    Kapoor, A K; Buckmaster, A; Nash, A A; Field, H J; Wildy, P

    1982-11-01

    Congenitally athymic nude mice were infected with 10(4) p.f.u. herpes simplex type 1 (strain SC16). Following the passive transfer of neutralizing monoclonal antibodies (AP7, AP8 and AP12) it was observed that AP7 alone reduced the virus infectivity in the nervous system; AP8 and AP12 failed to protect mice probably due to poor in vivo binding to the neutralization site on the virus. Latent ganglionic infection could be established in nude mice following adoptive transfer of optimum number (2 x 10(7) cells/mouse) of immune lymph node cells from day 7 herpes virus-infected hairy immunocompetent donor mice. Moreover, in some of the immune lymph node cell protected nudes, latency could be maintained even in complete absence of neutralizing antibodies. Results of ear-ablation experiments revealed that removal of primary source of infection after day 5 of infection reduced the amount of virus in the ganglia and spinal cord. Acute neurological infection was not detected following transfer of protective anti-gp-D neutralizing antibody (LP2) in combination with removal of infected pinna. These data suggest that continuous seeding of virus occurs in related ganglia via the axonal route from infected ear pinna. It appears that local T-cell-mediated immune mechanisms are involved in maintenance of latency.

  16. Simvastatin protects against the development of endometriosis in a nude mouse model.

    PubMed

    Bruner-Tran, Kaylon L; Osteen, Kevin G; Duleba, Antoni J

    2009-07-01

    Endometriosis is a common condition associated with infertility and pelvic pain in women. Recent in vitro studies have shown that statins decrease proliferation of endometrial stroma (ES) and inhibit angiogenesis. The aim was to evaluate effects of simvastatin on development of endometriosis in a nude mouse model. Proliferative phase human endometrial biopsies were obtained from healthy donors and established as organ cultures or used to isolate ES cells. To establish endometriosis in the nude mouse, endometrial tissues were maintained in 1 nm estradiol (E) for 24 h and subsequently injected into ovariectomized nude mice. Mice (n = 37) were treated with E (8 mg, SILASTIC capsule implants; made in author laboratory) alone or with E plus simvastatin (5 or 25 mg/kg x d) for 10 d beginning 1 d after tissue injection (from three donors). Mice were killed and examined for disease. Effects of simvastatin on matrix metalloproteinase-3 (MMP-3) were evaluated in cultures of ES cells. The number and size of endometriotic implants were measured. Simvastatin induced a dose-dependent decrease of the number and size of endometrial implants in mice. At the highest dose of simvastatin, the number of endometrial implants decreased by 87%, and the volume by 98%. Simvastatin also induced a concentration-dependent decrease in MMP-3 in the absence and presence of inflammatory challenge (using IL-1alpha). Simvastatin exerted a potent inhibitory effect on the development of endometriosis in the nude mouse. Mechanisms of action of simvastatin may include inhibition of MMP-3. The present findings may lead to the development of novel treatments of endometriosis involving statins.

  17. Simvastatin Protects against the Development of Endometriosis in a Nude Mouse Model

    PubMed Central

    Bruner-Tran, Kaylon L.; Osteen, Kevin G.; Duleba, Antoni J.

    2009-01-01

    Context: Endometriosis is a common condition associated with infertility and pelvic pain in women. Recent in vitro studies have shown that statins decrease proliferation of endometrial stroma (ES) and inhibit angiogenesis. Objective: The aim was to evaluate effects of simvastatin on development of endometriosis in a nude mouse model. Methods: Proliferative phase human endometrial biopsies were obtained from healthy donors and established as organ cultures or used to isolate ES cells. To establish endometriosis in the nude mouse, endometrial tissues were maintained in 1 nm estradiol (E) for 24 h and subsequently injected into ovariectomized nude mice. Mice (n = 37) were treated with E (8 mg, SILASTIC capsule implants; made in author laboratory) alone or with E plus simvastatin (5 or 25 mg/kg · d) for 10 d beginning 1 d after tissue injection (from three donors). Mice were killed and examined for disease. Effects of simvastatin on matrix metalloproteinase-3 (MMP-3) were evaluated in cultures of ES cells. Primary Outcome: The number and size of endometriotic implants were measured. Results: Simvastatin induced a dose-dependent decrease of the number and size of endometrial implants in mice. At the highest dose of simvastatin, the number of endometrial implants decreased by 87%, and the volume by 98%. Simvastatin also induced a concentration-dependent decrease in MMP-3 in the absence and presence of inflammatory challenge (using IL-1α). Conclusions: Simvastatin exerted a potent inhibitory effect on the development of endometriosis in the nude mouse. Mechanisms of action of simvastatin may include inhibition of MMP-3. The present findings may lead to the development of novel treatments of endometriosis involving statins. PMID:19366846

  18. Hair growth cycles and wave patterns in "nude" mice.

    PubMed

    Eaton, G J

    1976-09-01

    Hair growth cycles and waves were studied through five generations of hair growth in C57BL/6Icr "nude" mice. One group of nudes received thymus grafts, a second group was composed of athymid nudes and a third consisted of heterozygous (nu/&) haired littermates. The results showed that hair growth cycles and wave patterns were essentially the same in thymus-restored nudes and athymic nudes which indicated that thymus did not play a role in these phenomena. The time interval between hair cycles was considerably shorter in both groups of nude mice as compared to heterozygotes (nu/&). Finally, the hair growth wave pattern in nude mice did not change throughout the generation of hair growth whereas profound changes in wave patterns were observed in heterozygous (nu/&) littermates.

  19. Diethylcarbamazine-mediated clearance of Brugia pahangi microfilariae in immunodeficient nude mice.

    PubMed

    Vickery, A C; Nayar, J K; Tamplin, M L

    1985-05-01

    Congenitally athymic nude C3H/HeN mice, microfilaremic with Brugia pahangi, were treated with diethylcarbamazine citrate (DEC). A single oral dose (100 mg/Kg body weight) of DEC resulted in the rapid reduction of numbers of circulating microfilariae in nude, thymus-grafted nude and complement-depleted nude mice. Antibodies of the IgM and IgG isotypes were not detected in the serum of microfilaremic nudes or on the microfilarial surface. These results suggest that DEC-mediated clearance of microfilariae from the circulation of nude mice is probably independent of thymus-dependent immunological mechanisms.

  20. Neonatal Thymulin Gene Therapy Prevents Ovarian Dysgenesis and Attenuates Reproductive Derangements in Nude Female Mice

    PubMed Central

    Reggiani, Paula C.; Barbeito, Claudio G.; Zuccolilli, Gustavo O.; Cónsole, Gloria M.; Flamini, Alicia M.; Dardenne, Mireille

    2012-01-01

    Congenitally athymic (nude) female mice show severe ovarian dysgenesis after puberty, which seems to be consequential to a number of neuroendocrine derangements described in these mutants. Thus, considerable evidence suggests that thymulin, a thymic peptide, may be involved in thymus-pituitary communication. In order to clarify the relevance of thymulin for the maturation of the female reproductive system, we assessed at hypothalamic, pituitary, ovarian, and uterine level the preventive action of neonatal thymulin gene therapy (NTGT) on the changes that typically occur after puberty in congenitally athymic female mice. We injected (im) an adenoviral vector harboring a synthetic DNA sequence encoding a biologically active analog of thymulin, methionine-serum thymic factor, in newborn nude mice (which are thymulin deficient) and killed the animals at 70–71 d of age. NTGT in the athymic mice restored the serum thymulin levels. Morphometric analysis revealed that athymic nudes have reduced numbers of brain GnRH neurons and pituitary gonadotropic cells as compared with heterozygous controls. NTGT prevented these changes and also rescued the premature ovarian failure phenotype typically observed in athymic nude mice (marked reduction in the number of antral follicles and corpora lutea, increase in atretic follicles). Serum estrogen, but not progesterone, levels were low in athymic nudes, a reduction that was partially prevented by NTGT. Little to no morphological changes were observed in the endometrium of female nudes. The delay in the age of vaginal opening that occurs in athymic nudes was significantly prevented by NTGT. Our results suggest that thymulin plays a relevant physiologic role in the thymus-hypothalamo-pituitary-gonadal axis. PMID:22700775

  1. Neonatal thymulin gene therapy prevents ovarian dysgenesis and attenuates reproductive derangements in nude female mice.

    PubMed

    Reggiani, Paula C; Barbeito, Claudio G; Zuccolilli, Gustavo O; Cónsole, Gloria M; Flamini, Alicia M; Dardenne, Mireille; Goya, Rodolfo G

    2012-08-01

    Congenitally athymic (nude) female mice show severe ovarian dysgenesis after puberty, which seems to be consequential to a number of neuroendocrine derangements described in these mutants. Thus, considerable evidence suggests that thymulin, a thymic peptide, may be involved in thymus-pituitary communication. In order to clarify the relevance of thymulin for the maturation of the female reproductive system, we assessed at hypothalamic, pituitary, ovarian, and uterine level the preventive action of neonatal thymulin gene therapy (NTGT) on the changes that typically occur after puberty in congenitally athymic female mice. We injected (im) an adenoviral vector harboring a synthetic DNA sequence encoding a biologically active analog of thymulin, methionine-serum thymic factor, in newborn nude mice (which are thymulin deficient) and killed the animals at 70-71 d of age. NTGT in the athymic mice restored the serum thymulin levels. Morphometric analysis revealed that athymic nudes have reduced numbers of brain GnRH neurons and pituitary gonadotropic cells as compared with heterozygous controls. NTGT prevented these changes and also rescued the premature ovarian failure phenotype typically observed in athymic nude mice (marked reduction in the number of antral follicles and corpora lutea, increase in atretic follicles). Serum estrogen, but not progesterone, levels were low in athymic nudes, a reduction that was partially prevented by NTGT. Little to no morphological changes were observed in the endometrium of female nudes. The delay in the age of vaginal opening that occurs in athymic nudes was significantly prevented by NTGT. Our results suggest that thymulin plays a relevant physiologic role in the thymus-hypothalamo-pituitary-gonadal axis.

  2. Heterotransplantation of human cervix cancers in radiation-conditioned or nonconditioned athymic mice

    SciTech Connect

    Maruyama, Y.; Feola, J.M.; van Nagell, J.R.

    1985-12-01

    Primary human cervix cancers were implanted into athymic nude mice from 23 patient biopsy specimens. Tissue/tumor samples were implanted as chunks by trocar in different sites in irradiated (400 rad) or nonirradiated nude mice. Without irradiation 1 of 9 (11%) implanted tumors grew progressively and 13 of 26 (50%) implanted sites formed small implantation nodules that remained stable and usually regressed. In nude mice given 400-rad irradiation, 3 of 12 (25%) showed progressive tumor growth, 8 of 12 (67%) patient samples showed growth, and 24 of 36 (67%) implanted sites showed growth. Correlation with clinical data showed that the higher-stage and more malignant tumors were more likely to show progressive growth patterns, as was noted in three of five Stage III/IV cervix tumors grafted into 400-rad conditioned mice. Conversely, the lower-stage tumors were much less likely to show growth, and zero of nine samples with Stage I/II tumors showed progressive growth.

  3. Altered schistosome granuloma formation in nude mice.

    PubMed

    Byram, J E; von Lichtenberg, F

    1977-09-01

    Schistosome egg-induced lesions in congenitally athymic mice differed from those found in normal heterozygous controls. Heterozygote liver granulomas were chareacterized by poorly phagocytic epithelioid macrophages, and were rich in eosinophils and fibroblasts, with peripheral lymphocytes and plasma cells. Hepatic lesions in nude mice were much smaller and lacked epithelioid macrophages, with lesions about mature eggs, typically consisting of monocytes and macrophages filled with pigment, occasional neutrophils, and rarely one or more eosinophils or giant cells. While heterozygote granulomas damaged liver cells mainly by encroachment or by their vascular effects, in the nudes hepatocytes bordering the lesions showed microvesicular cytoplasmic damage and either hydropic degeneration or focal acidophilic necrosis of individual liver cells. In heterozygotes, immunofluorescent-stainable schistosome egg antigen (SEA) was concentrated in the granuloma center. In nude mice, SEA, was distributed throughout the infiltrates and in and around hepatocytes adjacent to egg lesions corresponding to the observed pattern of hepatocyte necrosis. We conclude that, in contrast to heterozygotes, nude mice lack hypersensitivity granulomas and fail to sequester toxic egg products, this resulting in zonal hepatocellular damage. Alternative explanations include the possibility of a latent hepatitis virus being activated by the schistosome infection; however, several cogent arguments are presented against that alternative.

  4. [History for animal model of Hansen's disease and characteristics of leprosy in hypertensive nude rat].

    PubMed

    Yogi, Yasuko; Fujimura, Takao; Suzuki, Koichi

    2008-09-01

    The long search of an animal model for leprosy were carried out as many researchers since the Mycobacterium leprae discovery by Dr. Hansen in 1874. The remarkable results were left after the development of the foot-pad method by Dr. Shepard in 1960. The introduction of the T-R mouse and athymic (nude) mouse for leprosy research, alsospontaneity examples of Hansen's disease was reported to armadillo, chimpanzee and mangabay monkey, and it was confirmed that Hansen's disease was the zoonosis. Although, We have established a congenic hypertensive nude rat, SHR/NCrj-rnu (SHR.F344-Foxn(rnu)), carrying nude (rnu) and hypertension genes. SHR/NCrj-rnu rats obtained showed high susceptibility to M. leprae and showed a characteristic disease with a progressive pattern of leproma formation. Also this hypertensive nude rat strain produce high level of IL-10. Therefore, congenic hypertensive nude rat may be useful for an animal model to leprosy.

  5. Effect of dietary selenium and cancer cell xenograft on peripheral T and B lymphocytes in adult nude mice

    USDA-ARS?s Scientific Manuscript database

    Selenium (Se) is known to regulate tumorigenesis and immunity at nutritional and supranutritional levels. Because the immune system provides critical defenses against cancer and the athymic, immune-deficient NU/J nude mice are known to gradually develop CD8+ and CD4+ T cells, we asked whether B and ...

  6. Nutritional and supranutritional levels of selenate differentially suppress prostate tumor growth in adult but not young nude mice

    USDA-ARS?s Scientific Manuscript database

    Selenium (Se) is known to regulate carcinogenesis and immunity at nutritional and 26 supranutritional levels. Because the immune system provides critical defenses against 27 cancer and the athymic, immune-deficient NU/J nude mice are known to gradually develop 28 CD8+ and CD4+ T cells extrathymicall...

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

    PubMed

    Ito, A; Ma, L; Sato, Y

    1997-08-01

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

  8. Nature of the thymus dependency of mucosal mast cells. III. Mucosal mast cells in nude mice and nude rats, in B rats and in a child with the Di George syndrome.

    PubMed

    Mayrhofer, G; Bazin, H

    1981-01-01

    Mucosal mast cells have been examined in the small intestinal mucosae of nude mice and nude rats, B rats and a child with the DiGeorge syndrome. In all three species, mast cells were present in normal numbers despite the athymic status of the nude mice and nude rats, the vestigial nature of the thymus in the child, and the functionally T lymphocyte-deprived status of the B rats. Connective tissue mast cells were also plentiful in skins and tongues of the nude mice and the child with thymic aplasia. It is concluded that normally neither population of mast cells has a obligatory dependence on the thymus or T lymphocytes for its differentiation, but that mucosal mast cells, under certain conditions of rapid hyperplasia, require an inductive influence provided by T lymphocytes.

  9. Immunoglobulin levels of congenitally athymic rats immunized with thymus-dependent-independent antigens.

    PubMed Central

    Taubman, M A; Ebersole, J L; Smith, D J

    1986-01-01

    The levels of immunoglobulins (Ig) in the serum and saliva of nude (rnu/rnu), congenitally athymic rats and control (rnu/+) rats were studied after injection in the vicinity of the salivary glands with several different T-dependent or T-independent dinitrophenylated antigens. Serum IgG levels were higher in rnu/+ rats than rnu/rnu rats after both primary and secondary immunizations. WHile serum IgM levels were higher in rnu/+ rats after primary immunization, secondary immunization with the most thymic-dependent antigens elicited higher IgM levels in rnu/rnu rats. After primary immunization, serum IgA levels in rnu/rnu rats were significantly lower than rnu/+ levels but no differences between the groups were noted after secondary immunization. Primary immunization with these antigens also demonstrated a markedly reduced salivary IgA producing capability by the athymic rats. Importantly, no such differences in serum or salivary IgA were previously found in the absence of immunization. Thus, immunization accentuated differences in Ig level and isotype distribution between rnu/rnu and rnu/+ rats. PMID:3486816

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

    PubMed

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

    2017-01-01

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

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

    PubMed Central

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

    2017-01-01

    Success of cell therapy in avascular sites will depend on providing sufficient blood supply to transplanted tissues. A popular strategy of providing blood supply is to embed cells within a functionalized hydrogel implanted within the host to stimulate neovascularization. However, hydrogel systems are not always amenable for removal post-transplantation; thus, it may be advantageous to implant a device that contains cells while also providing access to the circulation so retrieval is possible. Here we investigate one instance of providing access to a vessel network, a thin sheet with through-cut slits, and determine if it can be vascularized from autologous materials. We compared the effect of slit width on vascularization of a thin sheet following subcutaneous implantation into an animal model. Polydimethylsiloxane sheets with varying slit widths (approximately 150, 300, 500, or 1500 µm) were fabricated from three-dimensional printed molds. Subcutaneous implantation of sheets in immunodeficient mice revealed that smaller slit widths have evidence of angiogenesis and new tissue growth, while larger slit widths contain native mature tissue squeezing into the space. Our results show that engineered slit sheets may provide a simple approach to cell transplantation by providing a prevascularized and innervated environment. PMID:28228933

  12. Human islet oxygen consumption rate and DNA measurements predict diabetes reversal in nude mice.

    PubMed

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

    2007-03-01

    There is a need for simple, quantitative and prospective assays for islet quality assessment that are predictive of islet transplantation outcome. The current state-of-the-art athymic nude mouse bioassay is costly, technically challenging and retrospective. In this study, we report on the ability of 2 parameters characterizing human islet quality: (1) oxygen consumption rate (OCR), a measure of viable volume; and (2) OCR/DNA, a measure of fractional viability, to predict diabetes reversal in nude mice. Results demonstrate that the probability for diabetes reversal increases as the graft's OCR/DNA and total OCR increase. For a given transplanted OCR dose, diabetes reversal is strongly dependent on OCR/DNA. The OCR and OCR/DNA (the 'OCR test') data exhibit 89% sensitivity and 77% specificity in predicting diabetes reversal in nude mice (n = 86). We conclude that the prospective OCR test can effectively replace the retrospective athymic nude mouse bioassay in assessing human islet quality prior to islet transplantation.

  13. Systemic Coccidioides immitis infection in nude and beige mice.

    PubMed Central

    Clemons, K V; Leathers, C R; Lee, K W

    1985-01-01

    The course of experimental systemic Coccidioides immitis infection was assessed quantitatively and histologically in beige mice, congenitally athymic nude mice, and their respective normal counterparts. After intravenous inoculation with 50 arthroconidia, the number of viable C. immitis cultured from the spleens, livers, and lungs progressively increased throughout the assay in the organs of all mice. During the first 2 weeks of infection, significantly greater numbers of CFU were recovered from the spleens and livers, but not the lungs, of nude mice than from the respective organs of their phenotypically normal littermates. Significantly greater numbers of CFU were cultured from the lungs and spleens of beige mice compared with the number recovered from their functionally normal littermates. After intranasal inoculation, extrapulmonary dissemination of C. immitis occurred at an equal rate and resulted in similar organ burdens in nude mice and their normal littermates. Histological examination of infected tissues revealed a characteristic mixed inflammatory cell infiltrate in euthymic mice; the response in nude mice was less severe, consisting predominantly, if not solely, of granulocytes. In addition, in tissue sections from nude mice, but not in those from their euthymic counterparts, mature spherules were frequently observed to be devoid of an associated inflammatory response. The inflammatory lesion in beige mice contained a predominance of mononuclear cells, whereas their littermates responded with a typical mixed granulomatous infiltrate. Collectively, these results provide evidence supporting the hypothesis that resistance to C. immitis infection involves two primary cell populations, one under the direct influence of T-cells and the other independent of T-lymphocytes. Images PMID:3972455

  14. Effect of Enrichment Devices on Aggression in Manipulated Nude Mice.

    PubMed

    Lockworth, Cynthia R; Kim, Sun-Jin; Liu, Jun; Palla, Shana L; Craig, Suzanne L

    2015-11-01

    Agonistic behavior in group-housed male mice is a recurring problem in many animal research facilities. Common management procedures, such as the removal of aggressors, are moderately successful but often fail, owing to recurrence of aggressive behavior among cagemates. Studies have incorporated enrichment devices to attenuate aggression, but such devices have had mixed results. However, these studies did not include research manipulations when assessing the benefits of various enrichment devices. We obtained 100 male athymic nude mice and studied the efficacy of various enrichment devices, including cotton squares, paper rolls, shredded paper, nylon bones, and a mouse house and wheel combination in the reduction of fighting during an ongoing study that involved randomization followed by prostate and intratibial injections. Groups were evaluated according to a numerical grading system for wound assessment. Examination of the data revealed that the enrichment devices had no effect on the presence of wounds, thus none of the devices tested affected fighting in nude mice. However, when mice began experimental use, fight wounds increased significantly at cage change and after randomization, reflecting a disruption of existing social hierarchies. Therefore, in the context of an actual research study that involves common manipulations, the specific enrichment device had less effect on aggression in male nude mice than did the destruction and reconstruction of social structures within each group.

  15. Orthotopic model of canine osteosarcoma in athymic rats for evaluation of stereotactic radiotherapy.

    PubMed

    Schwartz, Anthony L; Custis, James T; Harmon, Joseph F; Powers, Barbara E; Chubb, Laura S; LaRue, Susan M; Ehrhart, Nicole P; Ryan, Stewart D

    2013-03-01

    To develop an orthotopic model of canine osteosarcoma in athymic rats as a model for evaluating the effects of stereotactic radiotherapy (SRT) on osteosarcoma cells. 26 athymic nude rats. 3 experiments were performed. In the first 2 experiments, rats were injected with 1 × 10(6) Abrams canine osteosarcoma cells into the proximal aspect of the tibia (n = 12) or distal aspect of the femur (6). Tumor engraftment and progression were monitored weekly via radiography, luciferase imaging, and measurement of urine pyridinoline concentration for 5 weeks and histologic evaluation after euthanasia. In the third experiment, 8 rats underwent canine osteosarcoma cell injection into the distal aspect of the femur and SRT was administered to the affected area in three 12-Gy fractions delivered on consecutive days (total radiation dose, 36 Gy). Percentage tumor necrosis and urinary pyridinoline concentrations were used to assess local tumor control. The short-term effect of SRT on skin was also evaluated. Tumors developed in 10 of 12 tibial sites and all 14 femoral sites. Administration of SRT to rats with femoral osteosarcoma was feasible and successful. Mean tumor necrosis of 95% was achieved histologically, and minimal adverse skin effects were observed. The orthotopic model of canine osteosarcoma in rats developed in this study was suitable for evaluating the effects of local tumor control and can be used in future studies to evaluate optimization of SRT duration, dose, and fractionation schemes. The model could also allow evaluation of other treatments in combination with SRT, such as chemotherapy or bisphosphonate, radioprotectant, or parathyroid hormone treatment.

  16. The let-7a microRNA protects from growth of lung carcinoma by suppression of k-Ras and c-Myc in nude mice.

    PubMed

    He, Xiao-Yan; Chen, Jun-xia; Zhang, Zheng; Li, Chun-lei; Peng, Qiong-le; Peng, Hui-min

    2010-07-01

    Down-regulation of let-7 microRNA (miRNA) plays an important role in the pathogenesis of lung cancer. k-Ras and c-Myc, two key oncogenes in lung cancer, have been found to be targeted by let-7 in vitro. However, the in vivo relevance of these findings is unknown. The aim of the present study is to determine the effect of let-7a, a member of let-7 family, on the growth of lung cancer in vivo and to investigate whether let-7-induced suppression of k-Ras and c-Myc is involved in lung cancer. A549-let-7a cell line and A549-control cell line, two stable transfected cell lines over-expressing let-7a and the control miRNA, were established and preserved in our lab. A549, A549-control, and A549-let-7a cells were injected subcutaneously into nude mice, respectively. After 30 days, the mice were killed; the xenografts were excised and weighed. The expression of let-7a in tumor xenografts was assessed by real-time reverse transcription-PCR (RT-PCR). The expression of k-Ras and c-Myc in xenografts were determined by western blot and immunohistochemistry detection. Real-time RT-PCR showed the expression of let-7a was increased significantly in A549-let-7a cells-injected group, compared with A549-control cells-injected group and A549 cells-injected group (P < 0.01). In the xenografts of A549-let-7a cells-injected group, a significant depression in tumor weight (P < 0.05) and significant decrease of k-Ras and c-Myc protein were observed (P < 0.01), compared to A549 cells-injected group and A549-control cells-injected group. Overexpression of let-7a can inhibit the growth of lung cancer transplanted subcutaneously in nude mice by suppression of k-Ras and c-Myc.

  17. Estradiol-stimulated growth of MCF-7 tumors implanted in athymic mice: a model to study the tumoristatic action of tamoxifen.

    PubMed

    Gottardis, M M; Robinson, S P; Jordan, V C

    1988-01-01

    Ovariectomized athymic (nude) mice were inoculated (10(7) cells) with the breast cancer cell line, MCF-7, into the axillary mammary fat pads. Tumors did not grow unless animals were implanted with a 1.7 mg estradiol sustained (8-week)-release cholesterol pellet. Co-implantation with tamoxifen (5 mg, 4-week release) caused an inhibition of estradiol-stimulated growth but did not cause tumor growth when implanted alone. The metabolism of [3H]tamoxifen was determined in the athymic mouse bearing MCF-7 tumors. Metabolites in the liver, uterus and tumor were determined by TLC. The principal metabolite in each of the tissues was 4-hydroxytamoxifen (by comparison of Rfs with authentic standards). Studies with 4-hydroxytamoxifen and N-desmethyltamoxifen (the principal metabolites in patients) showed that each was effective in inhibiting estradiol-stimulated tumor growth. However, tumor growth could be reactivated by treatment with estradiol alone. In a separate experiment, tumor-implanted animals were treated with tamoxifen for 1, 2 and 6 months. Tamoxifen did not cause tumor growth. Nevertheless, tumor growth was reactivated by estradiol on each occasion. These studies confirm the tumoristatic actions of tamoxifen and strongly support the view that therapy must be given indefinitely to patients to control tumor recurrence. The athymic mouse model can be used in the future to determine the efficacy of novel antiestrogens and the development of antiestrogen drug resistance.

  18. Mode of transmission and histology of M. leprae infection in nude mice.

    PubMed Central

    McDermott-Lancaster, R. D.; McDougall, A. C.

    1990-01-01

    Athymic (nude) mice were experimentally infected with Mycobacterium leprae via the alimentary and respiratory tracts and through the skin. Animals were allowed to inhale aerosols of M. leprae or had bacilli instilled into the nostrils or directly into the lungs. Others were fed M. leprae by gastric tube or had bacilli placed on the tongue. Attempts were also made to transmit M. leprae from infected footpads by Aedes aegyptii mosquitoes. The most successful infections resulted from nasal instillations and from bacilli inoculated onto the tongue surface: in these cases heavy systemic infections occurred. M. leprae was also shown to survive passage through the alimentary tract and bacilli recovered from the faeces were capable of causing infection in recipient nude mice. The possible epidemiological significance of these findings for the transmission of leprosy in man is discussed. Images Fig. 2 Fig. 4 Fig. 5 PMID:2206990

  19. Localization of the defect in skin diseases analyzed in the human skin graft-nude mouse model.

    PubMed

    Briggaman, R A

    1980-01-01

    Human skin can be grown away from its donor for prolonged periods as grafts on congenitally athymic "nude" mice. This system has been used to analyze the defect in several skin diseases, specifically to localize the site of the defect to the skin itself or to the epidermal or dermal components of the skin. In order to validate the use of the nude mouse human skin graft system in the analysis of skin defects, we have demonstrated that a systemic metabolic defect which involves the skin, namely essential fatty acid deficiency, can be differentiated from a defect residing primarily in the skin itself. Skin-marker systems have been developed for use with the nude mouse-human skin graft model to document the identity of human skin grafts and epidermal and dermal components of the grafts after prolonged periods of growth on the nude athymic mice. Y-body, a small fluorescent segment of the Y-chromosome seen in interphase cells, is used as a sex marker and serves to distinguish sex differences between the graft and the mouse recipient or between skin components of the graft. The ABH "blood-group" antigens are present on differentiated epidermal cell surfaces and identify the grafted epidermis according to the blood groups of the donor. In previous studies, lamellar ichthyosis was shown to be well maintained after prolonged periods of growth on nude athymic mice, indicating that the defect in this disease resides in the skin itself. Recombinant grafts composed of normal and lamellar ichthyosis epidermis and dermis further localize the defect to lamellar ichthyosis epidermis. Psoriasis is well maintained on the nude mouse-skin graft model. The epidermal hyperplasia and hyperproliferative epidermal cell kinetics of psoriasis are manifested in the grafts of active psoriasis maintained for prolonged periods on the nude mice, but the inflammatory component of psoriasis is absent. Recombinant graft studies utilizing normal and psoriatic epidermis and dermis demonstrate psoriasis

  20. Another look at the reclining nude

    NASA Astrophysics Data System (ADS)

    Lieberman, Larry A.

    1995-02-01

    Throughout art history the reclining nude won much of its attention from shocking its viewers. Historically, such masters as Velazquez, Titian, Goya, Manet, Moore, and Matisse depicted the reclining nudes in their art. Today, it is commonplace to see a nude or partial nude figure on magazines, movies, billboards or numerous other places. Yet, as a hologram the reclining nude seems to evoke response similar to that of its historical past.

  1. Morphological restoration of gonadotrope population by thymulin gene therapy in nude mice

    PubMed Central

    Reggiani, Paula; Martines, Eliana; Ferese, Celia; Goya, Rodolfo; Cónsole, Gloria

    2009-01-01

    Summary The integrity of the thymus during the first week of life is necessary for a proper maturation of the pituitary-gonadal axis as revealed by the significantly reduced levels of circulating gonadotropins in congenitally athymic (nude) mice. In the present work we studied the impact of athymia and the effect of neonatal thymulin gene therapy on the pituitaries of adult nude mice. Also circulating thymulin and gonadotropin levels were evaluated. We used an adenoviral vector expressing a synthetic gene for the thymic peptide thymulin (metFTS) termed RAd-FTS. On postnatal day 1, each experimental heterozygous (nu/+) and homozygous (nu/nu) pup of both sexes received a single bilateral i.m. injection of RAd-FTS or RAd-GFP/TK, a control vector expressing green fluorescent protein. On postnatal days 51-52, mice were bled and sacrificed, their pituitaries were immediately dissected, fixed and immunostained. Morphometry was performed by means of an image analysis system. The following parameters were calculated: volume density (VD: cell area/reference area), cell density (CD: number of cells/reference area), and cell size (expressed in μm2). Serum thymulin levels were measured by a bioassay and gonadotropin levels were assayed by RIA. It was observed that neonatal thymulin gene therapy in the athymic mice restored their serum thymulin levels and prevented the reduction in circulating gonadotropin levels. The histometrical analysis revealed that the treatment prevented the reduction in gonadotrope CD and the VD in athymic mice. Our data suggest that thymulin gene therapy may be an effective strategy to approach reproductive deficits associated with endocrine thymus dysfunction. PMID:19337971

  2. Nude mice produce a T cell-derived antigen-binding factor that mediates the early component of delayed-type hypersensitivity.

    PubMed

    Herzog, W R; Meade, R; Pettinicchi, A; Ptak, W; Askenase, P W

    1989-03-15

    The elicitation of delayed-type hypersensitivity (DTH) reactions in mice is caused by the sequential action of two different T cells. An early-acting, DTH-initiating T cell produces an Ag-specific T cell factor, that is analogous to IgE antibody and initiates DTH by sensitizing the local tissues for release of the vasoactive amine serotonin. In picryl chloride or oxazolone contact sensitivity, this T cell factor is Ag-specific, but MHC unrestricted. We, therefore, hypothesized that DTH-initiating T cells are primitive T cells with Ag receptors that can bind Ag without MHC restriction. In order to characterize the origin of this DTH-initiating T cell and the conditions that are necessary for its development, we contact-sensitized various strains of immunodeficient mice. Surprisingly, we found that the early phase of DTH was present in athymic nude mice. In contrast, the early component of DTH was absent in mice with severe combined immunodeficiency. These mice lack T and B cells, but have NK cells. These findings suggested that the early component of DTH was not caused by NK cells, and was caused by cells belonging to a lineage from a rearranging gene family. The early component of DTH in nude mice was Ag specific, was caused by MHC unrestricted Thy-1+ T cells, and was mediated by Ag-binding, Ag-specific T cell factors. We found that DTH-initiating, T cell-derived, Ag-binding molecules from nude mice and normal CBA/J mice had the same functional properties. The early component of DTH was elicited in two different systems (contact sensitivity and SRBC-specific DTH) in two strains of nude mice (BALB/c athymic nudes and CByB6F1/J-nu) from two different suppliers, but not in BALB/c and athymic nudes from a third supplier. From these findings we concluded that DTH-initiating T cells, which produce IgE-like Ag-specific T cell factors, are present in some strains of athymic nude mice and thus are relatively thymic independent T cells.

  3. Lack of correlation between natural killer activity and tumor growth control in nude mice with different immune defects.

    PubMed

    Fodstad, O; Hansen, C T; Cannon, G B; Statham, C N; Lichtenstein, G R; Boyd, M R

    1984-10-01

    To elucidate the in vivo role of natural killer (NK) cells, the growth of several murine and human tumors was studied in four variants of athymic, nude mice with different levels of NK activity. Beige-nude mice, homozygous for both the beige and the nude genes, had very low levels of NK activity, and their response to the B-cell mitogen, bacterial lipopolysaccharide, was lower than that of high-NK, adult NIH nude mice. Young and adult NIH nudes had different NK levels and showed different response in assays for K-cell, T-cell, and B-cell activity. The B-cell-defective NIH-II mice had slightly lower NK levels than adult NIH animals, but much lower response in the antibody-dependent cell-mediated cytotoxicity assay. No correlation was found between host NK activity and the s.c. growth of various human (LOX, CEM, K562) and murine (YAC-1) tumor cells. Low NK activity was not associated with increased lung colony formation in a metastasis model using i.v.-injected human (LOX) and murine (B16F10) melanoma cells. No relationship was found between host NK activity and the rate of elimination of i.v.-injected 5-iodo-2'-deoxyuridine-labeled LOX, B16F10, and YAC-1 cells from lungs, liver, or spleen. The results fail to support the view that NK cells exert significant direct effects on tumor cells in vivo.

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

    PubMed

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

    1987-04-01

    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 performed in some animals in order to obtain a possible enhancement of the immunological reconstitution. Both groups of isogeneic-thymus-grafted animals had more T helper cells than the nude controls. Furthermore, they had more densely populated paracortical areas in the inguinal lymph nodes and higher 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 and non-adrenalectomized thymic-isografted animals. We therefore conclude that of all the experimental animals examined the isografted nude rats show by far the best response and that adrenalectomy seems unnecessary for the success of neonatal isogeneic thymus grafts. We also conclude that the isogeneic-thymus-grafted nude rat is a suitable tool for immunological reconstitution studies.

  5. Thymic education curtailed: defective immune responses in nude rats reconstituted with immature thymocyte subsets.

    PubMed

    Yang, C P; Bell, E B

    1994-04-01

    We have studied the ability of thymocyte subsets from allotype marked donors to populate athymic nude rats with T cells and to restore immune responsiveness. Following adoptive transfer, CD4-CD8- double-negative (DN) thymocytes (lymphoid precursor cells) or the CD4+CD8+ double-positive (DP) subset (intermediate thymocytes) or CD4+CD8- single-positive (CD4 SP) cells (mature thymocytes) each generated a permanent population of CD4+ progeny in syngeneic nude recipients. DN and DP thymocytes also produced small numbers of CD8+ cells; there was no evidence of a CD4-CD8- or CD4+CD8+ donor cell population. CD4 SP thymocytes conferred T cell functions [graft-versus-host (GVH) responses, allograft rejection and thymus-dependent antibody responses] on nude rats that were almost indistinguishable from those conferred by mature peripheral recirculating CD4 T cells. Transfer of DP thymocytes extended the life-span of the immunoincompetent nudes and produced CD4+ progeny with near normal GVH responsiveness. However, DP-derived CD4+ cells were deficient at inducing allograft rejection and provided little or no help for antibody synthesis. The CD4+ progeny of DN thymocytes did not prolong the survival of nude recipients, gave reduced GVH reactivity, showed almost no capacity to initiate skin allograft rejection and failed to help B cells produce antibody. The results suggest that intrathymic development proceeds stepwise; each stage is accompanied by acquisition of additional properties that are reflected by T cell responses in the periphery. Thymic education does not become complete until the SP stage is reached when thymocytes become fully independent of the thymic microenvironment.

  6. Effect of dietary selenium and cancer cell xenograft on peripheral T and B lymphocytes in adult nude mice.

    PubMed

    Cheng, Wen-Hsing; Holmstrom, Alexandra; Li, Xiangdong; Wu, Ryan T Y; Zeng, Huawei; Xiao, Zhengguo

    2012-05-01

    Selenium (Se) is known to regulate tumorigenesis and immunity at the nutritional and supranutritional levels. Because the immune system provides critical defenses against cancer and the athymic, immune-deficient NU/J nude mice are known to gradually develop CD8(+) and CD4(+) T cells, we investigated whether B and T cell maturation could be modulated by dietary Se and by tumorigenesis in nude mice. Fifteen homozygous nude mice were fed a Se-deficient, Torula yeast basal diet alone (Se-) or supplemented with 0.15 (Se+) or 1.0 (Se++) mg Se/kg (as Na(2)SeO(4)) for 6 months, followed by a 7-week time course of PC-3 prostate cancer cell xenograft (2 × 10(6) cells/site, 2 sites/mouse). Here, we show that peripheral B cell levels decreased in nude mice fed the Se -  or Se++ diet and the CD4(+) T cell levels increased in mice fed the Se++ diet. During the PC-3 cell tumorigenesis, dietary Se status did not affect peripheral CD4(+) or CD8(+) T cells in nude mice whereas mice fed with the Se++ diet appeared to exhibit greater peripheral CD25(+)CD4(+) T cells on day 9. Dietary Se status did not affect spleen weight in nude mice 7 weeks after the xenograft. Spleen weight was associated with frequency of peripheral CD4(+), but not CD8(+) T cells. Taken together, dietary Se at the nutritional and supranutritional levels regulates peripheral B and T cells in adult nude mice before and after xenograft with PC-3 prostate cancer cells.

  7. HeLa cell tumor response to 60Co, Cs-137, Cf-252 radiations and cisplatin chemotherapy in nude mice.

    PubMed

    Maruyama, Y; Feola, J M; Beach, J L

    1984-07-15

    HeLa cells were implanted into athymic nude mice from tissue culture and solid tumors established (HeLa cell tumor or HCT). Large cell numbers of 1 X 10(7) were required to obtain consistent and progressive growth, and tumor growth followed a Gompertzian mode. Irradiation studies were carried out using acute Cobalt-60 (60Co), low-dose-rate (LDR) Cs-137 and LDR Cf-252. Cf-252, a neutron-emitting radioisotope, produced an immediate tumor shrinkage and regression response after a dose of 279 cGy. Acute 60Co or LDR Cs-137 irradiation with 1000 cGy had little effect on the HCT. After a dose of 2000 cGy of 60Co radiation tumor shrinkage followed a latent period of approximately 5 days. Cisplatin had no effect on the HCT in nude mice in stationary or late exponential growth.

  8. HeLa cell tumor response to 60Co, Cs-137, Cf-252 radiations and cisplatin chemotherapy in nude mice

    SciTech Connect

    Maruyama, Y.; Feola, J.M.; Beach, J.L.

    1984-07-15

    HeLa cells were implanted into athymic nude mice from tissue culture and solid tumors established (HeLa cell tumor or HCT). Large cell numbers of 1 X 10/sup 7/ were required to obtain consistent and progressive growth, and tumor growth followed a Gompertzian mode. Irradiation studies were carried out using acute Cobalt-60 (60Co), low-dose-rate (LDR) Cs-137 and LDR Cf-252. Cf-252, a neutron-emitting radioisotope, produced an immediate tumor shrinkage and regression response after a dose of 279 cGy. Acute 60Co or LDR Cs-137 irradiation with 1000 cGy had little effect on the HCT. After a dose of 2000 cGy of 60Co radiation tumor shrinkage followed a latent period of approximately 5 days. Cisplatin had no effect on the HCT in nude mice in stationary or late exponential growth.

  9. Neonatal thymulin gene therapy in nude mice: Effects on the morphology of the pituitary corticotrope population.

    PubMed

    Martines, Eliana; Reggiani, Paula C; Schwerdt, José I; Goya, Rodolfo G; Cónsole, Gloria

    2011-04-01

    The integrity of the thymus during early life is necessary for a proper maturation of the neuroendocrine system, including the adrenal axis. The thymic metallopeptide thymulin seems to be a central physiologic mediator of thymus-pituitary communication. Furthermore, neonatal thymulin gene therapy has been shown to prevent the typical alterations of gonadotrophic cell number and morphology and serum gonadotropin levels in nude female mice. In the present study we assessed the impact of athymia and the effect of neonatal thymulin gene therapy on the corticotropic cell population in nude mice. The effect of thymulin administration to adult nudes on their hypothalamic content of corticotropin-releasing hormone (CRH) and the adrenal content of corticosterone was also determined. We used an adenoviral vector expressing a synthetic gene for the thymic peptide thymulin (metFTS) termed RAd-FTS. On postnatal day 1 or 2, heterozygous (nu/+) and homozygous (nu/nu) pups of both sexes received a single bilateral i.m. injection of RAd-FTS or RAd-GFP, a control vector. On postnatal day 71, mice were bled and sacrificed, and their pituitaries were immediately dissected, fixed and immunostained for corticotropin. Morphometry was performed by means of an image-analysis system. The following parameters were calculated: volume density (VD: Σ cell area/reference area), cell density (CD: number of cells/reference area), and cell surface (CS: expressed in μm²). Serum thymulin levels were measured by a bioassay, and CRH as well as corticosterone were determined by IRMA and RIA, respectively. Neonatal thymulin gene therapy in the athymic mice restored their serum thymulin levels and increased corticotrope CD, VD and CS in both control and athymic mice. Athymic mice showed only a marginal reduction in corticotrope CD, VD and CS. In these mutants hypothalamic CRH content was slightly increased, whereas adrenal corticosterone tended to be lower. Thymulin administration to adult mice tended

  10. Chronic fatal pneumocystosis in nude mice.

    PubMed

    Ueda, K; Goto, Y; Yamazaki, S; Fujiwara, K

    1977-12-01

    A chronic pulmonary disease was encountered in nude mice of a barrier sustained colony, and Pneumocystis carinii was identified as the causative agent histopathologically as well as on impression smear preparations in the affected lungs. Fatal infection was seen only in old nude mice aged more than 6 months, while focal pulmonary lesions were developed without clinical signs in young adult nudes 2 to 3 months of age. The lesions produced in aged nude mice were characterized by propagation of mononuclear cells with the presence of foamy masses of P. carinii. Heterozygous littermates were much less susceptible to the infection but pneumocystic lesions could be produced readily by multiple treatment with immunosuppressants. The infection could be transmitted without immunosuppressant to non-infected nudes but not to heterozygous littermates after intranasal inoculation of affected tissue emulsion or by cage mating with severely affected nudes.

  11. Immunological responses of `nude' mice

    PubMed Central

    Wortis, H. H.

    1971-01-01

    Mice homozygous for the mutation nude which lack a thymus, were found to have a marked lymphopenia. They had a marked granulocytosis following administration of B. pertussis, but only slight lymphocytosis. Unlike littermates they failed to develop an increased cellularity of lymph nodes draining a local injection of PHA. They had reduced levels of immunoglobulin but produced some antibody to sheep-RBC. They accepted allografts. Cell cooperation experiments suggest that the immunological deficits of nu/nu mice can be explained by the absence of a thymusderived cell population. ImagesFIG. 5 PMID:4929778

  12. Inhibition of histone deacetylases by trans-cinnamic acid and its antitumor effect against colon cancer xenografts in athymic mice

    PubMed Central

    ZHU, BINGYAN; SHANG, BOYANG; LI, YI; ZHEN, YONGSU

    2016-01-01

    Previous studies have shown that trans-cinnamic acid (tCA) has a broad spectrum of biological activities, and exhibits antioxidant, anti-inflammatory and anticancer properties. In addition, tCA and a variety of its analogs have been detected as gut microbe-derived metabolites exerting various biological effects in the colon. The aim of this study was to assess the antitumor activity of tCA in vitro and in vivo, in particular its therapeutic efficacy against colon cancer xenografts in athymic mice. Furthermore, it aimed to examine the effects of tCA on histone deacetylases (HDACs) and to identify the underlying molecular mechanisms. Using an MTT assay, tCA was observed to inhibit the proliferation of several cancer cell lines, and the half maximal inhibitory concentration (IC50) in HT29 colon carcinoma cells was ~1 mM. Western blot analysis demonstrated that tCA upregulated the expression of acetyl-H3 and acetyl-H4 proteins, which was consistent with the effects of the HDAC inhibitor, trichostatin A (TSA). Furthermore, expression of Bcl-2 (a marker of cell proliferation) was reduced, and apoptosis was induced. Apoptosis was shown by the activation of cleavage of poly ADP ribose polymerase and the increased expression of Bax. Apoptosis was also confirmed using APC Annexin V and SYTOX Green Nucleic Acid Stain. In addition, the tCA-induced inhibition of the expression of HDAC markers and activation of apoptosis in tumor tissues were further confirmed by immunohistochemistry. Intragastric administration of tCA at doses of 1.0 and 1.5 mmol/kg body weight suppressed the growth of HT29 human colon carcinoma xenografts in athymic mice at well-tolerated doses. No toxic changes were found in the heart, lung, liver, kidney, colon or bone marrow following histopathological examination. This study indicated that tCA is effective against colon cancer xenograft in nude mice. The antitumor mechanism of tCA was mediated, at least in part, by inhibition of HDACs in cancer cells. As

  13. Effect of all-trans and 9-cis retinoic acid on growth and metastasis of xenotransplanted canine osteosarcoma cells in athymic mice.

    PubMed

    Hong, S H; Kadosawa, T; Mochizuki, M; Matsunaga, S; Nishimura, R; Sasaki, N

    2000-10-01

    To determine effects of all-trans and 9-cis retinoic acid (RA) on tumor growth and metastatic ability of canine osteosarcoma cells transplanted into athymic (nude) mice. Forty-five 5-week-old female BALB/c nude mice. 1 X 10(7) POS osteosarcoma cells were transplanted subcutaneously into the intrascapular region of mice. All-trans RA (3 or 30 microg/kg of body weight in 0.1 ml of sesame oil), 9-cis RA (3 or 30 mg/kg in 0.1 ml of sesame oil), or sesame oil (0.1 ml; control treatment) were administered intragastrically 5 d/wk for 4 weeks beginning 3 days after transplantation (n = 4 mice/group) or after formation of a palpable tumor (5 mice/group). Tumor weight was estimated weekly by measuring tumor length and width, and retinoid toxic effects were evaluated daily. Two weeks after the final treatment, mice were euthanatized, and number of mice with pulmonary metastases was determined. Adverse treatment effects were not detected. Tumor weight was less in mice treated with either dose of 9-cis RA than in control mice, although this difference was not significant. Treatment with 30 mg of 9-cis RA/kg initiated after tumor formation significantly reduced the incidence of pulmonary metastasis, compared with the control group. 9-cis RA decreased the incidence of pulmonary metastasis in nude mice transplanted with canine osteosarcoma cells and may be a potential adjunct therapy for treatment of osteosarcoma in dogs.

  14. Outcome of xenografted fetal porcine pancreatic tissue is superior in inbred scid (C.B-17/Icr-scid/scid) compared to outbred nude (CD-1-nu/nu) mice.

    PubMed

    Tuch, B E; Casamento, F M

    1999-01-01

    Nude mice are used as recipients of foreign tissue because of their inability to reject these grafts. Our experience has been that there is variable rejection of fetal porcine insulin-producing tissue transplanted into CD-1 (athymic) outbred nude mice. To examine the suitability of this line of nude mouse as a recipient of the tissue, fetal porcine pancreas was grafted either into these outbred animals or into an inbred mutant strain of mice, the more immunocompromised severe combined immunodeficient (scid) mouse. Eight weeks after transplantation grafts were recovered from recipients and assayed for insulin content. Mean insulin levels were not significantly different between the two groups of mice, but a wider range of values was obtained from grafts recovered from nude (CD-1-nu/nu) mice. Reversal of diabetes in hyperglycemic recipients was achieved in 4 of 8 nude mice and 8 of 8 scid (C.B-17/lcr-scid/scid) mice. The time taken to achieve this was longer in the nudes than the scid mice, 121 +/- 12 vs. 44 +/- 2 days, the grafts increasing in size at a slower rate in the nude mice. Time taken for the weight of the grafts to double in size was 94 +/- 17 vs. 32 +/- 1 days, respectively. Histologically the grafts in the scid mice contained mostly epithelial cell clusters, a majority of which were insulin containing. In the nude mice that achieved normoglycemia, a similar pattern was observed and, as well, there was a localized lymphoid infiltrate. In those nude mice that remained diabetic fibrous tissue predominated together with a lymphoid infiltrate. In summary, fetal porcine pancreatic tissue grows and develops more efficiently when xenografted into scid rather than outbred nude mice.

  15. Self-recognition specificity expressed by T cells from nude mice. Absence of detectable Ia-restricted T cells in nude mice that do exhibit self-K/D-restricted T cell responses

    SciTech Connect

    Kruisbeek, A.M.; Davis, M.L.; Matis, L.A.; Longo, D.L.

    1984-09-01

    The presence in athymic nude mice of precursor T cells with self-recognition specificity for either H-2 K/D or H-2 I region determinants was investigated. Chimeras were constructed of lethally irradiated parental mice receiving a mixture of F1 nude mouse (6-8 wk old) spleen and bone marrow cells. The donor inoculum was deliberately not subjected to any T cell depletion procedure, so that any potential major histocompatibility complex-committed precursor T cells were allowed to differentiate and expand in the normal parental recipients. 3 mo after reconstitution, the chimeras were immunized with several protein antigens in complete Freund's adjuvant in the footpads and their purified draining lymph node T cells tested 10 d later for ability to recognize antigen on antigen-presenting cells of either parental haplotype. Also, their spleen and lymph node cells were tested for ability to generate a cytotoxic T lymphocyte (CTL) response to trinitrophenyl (TNP)-modified stimulator cells of either parental haplotype. It was demonstrated that T cell proliferative responses of these F1(nude)----parent chimeras were restricted solely to recognizing parental host I region determinants as self and expressed the Ir gene phenotype of the host. In contrast, CTL responses could be generated (in the presence of interleukin 2) to TNP-modified stimulator cells of either parental haplotype. Thus these results indicate that nude mice which do have CTL with self-specificity for K/D region determinants lack proliferating T cells with self-specificity for I region determinants. These results provide evidence for the concepts that development of the I region-restricted T cell repertoire is strictly an intrathymically determined event and that young nude mice lack the unique thymic elements responsible for edu

  16. Biology of human skin transplanted to the nude mouse: I. Response to agents which modify epidermal proliferation.

    PubMed

    Krueger, G G; Shelby, J

    1981-06-01

    To accept human skin transplanted to the congenitally athymic (nude) mouse as a system to study human skin and its physiologic and pathologic states, it must be demonstrated that skin so maintained retains its function as a biologic unit. We have found that responses of grafted human skin and nude mouse skin to various agents differ. This difference in response has been utilized to assess barrier function and proliferative capacity of human skin grafts. Human skin grafts undergo a proliferative response when 10 ng of the tumor promoter, 12-O-tetradecanoyl phorbol 13-acetate (TPA) is applied. Nudes do not respond to this dose. Increasing the dose to 100 ng of TPA evokes a response in both. However, only in the human skin grafts can this response be blocked with betamethasone valerate (BV). In that human skin grafts do not take on their hosts' responsiveness, and the response of domestic pig skin to these agents before and after grafting is identical, the conclusion is reached that human skin appears to retain its inherent biologic unit function. The data also demonstrate some of the potential of this system to study kinetics of the epidermis of human skin.

  17. [Establishment and characterization of dual-color fluorescence nude mouse models of glioma].

    PubMed

    Zhang, Jinshi; Lu, Zhaohui; Fei, Xifeng; Dai, Xingliang; Wu, Jinding; Wan, Yi; Wang, Zhimin; Wang, Aidong; Dong, Jun; Lan, Qing; Huang, Qiang

    2014-02-01

    To establish red-green dual-color fluorescence glioma model in nude mice and to explore its practical values. CM-DiI-stained rat glioma C6 cells (C6-CM- DiI cells) expressing red fluorescence were inoculated into the brain of athymic nude mice expressing green fluorescence protein (NC-C57BL/6J-EGFP). Then the whole-body dual-color fluorescence imaging was detected dynamically. Finally whole brains of the tumor-bearing mice were removed and 5 µm thick serial frozen slices were made. Light microscopy, fluorescence microscopy and confocal laser scanning microscopy were performed to observe the transplanted tumor tissue structure and fluorescent cells. Tumor mass with red fluorescence increased gradually under continuous in-vivo fluorescence imaging monitoring. Under the fluorescence microscope, cells with red, green and yellow fluorescence were observed in the frozen sections of transplanted tumor tissue and the mutual structural relationship among them could be defined. The tumor cells migration, implantation and cell fusion between transplanted tumor cells and host cells could be observed. It could be distinguished according to the fluorescence, that blood vessels of tumor-origin displayed red fluorescence, blood vessels of host-origin displayed green fluorescence and mosaic blood vessels appeared yellow fluorescence. It was depicted that host innate astrocytes and oligodendrocytes in the microenvironment at the tumor periphery could be activated and dedifferentiated into nestin-positive cells. In contrast to traditional animal model, the dual-color fluorescence imaging of nude mouse models of glioma possesses enormous advantages in investigating tumor mass in-vivo fluorescence imaging, tumor cells migration and metastasis, tumor angiogenesis and reactive activation of host innate cells in the microenvironment at tumor periphery, thus, has highly practical application value.

  18. Inhibition of subcutaneously implanted human pituitary tumor cells in nude mice by LRIG1.

    PubMed

    Wang, X; He, X J; Xu, H Q; Chen, Z W; Fan, H H

    2016-05-06

    The aim of this study was to explore the inhibition of subcutaneously implanted human pituitary tumor cells in nude mice by LRIG1 and its mechanism. For this study, athymic nude mice were injected with either normal pituitary tumor RC-4B/C cells or LRIG1-transfected RC-4B/C cells. We then calculated the volume inhibition rate of the tumors, as well as the apoptosis index of tumor cells and the expression of Ras, Raf, AKt, and ERK mRNA in tumor cells. Tumor cell morphological and structural changes were also observed under electron microscope. Our data showed that subcutaneous tumor growth was slowed or even halted in LRIG1-transfected tumors. The tumor volumes were significantly different between the two groups of mice (χ2 = 2.14, P < 0.05). The tumor apoptosis index was found to be 8.72% in the control group and 39.7% in LRIG1-transfected mice (χ2 = 7.59, P < 0.05). The levels of Ras, Raf, and AKt mRNA in LRIG1-transfected RC-4B/C cells were significantly reduced after transfection (P < 0.01). Transfected subcutaneous tumor cells appeared to be in early or late apoptosis under an electron microscope, while only a few subcutaneous tumor cells appeared to be undergoing apoptosis in the control group. In conclusion, the LRIG1 gene is able to inhibit proliferation and promote apoptosis in subcutaneously implanted human pituitary tumors in nude mice. The mechanism of LRIG1 may involve the inhibition of the PI3K/ Akt and Ras/Raf/ERK signal transduction pathways.

  19. Partial prevention of hepatic lipid alterations in nude mice by neonatal thymulin gene therapy.

    PubMed

    García de Bravo, Margarita M; Polo, Mónica P; Reggiani, Paula C; Rimoldi, Omar J; Dardenne, Mireille; Goya, Rodolfo G

    2006-08-01

    During adult life athymic (nude) male mice display not only a severe T-cell-related immunodeficiency but also endocrine imbalances and a moderate hyperglycemia. We studied the impact of congenital athymia on hepatic lipid composition and also assessed the ability of neonatal thymulin gene therapy to prevent the effects of athymia. We constructed a recombinant adenoviral vector, RAd-metFTS, expressing a synthetic DNA sequence encoding met-FTS, an analog of the thymic peptide facteur thymique sérique (FTS), whose Zn-bound biologically active form is known as thymulin. On postnatal day 1-2 homozygous (nu/nu) nude and heterozygous (nu/+) mice were injected with 10(8) pfu of RAd-metFTS or RAd-betagal (control vector) intramuscularly. The animals were processed at 52 d of age. Serum thymulin, glycemia, hepatic phospholipid FA composition and free and esterified cholesterol were determined. Adult homozygous male nudes were significantly (P < 0.01) hyperglycemic when compared with their heterozygous counterparts (2.04 vs. 1.40 g/L, respectively). The relative percentage of 16:0, 18:1 n-9, and 18:1n-7 FA was lower, whereas that of 18:0, 20:4n-6, and 22:6n-3 FA was higher, in hepatic phospholipid (PL) of nu/nu animals as compared with their nu/+ counterparts. Some of these alterations, such as that in the relative content of 22:6n-3 in liver PL and the unsaturation index, were completely or partially prevented by neonatal thymulin gene therapy. We conclude that the thymus influences lipid metabolism and that thymulin is involved in this modulatory activity.

  20. The nude gene and the skin.

    PubMed

    Schlake, T

    2001-10-01

    The nude mutation has been known for a long time. Nevertheless, the gene responsible for the defect has been identified only recently. It encodes a transcriptional activator of the family of forkhead proteins mainly expressed in thymic epithelium and distinct keratinocyte populations in the epidermis and hair follicles. The present review focuses on the molecular and functional characterization of the nude gene and its product and gives an overview as to its role in skin biology and the first identified target genes in the skin. In addition, evolutionary aspects are highlighted stressing the importance of such investigations for a comprehensive understanding of the nude gene product and the regulation of its expression. Furthermore, these studies give a hint as to when the nude gene has occurred first and how it has developed in molecular and functional terms since then.

  1. High-risk gastrointestinal stromal tumour (GIST) and synovial sarcoma display similar angiogenic profiles: a nude mice xenograft study

    PubMed Central

    Giner, Francisco; Machado, Isidro; Lopez-Guerrero, Jose Antonio; Mayordomo-Aranda, Empar; Llombart-Bosch, Antonio

    2017-01-01

    Background Gastrointestinal stromal tumour (GIST) is the most common primary mesenchymal tumour of the gastrointestinal tract. Spindle cell monophasic synovial sarcoma (SS) can be morphologically similar. Angiogenesis is a major factor for tumour growth and metastasis. Our aim was to compare the angiogenic expression profiles of high-risk GIST and spindle cell monophasic SS by histological, immunohistochemical and molecular characterisation of the neovascularisation established between xenotransplanted tumours and the host during the initial phases of growth in nude mice. Methods The angiogenic profile of two xenotransplanted human soft-tissue tumours were evaluated in 15 passages in nude mice using tissue microarrays (TMA). Tumour pieces were also implanted subcutaneously on the backs of 14 athymic Balb-c nude mice. The animals were sacrificed at 24, 48, and 96 h; and 7, 14, 21, and 28 days after implantation to perform histological, immunohistochemical, and molecular studies (neovascularisation experiments). Results Morphological similarities were apparent in the early stages of neoplastic growth of these two soft-tissue tumours throughout the passages in nude mice and in the two neovascularisation experiments. Immunohistochemistry demonstrated overexpression of pro-angiogenic factors between 24 h and 96 h after xenotransplantation in both tumours. Additionally, neoplastic cells coexpressed chemokines (CXCL9, CXCL10, GRO, and CXCL12) and their receptors in both tumours. Molecular studies showed two expression profiles, revealing an early and a late phase in the angiogenic process. Conclusion This model could provide information on the early stages of the angiogenic process in monophasic spindle cell SS and high-risk GIST and offers an excellent way to study possible tumour response to antiangiogenic drugs. PMID:28386296

  2. Human hematopoietic tumors in nude mice.

    PubMed

    Sordillo, P P; Hansen, H; Jhanwar, S C; Beck, J; Lieberman, P; Helson, L

    1981-01-01

    Despite the difficulty in establishing human hematopoietic tumors in nude mice, four human lymphomas were successfully heterotransplanted and passaged serially in our laboratory. Additional immunosuppression with chemotherapy, whole-body radiation or splenectomy was not required for establishment of these tumors. All four of these tumors were of the non-Hodgkin's lymphoma type. In each case the tumors in the nude mice were histologically identical to the biopsy specimens from the patient in whom they were derived. Attempts to transplant tumor from 17 patients with Hodgkin's disease or 4 patients with immunoblastic lymphadenopathy were unsuccessful. Tumors from 2 patients with chronic myelogenous leukemia and 1 with hairy cell leukemia could be grown in nude mice conditioned with whole-body radiation or cytosine arabinoside, but these tumors could not be passaged to other nude mice. Cell surface markers were determined on the four serially passaged lymphomas. These surface markers were similar to the markers on the original tumors, even after long periods of mouse-to-mouse passage. In 1 patient with fevers, night sweats and mediastinal mass in whom a diagnosis had not been made after several biopsies, examination of tumor tissue that had been transplanted from the patient to the nude mouse clearly established the diagnosis of lymphoma.

  3. Normal keratinized mucosa transplants in nude mice.

    PubMed

    Holmstrup, P; Dabelsteen, E; Reibel, J; Harder, F

    1981-01-01

    Two types of normal keratinized mucosa were transplanted to subcutaneous sites of nude mice of two different strains. 24 intact specimens of clinically normal human palatal mucosa were transplanted to nude mice of the strain nu/nu NC. The transplants were recovered after 42 d with a recovery rate of 96%. Moreover, 22 intact specimens of normal rat forestomach mucosa were transplanted to nude mice of the strain nu/nu BALB/c/BOM. These transplants were recovered after 21 d with a recovery rate of 63%. The histologic features of the transplants were essentially the same as those of the original tissues. However, epithelial outgrowths from the transplants differed with respect to the pattern of keratinization. The outgrowths of human palatal mucosa transplants were essentially unkeratinized, while the outgrowths of the rat forestomach transplants showed continued keratinization.

  4. A Novel Nude Mouse Model of Hypertrophic Scarring Using Scratched Full Thickness Human Skin Grafts

    PubMed Central

    Alrobaiea, Saad M.; Ding, Jie; Ma, Zengshuan; Tredget, Edward E.

    2016-01-01

    Objective: Hypertrophic scar (HTS) is a dermal form of fibroproliferative disorder that develops following deep skin injury. HTS can cause deformities, functional disabilities, and aesthetic disfigurements. The pathophysiology of HTS is not understood due to, in part, the lack of an ideal animal model. We hypothesize that human skin with deep dermal wounds grafted onto athymic nude mice will develop a scar similar to HTS. Our aim is to develop a representative animal model of human HTS. Approach: Thirty-six nude mice were grafted with full thickness human skin with deep dermal scratch wound before or 2 weeks after grafting or without scratch. The scratch on the human skin grafts was made using a specially designed jig that creates a wound >0.6 mm in depth. The xenografts were morphologically analyzed by digital photography. Mice were euthanized at 1, 2, and 3 months postoperatively for histology and immunohistochemistry analysis. Results: The mice developed raised and firm scars in the scratched xenografts with more contraction, increased infiltration of macrophage, and myofibroblasts compared to the xenografts without deep dermal scratch wound. Scar thickness and collagen bundle orientation and morphology resembled HTS. The fibrotic scars in the wounded human skin were morphologically and histologically similar to HTS, and human skin epithelial cells persisted in the remodeling tissues for 1 year postengraftment. Innovation and Conclusions: Deep dermal injury in human skin retains its profibrotic nature after transplantation, affording a novel model for the assessment of therapies for the treatment of human fibroproliferative disorders of the skin. PMID:27366591

  5. Tumorigenicity and Validity of Fluorescence Labelled Mesenchymal and Epithelial Human Oral Cancer Cell Lines in Nude Mice.

    PubMed

    Cai, Wei Xin; Zheng, Li Wu; Ma, Li; Huang, Hong Zhang; Yu, Ru Qing; Zwahlen, Roger A

    2016-01-01

    Tumorigenicity and metastatic activity can be visually monitored in cancer cells that were labelled with stable fluorescence. The aim was to establish and validate local and distant spread of subcutaneously previously injected fluorescence transduced human tongue cancer cell lines of epithelial and mesenchymal phenotype in nude mice. A total of 32 four-week-old male athymic Balb/c nude mice were randomly allocated into 4 groups (n = 8). A single dose of 0.3 mL PBS containing 1 × 107 of four different cancer cell-lines (UM1, UM1-GFP, UM2, and UM2-RFP) was injected subcutaneously into the right side of their posterolateral back. Validity assessment of the labelled cancer cells' tumorigenicity was assessed by physical examination, imaging, and histology four weeks after the injection. The tumor take rate of cancer cells was similar in animals injected with either parental or transduced cancer cells. Transduced cancer cells in mice were easily detectable in vivo and after cryosection using fluorescent imaging. UM1 cells showed increased tumor take rate and mean tumor volume, presenting with disorganized histopathological patterns. Fluorescence labelled epithelial and mesenchymal human tongue cancer cell lines do not change in tumorigenicity or cell phenotype after injection in vivo.

  6. From Murine to Human Nude/SCID: The Thymus, T-Cell Development and the Missing Link

    PubMed Central

    Romano, Rosa; Palamaro, Loredana; Fusco, Anna; Iannace, Leucio; Maio, Stefano; Vigliano, Ilaria; Giardino, Giuliana; Pignata, Claudio

    2012-01-01

    Primary immunodeficiencies (PIDs) are disorders of the immune system, which lead to increased susceptibility to infections. T-cell defects, which may affect T-cell development/function, are approximately 11% of reported PIDs. The pathogenic mechanisms are related to molecular alterations not only of genes selectively expressed in hematopoietic cells but also of the stromal component of the thymus that represents the primary lymphoid organ for T-cell differentiation. With this regard, the prototype of athymic disorders due to abnormal stroma is the Nude/SCID syndrome, first described in mice in 1966. In man, the DiGeorge Syndrome (DGS) has long been considered the human prototype of a severe T-cell differentiation defect. More recently, the human equivalent of the murine Nude/SCID has been described, contributing to unravel important issues of the T-cell ontogeny in humans. Both mice and human diseases are due to alterations of the FOXN1, a developmentally regulated transcription factor selectively expressed in skin and thymic epithelia. PMID:22474479

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

    SciTech Connect

    Kjonniksen, I.; Hoifodt, H.K.; Pihl, A.; Fodstad, O. )

    1991-07-17

    The metastatic capacity of intravenously injected human FEMX-I melanoma cells in athymic nude mice and rats was compared. Young rats given 1 {times} 10(6) ascites tumor cells all died of lung tumors with a life span of 50 {plus minus} 10 days (mean{plus minus} 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.

  8. A New Apparatus and Surgical Technique for the Dual Perfusion of Human Tumor Xenografts in Situ in Nude Rats

    PubMed Central

    Dauchy, Robert T; Dauchy, Erin M; Mao, Lulu; Belancio, Victoria P; Hill, Steven M; Blask, David E

    2012-01-01

    We present a new perfusion system and surgical technique for simultaneous perfusion of 2 tissue-isolated human cancer xenografts in nude rats by using donor blood that preserves a continuous flow. Adult, athymic nude rats (Hsd:RH-Foxn1rnu) were implanted with HeLa human cervical or HT29 colon adenocarcinomas and grown as tissue-isolated xenografts. When tumors reached an estimated weight of 5 to 6 g, rats were prepared for perfusion with donor blood and arteriovenous measurements. The surgical procedure required approximately 20 min to complete for each tumor, and tumors were perfused for a period of 150 min. Results showed that tumor venous blood flow, glucose uptake, lactic acid release, O2 uptake and CO2 production, uptake of total fatty acid and linoleic acid and conversion to the mitogen 13-HODE, cAMP levels, and activation of several marker kinases were all well within the normal physiologic, metabolic, and signaling parameters characteristic of individually perfused xenografts. This new perfusion system and technique reduced procedure time by more than 50%. These findings demonstrate that 2 human tumors can be perfused simultaneously in situ or ex vivo by using either rodent or human blood and suggest that the system may also be adapted for use in the dual perfusion of other organs. Advantages of this dual perfusion technique include decreased anesthesia time, decreased surgical manipulation, and increased efficiency, thereby potentially reducing the numbers of laboratory animals required for scientific investigations. PMID:22546915

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

    PubMed

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

    2000-05-01

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

  10. Experimental Porphyromonas gingivalis infection in nonimmune athymic BALB/c mice.

    PubMed Central

    Chen, P B; Davern, L B; Aguirre, A

    1991-01-01

    The purpose of this report was to study the role of T lymphocytes following injection of Porphyromonas gingivalis in a mouse abscess model. Three invasive P. gingivalis isolates (ATCC 53977, W83, and AJW4) were injected into athymic BALB/c mice and their heterozygous (nu/+) littermates. The athymic BALB/c (nu/nu) mice were able to localize the invasive P. gingivalis isolates at the injection site. By comparison, the heterozygous BALB/c (nu/+) littermates developed hemorrhagic secondary lesions within 24 h after subcutaneous injection of the same invasive P. gingivalis isolates. These results suggest that naive T lymphocytes may contribute to the pathology associated with P. gingivalis infection. PMID:1657788

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

    PubMed

    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.

  12. Split tolerance in nude mice transplanted with 2'-deoxyguanosine-treated allogeneic thymus lobes

    SciTech Connect

    Suzuki, G.; Moriyama, T.; Takeuchi, Y.; Kawase, Y.; Habu, S.

    1989-03-01

    To elucidate the acquisition of self tolerance in the thymus, full-allogeneic thymic chimeras were constructed. Athymic C3H and BALB/c nude mice were reconstituted with the thymic lobes of BALB/c and B10.BR fetuses, respectively, that were organ cultured for 5 days in the presence of 2'-deoxyguanosine. T cells in these chimeras were tolerized to the host MHC in both MLR and CTL assays. In contrast, T cells in the chimeras exhibited split tolerance for the thymic MHC haplotype. CTL specific for class I MHC of the thymic haplotype were generated not only from the peripheral T cells of the chimeras but also from thymocytes re-populated in the engrafted thymic lobes. However, T cells in these chimeras responded poorly to the class II MHC of the thymic haplotype in a standard MLR assay. In a syngeneic MLR culture upon stimulation with enriched APC of the thymic haplotype, only 22 to 48% of the responses were mediated by CD4+ cells, and proliferations of CD4- cells were prominent. There were no haplotype-specific suppressor cells detected which would cause the unresponsiveness to the thymic class II MHC. These results indicated that the thymic lobes treated with 2'-deoxyguanosine were defective in the ability to induce the transplantation tolerance for the class I MHC expressed on the thymus, although the same thymic lobes were able to induce the transplantation tolerance for the thymic class II MHC.

  13. Suppression of matrix metalloproteinases inhibits establishment of ectopic lesions by human endometrium in nude mice.

    PubMed

    Bruner, K L; Matrisian, L M; Rodgers, W H; Gorstein, F; Osteen, K G

    1997-06-15

    Matrix metalloproteinases of the stromelysin family are expressed in the human endometrium as a consequence of cellular events during the menstrual cycle that require extracellular matrix remodeling. We have recently documented the presence of these enzymes in lesions of endometriosis, a benign disease that presents as persistent ectopic sites of endometrial tissue, usually within the peritoneal cavity. Endometriosis can develop after retrograde menstruation of endometrial tissue fragments, and establishment of ectopic sites within the peritoneal cavity requires breakdown of extracellular matrix. To examine whether matrix metalloproteinases might contribute to the steroid-dependent epidemiology and cellular pathophysiology of endometriosis, we have developed an experimental model of endometriosis using athymic nude mice as recipients of human endometrial tissue. Our results demonstrate that estrogen treatment of human endometrial tissue in organ culture maintains secretion of matrix metalloproteinases, and promotes establishment of ectopic peritoneal lesions when injected into recipient animals. In contrast, suppressing metalloproteinase secretion in vitro with progesterone treatment, or blocking enzyme activity with a natural inhibitor of metalloproteinases, inhibits the formation of ectopic lesions in this experimental model.

  14. Immune and mitogenic responses by BALB/c, C3H/HeJ, and nude mice to Brucella abortus bacterin and lipopolysaccharide.

    PubMed

    Spellman, J M; Reed, N D

    1979-05-01

    The immunogenic and mitogenic properties of Brucella abortus 1119-3 bacterin (BA) and biologically active B. abortus lipopolysaccharide (BA-LPS) were studied using normal and athymic (nude) BALB/c and C3H/HeJ mice. Although BA stimulated 2-mercaptoethanol-sensitive (2-ME-S) primary and secondary antibody responses in all mice, nude mice, in contrast to normal BALB/c and C3H/HeJ mice, did not make substantial 2-mercaptoethanol-resistant (2-ME-R) antibody responses. Similarly, all mice injected with BA-LPS made 2-ME-S primary responses, and the secondary response of thymus-bearing mice contained a substantial 2-ME-R component. Collectively, these observations suggest that although both BA and BA-LPS can stimulate thymus-independent 2-ME-S antibody synthesis, thymus-derived cells are required for optimal immune responses containing a 2-ME-R component. The antibody responses of normal BALB/c and C3H/HeJ mice to BA and BA-LPS were qualitatively and quantitatively similar. Both BA and BA-LPS were mitogenic for spleen cells from normal and nude BALB/c and C3H/HeJ mice but not for thymus cells from normal BALB/c or C3H/HeJ mice, suggesting that both preparations are B-cell mitogens.

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

    PubMed Central

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

    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 concentrations of loquat water or ethanol extract. Proliferation, adhesion, migration, invasion and matrix metalloproteinase (MMP) activity were examined. RESULTS Tumor growth of xenograft nude mouse was significantly reduced by loquat extracts. The results of mitotic examination revealed that loquat extracts reduced tumor cell division. Both ethanol and water extracts significantly inhibited MDA-MB-231 cell proliferation. The protein expression of ErbB3 was significantly down-regulated by loquat leaf extracts. Loquat leaf extracts increased apoptosis of MDA-MB-231 cells following 24 hour incubation and the ethanol extract was more potent in inducing apoptosis than the water extract. Furthermore, loquat extracts inhibited adhesion, migration and invasion of MDA-MB-231 cells. MMP activity was significantly inhibited by loquat extracts. CONCLUSION Our results show that extracts of loquat inhibit the growth of tumor in MDA-MB-231 xenograft nude mice and the invasion of human breast cancer cells, indicating the inhibition of tumor cell proliferation and invasion. PMID:27087896

  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.

    PubMed

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

    2016-04-01

    The present study was conducted to examine the inhibitory effect of loquat leaves on MDA-MB-231 cell proliferation and invasion. Female athymic nude mice were given a subcutaneous (s.c.) inoculation of MDA-MB-231 cells and randomly grouped to receive a s.c. injection of either 500 mg/kg ethanol, water extract or vehicle five times a week. Tumor growth, mitotic rate and necrosis were examined. MDA-MB-231 cells were cultured with DMSO or with various concentrations of loquat water or ethanol extract. Proliferation, adhesion, migration, invasion and matrix metalloproteinase (MMP) activity were examined. Tumor growth of xenograft nude mouse was significantly reduced by loquat extracts. The results of mitotic examination revealed that loquat extracts reduced tumor cell division. Both ethanol and water extracts significantly inhibited MDA-MB-231 cell proliferation. The protein expression of ErbB3 was significantly down-regulated by loquat leaf extracts. Loquat leaf extracts increased apoptosis of MDA-MB-231 cells following 24 hour incubation and the ethanol extract was more potent in inducing apoptosis than the water extract. Furthermore, loquat extracts inhibited adhesion, migration and invasion of MDA-MB-231 cells. MMP activity was significantly inhibited by loquat extracts. Our results show that extracts of loquat inhibit the growth of tumor in MDA-MB-231 xenograft nude mice and the invasion of human breast cancer cells, indicating the inhibition of tumor cell proliferation and invasion.

  17. Facilitated early cortical processing of nude human bodies.

    PubMed

    Alho, Jussi; Salminen, Nelli; Sams, Mikko; Hietanen, Jari K; Nummenmaa, Lauri

    2015-07-01

    Functional brain imaging has identified specialized neural systems supporting human body perception. Responses to nude vs. clothed bodies within this system are amplified. However, it remains unresolved whether nude and clothed bodies are processed by same cerebral networks or whether processing of nude bodies recruits additional affective and arousal processing areas. We recorded simultaneous MEG and EEG while participants viewed photographs of clothed and nude bodies. Global field power revealed a peak ∼145ms after stimulus onset to both clothed and nude bodies, and ∼205ms exclusively to nude bodies. Nude-body-sensitive responses were centered first (100-200ms) in the extrastriate and fusiform body areas, and subsequently (200-300ms) in affective-motivational areas including insula and anterior cingulate cortex. We conclude that visibility of sexual features facilitates early cortical processing of human bodies, the purpose of which is presumably to trigger sexual behavior and ultimately ensure reproduction.

  18. Human malignant melanoma heterotransplanted to nude mice.

    PubMed

    Tropé, C; Johnsson, J E; Alm, P; Landberg, T; Olsson, H; Wennerberg, J

    1981-01-01

    Five different human malignant melanoma were heterotransplanted subcutaneously to nude mice. When small tissue pieces were used 3 out of 5 tumors grew. Subcutaneous injections of suspended tumor cells were also made, but all failed to take. Metastatic or infiltrative growth was never seen in the mice observed for up to 2.5 months. The successful grafts largely retained the original morphologicaL features. The three successfully transplanted tumors could all be serially transferred with 100% tumor take. In one case passage time was reduced from 40 days to 15 days. As measured with 3H-thymidine incorporation the proliferation rate increased during the passages. These changes might be due to a selection of more rapidly growing tumor cells in the nudes.

  19. Resveratrol attenuates doxorubicin-induced cardiomyocyte apoptosis in lymphoma nude mice by heme oxygenase-1 induction.

    PubMed

    Gu, Jun; Song, Zhi-ping; Gui, Dong-mei; Hu, Wei; Chen, Yue-guang; Zhang, Da-dong

    2012-12-01

    Doxorubicin (DOX) has been used in a variety of human malignancies for decades, in particular of lymphoma. But increased cardiomyocyte apoptosis has been implicated in its cardiotoxicity. Resveratrol (RES) generates cardiovascular protective effects by heme oxygenase-1(HO-1)-mediated mechanism. The present study was designed to determine whether RES protected cardiomyocyte against apoptosis through induction of HO-1 in lymphoma nude mouse in vivo. After being developed into lymphoma model, 40 male Balb/c nude mice were randomized to one of the following four treatments (10 mice per group): control, DOX, DOX + RES and DOX + RES + HO-1 inhibitor (zinc protoporphyrin IX, ZnPP). The results showed that DOX injection markedly decreased the body weight, the heart weight and the ratio of heart weight to body weight, but inversely increased cardiomyocyte apoptosis and the level of serum lactate dehydrogenase and creatine kinase. Moreover, DOX injection attenuated HO-1 expression and enzymatic activity as well as increased P53 expression, modulated Bcl-2/Bax expression and enhanced caspase 3 activity. These cardiotoxic effects of DOX were ameliorated by its combination with RES. However, the protective effects of RES were reversed by the addition of ZnPP. Taken together, it is concluded that HO-1 plays a core role for protective action of RES in DOX-induced cardiomyocyte apoptosis in lymphoma nude mice.

  20. Soy isoflavone extracts stimulate the growth of nude mouse xenografts bearing estrogen-dependent human breast cancer cells (MCF-7)☆

    PubMed Central

    Wu, Qian; Yang, Ye; Yu, Jing; Jin, Nianzu

    2012-01-01

    We explored the effects of different lifetime exposures to soy isoflavone extracts on the growth of estrogen-dependent human breast cancer cells (MCF-7) implanted into athymic mice of different ovarian statuses. The athymic mice, ovariectomized or not, were implanted with MCF-7 cells. Mice were fed with low, moderate and high doses of soy isoflavone extract, at dietary concentrations of 6.25, 12.5 and 25 g/kg, in different reproductive models, respectively. The expression of ki-67 was detected by immunohistochemistry. pS2 expression in tumors was analyzed by real-time PCR. Estrogen level in the serum was measured by chemiluminescence enzyme immunoassay. Total genistein and daidzein levels in serum and urine were determined by liquid chromatography-electrospray tandem mass spectrometry (LC-ES/MS/MS). In Group A, on week 4, nude mice were exposed to different doses of soy iosflavone extracts. In Group B, the experimental diets were given to the nude mice following ovariectomy and tumor implantation. In both groups, 6.25 and 12.5 g/kg soy isoflavone extracts stimulated the growth of MCF-7 xenografts, increased pS2 expression, proliferation and estrogen level in serum. In both Group B (postmenopausal mouse model) and Group C (premenopausal mouse model), soy isoflavone extracts at doses of 6.25 and 12.5 g/kg showed stimulatory effects on the growth of MCF-7 tumors. In conclusion, administration of soy isoflavone extracts at doses of 6.25 and 12.5 g/kg during adolescence or later in life stimulated tumor growth in both menopausal and postmenopausal mouse models. PMID:23554729

  1. Experimental chemotherapy of human tumors heterotransplanted in nude mice.

    PubMed

    Giovanella, B C

    1980-01-01

    Human tumors heterotransplanted in nude mice offer the most realistic model for experimental chemotherapy of human neoplasms. Almost all the known human malignancies have been successfully transplanted in the nudes, although the rate of takes varies considerably between different tumor types. So far, a good correlation has been observed between the results obtained treating with the same drug the same tumor in the patient and in the nude mouse. Our experience in this field is, however, still too limited for the direct extrapolation of chemotherapeutic results obtained in the nudes to human tumors.

  2. Improvement of epidermal barrier properties in cultured skin substitutes after grafting onto athymic mice.

    PubMed

    Barai, Namrata D; Supp, Andrew P; Kasting, Gerald B; Visscher, Marty O; Boyce, Steven T

    2007-01-01

    Barrier function in cultured skin substitutes (CSS) prepared from human cell sources was measured by noninvasive (surface hydration, transepidermal water loss) and invasive methods (water permeation, niacinamide flux) before and after grafting onto athymic mice. In vitro measurements were made on days 7 and 14. Although three of the four measures of barrier function improved markedly from day 7 to 14, the values obtained were still far from those obtained with native human skin controls. Additional CSS were grafted onto athymic mice on day 14, and skin was harvested 2 and 6 weeks after grafting. Grafting brought about a substantial decrease in all measurements by 2 weeks and almost complete normalization of barrier function after 6 weeks. The most sensitive measure of this recovery was niacinamide permeability, which decreased from (280 +/- 40) x 10(-4) cm/h in vitro to (17 +/- 30) x 10(-4) cm/h 2 weeks after grafting and (5 +/- 2) x 10(-4) cm/h 6 weeks after grafting, versus control values of (2 +/- 2) x 10(-4) cm/h in human cadaver skin and (0.6 +/- 0.4) x 10(-4) cm/h in human epidermal membrane prepared from freshly excised breast skin. These results demonstrate the reformation of epidermal barrier function after transplantation and provide insights for the development of a functional epidermal barrier in CSS in vitro.

  3. The role of B- and T-cell immunity in toltrazuril-treated C57BL/6 WT, microMT and nude mice experimentally infected with Neospora caninum.

    PubMed

    Ammann, Petra; Waldvogel, Andreas; Breyer, Isabel; Esposito, Marco; Müller, Norbert; Gottstein, Bruno

    2004-06-01

    Neospora caninum is a protozoan parasite predominantly known for causing abortion in cattle and neuromuscular disease in dogs. So far, no efficient metaphylactic chemotherapy has been developed. In preliminary studies, toltrazuril had been successfully used against experimental neosporosis in mice and calves. In the present study, we used immunocompetent and immunodeficient mouse strains to address the role of immunity in supporting the chemotherapy of experimental N. caninum infection. WT, microMT and athymic nude mice were intraperitoneally inoculated with 1x10(6) Nc-1 tachyzoites. The drug was administered in the drinking water for 6 consecutive days so as to obtain a daily dose of approximately 20 mg toltrazuril/kg body weight. The course of infection was monitored by clinical, histological and immunohistochemical means, as well as by the search for parasite DNA using PCR-analyses of various organs. In immunocompetent WT mice, treatment proved to be of high efficacy by abrogation of any lesion formation or PCR-positivity in medicated C57BL/6 mice and a significant reduction of lesion formation or PCR-positivity in BALB/c animals. Similarly, treated microMT mice exhibited a significant reduction in cerebral lesion formation as well as in parasite DNA detectability by PCR when compared to untreated animals. Athymic nude mice, however, did not respond to treatment in that only a delay of the parasite dissemination was achieved, and nude mice still showed the neosporosis disease symptoms, although later than untreated animals. We conclude that treatment with toltrazuril appears to act parasitostatically rather than parasitocidically. This is supported by the fact that: (1) although the lack of B-cells did not impair the effect of toltrazuril, (2) the lack of T-cells did not allow for a full efficacy of treatment. Therefore, chemotherapy with toltrazuril against experimental infections with N. caninum requires the support of T-cell immunity in order to be successful.

  4. Dendrite arborization requires the dynein cofactor NudE.

    PubMed

    Arthur, Ashley L; Yang, Sihui Z; Abellaneda, Allison M; Wildonger, Jill

    2015-06-01

    The microtubule-based molecular motor dynein is essential for proper neuronal morphogenesis. Dynein activity is regulated by cofactors, and the role(s) of these cofactors in shaping neuronal structure are still being elucidated. Using Drosophila melanogaster, we reveal that the loss of the dynein cofactor NudE results in abnormal dendrite arborization. Our data show that NudE associates with Golgi outposts, which mediate dendrite branching, suggesting that NudE normally influences dendrite patterning by regulating Golgi outpost transport. Neurons lacking NudE also have increased microtubule dynamics, reflecting a change in microtubule stability that is likely to also contribute to abnormal dendrite growth and branching. These defects in dendritogenesis are rescued by elevating levels of Lis1, another dynein cofactor that interacts with NudE as part of a tripartite complex. Our data further show that the NudE C-terminus is dispensable for dendrite morphogenesis and is likely to modulate NudE activity. We propose that a key function of NudE is to enhance an interaction between Lis1 and dynein that is crucial for motor activity and dendrite architecture.

  5. Looking at Nude Artwork in a Museum Context

    ERIC Educational Resources Information Center

    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…

  6. Looking at Nude Artwork in a Museum Context

    ERIC Educational Resources Information Center

    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…

  7. The naked truth about my classical nude figures.

    PubMed

    Burnett, Roger

    2002-02-28

    The story 'Concerns raised over nudes at cancer clinic' (news February 13) does not truly reflect the situation. Although the hospital authorities had concerns about placing the classical nude figures in the hospital environment, the overwhelming response from the public has been positive. Moreover, considerable support for the figures has come from cancer patients.

  8. Husbandry of the "nude" mouse in conventional and germfree environments.

    PubMed

    Eaton, G J; Outzen, H C; Custer, R P; Johnson, F N

    1975-06-01

    The "nude" mouse is a unique tool for immunologic studies. Its relatively short life span dictates the application of rigid environmental controls to increase longevity if the mouse is to assume the role of a practical experimental animal. In this paper we discussed the husbandry procedures employed to raise "nude" mice in our facilities under conventional, defined flora, and germfree conditions. Conventional and defined flora mice were raised on laminar flow stay-clean rocks, and germfree "nudes" were housed in self-contained germfree isolators. The major cause of morbidity and mortality among conventional and defined flora "nude" mice was fulminating hepatitis. We presented evidence that the etiologic agent of the disease was mouse hepatitis virus (MHV). Germfree "nude" mice were completely free from viral and bacterial diseases.

  9. Photoimmunotherapy lowers recurrence after pancreatic cancer surgery in orthotopic nude mouse models

    PubMed Central

    Maawy, Ali A.; Hiroshima, Yukihiko; Zhang, Yong; Garcia-Guzman, Miguel; Luiken, George A.; Kobayashi, Hisataka; Hoffman, Robert M.; Bouvet, Michael

    2015-01-01

    Introduction Photoimmunotherapy (PIT) is based on the use of a monoclonal antibody specific to cancer epitopes conjugated to a photosensitizer near-infrared (NIR) phthalocyanine dye (IR700). In this study, PIT with IR700 conjugated to anti-carcinoembryonic antigen (CEA) was used as an adjunct to surgery in orthotopically-implanted human pancreatic cancer in a nude mouse model in order to eliminate microscopic disease in the tumor bed and prevent local as well as metastatic recurrence. Materials & Methods Athymic nude mice were orthotopically implanted with the human pancreatic cancer cell line BxPC3 expressing green fluorescent protein (GFP). After tumor engraftment, the mice were divided into two groups: bright light surgery (BLS) + anti-CEA-IR700 + 690 nm laser (PIT) and BLS only. Anti-CEA-IR700 (100 μg) was administered to the treatment group via tail vein injection 24 hours prior to therapy. Tumors were resected and the surgical bed was treated with intraoperative phototherapy at an intensity of 150 mW/cm2 for 30 minutes. Mice were imaged non-invasively for 8 weeks using an OV-100 small animal fluorescence imager. Results BLS+PIT reduced local recurrence to 1/7 mice to 7/7 mice with BLS-only (p=0.001) and metastatic recurrence to 2/7 mice compared to 6/7 mice with BLS-only (p=0.03). Local tumor growth continued at a rapid rate after BLS only compared to BLS+PIT where almost no local growth occurred. There was a significant difference in tumor size between mice in the BLS+PIT (2.14 mm2, 95% CI [6.34, −2.06] and BLS-only groups (115.2 mm2, 95% CI [141.6, 88.8]) (p<0.001) at 6 weeks after surgery. There was also a significant difference in tumor weight between the BLS+PIT group (6.65 mg, 95% CI [19.65, −6.35] and BLS-only group (1100 mg, 95% CI [1406, 794] at 8 weeks (p<0.001) after surgery. Conclusions PIT holds promise in the treatment of pancreatic cancer and may serve as a useful adjunct to surgery in the eradication of microscopic residual disease that

  10. Dual cancer-specific targeting strategy cures primary and distant breast carcinomas in nude mice

    PubMed Central

    Sarkar, Devanand; Su, Zao-zhong; Vozhilla, Nicolaq; Park, Eun Sook; Gupta, Pankaj; Fisher, Paul B.

    2005-01-01

    Limitations of current viral-based gene therapies for malignant tumors include lack of cancer-specific targeting and insufficient tumor delivery. To ameliorate these problems and develop a truly effective adenovirus gene-based therapy for cancer, we constructed a conditionally replication competent adenovirus (CRCA) manifesting the unique properties of tumor-specific virus replication in combination with production of a cancer-selective cytotoxic cytokine, melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24), which embodies potent bystander antitumor activity. Cancer cell selective tropism was ensured by engineering the expression of the adenoviral E1A protein, necessary for viral replication, under the control of a minimal promoter region of progression elevated gene-3 (PEG-3), which functions selectively in diverse cancer cells with minimal activity in normal cells. In the E3 region of this CRCA, we introduced the mda-7/IL-24 gene, thereby mediating robust production of this cytokine as a function of adenovirus replication. Infection of this CRCA (designated Ad.PEG-E1A-mda-7) in normal mammary epithelial cells and breast cancer cells confirmed cancer cell selective adenoviral replication, mda-7/IL-24 expression, growth inhibition, and apoptosis induction. Injecting Ad.PEG-E1A-mda-7 into human breast cancer xenografts in athymic nude mice completely eradicated not only the primary tumor but also distant tumors (established on the opposite flank of the animal) thereby implementing a cure. This dual cancer-specific targeting strategy provides an effective approach for treating breast and other human neoplasms with the potential for eradicating both primary tumors and metastatic disease. Additionally, these studies support the potential use of mda-7/IL-24 in the therapy of malignant cancers. PMID:16172403

  11. A nude mouse model of obesity to study the mechanisms of resistance to aromatase inhibitors.

    PubMed

    Schech, Amanda; Yu, Stephen; Goloubeva, Olga; McLenithan, John; Sabnis, Gauri

    2015-08-01

    Obesity is a risk factor for breast cancer progression. Breast cancer patients who are overweight or obese or have excess abdominal fat have an increased risk of local or distant recurrence and cancer-related death. Hormone depletion therapies can also cause weight gain, exacerbating the risk for these patients. To understand the effect of obesity on hormone-dependent human breast cancer tumors, we fed ovariectomized athymic nude mice a diet containing 45% kcal fat and 17% kcal sucrose (high fat sucrose diet (HFSD)), 10% kcal fat (low fat diet (LFD)), or a standard chow diet (chow). The mice fed the HFSD developed metabolic abnormalities consistent with the development of obesity such as weight gain, high fasting blood glucose, and impaired glucose tolerance. These mice also developed hyperinsulinemia and insulin resistance. The obese mice also had a higher tumor growth rate compared to the lean mice. Furthermore, the obese mice showed a significantly reduced responsiveness to letrozole. To understand the role of obesity in this reduced responsiveness, we examined the effect of insulin on the growth of MCF-7Ca cells in response to estrogen or letrozole. The presence of insulin rendered MCF-7Ca cells less responsive to estrogen and letrozole. Exogenous insulin treatment of MCF-7Ca cells also resulted in increased p-Akt as well as ligand-independent phosphorylation of ERα. These findings suggest that diet-induced obesity may result in reduced responsiveness of tumors to letrozole due to the development of hyperinsulinemia. We conclude that obesity influences the response and resistance of breast cancer tumors to aromatase inhibitor treatment. © 2015 Society for Endocrinology.

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

    PubMed

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

    1993-09-01

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

  13. Dual cancer-specific targeting strategy cures primary and distant breast carcinomas in nude mice.

    PubMed

    Sarkar, Devanand; Su, Zao-Zhong; Vozhilla, Nicolaq; Park, Eun Sook; Gupta, Pankaj; Fisher, Paul B

    2005-09-27

    Limitations of current viral-based gene therapies for malignant tumors include lack of cancer-specific targeting and insufficient tumor delivery. To ameliorate these problems and develop a truly effective adenovirus gene-based therapy for cancer, we constructed a conditionally replication competent adenovirus (CRCA) manifesting the unique properties of tumor-specific virus replication in combination with production of a cancer-selective cytotoxic cytokine, melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24), which embodies potent bystander antitumor activity. Cancer cell selective tropism was ensured by engineering the expression of the adenoviral E1A protein, necessary for viral replication, under the control of a minimal promoter region of progression elevated gene-3 (PEG-3), which functions selectively in diverse cancer cells with minimal activity in normal cells. In the E3 region of this CRCA, we introduced the mda-7/IL-24 gene, thereby mediating robust production of this cytokine as a function of adenovirus replication. Infection of this CRCA (designated Ad.PEG-E1A-mda-7) in normal mammary epithelial cells and breast cancer cells confirmed cancer cell selective adenoviral replication, mda-7/IL-24 expression, growth inhibition, and apoptosis induction. Injecting Ad.PEG-E1A-mda-7 into human breast cancer xenografts in athymic nude mice completely eradicated not only the primary tumor but also distant tumors (established on the opposite flank of the animal) thereby implementing a cure. This dual cancer-specific targeting strategy provides an effective approach for treating breast and other human neoplasms with the potential for eradicating both primary tumors and metastatic disease. Additionally, these studies support the potential use of mda-7/IL-24 in the therapy of malignant cancers.

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

    PubMed Central

    Cheong, Jit Kong; Gunaratnam, Lakshman; Zang, Zhi Jiang; Yang, Christopher M; Sun, Xiaoming; Nasr, Susan L; Sim, Khe Guan; Peh, Bee Keow; Rashid, Suhaimi Bin Abdul; Bonventre, Joseph V; Salto-Tellez, Manuel; Hsu, Stephen I

    2009-01-01

    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. PMID:19152710

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

    PubMed

    Cheong, Jit Kong; Gunaratnam, Lakshman; Zang, Zhi Jiang; Yang, Christopher M; Sun, Xiaoming; Nasr, Susan L; Sim, Khe Guan; Peh, Bee Keow; Rashid, Suhaimi Bin Abdul; Bonventre, Joseph V; Salto-Tellez, Manuel; Hsu, Stephen I

    2009-01-20

    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). 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. 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. 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.

  16. Radiotherapy of CD19 expressing Daudi tumors in nude mice with Yttrium-90-labeled anti-CD19 antibody.

    PubMed

    Vallera, Daniel A; Elson, Michael; Brechbiel, Martin W; Dusenbery, Kathryn E; Burns, Linda J; Jaszcz, Waclaw B; Ramsay, Norma K; Panoskaltsis-Mortar, Angela; Kuroki, David W; Wagner, John E; Vitetta, Ellen S; Kersey, John H

    2004-02-01

    Studies were performed to determine the suitability of using two different anti-CD19 monoclonal antibodies to deliver the high energy beta-particle emitting isotope 90Y to B-cell lymphoma grown as flank tumors in athymic nude mice. The antibodies BU12 and HD37, both of the IgG1 subclass, recognize CD19, an internalizing B-lineage-specific membrane glycoprotein and member of the Ig supergene family. The antibodies were readily labeled with 90Y using the highly stable chelate, 1B4M-MX-DTPA. The radioimmunoconjugates selectively bound to the CD19 expressing B cell line Daudi, but not to CD19 negative control cells. Significantly more 90Y anti-CD19 bound to Daudi tumors growing in nude mice than did a control non-binding antibody (p = 0.001). The biodistribution data correlated with an anti-tumor effect. Anti-tumor activity was dose dependent and the best results were observed in mice receiving a single dose of approximately 300 uCi. The anti-CD19 antibody had significantly better anti-tumor activity as compared to a control 90Y-labeled antibody and most mice survived over 119 days with no evidence of tumor (p < 0.003). Histology studies showed no significant injury to the kidney, liver, or small intestine. Because radiolabeled anti-CD19 antibody can be used to deliver radiation selectively to lymphohematopoietic tissue, these data support the use of 90Y anti-CD19 antibodies in treating B-cell malignancies.

  17. Distinct courses of infection with Leishmania (L.) amazonensis are observed in BALB/c, BALB/c nude and C57BL/6 mice.

    PubMed

    Velasquez, Leonardo G; Galuppo, Mariana K; DE Rezende, Eloiza; Brandão, Wesley N; Peron, Jean Pierre; Uliana, Silvia R B; Duarte, Maria Irma; Stolf, Beatriz S

    2016-05-01

    Leishmania (L.) amazonensis [L. (L.) amazonensis] is widely distributed in Brazil and its symptomatic infections usually lead to few localized lesions and sometimes to diffuse cutaneous form, with nodules throughout the body, anergy to parasite antigens and poor therapeutic response. The variability of these manifestations draws attention to the need for studies on the pathophysiology of infection by this species. In this study, we analysed the course and immunological aspects of L. (L.) amazonensis infection in BALB/c and C57BL/6 strains, both susceptible, but displaying different clinical courses, and athymic BALB/c nude, to illustrate the role of T cell dependent responses. We analysed footpad thickness and parasite burden by in vivo imaging. Furthermore, we evaluated the cellular profile and cytokine production in lymph nodes and the inflammatory infiltrates of lesions. Nude mice showed delayed lesion development and less inflammatory cells in lesions, but higher parasite burden than BALB/c and C57BL/6. BALB/c and C57BL/6 mice had similar parasite burdens, lesion sizes and infiltrates until 6 weeks after infection, and after that C57BL/6 mice controlled the infection. Small differences in parasite numbers were observed in C57BL/6 macrophages in vitro, indicating that in vivo milieu accounts for most differences in infection. We believe our results shed light on the role of host immune system in the course of L. (L.) amazonensis infection by comparing three mouse strains that differ in parasitaemia and inflammatory cells.

  18. Antifungal Therapy in an Athymic Murine Model of Chromoblastomycosis by Fonsecaea pedrosoi▿

    PubMed Central

    Calvo, Enrique; Pastor, F. Javier; Mayayo, Emilio; Hernández, Pilar; Guarro, Josep

    2011-01-01

    We have compared the efficacy of terbinafine (TRB) and itraconazole (ITZ), the recommended drugs for the treatment of chromoblastomycosis, with that of posaconazole (PSC) and voriconazole (VRC) in athymic mice infected with the fungus Fonsecaea pedrosoi. Three weeks after challenge, mice were treated for 4 months with PSC at 10 or 20 mg/kg of body weight/day, with VRC at 10 or 20 mg/kg/day, with ITZ at 25 or 50 mg/kg/day, or with TRB at 150 or 250 mg/kg/day. The progress of the infection was evaluated by measuring the size of the lesions, by histopathological studies, and by cultures of the excised tissue. The two doses of PSC followed by the highest doses of ITZ and TRB showed the best results while VRC did not show efficacy. PSC could be an alternative in the treatment of chromoblastomycosis. PMID:21576429

  19. Distinct morphological and immunohistochemical features and different growth rates among four human neuroblastomas heterotransplanted into nude mice.

    PubMed

    Hoshi, Nobuo; Hitomi, Jiro; Kusakabe, Takashi; Fukuda, Takeaki; Hirota, Masayuki; Suzuki, Toshimitsu

    2008-09-01

    To elucidate more precisely the biological characteristics of neuroblastomas, we examined four human neuroblastomas heterotransplanted into athymic nude mice NB-39 (undifferentiated type), NB-45 (poorly differentiated type with undifferentiated component), NB-52 (poorly differentiated type), and NB-726 (differentiating type) by electron microscopy, immunohistochemistry, and radioimmunoassay for the peptides in tumors. Ultrastructurally, NB-45, NB-52, and NB-726 contained more numerous and variously sized neurosecretory granules than did NB-39. Immunohistochemistry revealed neurofilament proteins, tyrosine hydroxylase, neuropeptide Y (NPY), and chromogranin A-positive cells in the four tumors in the following order of frequency: NB-726, NB-45, NB-52, and NB-39. NB-726, NB-45, and NB-52, but not NB-39, contained galanin-positive tumor cells. NB-45 and NB-726 harbored a few positive cells for calcitonin gene-related peptide. Furthermore, NB-726 exhibited positivity to leu-enkephalin, met-enkephalin, vasoactive intestinal peptide (VIP), and serotonin. Radioimmunoassay substantiated the results of immunohistochemistry, showing NPY in all tumors and either galanin or VIP in three tumors, excepting NB-39. Average doubling time of the tumor was as follows: 2 days in NB-39, 10 days in NB-45, 22 days in NB-52, and 45 days in NB-726. These results indicate that human neuroblastoma cells have different biological characteristics and reduced growth rate with differentiation in terms of ultrastructure and of peptide production abilities.

  20. Implantation of preadipocyte-loaded hyaluronic acid-based scaffolds into nude mice to evaluate potential for soft tissue engineering.

    PubMed

    Hemmrich, Karsten; von Heimburg, Dennis; Rendchen, Raoul; Di Bartolo, Chiara; Milella, Eva; Pallua, Norbert

    2005-12-01

    The reconstruction of soft tissue defects following extensive deep burns or tumor resections remains an unresolved problem in plastic and reconstructive surgery since adequate implant materials are still not available. Preadipocytes, immature precursor cells found between mature adipocytes in adipose tissue, are a potential material for soft tissue engineering since they can proliferate and differentiate into adipose tissue after transplantation. In previous studies, we identified hyaluronan benzyl ester (HYAFF 11) sponges to be promising carrier matrices. This study now evaluates, in vitro and in vivo, a new sponge architecture with pores of 400 microm either made of plain HYAFF 11 or HYAFF 11 coated with the extracellular matrix glycosaminoglycan hyaluronic acid. Human preadipocytes were isolated, seeded onto carriers and implanted into nude athymic mice. Explants harvested after 3, 8, and 12 weeks were examined for macroscopical appearance, thickness, weight, pore structure, histology, and immunohistochemistry. Compared to previous studies, we found better penetration of cells into both types of scaffolds, with more extensive formation of new vessels throughout the construct but with only minor adipose tissue. Our encouraging results contribute towards a better seeded and vascularised scaffold but also show that the enhancement of adipogenic conversion of preadipocytes remains a major task for further in vivo experiments.

  1. Anti-tumour activity of photodynamic therapy in combination with mitomycin C in nude mice with human colon adenocarcinoma.

    PubMed Central

    Ma, L. W.; Moan, J.; Steen, H. B.; Iani, V.

    1995-01-01

    The interaction of photodynamic therapy (PDT) and a chemotherapeutic drug, mitomycin C (MMC), was investigated using WiDr human colon adenocarcinoma tumours implanted on Balb/c athymic nude mice. The WiDr tumours were treated with PDT alone, MMC alone or with both. It was found that the combined treatment produced a greater retardation in the growth of the WiDr tumour than monotherapy with MMC or PDT. The synergistic effect was especially prominent when PDT was used in combination with a low dose of MMC (1 mg kg-1), since treatment of 1 mg kg-1 MMC alone had no effect on the tumour. The anti-tumour activity of PDT was found to be increased with MMC of 5 mg kg-1. The response of normal skin on mice feet to PDT slightly greater when PDT was combined with 5 mg kg-1 MMC than when PDT was applied alone, while no detectable additional effect on skin photosensitivity was observed when PDT was combined with 1 mg kg-1 MMC. An enhanced uptake of Photofrin in tumours was found 12 h and 24 h after administration of MMC. The effect of MMC on the cell cycle distribution of cell dissociated directly from the tumours was studied. The results suggest that the increased susceptibility to photoinactivation of Photofrin-sensitised tumours may be due to MMC-induced accumulation of the tumour cells in S-phase. PMID:7734319

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

    PubMed

    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.

  3. Thermoneutral housing is a critical factor for immune function and diet-induced obesity in C57BL/6 nude mice

    PubMed Central

    Stemmer, K; Kotzbeck, P; Zani, F; Bauer, M; Neff, C; Müller, TD; Pfluger, PT; Seeley, RJ; Divanovic, S

    2014-01-01

    OBJECTIVES Obesity-related cancers represent public health burdens of the first order. Nevertheless, suitable mouse models to unravel molecular mechanisms linking obesity to human cancer are still not available. One translational model is the immunocompromised Foxn1 (winged-helix/forkead transcription factor) nude mouse transplanted with human tumor xenografts. However, most xenograft studies are conducted in nude mice on an in-bred BALB/c background that entails protection from diet-induced obesity. To overcome such resistance to obesity and its sequelae, we here propose the dual strategy of utilizing Foxn1 nude mice on a C57BL/6 background and housing them at their thermoneutral zone. METHODS C57BL/6 nude and corresponding wild-type mice, housed at 23 or 33 °C, were subjected to either low-fat diet or high-fat diet (HFD). Energy expenditure, locomotor activity, body core temperature, respiratory quotient as well as food and water intake were analyzed using indirect calorimetry. Immune function at different housing temperatures was assessed by using an in vivo cytokine capture assay. RESULTS Our data clearly demonstrate that conventional housing protects C57BL/6 nude mice from HFD-induced obesity, potentially via increased energy expenditure. In contrast, HFD-fed C57BL/6 nude mice housed at thermoneutral conditions develop adiposity, increased hepatic triglyceride accumulation, adipose tissue inflammation and glucose intolerance. Moreover, increased circulating levels of lipopolysaccharide-driven cytokines suggest a greatly enhanced immune response in C57BL/6 nude mice housed at thermoneutrality. CONCLUSION Our data reveals mild cold stress as a major modulator for energy and body weight homeostasis as well as immune function in C57BL/6 nude mice. Adjusting housing temperatures to the thermoneutral zone may ultimately be key to successfully study growth and progression of human tumors in a diet-induced obese environment. PMID:25349057

  4. Thermoneutral housing is a critical factor for immune function and diet-induced obesity in C57BL/6 nude mice.

    PubMed

    Stemmer, K; Kotzbeck, P; Zani, F; Bauer, M; Neff, C; Müller, T D; Pfluger, P T; Seeley, R J; Divanovic, S

    2015-05-01

    Obesity-related cancers represent public health burdens of the first order. Nevertheless, suitable mouse models to unravel molecular mechanisms linking obesity to human cancer are still not available. One translational model is the immunocompromised Foxn1 (winged-helix/forkead transcription factor) nude mouse transplanted with human tumor xenografts. However, most xenograft studies are conducted in nude mice on an in-bred BALB/c background that entails protection from diet-induced obesity. To overcome such resistance to obesity and its sequelae, we here propose the dual strategy of utilizing Foxn1 nude mice on a C57BL/6 background and housing them at their thermoneutral zone. C57BL/6 nude and corresponding wild-type mice, housed at 23 or 33 °C, were subjected to either low-fat diet or high-fat diet (HFD). Energy expenditure, locomotor activity, body core temperature, respiratory quotient as well as food and water intake were analyzed using indirect calorimetry. Immune function at different housing temperatures was assessed by using an in vivo cytokine capture assay. Our data clearly demonstrate that conventional housing protects C57BL/6 nude mice from HFD-induced obesity, potentially via increased energy expenditure. In contrast, HFD-fed C57BL/6 nude mice housed at thermoneutral conditions develop adiposity, increased hepatic triglyceride accumulation, adipose tissue inflammation and glucose intolerance. Moreover, increased circulating levels of lipopolysaccharide-driven cytokines suggest a greatly enhanced immune response in C57BL/6 nude mice housed at thermoneutrality. Our data reveals mild cold stress as a major modulator for energy and body weight homeostasis as well as immune function in C57BL/6 nude mice. Adjusting housing temperatures to the thermoneutral zone may ultimately be key to successfully study growth and progression of human tumors in a diet-induced obese environment.

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

    PubMed

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

    2015-02-01

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

  6. Regulation of Leishmania (L.) amazonensis Protein Expression by Host T Cell Dependent Responses: Differential Expression of Oligopeptidase B, Tryparedoxin Peroxidase and HSP70 Isoforms in Amastigotes Isolated from BALB/c and BALB/c Nude Mice

    PubMed Central

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

    2015-01-01

    Leishmaniasis is an important disease that affects 12 million people in 88 countries, with 2 million new cases every year. Leishmania amazonensis is an important agent in Brazil, leading to clinical forms varying from localized (LCL) to diffuse cutaneous leishmaniasis (DCL). One interesting issue rarely analyzed is how host immune response affects Leishmania phenotype and virulence. Aiming to study the effect of host immune system on Leishmania proteins we compared proteomes of amastigotes isolated from BALB/c and BALB/c nude mice. The athymic nude mice may resemble patients with diffuse cutaneous leishmaniasis, considered T-cell hyposensitive or anergic to Leishmania´s antigens. This work is the first to compare modifications in amastigotes’ proteomes driven by host immune response. Among the 44 differentially expressed spots, there were proteins related to oxidative/nitrosative stress and proteases. Some correspond to known Leishmania virulence factors such as OPB and tryparedoxin peroxidase. Specific isoforms of these two proteins were increased in parasites from nude mice, suggesting that T cells probably restrain their posttranslational modifications in BALB/c mice. On the other hand, an isoform of HSP70 was increased in amastigotes from BALB/c mice. We believe our study may allow identification of potential virulence factors and ways of regulating their expression. PMID:25692783

  7. Cellular tumorigenicity in nude mice. Test of associations among loss of cell-surface fibronectin, anchorage independence, and tumor-forming ability

    PubMed Central

    1979-01-01

    Fibronectin (FN; also called large external transformation-sensitive [LETS] protein or cell-surface protein [CSP]) is a large cell-surface glycoprotein that is frequently observed to be either absent or greatly reduced on the surfaces of malignant cells grown in vitro. Because FN may be a useful molecular marker of cellular malignancy, we have carried out an extensive screening to test the specific association among the degree of expression of FN, anchorage-independent growth, and tumorigenicity in the athymic nude mouse. A variety of diploid cell strains and established cell lines were tested for the expression of surface FN by indirect immunofluorescence using rabbit antisera against human cold insoluble globulin, rodent plasma FN, or chicken cell- surface FN. Concomitantly, the cells were assayed for tumor formation in nude mice and for the ability to form colonies in methylcellulose. Tumorigenic cells often showed very low surface fluorescence, confirming earlier reports. However, many highly tumorigenic fibroblast lines from several species stained strongly with all three antisera. In contrast, the anchorage-independent phenotype was nearly always associated with tumorigenicity in approximately 35 cell lines examined in this study. In another series of experiments, FN-positive but anchorage-independent cells were grown as tumors in nude mice and then reintroduced into culture. In five of the six tumor-derived cell lines, cell-surface FN was not significantly reduced; one such cell line showed very little surface FN. Our data thus indicate that the loss of cell-surface FN is not a necessary step in the process of malignant transformation and that the growth of FN-positive cells as tumors does not require a prior selection in vivo for FN-negative subpopulations. PMID:383723

  8. Ischemic post-conditioning facilitates brain recovery after stroke by promoting Akt/mTOR activity in nude rats.

    PubMed

    Xie, Rong; Wang, Peng; Ji, Xunming; Zhao, Heng

    2013-12-01

    While pre-conditioning is induced before stroke onset, ischemic post-conditioning (IPostC) is performed after reperfusion, which typically refers to a series of mechanical interruption of blood reperfusion after stroke. IPostC is known to reduce infarction in wild-type animals. We investigated if IPostC protects against brain injury induced by focal ischemia in Tcell-deficient nude rats and to examine its effects on Akt and the mammalian target of rapamycin (mTOR) pathway. Although IPostC reduced infarct size at 2 days post-stroke in wild-type rats, it did not attenuate infarction in nude rats. Despite the unaltered infarct size in nude rats, IPostC increased levels of phosphorylated Akt (p-Akt) and Akt isoforms (Akt1, Akt2, Akt3), and p-mTOR, p-S6K and p-4EBP1 in the mTOR pathway, as well as growth associated Protein 43 (GAP43), both in the peri-infarct area and core, 24 h after stroke. IPostC improved neurological function in nude rats 1-30 days after stroke and reduced the extent of brain damage 30 days after stroke. The mTOR inhibitor rapamycin abolished the long-term protective effects of IPostC. We determined that IPostC did not inhibit acute infarction in nude rats but did provide long-term protection by enhancing Akt and mTOR activity during the acute post-stroke phase. Post-conditioning did not attenuate infarction in nude rats measured 2 days post-stroke, but improved neurological function in nude rats and reduced brain damage 30 days after stroke. It resulted in increased-activities of Akt and mTOR, S6K and p-4EBP1. The mTOR inhibitor rapamycin abolished the long-term protective effects of IPostC.

  9. Growth and functional behavior neuroblastomas in man and nude mice.

    PubMed

    Hata, J; Ueyama, Y; Tamaoki, N

    1983-12-01

    Nine human neuroblastoma were serially transplanted in nude mice. These tumor lines were established from the patients older than 1 year 10 month year old. None of the tumors taken from under the age of 1 year and 7 months grew in nude mice. All transplanted tumors produced catecholamines in varying degree. The growth of low catecholamines producing tumors was apparently aggressive compared with high catecholamines producing tumor lines. These results may indicate that tumor aggressiveness decreases with increased functional differentiation in human neuroblastoma in nude mice. The contents of catecholamine was closely correlated with the number and size of secretory granules in tumor cells. This human neuroblastoma/nude mice system may prove to be a useful tool for basic research on the biological behavior as well as on the cytological and functional differentiation of human neuroblastoma.

  10. Radiolocalization of bovine lymphosarcoma cells in athymic mice, using a monoclonal antibody against tumor-associated antigens

    SciTech Connect

    Aida, Y.; Ochiai, K.; Ito, K.; Onuma, M.; Fujimori, F.; Fujimoto, Y.; Izawa, H.

    1987-08-01

    Mouse monoclonal antibody c 143 was purified and F(ab')2 fragments were generated by pepsin digestion and then radiolabeled with /sup 125/I. The /sup 125/I-labeled c 143 F(ab')2 fragments were injected into athymic mice bearing bovine lymphoid tumor cells. The fragments became preferentially localized in tumor tissues, but not in normal tissues, as determined by differential counting of tissue radioactivity. The fragments became localized specifically in those tumors that were reactive with c 143 in vitro, but did not become localized in unrelated tumors. Localization of labeled F(ab')2 fragments of a monoclonal antibody of the same isotype directed against Taka virus (a variant of Newcastle disease virus) was not observed in athymic mice bearing bovine lymphoid tumor cells. Tumors were detectable by radioimmunoscintigraphy, using radiolabeled c 143 F(ab')2 fragments, without background subtraction, and by use of silver-grain scattering in light microscopic autoradiography.

  11. The effect of an antigenic stimulation on proliferative response in athymic mice.

    PubMed

    Síma, P; Bilej, M; Kovárů, F; Vĕtvicka, V; Holub, M

    1992-01-01

    The proliferation activity of the main cellular categories of bone marrow after infusion of 3H-thymidine was studied in nu/nu and +/+ 1-month- and 3-month-old BALB/c mice in comparison with lymphoid cells in the spleen and mesenteric lymph nodes. The stem cell defect in nu/nu mouse bone marrow is compensated by an increased proliferation in myeloid series and in agranulocytes. The increase of proliferation activity among lymphoid cells in peripheral lymphoid organs was observed only in the 3-month-old mice with a delay in the nudes.

  12. Deletion of the vaccinia virus F13L gene results in a highly attenuated virus that mounts a protective immune response against subsequent vaccinia virus challenge.

    PubMed

    Vliegen, Inge; Yang, Guang; Hruby, Dennis; Jordan, Robert; Neyts, Johan

    2012-01-01

    Vaccinia virus F13L encodes the envelope protein p37, which is the target of the anti-pox virus drug ST-246 (Yang et al., 2005) and that is required for production of extracellular vaccinia virus. The F13L (p37)-deleted (and ST-246 resistant) vaccinia virus recombinant (Vac-ΔF13L) produced smaller plaques than the wild-type vaccinia (Western Reserve vaccinia). In addition, Vac-ΔF13L proved, when inoculated either intravenously or intracutaneously in both immunocompetent and immunodeficient (athymic nude or SCID) mice, to be severely attenuated. Intravenous or intracutaneous inoculation of immunocompetent mice with the ΔF13L virus efficiently protected against a subsequent intravenous, intracutaneous or intranasal challenge with vaccinia WR (Western Reserve). This was corroborated by the observation that Vac-ΔF13L induced a humoral immune response against vaccinia following either intravenous or intracutaneous challenge. In conclusion, F13L-deleted vaccinia virus may have the potential to be developed as a smallpox vaccine. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Dual isotope study of iodine-125 and indium-111-labeled antibody in athymic mice

    SciTech Connect

    Carney, P.L.; Rogers, P.E.; Johnson, D.K. )

    1989-03-01

    Monoclonal antibody B72.3 was coupled to a benzylisothiocyanate derivative of diethylenetriaminepentaacetic acid (DTPA). The maximum substitution achievable without loss of immunoreactivity was three DTPA groups per immunoglobulin molecule. The resulting conjugate was labeled with {sup 111}In by brief incubation with {sup 111}InCl{sub 3}, giving a mean radiochemical yield of {sup 111}In-labeled antibody of 96%. The ({sup 111}In)B72.3 preparation was mixed with an ({sup 125}I) B72.3 preparation, obtained by the chloramine-T method, and the mixture administered to athymic mice bearing subcutaneous LS174T colon carcinoma xenografts. There were no significant differences (p greater than 0.1) in the biodistributions of the two labels at 1, 2, 5, and 7 days postinjection. These results are contrasted with prior studies showing elevated levels of {sup 111}In in liver, spleen, and kidneys using B72.3-DTPA conjugates prepared via the bicyclic anhydride. It is concluded that protein cross-linking and/or the formation of unstable chelate sites in anhydride coupled conjugates underlie these disparities.

  14. Correlation of MRI Biomarkers with Tumor Necrosis in Hras5 Tumor Xenograft in Athymic Rats

    PubMed Central

    Bradley, Daniel P; Tessier, Jean J; Ashton, Susan E; Waterton, John C; Wilson, Zena; Worthington, Philip L; Ryan, Anderson J

    2007-01-01

    Magnetic resonance imaging (MRI) can measure the effects of therapies targeting the tumor vasculature and has demonstrated that vascular-damaging agents (VDA) induce acute vascular shutdown in tumors in human and animal models. However, at subtherapeutic doses, blood flow may recover before the induction of significant levels of necrosis. We present the relationship between changes in MRI biomarkers and tumor necrosis. Multiple MRI measurements were taken at 4.7 T in athymic rats (n = 24) bearing 1.94 ± 0.2-cm3 subcutaneous Hras5 tumors (ATCC 41000) before and 24 hours after clinically relevant doses of the VDA, ZD6126 (0–10 mg/kg, i.v.). We measured effective transverse relaxation rate (R2*), initial area under the gadolinium concentration-time curve (IAUGC60/150), equivalent enhancing fractions (EHF60/150), time constant (Ktrans), proportion of hypoperfused voxels as estimated from fit failures in Ktrans analysis, and signal intensity (SI) in T2-weighted MRI (T2W). ZD6126 treatment induced > 90% dose-dependent tumor necrosis at 10 mg/kg; correspondingly, SI changes were evident from T2W MRI. Although R2* did not correlate, other MRI biomarkers significantly correlated with necrosis at doses of ≥ 5 mg/kg ZD6126. These data on Hras5 tumors suggest that the quantification of hypoperfused voxels might provide a useful biomarker of tumor necrosis. PMID:17534443

  15. [Photodynamic therapy of human tumor xenotransplants in athymic nu/nu mice].

    PubMed

    Poucková, P; Pospísil, J; Zadinová, M; Jirsa, M; Kodousek, R; Horák, L

    1990-10-01

    The effect of phototherapy on the growth of two human tumors, i.e. carcinoma of the rectum I and III, was studied. The tumors were xenotransplated into athymic nu/nu mice. Meso-tetra-(para-sulfophenyl)-porphin, TPPS4, was used as photosensitizer. Incorporation studies showed the optimal dose for phototherapy to be 10 mg/kg TPPS4 and the time interval 72 hours. Under these experimental conditions (helium-neon laser, 632, 8, 300 J/cm2) one of six tumors was cured in the group with carcinoma of the rectum I, and that both after IV and IT administration of the photosensitizer. The other five experimental animals exhibited only partial responses to phototherapy. In the group with carcinoma of the rectum III, five out of six tumors were cured by IT administration of TPPS4 under the same experimental conditions. In one mouse there was only partial response to phototherapy. After IV administration of TPPS4, however, not a single tumor was cured and the response to phototherapy was only partial in all the six experimental animals.

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

    SciTech Connect

    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.

  17. [Establishment of endometriosis subcutaneous model in immunodeficient nude mice].

    PubMed

    Ni, H J; Zhang, Z; Dai, Y D; Zhang, S Y

    2016-09-06

    Objective: To establish a model of endometriosis in immunodeficient nude mice and compare the outcome of the model construction between two different techniques. Methods: Eighteen nude mice were divided into 2 groups, with 9 mice in each group. All nude mice received a subcutaneous transplantation of endometrial fragments, followed by sutured the wounded skin (sutured group) or not (no-sutured group). Then the success rate of the model construction, inflammation of the wounds and the animal survival rate in the two groups were analyzed. Result: In no-sutured group, the survival rate of animal and the success rate of the model construction were 9/9 and 8/9 respectively, with 8/9 survival rate and 7/9 success rate in sutured group. No significant difference was found between the two groups. And no obvious inflammation was presented in the wounds for both groups. Conclusion: It is an effective method to establish animal model of endometriosis by subcutaneous transplantation in nude mice. After transplantation, it does not affect the outcome of the survival rate of the animal and the success rate of the model construction whether we suture the wounded skin. Considering the shorter operation time, we found it's a simpler and time saving method to establish endometriosis by subcutaneously transplanting endometrial fragments in nude mice with no skin-sutured. And this model is worth of promotion.

  18. Comparative effects of sesame seed lignan and flaxseed lignan in reducing the growth of human breast tumors (MCF-7) at high levels of circulating estrogen in athymic mice.

    PubMed

    Truan, Jennifer S; Chen, Jian-Min; Thompson, Lilian U

    2012-01-01

    Flaxseed (FS) has a breast tumor-reducing effect, possibly because of its high content of secoisolariciresinol diglucoside (SDG) lignan. Sesame seed (SS) is rich in the lignan sesamin (SES) but is non-protective. Both lignans are metabolized to estrogen-like enterodiol and enterolactone. The objective of this study was to differentiate the effects of SDG and SES on established human estrogen receptor-positive breast tumors (MCF-7) in athymic mice with high serum estrogen to help explain the different effects of FS and SS. Mice were fed for 8 wk the basal diet (BD, control) or BD supplemented with 1 g/kg SDG or SES. SES reduced palpable tumor size by 23% compared to control, whereas SDG did not differ from SES or control. Both treatments reduced tumor cell proliferation, but only SES increased apoptosis. SDG and SES reduced human epidermal growth factor receptor 2 and endothelial growth factor receptor expressions, but only SES reduced downstream pMAPK. Neither treatment affected IGF-1R, vascular endothelial growth factor receptor-2, Akt, pAkt, or MAPK of the growth factor signaling pathway. Thus, at high serum estrogen levels, SDG may not account for the tumor reducing effect of FS. SES was more effective than SDG in reducing breast tumor growth, but its effect may have been lost when consumed as a component of SS.

  19. Effects of non-digestible carbohydrates on the growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in ovariectomized athymic mice.

    PubMed

    Kondegowda, Nagesha Guthalu; Meaney, Mary Pat; Baker, Chandra; Ju, Young H

    2011-01-01

    Non-digestible carbohydrates (NDC(4)) have been used as a low-calorie sweetener and prebiotics that stimulate the growth of certain intestinal bacteria that support healthy colon conditions. In this study, we examined the dietary effect of commercially available NDCs on estrogen receptor positive (ER+) human breast cancer. We conducted a feeding study of fructooligosaccharides (FOSs), Fibersol 2 (F2; digestion resistant maltodextrin), Hi-Maize (HM; high amylose cornstarch), and Frutafit (FF; a range of powdered inulins) (5% in diet, w/w) to evaluate their effects on the growth of ER(+) human breast cancer (MCF-7) tumors in the presence of 17β-estradiol (E(2)) using an athymic xenograft model. F2, HM, and FOSs supplementation significantly reduced E(2)-stimulated MCF-7 tumor growth by inhibiting cellular proliferation (Ki-67) and increasing apoptosis (M30) in tumors. F2, HM, and FOSs treatments also lowered serum E(2) level and reduced uterine weight compared to the control diet. NDCs treatments downregulated relative mRNA expression of the E(2)-responsive gene markers pS2, bcl2, bcl-xL, and cyclin D1 in MCF-7 tumors. In conclusion, the NDC intake may have a protective effect against ER(+) tumors by inhibiting cellular proliferation and increasing apoptosis.

  20. Pc 4 photodynamic therapy of U87 (human glioma) orthotopic tumor in nude rat brain

    NASA Astrophysics Data System (ADS)

    Dean, David; George, John E., III; Ahmad, Yusra; Wolfe, Michael S.; Lilge, Lothar; Morris, Rachel L.; Peterson, Allyn; Lust, W. D.; Totonchi, Ali; Varghai, Davood; Li, Xiaolin; Hoppel, Charles L.; Sun, Jiayang; Oleinick, Nancy L.

    2005-04-01

    Introduction: Photodynamic therapy (PDT) for Barrett"s esophagus, advanced esophageal cancer, and both early and late inoperable lung carcinoma is now FDA-approved using the first generation photosensitizer PhotofrinTM (Axcan Pharma, Birmingham, AL). Photofrin-mediated PDT of glioma is now in Phase III clinical trials. A variety of second generation photosensitizers have been developed to provide improved: (1) specificity for the target tissue, (2) tumoricidal capability, and (3) rapid clearance the vascular compartment, skin, and eyes. The phthalocyanine Pc 4 is a second generation photosensitizer that is in early phase I clinical trials for skin cancer. We have undertaken a preclinical study that seeks to determine if Pc 4-mediated PDT can be of benefit for the intra-operative localization and treatment of glioma. Methods: Using a stereotactic frame, 250,000 U87 cells were injected via Hamilton syringe through a craniotomy, and the dura, 1-2 mm below the cortical surface of nude (athymic) rat brains (N=91). The craniotomy was filled with a piece of surgical PVC and the scalp closed. After two weeks of tumor growth, the animals received 0.5 mg/kg Pc 4 via tail vein injection. One day later the scalp was re-incised, and the PVC removed. The tumor was then illuminated with either 5 or 30 Joule/cm2 of 672-nm light from a diode laser at 50 mW/cm2. The animals were sacrificed one day later and the brain was cold-perfused with formaldehyde. Two thirds of the explanted brains are now being histologically surveyed for necrosis after staining with hematoxylin and eosin and for apoptosis via immunohistochemistry (i.e., TUNEL assay). The other third were analyzed by HPLC-mass spectrometry for the presence of drug in tumor, normal brain, and plasma at sacrifice. Initial histological results show PDT-induced apoptosis and necrosis confined to the growing (live) portion of the tumor. Preliminary analysis shows an average selectivity of Pc 4 uptake in the bulk tumor to be 3

  1. Baring the soul: Paul Bindrim, Abraham Maslow and 'nude psychotherapy'.

    PubMed

    Nicholson, Ian

    2007-01-01

    Nude psychotherapy is one of the most flamboyant therapeutic techniques ever developed in American psychology. Largely forgotten today, the therapy was an academic and popular sensation upon its introduction in 1967. Developed by psychologist Paul Bindrim, the therapy promised to guide clients to their authentic selves through the systematic removal of clothing. This paper explores the intellectual, cultural and ethical context of nude therapy and its significance as a form of unchurched spirituality. Although nude therapy has an indisputable tabloid character, it is also rooted in a long-standing academic search for authenticity and ultimate meaning through science. Bindrim's career demonstrates the historically long-standing interweaving of spirituality and science within American psychology while simultaneously highlighting the field's extraordinary capacity for adaptive reinvention.

  2. Sensitization of cerebral tissue in nude mice with photodynamic therapy induces ADAM17/TACE and promotes glioma cell invasion

    PubMed Central

    Zheng, Xuguang; Jiang, Feng; Katakowski, Mark; Zhang, Xuepeng; Jiang, Hao; Zhang, Zheng Gang; Chopp, Michael

    2008-01-01

    In the present study, we tested the hypothesis that a mild cerebral tissue injury promotes subsequent glioma invasion via activation of the ADAM17-EGFR-PI3K-Akt pathway. Mild injury was induced by Photodynamic therapy (PDT), which employs tissue-penetrating laser light exposure following systemic administration of a tumor-localizing photosensitizer. Athymic nude mice were treated with sublethal PDT (80J/cm2 with 2mg/kg Photofrin). Hypoxic stress and ADAM17-EGFR-PI3K-Akt were measured using Western blot and immunostaining. Additional groups with/without pro-sublethal PDT were subsequently implanted with U87 glioma tumor cell. Tumor invasion and ADAM17-EGFR-PI3K-Akt pathway in tumor area were measured. After a sublethal dose of PDT, HIF-1α expression was increased by a factor of three in PDT-treated normal brain tissue compared to contralateral control brain tissue. PDT-treated brain tissue exhibited a significant increase in ADAM17, p-EGFR, p-Akt expression compared to non-treated tissue. ADAM17 positive area significantly increased from 1.78% to 10.89%. The percentage of p-EGFR and p-Akt positive cells significantly increased from 9.50% and 14.50% to 21.31% and 32.29%,respectively, PDT treatment significantly increased subsequent implanted U87 glioma cell invasion by 3.68-fold and increased ADAM17, EGFR, p-EGFR, Akt, p-Akt expression by 178%, 43.9%,152.7%, 89.6%,and 164.2%, respectively, compared to control group. Our data showed that a sublethal sensitization of cerebral tissue with PDT significantly increased U87 cell invasion in nude mice, and that glioma cell invasion is highly correlated with activation of the ADAM17-EGFR-PI3K-Akt pathway (r=0.928, 0.775, 0.870, 0.872, and 0.883, respectively), most likely via HIF-1α. PMID:18358600

  3. In vivo effects of human adipose-derived stem cells reseeding on acellular bovine pericardium in nude mice

    PubMed Central

    Dai, Miao; Xu, Peirong; Hou, Min; Teng, Yincheng; Feng, Jie

    2015-01-01

    Tissue-engineered biologic products may be a viable option in the reconstruction of pelvic organ prolapse (POP). This study was based on the hypothesis that human adipose-derived stem cells (hASCs) are viable in acellular bovine pericardium (ABP), when reseeded by two different techniques, and thus, aid in the reconstruction. To investigate the reseeding of hASCs on ABP grafts by using non-invasive bioluminescence imaging (BLI), and to identify the effective hASCs–scaffold combinations that enabled regeneration. Thirty female athymic nude mice were randomly divided into three groups: In the VIVO group, ABPs were implanted in the subcutaneous pockets and enhanced green fluorescent protein luciferase (eGFP·Luc)-hASCs (1 × 106 cells/50 µL) were injected on the ABP at the same time. In the VITRO group, the mice were implanted with grafts that ABP were co-cultured with eGFP·Luc-hASCs in vitro. The BLANK group mice were implanted with ABP only. The eGFP·Luc-hASCs reseeded on ABP were analyzed by BLI, histology, and immunohistochemistry. The eGFP·Luc-hASCs reseeded on ABP could be visualized at 12 weeks in vivo. Histology revealed that the VIVO group displayed the highest cell ingrowths, small vessels, and percent of collagen content per unit area. Desmin and α-smooth muscle actin were positive at the same site in the VIVO group cells. However, few smooth muscles were observed in the VITRO and BLANK groups. These results suggest that hASCs reseeded on ABP in vivo during surgery may further enhance the properties of ABP and may promote regeneration at the recipient site, resulting in a promising treatment option for POP. PMID:26253192

  4. Hair growth in human split-thickness skin grafts transplanted onto nude rats: the role of cyclosporin.

    PubMed

    Gilhar, A; Etzioni, A; Krueger, G G

    1990-01-01

    To date, there have been no descriptions of hair growth following transplantation of human split-thickness skin grafts (HSTSG) to congenitally athymic (nude) mice or rats. Recently, we noted hair growth in HSTSG from scalp skin (HSTSG-SS) transplanted onto rats treated with ciclosporin (CS). By definition, HSTSG-SS of 0.4 mm had all the anagen hairs cut from the papillae. Two months after engraftment, there was histological evidence of the formation of new papillae. Density of hair correlated with thickness of HSTSG, i.e. there were more hairs/square centimeter in HSTSG-SS of 1 mm thickness than in those of 0.4 mm thickness. New hairs appeared on an average of 1 cm2/week in HSTSG-SS that were 1 mm thick; by 10 weeks, the mean density was 7.9 hairs/cm2. In the thinner grafts, the density was 3.5 hairs/cm2 (p less than 0.025). The rate of growth in the thicker grafts ranged from 0 to 0.25 mm/day, with an average of 0.1 mm/day. At 10 weeks after grafting, the hairs had a mean length of 4.4 mm in the thicker and 1.7 mm in the thinner grafts (p less than 0.001). The average diameter of the hair shafts was 0.05 mm at the various times tested. These observations identify a previously unrecognized process of hair growth and present an in vivo model to study human hair growth process, including the role of CS in hair growth.

  5. In vivo effects of human adipose-derived stem cells reseeding on acellular bovine pericardium in nude mice.

    PubMed

    Wu, Qingkai; Dai, Miao; Xu, Peirong; Hou, Min; Teng, Yincheng; Feng, Jie

    2016-01-01

    Tissue-engineered biologic products may be a viable option in the reconstruction of pelvic organ prolapse (POP). This study was based on the hypothesis that human adipose-derived stem cells (hASCs) are viable in acellular bovine pericardium (ABP), when reseeded by two different techniques, and thus, aid in the reconstruction. To investigate the reseeding of hASCs on ABP grafts by using non-invasive bioluminescence imaging (BLI), and to identify the effective hASCs-scaffold combinations that enabled regeneration. Thirty female athymic nude mice were randomly divided into three groups: In the VIVO group, ABPs were implanted in the subcutaneous pockets and enhanced green fluorescent protein luciferase (eGFP·Luc)-hASCs (1 × 10(6) cells/50 µL) were injected on the ABP at the same time. In the VITRO group, the mice were implanted with grafts that ABP were co-cultured with eGFP·Luc-hASCs in vitro. The BLANK group mice were implanted with ABP only. The eGFP·Luc-hASCs reseeded on ABP were analyzed by BLI, histology, and immunohistochemistry. The eGFP·Luc-hASCs reseeded on ABP could be visualized at 12 weeks in vivo. Histology revealed that the VIVO group displayed the highest cell ingrowths, small vessels, and percent of collagen content per unit area. Desmin and α-smooth muscle actin were positive at the same site in the VIVO group cells. However, few smooth muscles were observed in the VITRO and BLANK groups. These results suggest that hASCs reseeded on ABP in vivo during surgery may further enhance the properties of ABP and may promote regeneration at the recipient site, resulting in a promising treatment option for POP. © 2016 by the Society for Experimental Biology and Medicine.

  6. Negligible Colon Cancer Risk from Food-Borne Acrylamide Exposure in Male F344 Rats and Nude (nu/nu) Mice-Bearing Human Colon Tumor Xenografts

    PubMed Central

    Raju, Jayadev; Roberts, Jennifer; Sondagar, Chandni; Kapal, Kamla; Aziz, Syed A.; Caldwell, Don; Mehta, Rekha

    2013-01-01

    Acrylamide, a possible human carcinogen, is formed in certain carbohydrate-rich foods processed at high temperature. We evaluated if dietary acrylamide, at doses (0.5, 1.0 or 2.0 mg/kg diet) reflecting upper levels found in human foods, modulated colon tumorigenesis in two rodent models. Male F344 rats were randomized to receive diets without (control) or with acrylamide. 2-weeks later, rats in each group received two weekly subcutaneous injections of either azoxymethane (AOM) or saline, and were killed 20 weeks post-injections; colons were assessed for tumors. Male athymic nude (nu/nu) mice bearing HT-29 human colon adenocarcinoma cells-derived tumor xenografts received diets without (control) or with acrylamide; tumor growth was monitored and mice were killed 4 weeks later. In the F344 rat study, no tumors were found in the colons of the saline-injected rats. However, the colon tumor incidence was 54.2% and 66.7% in the control and the 2 mg/kg acrylamide-treated AOM-injected groups, respectively. While tumor multiplicity was similar across all diet groups, tumor size and burden were higher in the 2 mg/kg acrylamide group compared to the AOM control. These results suggest that acrylamide by itself is not a “complete carcinogen”, but acts as a “co-carcinogen” by exacerbating the effects of AOM. The nude mouse study indicated no differences in the growth of human colon tumor xenografts between acrylamide-treated and control mice, suggesting that acrylamide does not aid in the progression of established tumors. Hence, food-borne acrylamide at levels comparable to those found in human foods is neither an independent carcinogen nor a tumor promoter in the colon. However, our results characterize a potential hazard of acrylamide as a colon co-carcinogen in association with known and possibly other environmental tumor initiators/promoters. PMID:24040114

  7. Vitamin D3 analogs stimulate hair growth in nude mice.

    PubMed

    Vegesna, Vijaya; O'Kelly, James; Uskokovic, Milan; Said, Jonathan; Lemp, Nathan; Saitoh, Takayuki; Ikezoe, Takayuki; Binderup, Lise; Koeffler, H Phillip

    2002-11-01

    The active form of vitamin D3 can regulate epidermal keratinization by inducing terminal differentiation; and mice lacking the vitamin D receptor display defects leading to postnatal alopecia. These observations implicate the vitamin D3 pathway in regulation of hair growth. We tested the ability of 1,25 dihydroxyvitamin D3 and its synthetic analogs to stimulate hair growth in biege/nude/xid (BNX) nu/nu (nude) mice exhibiting congenital alopecia. Nude mice were treated with different vitamin D3 analogs at doses that we had previously found to be the highest dose without inducing toxicity (hypercalcemia). The mice were monitored for hair growth and were scored according to a defined scale. Skin samples were taken for histological observation of hair follicles and for extraction of RNA and protein. Vitamin D3 analogs dramatically stimulated the hair growth of nude mice, although parental 1,25 dihydroxyvitamin D3 had no effect. Hair growth occurred in a cyclical pattern, accompanied by formation of normal hair follicles and increased expression of certain keratins (Ha7, Ha8, and Hb3). Vitamin D3 analogs seem to act on keratinocytes to initiate hair follicle cycling and stimulate hair growth in mice that otherwise do not grow hair.

  8. T-cell receptor expression in intestinal intra-epithelial lymphocyte subpopulations of normal and athymic mice.

    PubMed Central

    Viney, J L; MacDonald, T T; Kilshaw, P J

    1989-01-01

    Intra-epithelial lymphocytes (IEL) in murine small intestine were analysed for the presence of cell-surface antigens and T-cell receptor allotype in normal and athymic BALB/c mice by immunoperoxidase histochemistry on frozen sections and immunofluorescence on isolated IEL. In frozen sections, IEL of normal mice were 97.7% CD45+, 93.5% CD3+, 46.2% Thy-1+, 91.1% CD8+, 10.7% CD4+ and 21.1% KJ16+ (V beta 8.1 and 8.2). FACS analysis of isolated IEL confirmed the level of KJ16 expression and also demonstrated that 25% of IEL were F23.1+ (V beta 8.1-8.3). Immunofluorescent double-staining revealed a skewed distribution of T-cell receptor (TcR) expression on Thy-1+ and Thy-1- IEL. KJ16 and F23.1 were expressed on 25.9% and 32.7% of Thy-1+ IEL, respectively; however, the frequency of V beta 8 expression was diminished on Thy-1- IEL (4.1% KJ16+ and 12.1% F23.1+). IEL are present in athymic mice, but at reduced levels. In frozen sections these cells were 91.9% CD45+, 69.5% CD3+, less than 1% Thy-1+, 83.6% CD8+, less than 1% CD4+ and less than 1% KJ16+. Thus it appears that in normal mice there may be two distinct lineages of IEL, a thymus-dependent Thy-1+ population which utilizes the alpha beta T-cell receptor and a thymus-independent Thy-1- population (represented in athymic mice), which may possibly utilize the alternative gamma delta TcR. Images Figure 1 PMID:2565884

  9. Glomerular common gamma chain confers B- and T-cell-independent protection against glomerulonephritis.

    PubMed

    Luque, Yosu; Cathelin, Dominique; Vandermeersch, Sophie; Xu, Xiaoli; Sohier, Julie; Placier, Sandrine; Xu-Dubois, Yi-Chun; Louis, Kevin; Hertig, Alexandre; Bories, Jean-Christophe; Vasseur, Florence; Campagne, Fabien; Di Santo, James P; Vosshenrich, Christian; Rondeau, Eric; Mesnard, Laurent

    2017-01-19

    Crescentic glomerulonephritis is a life-threatening renal disease that has been extensively studied by the experimental anti-glomerular basement membrane glomerulonephritis (anti-GBM-GN) model. Although T cells have a significant role in this model, athymic/nude mice and rats still develop severe renal disease. Here we further explored the contribution of intrinsic renal cells in the development of T-cell-independent GN lesions. Anti-GBM-GN was induced in three strains of immune-deficient mice (Rag2(-/-), Rag2(-/-)Il2rg(-/-), and Rag2(-/-)Il2rb(-/-)) that are devoid of either T/B cells or T/B/NK cells. The Rag2(-/-)Il2rg(-/-) or Rag2(-/-)Il2rb(-/-) mice harbor an additional deletion of either the common gamma chain (γC) or the interleukin-2 receptor β subunit (IL-2Rβ), respectively, impairing IL-15 signaling in particular. As expected, all these strains developed severe anti-GBM-GN. Additionally, bone marrow replenishment experiments allowed us to deduce a protective role for the glomerular-expressed γC during anti-GBM-GN. Given that IL-15 has been found highly expressed in nephritic kidneys despite the absence of lymphocytes, we then studied this cytokine in vitro on primary cultured podocytes from immune-deficient mice (Rag2(-/-)Il2rg(-/-) and Rag2(-/-)Il2rb(-/-)) compared to controls. IL-15 induced downstream activation of JAK1/3 and SYK in primary cultured podocytes. IL-15-dependent JAK/SYK induction was impaired in the absence of γC or IL-2Rβ. We found γC largely induced on podocytes during human glomerulonephritis. Thus, renal lesions are indeed modulated by intrinsic glomerular cells through the γC/IL-2Rβ receptor response, to date classically described only in immune cells.

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

    NASA Astrophysics Data System (ADS)

    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.

  11. Gender differences in response to pictures of nudes: a magnetoencephalographic study.

    PubMed

    Costa, Marco; Braun, Christoph; Birbaumer, Niels

    2003-05-01

    The magnetic equivalent of the contingent negative variation (CMV) and visual evoked magnetic fields (VEF) in anticipation of pictures of opposite-sex nude, same-sex nude, and neutral photographs has been recorded with whole-head MEG in 12 males and 12 females. Subjective ratings of valence indicated a strong gender effect. While females rated both male and female nudes as neutral, males rated male nudes similar to neutrals but female nudes received higher scores of pleasantness. Gender differences were also found for ratings of picture-induced arousal. While females rated male and female nudes as equally arousing, males attributed more arousal to opposite-sex nudes. The CMV instead revealed, for both male and female participants, higher amplitudes for opposite-sex nudes. VEF in response to nudes revealed two components with mean latencies of 126 and 203 ms. The amplitude of the first component was stronger in males than in females, and only in males the magnetic activity was increased in response to male and female nudes compared to neutral pictures. For the second component the mean magnetic activity was higher in response to nudes than to neutral contents for both male and female participants. The results are discussed in terms of an evolutionary view of sexual selection, which predicts a greater response in male subjects to stimuli relevant for mate choice.

  12. Maintenance of donor phenotype after full-thickness skin transplantation from mice with chronic proliferative dermatitis (cpdm/cpdm) to C57BL/Ka and nude mice and vice versa.

    PubMed

    Gijbels, M J; HogenEsch, H; Bruijnzeel, P L; Elliott, G R; Zurcher, C

    1995-12-01

    Chronic proliferative dermatitis is a spontaneous mutation in C57BL/Ka mice (cpdm/cpdm) and is characterized by epithelial hyperproliferation, infiltration by eosinophils and macrophages, and vascular dilatation. To elucidate whether these pathologic features are the result of a local (skin) process or a consequence of a systemic disorder, transplantations were performed of full-thickness grafts of affected skin from cpdm/cpdm mice and normal skin from control (C57BL/Ka) mice on the back of cpdm/cpdm, C57BL/Ka and athymic nude mice. After 3 months, the grafts maintained the histologic phenotype of the donor animal. Intercellular adhesion molecule-1 continued to be expressed by basal keratinocytes of the cpdm/cpdm grafts after transplantation. In contrast, the basal keratinocytes of the C57BL/Ka grafts onto cpdm/cpdm mice remained negative for intercellular adhesion molecule-1 3 months after transplantation. An increased number of proliferating keratinocytes was present in the cpdm/cpdm skin-graft transplanted to nudes or to C57BL/Ka mice based on short-term bromodeoxyuridine labeling. The bromodeoxyuridine incorporation in the keratinocytes of the control C57BL/Ka skin grafts transplanted to cpdm/cpdm, nude, or C57BL/Ka mice was the same as in the keratinocytes of normal C57BL/Ka mice. This study demonstrates that the pathologic features found in the cpdm/cpdm mice are the result of a disorder in the epidermis or dermis and not due to a systemic defect.

  13. Outstanding memories: the positive and negative effects of nudes on memory.

    PubMed

    Schmidt, Stephen R

    2002-03-01

    A picture of a nude isolated in a series of pictures of clothed models was quite memorable, but when compared with a clothed picture, the nude impaired memory for background picture derails as well as pictures immediately following the nude (anterograde amnesia). Recall of details given picture-gist recall, as well as recognition of person details, were equivalent in the clothed and nude conditions. A clothed picture isolated in a series of nudes did not hurt memory for background information, nor did it produce anterograde amnesia. Apparently, distinctiveness supports good memory for the gist of the nude or clothed pictures. However, distinctiveness is not responsible for the anterograde amnesia and poor memory for background details found with nudes.

  14. Analysis of Stroma Labeling During Multiple Passage of a Sarcoma Imageable Patient-derived Orthotopic Xenograft (iPDOX) in Red Fluorescent Protein Transgenic Nude Mice.

    PubMed

    Kiyuna, Tasuku; Murakami, Takashi; Tome, Yasunori; Kawaguchi, Kei; Igarashi, Kentaro; Miyake, Kentaro; Kanaya, Fuminori; Singh, Arun; Eilber, Fritz C; Hoffman, Robert M

    2017-03-16

    A patient-derived orthotopic xenograft (PDOX) model of undifferentiated pleomorphic sarcoma (UPS) was previously established that acquired red fluorescent protein (RFP)-expressing stroma by growth in an RFP transgenic nude mouse. In the present study, an imageable PDOX model (iPDOX) of UPS was established by orthotopic implantation in the biceps femoris of transgenic RFP nude mice. After the tumors grew to a diameter of 10 mm, they were harvested and the brightest portion of the tumors were subsequently orthotopically transplanted to both RFP and non-colored nude mice. The UPS PDOX tumor was again transplanted to RFP transgenic and non-colored nude mice and finally a 3(rd) passage was made in the same manner. Five UPS tumors from each passage in both RFP and non-colored mouse models were harvested. The FV1000 confocal microscope was used to visualize and quantitate the RFP area of the resected tumors. The average percent fluorescent area in the first passage of RFP mice was 34 ± 22%; in the second passage, 34 ± 20%; and 36 ± 11% in the third passage of RFP transgenic nude mice. The average tumor RFP area in the first passage from RFP mice to non-colored mice was 20 ± 7%; in the second passage, 28 ± 11%; in the third passage was 27 ± 13%. The present results demonstrate the extensive and stable acquisition of stroma by the UPS-tumor growing orthotopically in transgenic RFP nude mice (iPDOX). This model can be used for screening for effective drugs for individual patients and drug discovery. This article is protected by copyright. All rights reserved.

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

    PubMed

    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. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  16. Sulforaphane retards the growth of UM-UC-3 xenographs, induces apoptosis, and reduces survivin in athymic mice.

    PubMed

    Wang, Fengqian; Shan, Yujuan

    2012-05-01

    Sulforaphane (SFN), an isothiocyanate that exists exclusively in cruciferous vegetables, may be the most promising preventive agent for bladder cancer (BC) to date. We previously observed that SFN dramatically inhibits human BC T24 cells in vitro. Our hypothesis is that SFN may attenuate BC growth. To test our hypothesis, we investigated the effect of SFN on human BC UM-UC-3 cell xenografts implanted into athymic mice. Sulforaphane extract was routinely prepared in our laboratory, and its content was measured with high-performance liquid chromatography. Athymic mice were injected subcutaneously with a UM-UC-3 cell suspension (2.0×10(6) cells/200 μL per mouse) and randomly divided into 2 groups. The positive control group was orally gavaged with water, and the treatment group was orally administered SFN from broccoli sprout (12 mg/kg body weight) for 5 weeks. At the end of the experiment, tumor tissues were harvested and processed for hematoxylin and eosin staining and immunohistochemistry. The average tumor volume decreased from 4.1±1.67 cm(3) in the positive control mice to 1.5±0.72 cm(3) in the SFN-treated mice, evidencing an inhibitory rate of 63%. The SFN extract also reduced the appearance of tumors, including karyopyknosis and angiogenesis. Sulforaphane extract induced caspase 3 and cytochrome c expression but reduced the expression of survivin. Sulforaphane extract retards the growth of UM-UC-3 xenografts in vivo, confirming its future potential in BC therapy.

  17. IL-17 mediates neutrophil infiltration and renal fibrosis following recovery from ischemia reperfusion: compensatory role of natural killer cells in athymic rats.

    PubMed

    Mehrotra, Purvi; Collett, Jason A; McKinney, Seth D; Stevens, Jackson; Ivancic, Carlie M; Basile, David P

    2017-03-01

    T cells have been implicated in the pathogenesis of acute kidney injury (AKI) and its progression to chronic kidney disease (CKD). Previous studies suggest that Th17 cells participate during the AKI-to-CKD transition, and inhibition of T cell activity by mycophenolate mofetil (MMF) or losartan attenuates the development of fibrosis following AKI. We hypothesized that T cell-deficient rats may have reduced levels of IL-17 cytokine leading to decreased fibrosis following AKI. Renal ischemis-reperfusion (I/R) was performed on T cell-deficient athymic rats (Foxn1(rnu-/rnu-)) and control euthymic rats (Foxn1(rnu-/+)), and CKD progression was hastened by unilateral nephrectomy at day 33 and subsequent exposure to 4.0% sodium diet. Renal fibrosis developed in euthymic rats and was reduced by MMF treatment. Athymic rats exhibited a similar degree of fibrosis, but this was unaffected by MMF treatment. FACS analysis demonstrated that the number of IL-17(+) cells was similar between postischemic athymic vs. euthymic rats. The source of IL-17 production in euthymic rats was predominately from conventional T cells (CD3(+)/CD161(-)). In the absence of conventional T cells in athymic rats, a compensatory pathway involving natural killer cells (CD3(-)/CD161(+)) was the primary source of IL-17. Blockade of IL-17 activity using IL-17Rc receptor significantly decreased fibrosis and neutrophil recruitment in both euthymic and athymic rats compared with vehicle-treated controls. Taken together, these data suggest that IL-17 secretion participates in the pathogenesis of AKI-induced fibrosis possibly via the recruitment of neutrophils and that the source of IL-17 may be from either conventional T cells or NK cells. Copyright © 2017 the American Physiological Society.

  18. The nude mouse model for the study of human skin disorders.

    PubMed

    Gilhar, A; Etzioni, A

    1994-01-01

    Normal human skin grafted onto the nude mouse can be maintained without any signs of rejection throughout the life-span of the animal. Indeed, the nude mouse model is a powerful tool for understanding the pathological process of the skin. Until now many skin diseases such as psoriasis, cutaneous lupus, pemphigus and vitiligo have been looked at using the nude mouse model, which has helped to clarify the role of the various factors involved.

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

    PubMed

    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.

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

    PubMed

    Hauff, P; Arnold, W

    1990-01-01

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

  1. Polyphenolics from mango (Mangifera indica L.) suppress breast cancer ductal carcinoma in situ proliferation through activation of AMPK pathway and suppression of mTOR in athymic nude mice.

    PubMed

    Nemec, Matthew J; Kim, Hyemee; Marciante, Alexandria B; Barnes, Ryan C; Hendrick, Erik D; Bisson, William H; Talcott, Stephen T; Mertens-Talcott, Susanne U

    2017-03-01

    The objective of this study was to assess the underlying mechanisms of mango polyphenol decreased cell proliferation and tumor volume in ductal carcinoma in situ breast cancer. We hypothesized that mango polyphenols suppress signaling along the AKT/mTOR axis while up-regulating AMPK. To test this hypothesis, mango polyphenols (0.8 mg gallic acid equivalents per day) and pyrogallol (0.2 mg/day) were administered for 4 weeks to mice xenografted with MCF10DCIS.com cells subcutaneously (n=10 per group). Tumor volumes were significantly decreased, both mango and pyrogallol groups displayed greater than 50% decreased volume compared to control. There was a significant reduction of phosphorylated protein levels of IR, IRS1, IGF-1R, and mTOR by mango; while pyrogallol significantly reduced the phosphorylation levels of IR, IRS1, IGF-1R, p70S6K, and ERK. The protein levels of Sestrin2, which is involved in AMPK-signaling, were significantly elevated in both groups. Also, mango significantly elevated AMPK phosphorylation and pyrogallol significantly elevated LKB1 protein levels. In an in vitro model, mango and pyrogallol increased reactive oxygen species (ROS) generation and arrested cells in S phase. In silico modeling indicates that pyrogallol has the potential to bind directly to the allosteric binding site of AMPK, inducing activation. When AMPK expression was down-regulated using siRNA in vitro, pyrogallol reversed the reduced expression of AMPK. This indicates that pyrogallol not only activates AMPK, but also increases constitutive protein expression. These results suggest that mango polyphenols and their major microbial metabolite, pyrogallol, inhibit proliferation of breast cancer cells through ROS-dependent up-regulation of AMPK and down-regulation of the AKT/mTOR pathway.

  2. Microenvironment influence on human colon adenocarcinoma phenotypes and matrix metalloproteinase-2, p53 and β-catenin tumor expressions from identical monoclonal cell tumor in the orthotopic model in athymic nude rats.

    PubMed

    Priolli, Denise Gonçalves; Abrantes, Ana Margarida; Neves, Silvia; Gonçalves, Ana Cristina; Lopes, Camila Oliveira; Martinez, Natalia Peres; Cardinalli, Izilda Aparecida; Ribeiro, Ana Bela Sarmento; Botelho, Maria Filomena

    2014-03-01

    The present study aims to identify differences between left and right colon adenocarcinoma arising from identical clonal cell and to find out if microenvironment has any influence on matrix metalloproteinase-2 (MMP2), p53 and β-catenin tumor expressions. MATERIAL AND METHODS. Rats (RNU) were submitted to cecostomy to obtain the orthotopic model of right colon tumor (n = 10), while for the left colon model (n = 10), a colon diversion and distal mucous fistula in the descending colon was used. Cultivated human colon adenocarcinoma cells (WiDr) were inoculated in stomas submucosa. Histopathological analysis, real-time reverse transcription-PCR for β-catenin, p53 and MMP2, as well as immunohistochemical analysis for p53 and β-catenin expression were conducted. Central tendency, variance analysis and the Livak delta-delta-CT method were used for statistical analysis, adopting a 5% significance level. RESULTS. All tumors from the left colon exhibited infiltrative ulceration, while in the right colon tumor growth was predominantly exophytic (67%). In the left colon, tumor growth was undifferentiated (100%), while it was moderately differentiated in the right colon (83%). In right colon tumors, MMP2, p53, and β-catenin gene expressions were higher than compared to left colon (p = 4.59354E-05, p = 0.0035179, p = 0.00093798, respectively, for MMP2, p53 and β-catenin). β-catenin and p53 results obtained by real-time polymerase chain reaction were confirmed by immunohistochemistry assay (p = 0.01 and p = 0.001, respectively, for β-catenin and p53). CONCLUSION. Left and right human colon adenocarcinomas developed in animal models have distinct phenotypes even when they have the same clonal origin. Microenvironment has influenced p53, β-catenin, and MMP2 expression in animal models of colon cancer.

  3. Beta-endorphin in genetically hypoprolactinemic rat: IPL nude rat

    SciTech Connect

    Cohen, H.; Sabbagh, I.; Abou-Samra, A.B.; Bertrand, J.

    1986-01-20

    Beta-endorphin has been reported to regulate not only stress- and suckling-induced but also basal prolactin secretion. In the aim to better evaluate the endogenous beta-endorphin-prolactin interrelation, the authors measured beta-endorphin levels in a new rat strain, genetically hypoprolactinemic and characterized by a total lack of lactation: IPL nude rat. Beta-endorphin was measured using a specific anti-h-..beta.. endorphin in plasma and extracts of anterior and neurointermediate lobes of the pituitary, hypothalamus and brain. Pituitary extracts were also chromatographed on Sephadex G50 column. Results obtained showed that in IPL nude females on diestrus and males, the beta-endorphin contents of the neurointermediate lobe was significantly lower than in normal rats, while the values found in the other organs and plasma were similar. However, elution pattern of the anterior pituitary extracts from male rats showed greater immunoactivity eluting as I/sup 125/ h-beta-endorphin than in normal rat; this was not the case for the female rat. These results are consistent with a differential regulation of beta-endorphin levels of anterior and neurointermediate lobe by catecholamines. Moreover they suggest that PRL secretion was more related to neurointermediate beta-endorphin. 40 references, 2 figures, 4 tables.

  4. The Acute Lymphoblastic Leukemia-associated JAK2 L611S Mutant Induces Tumorigenesis in Nude Mice*S⃞

    PubMed Central

    Funakoshi-Tago, Megumi; Tago, Kenji; Sumi, Kazuya; Abe, Miyuki; Aizu-Yokota, Eriko; Oshio, Tomoyuki; Sonoda, Yoshiko; Kasahara, Tadashi

    2009-01-01

    JAK2 plays important roles in the regulation of a variety of cellular processes including cell migration, proliferation, and protection from apoptosis. Recently the L611S point mutation in JAK2 has been identified in a child with acute lymphoblastic leukemia. Here we analyzed the mechanism by which JAK2 exhibits its oncogenicity. In BaF3 murine hematopoietic cells, L611S mutant increased the expression of antiapoptotic proteins including X chromosome-linked inhibitor of apoptosis protein, inhibitor of apoptosis protein, and Bcl-XL. We also showed that JAK2 L611S mutant protects BaF3 cells from cytokine withdrawal-induced apoptotic cell death and leads to cytokine-independent cell growth. Furthermore BaF3 cells expressing JAK2 L611S mutant gained the ability to induce tumorigenesis in nude mice. The L611S mutant also exhibited malignancy, including prompt invasion and spreading into various organs, leading to rapid lethality of the mice. Finally we showed that a specific JAK2 inhibitor, AG490, potently inhibited cytokine-independent cell growth induced by JAK2 L611S mutant via the induction of apoptotic cell death. In addition, treatment with AG490 significantly inhibited the JAK2 L611S mutant-induced tumorigenesis in nude mice. Thus, our results both in vitro and in vivo strongly suggest that L611S mutant of JAK2 harbors potent oncogenic activity, and this probably requires the antiapoptotic signaling pathway. PMID:19289461

  5. The acute lymphoblastic leukemia-associated JAK2 L611S mutant induces tumorigenesis in nude mice.

    PubMed

    Funakoshi-Tago, Megumi; Tago, Kenji; Sumi, Kazuya; Abe, Miyuki; Aizu-Yokota, Eriko; Oshio, Tomoyuki; Sonoda, Yoshiko; Kasahara, Tadashi

    2009-05-08

    JAK2 plays important roles in the regulation of a variety of cellular processes including cell migration, proliferation, and protection from apoptosis. Recently the L611S point mutation in JAK2 has been identified in a child with acute lymphoblastic leukemia. Here we analyzed the mechanism by which JAK2 exhibits its oncogenicity. In BaF3 murine hematopoietic cells, L611S mutant increased the expression of antiapoptotic proteins including X chromosome-linked inhibitor of apoptosis protein, inhibitor of apoptosis protein, and Bcl-XL. We also showed that JAK2 L611S mutant protects BaF3 cells from cytokine withdrawal-induced apoptotic cell death and leads to cytokine-independent cell growth. Furthermore BaF3 cells expressing JAK2 L611S mutant gained the ability to induce tumorigenesis in nude mice. The L611S mutant also exhibited malignancy, including prompt invasion and spreading into various organs, leading to rapid lethality of the mice. Finally we showed that a specific JAK2 inhibitor, AG490, potently inhibited cytokine-independent cell growth induced by JAK2 L611S mutant via the induction of apoptotic cell death. In addition, treatment with AG490 significantly inhibited the JAK2 L611S mutant-induced tumorigenesis in nude mice. Thus, our results both in vitro and in vivo strongly suggest that L611S mutant of JAK2 harbors potent oncogenic activity, and this probably requires the antiapoptotic signaling pathway.

  6. Employing human keratinocytes cultured on macroporous gelatin spheres to treat full thickness-wounds: an in vivo study on athymic rats.

    PubMed

    Gustafson, Carl-Johan; Birgisson, Agust; Junker, Johan; Huss, Fredrik; Salemark, Lars; Johnson, Hans; Kratz, Gunnar

    2007-09-01

    Providing cutaneous wounds with sufficient epidermis to prevent infections and fluid loss is one of the most challenging tasks associated with surgical treatment of burns. Recently, application of cultured keratinocytes in this context has allowed this challenge to be met without several of the limitations connected with the use of split-thickness skin grafts. The continuous development of this novel approach has now revealed that transplantation of cultured autologous keratinocytes as single-cell suspensions exhibits several advantages over the use of cultured epidermal grafts. However, a number of methodological problems remain to be solved, primarily with regards to the complexity of culturing these cells; loss of viability and other negative effects during their preparation and transportation; the relatively long period of time required following transplantation to obtain a sufficiently protective epidermis. In the present investigation we attempted to eliminate these limitations by culturing the keratinocytes on macroporous gelatin spheres. Accordingly, the efficacies of normal human keratinocytes in single-cell suspension or growing on macroporous gelatin spheres, as well as of split-thickness skin grafts in healing wounds on athymic rats were compared. Human keratinocytes were found to adhere and proliferate efficiently both on the surface and within the pores of such spheres. Transplantation of such cells adherent to the spheres resulted in significantly more rapid formation of a stratified epidermis than did transplantation of single-cell suspensions or spheres alone. Twenty-three days after transplantation, the epidermis formed from the cells bound to the spheres was not as thick as the epidermis on wounds covered with split-thickness skin grafts, but significantly thicker than on wounds to which single-cell suspensions, spheres alone or no transplant at all was applied. Furthermore, fluorescence in situ hybridisation revealed that the transplanted

  7. Extractable bone morphogenetic protein and correlation with induced new bone formation in an in vivo assay in the athymic mouse model.

    PubMed

    Honsawek, Sittisak; Powers, Ralph M; Wolfinbarger, Lloyd

    2005-01-01

    A correlation between extractable bone morphogenetic proteins (BMPs) in demineralized bone matrix (DBM) and osteoinduction has been suggested. Extractable BMP-4 and osteoinductivity of DBM from 40 donors were assessed using enzyme-linked immunosorbent assay (ELISA) and in vivo athymic mouse assay, respectively. Extractable BMP-4 level averaged 3.7 +/- 0.21 ng/g of DBM and correlated with osteoinductivity of the DBM in an in vivo assessment of induced newbone formation.

  8. Immunohistochemical demonstration of epidermal growth factor in human gastric cancer xenografts of nude mice.

    PubMed

    Yoshiyuki, T; Shimizu, Y; Onda, M; Tokunaga, A; Kiyama, T; Nishi, K; Mizutani, T; Matsukura, N; Tanaka, N; Akimoto, M

    1990-02-15

    Thirty-two surgical specimens and three cell lines of human gastric cancers were used for subcutaneous transplantation into nude mice, resulting in the establishment of eight (25%) xenografts from the surgical specimens and two (67%) from the cell lines. The localization of epidermal growth factor (EGF) in the surgical specimens and cell lines of the gastric cancers and their xenografts in nude mice was then investigated immunohistochemically. Epidermal growth factor was stained in the cytoplasm of the cancer cells, being detected in 16 (50%) of the 32 surgical specimens and in all of the cell lines. Seven (44%) of the sixteen EGF-positive surgical specimens and one (6%) of the 16 EGF-negative ones were tumorigenic in nude mice. All of the xenografts in nude mice were positive for EGF. The tumorigenicity of human gastric cancer xenografts in nude mice may, therefore, be correlated with the presence of EGF in cancer cells.

  9. The effect of single agent oral fusaric acid (FA) on the growth of subcutaneously xenografted SCC-1 cells in a nude mouse model.

    PubMed

    Ruda, James M; Beus, Kirt S; Hollenbeak, Christopher S; Wilson, Ronald P; Stack, Brendan C

    2006-09-01

    To determine whether oral administration of fusaric acid (FA) inhibits tumor growth in an animal model of head and neck cancer (HNSCC). In vivo murine model, two arm controlled study. Thirty-eight (38) 5-week-old athymic nude mice were randomly assigned to a fusaric acid treatment group (1 mg/mL) (n = 19) or a sterile saline group (n = 19). A left, lateral flank subcutaneous injection of 2.0 x 10(6) UM-SCC-1 cells were administered to all mice on day 1. Both groups were gavaged daily with either 0.25 mLs of oral FA or sterile saline throughout the experiment (32 days). Latency to a measurable tumor (> or =65 mm3), and tumor volumes were recorded after tumor xenografting. Tumor weights were recorded at the conclusion of the experiment. Tumor volume growth curves were modeled as polynomial functions of time with treatment interaction effects. Survivorship functions for time to measurable tumor were estimated using the Kaplan-Meier product limit estimator. Survival analysis showed mice treated with FA developed measurable tumors after a significantly longer interval post-xenografting than control mice (p = 0.00451). By Day 9, all mice in the control group had developed measurable tumors in comparison to only 78% of mice in the FA group. Likewise, estimated growth curves for both groups suggested that mice receiving FA demonstrated significantly slower tumor growth rates throughout the entire study period (p < 0.0001). At the conclusion of the experiment, tumor weights from both the control and FA groups were also significantly different (p = 0.0142). Single agent oral fusaric acid (1 mg/mL) is an inhibitor of UM-SCC-1 in a murine model. As an orally active agent, it may have a potential role in the treatment of human squamous cell carcinoma of the head and neck.

  10. Inhibition of growth of OV-1063 human epithelial ovarian cancer xenografts in nude mice by treatment with luteinizing hormone-releasing hormone antagonist SB-75.

    PubMed Central

    Yano, T; Pinski, J; Halmos, G; Szepeshazi, K; Groot, K; Schally, A V

    1994-01-01

    Female athymic nude mice bearing xenografts of OV-1063 human epithelial ovarian cancer cell line were treated with potent luteinizing hormone (LH)-releasing hormone (LH-RH) antagonist SB-75 (Cetrorelix; [Ac-D-Nal(2)1, D-Phe(4 CI)2, D-Pal(3)3, D-Cit6, D-Ala10]LH-RH in which Ac-D-Nal(2) = N-acetyl-3-(2-naphthyl)-D-alanine, D-Phe(4CI) = 4-chloro-D-phenylalanine, D-Pal(3) = 3-(3-pyridyl)-D-alanine, and D-Cit = D-Citrulline) or with the agonist [D-Trp6]LH-RH. In the first experiment, SB-75 and [D-Trp6]LH-RH were administered in the form of microcapsules releasing 60 and 25 micrograms/day, respectively. In the second study, the analogs were given by daily s.c. injections in doses of 100 micrograms/day. In both experiments, tumor growth, as measured by reduction in tumor volume, percentage change in tumor volume, tumor burden, and increase in tumor doubling time, was significantly inhibited by treatment with SB-75 but not with [D-Trp6]LH-RH. Uterine and ovarian weights were reduced and serum LH levels decreased by administration of either analog. Chronic treatment with SB-75 greatly reduced the concentration of receptors for epidermal growth factor and insulin-like growth factor I in tumor cell membranes, a phenomenon that might be related to tumor growth inhibition. It is possible that the antitumoral effects of SB-75 on OV-1063 ovarian cancers are exerted not only through the suppression of the pituitary-gonadal axis, but also directly. In view of its strong inhibitory effect on the growth of OV-1063 ovarian cancers in vivo, the potent LH-RH antagonist SB-75 might be considered for possible hormonal therapy of advanced epithelial ovarian carcinoma. PMID:7518926

  11. Transgenic nude mice ubiquitously expressing fluorescent proteins for color-coded imaging of the tumor microenvironment.

    PubMed

    Hoffman, Robert M

    2014-01-01

    We have developed a 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 β-actin promoter drives GFP expression in essentially all tissues. In the adult mice, many organs brightly expressed GFP, including the spleen, heart, lungs, spleen, pancreas, esophagus, stomach, and duodenum as well as the circulatory system. The liver expressed GFP at a lesser level. The red fluorescent protein (RFP) transgenic nude mouse was obtained by crossing non-transgenic nude mice with the transgenic C57/B6 mouse in which the beta-actin promoter drives RFP (DsRed2) expression in essentially all tissues. In the RFP nude mouse, the organs all brightly expressed RFP, including the heart, lungs, spleen, pancreas, esophagus, stomach, liver, duodenum, 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 RFP. The bone marrow and spleen cells were also RFP positive. The cyan fluorescent protein (CFP) nude mouse was developed by crossing nontransgenic nude mice with the transgenic CK/ECFP mouse in which the β-actin promoter drives expression of CFP in almost all tissues. In the CFP nude mice, the pancreas and reproductive organs displayed the strongest fluorescence signals of all internal organs, which vary in intensity. The GFP, RFP, and CFP nude mice when transplanted with cancer cells of another color are powerful models for color-coded imaging of the tumor microenvironment (TME) at the cellular level.

  12. The effect of human tissue factor pathway inhibitor-2 on the growth and metastasis of fibrosarcoma tumors in athymic mice.

    PubMed

    Chand, Hitendra Singh; Du, Xin; Ma, Duan; Inzunza, Hector David; Kamei, Shintaro; Foster, Donald; Brodie, Steven; Kisiel, Walter

    2004-02-01

    Human tissue factor pathway inhibitor-2 (TFPI-2) is a matrix-associated Kunitz inhibitor that inhibits the plasmin- and trypsin-mediated activation of zymogen matrix metalloproteinases involved in tumor progression, invasion, and metastasis. To directly assess its role in tumor growth and metastasis in vivo, we stably transfected HT-1080 fibrosarcoma cells expressing either fully active wild-type human TFPI-2 (WT) or inactive R24Q TFPI-2 (QT) and examined their ability to form tumors and metastasize in athymic mice in comparison to mock-transfected cells (MT). MT and QT fibrosarcoma tumors grew 2 to 3 times larger than WT tumors. Tumor metastasis was confined to the lung and was observed in 75% of mice treated with either MT or QT cells, whereas only 42% of mice treated with WT cells developed lung metastases. Real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analyses of each tumor group revealed 3- to 6-fold lower levels of murine vascular endothelial growth factor gene expression in WT tumors in relation to either MT or QT tumors. Comparative tumor gene expression analysis revealed that several human genes implicated in oncogenesis, invasion, metastasis, apoptosis, and angiogenesis had significantly altered levels of expression in WT tumors. Our collective data demonstrate that secretion of inhibitory TFPI-2 by a highly metastatic tumor cell markedly inhibits its growth and metastasis in vivo by regulating pericellular extracellular matrix (ECM) remodeling and angiogenesis.

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

    SciTech Connect

    Han, Miaojun; Wang, Hailun; Zhang, Hua-Tang; Han, Zhaozhong

    2012-05-25

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

  14. The citrus flavonone hesperetin inhibits growth of aromatase-expressing MCF-7 tumor in ovariectomized athymic mice.

    PubMed

    Ye, Lan; Chan, Franky L; Chen, Shiuan; Leung, Lai K

    2012-10-01

    Aromatase is responsible for the rate-determining reaction in estrogen synthesis and is a prime target for treating estrogen-receptor-positive breast cancer. Previous in vitro study has demonstrated that apigenin (APG), naringenin (NGN) and hesperetin (HSP) are three of the most potent natural aromatase inhibitors. Because the enzyme inhibition could potentially block breast cancer development, we employed an established postmenopausal breast cancer model to examine the chemopreventive effect of these flavonoids in vivo. Athymic mice were ovariectomized and transplanted with aromatase-overexpressing MCF-7 cells. Dietary administration of HSP at 1000 ppm and 5000 ppm significantly deterred the xenograft growth, while a null effect was observed in mice treated with APG or NGN. Further study illustrated that plasma estrogen in HSP-treated mice was reduced. Messenger RNA expression of the estrogen-responsive gene pS2 was also decreased in the tumors of mice treated with 1000 and 5000 ppm HSP. On the other hand, western analysis indicated that cyclin D1, CDK4 and Bcl-x(L) were reduced in the tumors. This study suggested that HSP could be a potential chemopreventive agent against breast carcinogenesis through aromatase inhibition.

  15. Wound healing on athymic mice with engineered skin substitutes fabricated with keratinocytes harvested from an automated bioreactor.

    PubMed

    Kalyanaraman, Balaji; Boyce, Steven T

    2009-04-01

    The Kerator is a computer controlled bioreactor for the automated culture and harvest of keratinocytes that can reduce labor and materials involved in the fabrication of engineered skin substitutes (ESS). Previous studies have shown that the Kerator is comparable to tissue culture flasks by keratinocyte confluence during culture, clonogenic potential of harvested keratinocytes and microanatomy, cell viability, and surface hydration of ESS fabricated with the harvested keratinocytes. In this study, the Kerator and tissue culture flasks were further compared by keratinocyte proliferation in vitro and wound healing after transplantation of ESS to athymic mice. The number of bromodeoxyuridine-positive keratinocytes in ESS fabricated with keratinocytes harvested from Kerator after 2 wk of in vitro maturation was 34 +/- 3 per high power field (hpf) (mean +/- SEM), which was not significantly different from that fabricated with keratinocytes harvested from flasks (34 +/- 1.5 per hpf). Percentage original wound area 6 wk after surgery of ESS fabricated with keratinocytes from the Kerator was 36% +/- 3.3%, which was not significantly different from that of ESS fabricated with keratinocytes from flasks (30% +/- 4.3%). In both cases, 78% (7 of 9) mice transplanted were positive for engraftment of human keratinocytes by direct immunofluorescence for HLA-ABC antigens. These results further confirm that the ESS fabricated with keratinocytes harvested from Kerator and flasks are equivalent in vitro and in vivo. Therefore, use of Kerator for large scale production of ESS can lead to increased availability at reduced cost while maintaining ESS quality for grafting.

  16. Molecular evidence for a thymus-independent partial T cell development in a FOXN1-/- athymic human fetus.

    PubMed

    Fusco, Anna; Panico, Luigi; Gorrese, Marisa; Bianchino, Gabriella; Barone, Maria V; Grieco, Vitina; Vitiello, Laura; D'Assante, Roberta; Romano, Rosa; Palamaro, Loredana; Scalia, Giulia; Vecchio, Luigi Del; Pignata, Claudio

    2013-01-01

    The thymus is the primary organ able to support T cell ontogeny, abrogated in FOXN1(-/-) human athymia. Although evidence indicates that in animal models T lymphocytes may differentiate at extrathymic sites, whether this process is really thymus-independent has still to be clarified. In an athymic FOXN1(-/-) fetus, in which we previously described a total blockage of CD4(+) and partial blockage of CD8(+) cell development, we investigated whether intestine could play a role as extrathymic site of T-lymphopoiesis in humans. We document the presence of few extrathymically developed T lymphocytes and the presence in the intestine of CD3(+) and CD8(+), but not of CD4(+) cells, a few of them exhibiting a CD45RA(+) naïve phenotype. The expression of CD3εεpTα, RAG1 and RAG2 transcripts in the intestine and TCR gene rearrangement was also documented, thus indicating that in humans the partial T cell ontogeny occurring at extrathymic sites is a thymus- and FOXN1-independent process.

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

    PubMed

    Han, Miaojun; Wang, Hailun; Zhang, Hua-Tang; Han, Zhaozhong

    2012-05-25

    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. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Near-Infrared Fluorescence Imaging of Carbonic Anhydrase IX in Athymic Mice Bearing HT-29 Tumor Xenografts

    PubMed Central

    2016-01-01

    Near-infrared fluorescence (NIRF) imaging technology is a highly sensitive imaging modality and has been widely used in noninvasively studying the status of receptor expression in small animal models, with an appropriate NIRF probe targeting a specific receptor. In this report, Cy5.5-conjugated anti-CAIX monoclonal antibody (Mab-Cy5.5) was evaluated in athymic mice bearing HT-29 tumor xenografts in order to investigate the effect of conjugate on tumor targeting efficacy. In vitro binding studies showed that Mab-Cy5.5 could specifically bind to the cells which expressed CAIX. Results from in vivo imaging showed that HT-29 tumor xenografts can be clearly visualized at 48 h after injection of Mab-Cy5.5, and in the blocking experiment, free anti-CAIX antibody effectively blocked the concentration of Mab-Cy5.5 in the tumors. Western blotting and immunohistochemistry analysis of HT-29 tumor xenografts verified the expression of CAIX in HT-29 tumors. Mab-Cy5.5 could specifically bind to the tumors which expressed CAIX. These results suggested that Mab-Cy5.5 was suitable for CAIX expression imaging in the preclinical research. PMID:27652266

  19. The naked truth: the face and body sensitive N170 response is enhanced for nude bodies.

    PubMed

    Hietanen, Jari K; Nummenmaa, Lauri

    2011-01-01

    Recent event-related potential studies have shown that the occipitotemporal N170 component--best known for its sensitivity to faces--is also sensitive to perception of human bodies. Considering that in the timescale of evolution clothing is a relatively new invention that hides the bodily features relevant for sexual selection and arousal, we investigated whether the early N170 brain response would be enhanced to nude over clothed bodies. In two experiments, we measured N170 responses to nude bodies, bodies wearing swimsuits, clothed bodies, faces, and control stimuli (cars). We found that the N170 amplitude was larger to opposite and same-sex nude vs. clothed bodies. Moreover, the N170 amplitude increased linearly as the amount of clothing decreased from full clothing via swimsuits to nude bodies. Strikingly, the N170 response to nude bodies was even greater than that to faces, and the N170 amplitude to bodies was independent of whether the face of the bodies was visible or not. All human stimuli evoked greater N170 responses than did the control stimulus. Autonomic measurements and self-evaluations showed that nude bodies were affectively more arousing compared to the other stimulus categories. We conclude that the early visual processing of human bodies is sensitive to the visibility of the sex-related features of human bodies and that the visual processing of other people's nude bodies is enhanced in the brain. This enhancement is likely to reflect affective arousal elicited by nude bodies. Such facilitated visual processing of other people's nude bodies is possibly beneficial in identifying potential mating partners and competitors, and for triggering sexual behavior.

  20. Lethal graft-versus-host disease in nude mice. I. Establishment of model systems

    SciTech Connect

    Kuribayashi, K.; Masuda, T.; Hanaoka, M.

    1988-08-01

    We examined whether nude mice, which are deficient in T cell function, could be used as a model for induction of lethal graft-versus-host disease. Nude mice injected with MHC-disparate spleen cells exhibited only transient GVH reaction such as splenomegaly. Inoculation of B6 spleen cells into BALB/c nude mice produced high titers of alloantibodies to the donor cells. These alloantibodies eliminated host-MHC-reactive donor T cells from the host. After abolition by 400 rads irradiation of the capacity of nude mice to produce antibody, lethal GVHD could be induced by allogeneic spleen cell transfer and was mediated by donor T cells. This lethal GVHD was prevented by prior administration of antidonor alloantibody to the irradiated recipients at least 24 hr before donor-cell grafting. The role of alloantibody was substantiated in 2 other combinations in which little or no alloantibodies to donor spleen cells were produced. Engraftment of either MHC-identical but non-MHC disparate donor spleen cells into BALB/c nude mice or of parental spleen cells into F1 nude mice resulted in death mediated by T cells. In addition, irradiated BALB/c nude mice inoculated with non-MHC-incompatible B10.D2 spleen cells were much more sensitive to alloaggression by the donor cells than were nonirradiated hosts, indicating the presence of some radiation-sensitive component(s) acting in nude mice against GVHD induction by donor T cells. Thus the nude mouse is considered to be a useful recipient for clarifying the basic mechanisms involved in lethal GVHD.

  1. [Preliminary establishment of transplanted human chronic myeloid leukemia model in nude mice].

    PubMed

    Li, Xian-Min; Ding, Xin; Zhang, Long-Zhen; Cen, Jian-Nong; Chen, Zi-Xing

    2011-12-01

    Chronic myeloid leukemia (CML) is a malignant clonal disease derived from hematopoietic stem cells. CML stem cells were thought to be the root which could lead disease development and ultimately rapid change. However, a stable animal model for studying the characteristics of CML stem cells is currently lacking. This study was aimed to establish a transplanted human CML nude-mice model to further explore the biological behavior of CML stem cells in vivo, and to enrich CML stem cells in nude mice by series transplantation. The 4 - 6 weeks old BALB/c nude mice pretreated by splenectomy (S), cytoxan intraperitoneal injection (C) and sublethal irradiation (I) were transplanted intravenously with (5 - 7) × 10(7) of bone marrow mononuclear cells from CML patients in chronic phase. Alternatively, 4 - 6 weeks old BALB/c nude mice pretreated by lethal irradiation were transplanted intravenously with 5 × 10(6) homologous bone marrow cells of BALB/c nude mice together with (5 - 7) × 10(7) of bone marrow mononuclear cells from CML patients in chronic phase simultaneously. The leukemic cells engrafted and infiltrated in organs and bone marrow of the mice were tracked by reverse transcription-polymerase chain reaction (RT-PCR), plastic-embedded biopsy and flow cytometry. The results of these two methods were compared. The results showed that human CML cells engrafted and infiltrating into the bone marrow of two nude mice pretreated with SCI could be detected. In spite of the low successful rate, results suggested the feasibility of this method by using BALB/c nude mice as a human CML animal model. In contrast, in nude mice pretreated by the lethal dose irradiation, CML cells in the bone marrow could not be found. It is concluded that human bone marrow CML cells can results in leukemia in nude mice pretreated by SCI. Thus this study provides a new strategy for establishment of CML animal models which deserves further elaboration.

  2. The Naked Truth: The Face and Body Sensitive N170 Response Is Enhanced for Nude Bodies

    PubMed Central

    Hietanen, Jari K.; Nummenmaa, Lauri

    2011-01-01

    Recent event-related potential studies have shown that the occipitotemporal N170 component - best known for its sensitivity to faces - is also sensitive to perception of human bodies. Considering that in the timescale of evolution clothing is a relatively new invention that hides the bodily features relevant for sexual selection and arousal, we investigated whether the early N170 brain response would be enhanced to nude over clothed bodies. In two experiments, we measured N170 responses to nude bodies, bodies wearing swimsuits, clothed bodies, faces, and control stimuli (cars). We found that the N170 amplitude was larger to opposite and same-sex nude vs. clothed bodies. Moreover, the N170 amplitude increased linearly as the amount of clothing decreased from full clothing via swimsuits to nude bodies. Strikingly, the N170 response to nude bodies was even greater than that to faces, and the N170 amplitude to bodies was independent of whether the face of the bodies was visible or not. All human stimuli evoked greater N170 responses than did the control stimulus. Autonomic measurements and self-evaluations showed that nude bodies were affectively more arousing compared to the other stimulus categories. We conclude that the early visual processing of human bodies is sensitive to the visibility of the sex-related features of human bodies and that the visual processing of other people's nude bodies is enhanced in the brain. This enhancement is likely to reflect affective arousal elicited by nude bodies. Such facilitated visual processing of other people's nude bodies is possibly beneficial in identifying potential mating partners and competitors, and for triggering sexual behavior. PMID:22110574

  3. Busulphan is active against neuroblastoma and medulloblastoma xenografts in athymic mice at clinically achievable plasma drug concentrations

    PubMed Central

    Boland, I; Vassal, G; Morizet, J; Terrier-Lacombe, M-J; Valteau-Couanet, D; Kalifa, C; Hartmann, O; Gouyette, A

    1999-01-01

    High-dose busulphan-containing chemotherapy regimens have shown high response rates in children with relapsed or refractory neuroblastoma, Ewing's sarcoma and medulloblastoma. However, the anti-tumour activity of busulfan as a single agent remains to be defined, and this was evaluated in athymic mice bearing advanced stage subcutaneous paediatric solid tumour xenografts. Because busulphan is highly insoluble in water, the use of several vehicles for enteral and parenteral administration was first investigated in terms of pharmacokinetics and toxicity. The highest bioavailability was obtained with busulphan in DMSO administered i.p. When busulphan was suspended in carboxymethylcellulose and given orally or i.p., the bioavailability was poor. Then, in the therapeutic experiments, busulphan in DMSO was administered i.p. on days 0 and 4. At the maximum tolerated total dose (50 mg kg−1), busulphan induced a significant tumour growth delay, ranging from 12 to 34 days in the three neuroblastomas evaluated and in one out of three medulloblastomas. At a dose level above the maximum tolerated dose, busulphan induced complete and partial tumour regressions. Busulphan was inactive in a peripheral primitive neuroectodermal tumour (PNET) xenograft. When busulphan pharmacokinetics in mice and humans were considered, the estimated systemic exposure at the therapeutically active dose in mice (113 μg h ml−1) was close to the mean total systemic exposure in children receiving high-dose busulphan (102.4 μg h ml−1). In conclusion, busulphan displayed a significant anti-tumour activity in neuroblastoma and medulloblastoma xenografts at plasma drug concentrations which can be achieved clinically in children receiving high-dose busulphan-containing regimens. 1999 Cancer Research Campaign PMID:10070870

  4. Flaxseed cotyledon fraction reduces tumour growth and sensitises tamoxifen treatment of human breast cancer xenograft (MCF-7) in athymic mice.

    PubMed

    Chen, Jianmin; Saggar, Jasdeep K; Corey, Paul; Thompson, Lilian U

    2011-02-01

    Dietary flaxseed (FS) inhibited the growth of human breast tumours and enhanced the effectiveness of tamoxifen (TAM) in athymic mice with low oestradiol (E2) levels. The present study determined whether the n-3 fatty acid-rich cotyledon fraction of FS (FC), alone or in combination with TAM, has a similar effect and thus can substitute for FS. In a 2 × 2 factorial design, ovariectomised mice with established oestrogen receptor (ER)-positive breast tumours (MCF-7) were treated as follows: groups 1 and 2 were fed the basal diet (BD, control) and FC diet (82 g FC/kg), respectively. Groups 3 and 4 with TAM implants (5 mg) were fed the BD and FC diet, respectively. At 8 weeks post-treatment, mice were euthanised, and tumours were analysed by immunohistochemistry and real-time PCR. BD, FC and FC/TAM groups significantly decreased tumour area, but the TAM group did not. Tumour regression in the FC/TAM group was greater compared to the TAM group. FC lowered cell proliferation but had no effect on apoptosis; the opposite was observed with TAM. FC suppressed mRNA expressions of pS2 and insulin-like growth factor 1 receptor (IGF-1R) and protein expressions of ERα, phosphospecific ERα, human epidermal growth factor receptor 2 (HER2), phosphospecific HER2 (pHER2) and amplified in breast 1 (AIB1), while TAM up-regulated mRNA expressions of Bcl2, progesterone receptor and IGF-1R and protein expression of pHER2, and down-regulated ERβ mRNA. FC modulated the effect of TAM on tumour growth biomarkers. In conclusion, FC reduced the growth of ER+ human breast tumours at low circulating E2, alone and combined with TAM, in part through modulation of ER- and growth factor-mediated signalling pathways; it may substitute for FS in increasing the effectiveness of TAM.

  5. Transplantation of acellular dermis and keratinocytes cultured on porous biodegradable microcarriers into full-thickness skin injuries on athymic rats.

    PubMed

    Seland, Håvard; Gustafson, Carl-Johan; Johnson, Hans; Junker, Johan P E; Kratz, Gunnar

    2011-02-01

    In search of an optimal transplantation regime for sufficient dermal and epidermal regeneration after a full-thickness skin injury, wounds on athymic rats were grafted with split-thickness skin grafts or acellular human dermis followed by transplantation with human keratinocytes either in single-cell suspension or cultured on porous biodegradable microcarriers. After 2 weeks, all wounds grafted with acellular human dermis showed a well organised and vascularised dermal component and reepithelialisation on the grafted dermal matrix was complete 21 days after transplantation with human keratinocytes. Wounds grafted with human keratinocytes seeded on biodegradable microcarriers or split-thickness skin grafts displayed over time (i.e. 16-21 days post-transplantation) a significantly thicker epithelial cell layer in comparison to wounds grafted with keratinocytes in single-cell suspensions or microcarriers not seeded with cells. Furthermore, measurements of dermal thickness in the closed wounds 21 days after grafting showed a significantly thicker and well organised neodermal component in wounds transplanted with keratinocytes seeded on microcarriers or split-thickness skin grafts compared to all other wounds. Positive immunostaining towards von Willebrand factor revealed the plausible proangiogenic effects of transplantation with keratinocytes seeded on microcarriers. Analysis of representative tissue sections after fluorescence in situ hybridisation visualised that grafted human keratinocytes were present in the epidermal layers covering the wounds 16 and 21 days after transplantation, strongly indicating preservation of cell viability. These results shows that the use of biodegradable microcarriers in the culture of autologous keratinocytes for treatment of full-thickness wounds not only facilitate the cultivation, transportation and transplantation processes but also enhances the dermal regeneration induced by a dermal scaffold which results in a clinical result

  6. Lymphoscintigraphy of human colorectal carcinoma metastases in athymic mice by use of radioiodinated B72. 3 monoclonal antibody

    SciTech Connect

    Shah, S.A.; Gallagher, B.M.; Sands, H.

    1987-06-01

    The potential of radioiodinated monoclonal antibody B72.3 for lymphoscintigraphy was evaluated, using suitable animal models of a human colorectal carcinoma. LS174T xenografts were grown at various sites in beta-estradiol-pretreated athymic mice, and the development of metastases in different organs was assessed histologically. After iv inoculation of the mice, 66% of the animals developed ''metastases'' to the axillary lymph nodes. Of these mice, 100% also developed multiple tumors on their backs and 79% had lung micrometastases. Livers, kidneys, and spleens showed no evidence of tumor growth. In 33% of the mice in which primary LS174T tumors had been removed from the hindfoot pad, metastases to the popliteal lymph nodes were observed 3 1/2 weeks after tumor implantation. BALB/c (nu/nu) female mice bearing axillary and popliteal lymph node metastases were used to test the potential of radiolabeled B72.3 antibody (an IgG1) as a lymphoscintigraphic agent. A monoclonal antibody against horseradish peroxidase (also an IgG1), which did not bind LS174T tumor cells in vitro, served as a control. Both normal and tumor-bearing axillary and popliteal lymph nodes imaged up to 6 hours after the sc injection of 20-40 mu Ci of /sup 125/I-labeled B72.3 into either the forefoot or hindfoot pads. The localization index (L.I.) (specific/nonspecific antibody in tumor divided by specific/nonspecific antibody in blood) for LS174T tumors in lymph nodes was approximately 1 during the first 6 hours after antibody injection, thus indicating no specific antibody accumulation.

  7. Resveratrol Is Rapidly Metabolized in Athymic (Nu/Nu) Mice and Does Not Inhibit Human Melanoma Xenograft Tumor Growth1

    PubMed Central

    Niles, Richard M.; Cook, Carla P.; Meadows, Gary G.; Fu, Ya-Min; McLaughlin, Jerry L.; Rankin, Gary O.

    2006-01-01

    Resveratrol has been shown to have anticarcinogenic activity. We previously found that resveratrol inhibited growth and induced apoptosis in 2 human melanoma cell lines. In this study we determined whether resveratrol would inhibit human melanoma xenograft growth. Athymic mice received control diets or diets containing 110 μmol/L or 263 μmol/L resveratrol, 2 wk prior to subcutaneous injection of the tumor cells. Tumor growth was measured during a 3-wk period. Metabolism of resveratrol was assayed by bolus gavage of 75 mg/kg resveratrol in tumor-bearing and nontumor-bearing mice. Pellets containing 10–100 mg resveratrol were implanted into the mice, next to newly palpated tumors, and tumor growth determined. We also determined the effect of a major resveratrol metabolite, piceatannol, on experimental lung metastasis. Resveratrol, at any concentration tested, did not have a statistically significant effect on tumor growth. The higher levels of resveratrol tested (0.006% in food or 100 mg in slow-release pellets) tended to stimulate tumor growth (P = 0.08–0.09). Resveratrol and its major metabolites, resveratrol glucuronide and piceatannol, were found in serum, liver, skin, and tumor tissue. Piceatannol did not affect the in vitro growth of a murine melanoma cell line, but significantly stimulated the number of lung metastases when these melanoma cells were directly injected into the tail vein of the mouse. These results suggest that resveratrol is not likely to be useful in the treatment of melanoma and that the effects of phytochemicals on cell cultures may not translate to the whole animal system. PMID:16988123

  8. Meta-[{sup 211}At]astatobenzylguanidine (MABG): In vivo evaluation in an athymic mouse human neuroblastoma xenograft model

    SciTech Connect

    Vaidyanathan, G.; Friedman, H.S.; Keir, S.T.

    1996-05-01

    Because of the short range and high linear energy transfer of {sup 211}At {alpha}-particles, the MIBG analogue MABG might be useful for the therapy of micrometastatic neuroblastoma and previous in vitro studies have demonstrated that under single-cell conditions, the cytotoxicity of MABG is > 1000 times higher than [{sup 131}I]MIBG. A paired label protocol was used to compare the tissue distribution of MABG and [{sup 131}I]MIBG in athymic mice bearing subcutaneous SK-N-SH human neuroblastoma xenografts from 1-24 hr after injection. In tumor, significantly higher (p < 0.05) uptake was observed for MABG (3.8 {plus_minus} 0.8%ID/g vs 3.1 {plus_minus} 0.7%ID/g at 8 hr). Pretreatment with desipramine reduced tumor uptake of MABG by 43%, suggesting that accumulation was related to the uptake-1 mechanism. Significantly higher uptake of MABG also was observed in normal tissue targets. For example, at 8 hr, heart uptake of MABG was 6.0 {plus_minus} 0.9 % ID/g compared with 4.5 {plus_minus} 0.8%ID/g for [{sup 131}I]MIBG. Two strategies were investigated to increase the tumor-to-hear uptake ratio. Pretreatment of mice with unlabeled MIBG (4 mg/kg) increased MABG tumor uptake by 1.5-fold while reducing uptake in several normal tissues including heart. The vesicular uptake blocker tetrabenazine (TBZ; 20 mg/kg), reduced MABG hear uptake by 30% of control values with not significant decrease in tumor levels. We conclude that MABG deserves further evaluation as a potential agent for the treatment of neuroblastoma, particularly in combination with strategies to minimize radiation dose to normal target tissues.

  9. Radiopharmacokinetic and dosimetric parameters of 188Re-lanreotide in athymic mice with induced human cancer tumors.

    PubMed

    Molina-Trinidad, Eva M; de Murphy, Consuelo Arteaga; Ferro-Flores, Guillermina; Murphy-Stack, Eduardo; Jung-Cook, Helgi

    2006-03-09

    Radiolabeled peptides, like the somatostatin analogs, have been used for peptide receptor-mediated radionuclide therapy (PRMRT) in metastatic neuroendocrine tumors. The eight amino acid peptide 3-(2-naphthalenyl)-D-alanyl-L-cysteinyl-L-tyrosyl-D-tryptophyl-L-lysyl-L-valyl-L-cysteinyl-L-threoninamide,cyclic(2-->7)-disulfide (9Cl) (lanreotide) was found to bind to the five somatostatin tumor receptors. Lanreotide has been labeled via the bifunctional chelating agent, DOTA, to (111)In, and (90)Y. A direct labeling method was used to label lanreotide with (188)Re. Athymic mice with implanted human cancer tumors (uterine-cervix, renal, and neuroblastoma) were injected with radiochemically pure (188)Re-lanreotide (1.11 MBq). The percent injected activity (%IA/g) from serial blood samples was the input data for the WinNonlin computer program to obtain radiopharmacokinetic parameters. The organs' percent injected activity per gram of tissue (%IA/g) was extrapolated to the weights of a 70 kg male model organs and the number of nuclear transitions (N) were the input for the OLINDA/EXM program to obtain dosimetry estimates. Induced uterine-cervix tumors (HeLa cells) show a mean 2.4 %IA/g uptake up to 24 h and the tumor/blood ratio was over 1.85 (1.5-24 h post-injection) confirming (188)Re-lanreotide remains bound to the tumor. The estimated tumor absorbed dose was 460 mGy/MBq. Human effective dose was 0.0182 mSv/MBq. Therefore, (188)Re-lanreotide is a good candidate for PRMRT and a clinical trial is being planned in order to acquire individual dosimetric data.

  10. The Nude Mouse as Model for Liver Deficiency Study and Treatment and Xenotransplantation

    PubMed Central

    Vidal, Isabelle; Richert, Lysiane

    2012-01-01

    We aimed at reviewing the various uses of Nude mouse for the development of liver deficiency models and evaluation of efficacy of hepatic cell xenotransplantation. The first part records the large range of liver deficiency models that can be developed in Nude mice: surgical partial hepatectomy, acute toxic liver deficiency, chronic cirrhosis, and transgenic liver injury. The second part tackles the outcome of rat hepatocyte as well as human cell transplantation, both mature hepatocyte and hepatic progenitor, into Nude mouse submitted to liver injury. Results are discussed and compared to other available immunodeficient mouse models. The issue of humanized liver creation is also addressed. Altogether, these results show that Nude mouse appears to be a suitable small animal model to expand our insight into liver cell engraftment and regeneration. PMID:23193481

  11. Role of the thymus in streptococcal cell wall-induced arthritis and hepatic granuloma formation. Comparative studies of pathology and cell wall distribution in athymic and euthymic rats.

    PubMed Central

    Allen, J B; Malone, D G; Wahl, S M; Calandra, G B; Wilder, R L

    1985-01-01

    Systemic administration of an aqueous suspension of group A streptococcal cell wall fragments to susceptible rats induces acute and chronic polyarthritis, as well as noncaseating hepatic granulomas. To gain insight into the role of the thymus in the pathogenesis of this experimental model, pathologic responses and cell wall tissue distribution were compared in congenitally athymic rats (rnu/rnu) and their euthymic littermates (NIH/rnu). Within 24 h, both rat strains developed acute arthritis, characterized by polymorphonuclear leukocytic exudate in the synovium and joint spaces. This acute process was maximal at day 3 and gradually subsided. Beginning 2-3 wk after injection, the euthymic, but not the athymic, rats developed the typical exacerbation of arthritis, characterized by synovial cell hyperplasia with villus formation and T helper/inducer lymphocyte-rich mononuclear cell infiltration. This process eventually resulted in marginal erosions and destruction of periarticular bone and cartilage. Parallel development of acute and chronic hepatic lesions was observed. Bacterial cell wall antigen distribution and persistence were similar in the athymic and euthymic rats. Cell wall antigens were demonstrated in the cytoplasm of cells within subchondral bone marrow, synovium, liver, and spleen, coincident with the development of the acute lesions, and persisted in these sites, although in decreasing amounts, for the duration of the experiment. Our findings provide evidence that the acute and chronic phases of the experimental model are mechanistically distinct. The thymus and functional thymus derived-lymphocytes appear not to be required for the development of the acute exudative disease but are essential for the development of chronic proliferative and erosive disease. Induction of disease is dependent upon cell wall dissemination to and persistence in the affected tissues. Images PMID:3876354

  12. Preferential radiation sensitization of prostate cancer in nude mice by nutraceutical antioxidant gamma-tocotrienol.

    PubMed

    Kumar, K Sree; Raghavan, Mythili; Hieber, Kevin; Ege, Christine; Mog, Steven; Parra, Nannette; Hildabrand, Annette; Singh, Vijay; Srinivasan, V; Toles, Raymond; Karikari, Patience; Petrovics, Gyorgy; Seed, Thomas; Srivastava, Shiv; Papas, Andreas

    2006-03-27

    Gamma-tocotrienol (GT) is a member of the vitamin E family. Our preliminary studies indicated that it protected mice from lethal irradiation, so we hypothesized that GT might be a radiation sensitizing agent for tumors. To test this, we induced prostate tumors by injecting PC3 cells into nude BALB/c mice. When the tumors were about 5 mm in diameter, mice were injected subcutaneously with 400 mg/kg gamma-tocotrienol and irradiated 24 h later at the site of the tumor with a dose of 12 Gy (60)Cobalt. Tumor size was monitored for 24 days after radiation. Tumor tissues as well as normal tissues like rectum, kidney, and liver were monitored for lipid peroxidation on day 4 and day 24 after radiation. The results indicated that the size of the tumors was reduced by almost 40%, but only in GT-treated and irradiated mice. In unstimulated and Fe-stimulated lipid peroxidation groups, lipid peroxidation in the tumors from irradiated mice increased to 135% and 150%, respectively, four days after irradiation and 33% and 66% in the same groups, respectively, 24 days after irradiation. In general, lipid peroxidation in the rectum did not increase in GT-treated and irradiated mice, although there was a slight increase in Fe-stimulated lipid peroxidation (29%) four days after irradiation. Unexpectedly, the kidneys were as equally sensitized to lipid peroxidation as the tumors. Liver tissue was protected in the short-term from radiation-induced lipid peroxidation. These studies indicate that the radiotherapy efficacy of prostate cancer can be increased with GT and a pro-oxidant if the kidneys can be shielded.

  13. Characterization of V beta-bearing cells in athymic (nu/nu) mice suggests an extrathymic pathway for T cell differentiation.

    PubMed

    Rocha, B

    1990-04-01

    In the present article, the expression of the T cell receptor (TcR) beta chain and other T cell molecules was evaluated in surface immunoglobulin-negative spleen cell populations of young and old BALB/c and C57BL/6 nude mice, using a panel of monoclonal antibodies. The results obtained show that in young nude mice, most Thy-1high cells do not express other T cell markers. These mice have, however, a sizable population of Thy-1low cells with the same phenotype of alpha/beta+, CD4-CD8- thymocytes or MRL/lpr peripheral T cells, expressing predominantly genes of the V beta 8 family. The evolution of alpha/beta+ cells in aging nudes is strongly suggestive of an extrathymic pathway of differentiation of these cells since (a) the acquisition of high density TcR and CD3, as well as Thy-1 or CD4CD8 antigens at the cell surface of nude V beta+ T cells is not simultaneous; (b) alpha/beta+ cells in nude mice co-express other T cell markers at random and, even in old mice, they never completely resemble to the predominant high Thy-1+ CD3+ TcR alpha/beta+, CD4+CD8+ cells of euthymic controls; and (c) BALB/c nude T cells express V beta 11 genes, that are deleted in euthymic BALB/c mice. This latter finding may also indicate differences in the mechanisms of selection of T cells specificities in the thymus vs. the peripheral pools.

  14. An athymic rat model of cutaneous radiation injury designed to study human tissue-based wound therapy

    PubMed Central

    2012-01-01

    Purpose To describe a pilot study for a novel preclinical model used to test human tissue-based therapies in the setting of cutaneous radiation injury. Methods A protocol was designed to irradiate the skin of athymic rats while sparing the body and internal organs by utilizing a non-occlusive skin clamp along with an x-ray image guided stereotactic irradiator. Each rat was irradiated both on the right and the left flank with a circular field at a 20 cm source-to-surface distance (SSD). Single fractions of 30.4 Gy, 41.5 Gy, 52.6 Gy, 65.5 Gy, and 76.5 Gy were applied in a dose-finding trial. Eight additional wounds were created using the 41.5 Gy dose level. Each wound was photographed and the percentage of the irradiated area ulcerated at given time points was analyzed using ImageJ software. Results No systemic or lethal sequelae occurred in any animals, and all irradiated skin areas in the multi-dose trial underwent ulceration. Greater than 60% of skin within each irradiated zone underwent ulceration within ten days, with peak ulceration ranging from 62.1% to 79.8%. Peak ulceration showed a weak correlation with radiation dose (r = 0.664). Mean ulceration rate over the study period is more closely correlated to dose (r = 0.753). With the highest dose excluded due to contraction-related distortions, correlation between dose and average ulceration showed a stronger relationship (r = 0.895). Eight additional wounds created using 41.5 Gy all reached peak ulceration above 50%, with all healing significantly but incompletely by the 65-day endpoint. Conclusions We developed a functional preclinical model which is currently used to evaluate human tissue-based therapies in the setting of cutaneous radiation injury. Similar models may be widely applicable and useful the development of novel therapies which may improve radiotherapy management over a broad clinical spectrum. PMID:22568958

  15. An athymic rat model of cutaneous radiation injury designed to study human tissue-based wound therapy.

    PubMed

    Rifkin, Lucas H; Stojadinovic, Strahinja; Stewart, Collin H; Song, Kwang H; Maxted, Michael C; Bell, Marcus H; Kashefi, Natalie S; Speiser, Michael P; Saint-Cyr, Michel; Story, Michael D; Rohrich, Rod J; Brown, Spencer A; Solberg, Timothy D

    2012-05-08

    To describe a pilot study for a novel preclinical model used to test human tissue-based therapies in the setting of cutaneous radiation injury. A protocol was designed to irradiate the skin of athymic rats while sparing the body and internal organs by utilizing a non-occlusive skin clamp along with an x-ray image guided stereotactic irradiator. Each rat was irradiated both on the right and the left flank with a circular field at a 20 cm source-to-surface distance (SSD). Single fractions of 30.4 Gy, 41.5 Gy, 52.6 Gy, 65.5 Gy, and 76.5 Gy were applied in a dose-finding trial. Eight additional wounds were created using the 41.5 Gy dose level. Each wound was photographed and the percentage of the irradiated area ulcerated at given time points was analyzed using ImageJ software. No systemic or lethal sequelae occurred in any animals, and all irradiated skin areas in the multi-dose trial underwent ulceration. Greater than 60% of skin within each irradiated zone underwent ulceration within ten days, with peak ulceration ranging from 62.1% to 79.8%. Peak ulceration showed a weak correlation with radiation dose (r = 0.664). Mean ulceration rate over the study period is more closely correlated to dose (r = 0.753). With the highest dose excluded due to contraction-related distortions, correlation between dose and average ulceration showed a stronger relationship (r = 0.895). Eight additional wounds created using 41.5 Gy all reached peak ulceration above 50%, with all healing significantly but incompletely by the 65-day endpoint. We developed a functional preclinical model which is currently used to evaluate human tissue-based therapies in the setting of cutaneous radiation injury. Similar models may be widely applicable and useful the development of novel therapies which may improve radiotherapy management over a broad clinical spectrum.

  16. Effects of homozygosity of the nude (rnu) gene in an inbred strain of rats: studies of lymphoid and non--lymphoid organs in different age groups of nude rats of LEW background at a stage in the gene transfer.

    PubMed

    Hougen, H P; Klausen, B

    1984-01-01

    Several age groups of nude homozygous rnu/rnu and heterozygous rnu/+ rats of the same genetic background at an early stage of back-crossing (LEW/Mol) were compared as to body and organ weights, histological appearance and cell density of lymphoid organs, haematological values and differential counts of bone marrow and peripheral blood. No thymic tissue was found in the nude animals. 7-week-old nudes were smaller than control animals and had relatively larger non-lymphoid organs and cell-depleted peripheral lymphoid organs. Other age groups showed little difference. Peripheral blood of nude rats showed no signs of lymphopaenia in contrast with the findings in nude mice. The number of thoracic duct lymphocytes was, however, significantly smaller in all age groups of the nude rats, and the bone marrow tended to contain fewer lymphocytes.

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

    PubMed

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

    2012-10-01

    This study was aimed to investigate the effects of baicalin on HL-60 cell xenografts in nude mice in vivo and explore its mechanism. Xenograft tumor model of HL-60 cells in nude mice was established, which was divided randomly into 6 groups: negative control group (injection of 5% NaHCO(3)), 25, 50 and 100 mg/kg baicalin groups, combination group (50 mg/kg baicalin + 2 mg/kg VP16) and positive control group (VP16 4 mg/kg). The nude mice with HL-60 cell xenografts were treated with drugs via intraperitoneal injection daily. After treatment for 14 days average weigh and inhibitory rate of transplanted tumor stripped from 5 nude mice in each group were calculated, and the ultrastructure change of xenografts cells were tested by transmission electron microscopy. Histopathologic examination was used to observed the change of main organs in nude mice. The expression of signaling molecular PI3K/Akt proteins extracted from xenografts was detected by Western blot. The effects of baicalin on overall survival time in nude mice with HL-60 cell xenografts were evaluated. The results showed that baicalin could inhibit the growth of transplanted tumors in dose-dependent manner. There were more necrotic and apoptotic cells in mice of baicalin-treated groups and combination group than that in mice of negative control group. Baicalin could inhibit the proliferation of HL-60 cells in vivo by down-regulating the PI3K/Akt/mTOR signal pathway, where the expressions of p-Akt, mTOR and p-mTOR proteins decreased compared with negative control group, and no significant difference of Akt expression was found between different groups. Compared with negative control group, the median survival time of mice in combination group was more prolongated (P < 0.05). It is concluded that baicalin can inhibit growth and induce apoptosis of HL-60 cell xenografts in nude mice, and prolong median survival time of nude mice. The possible mechanisms may be related to inhibition of Akt activity and down

  18. Five Stabilized 111In-labeled neurotensin analogs in nude mice bearing HT29 tumors.

    PubMed

    Janssen, Paul J J M; de Visser, Moniaue; Verwijnen, Suzanne M; Bernard, Bert F; Srinivasan, Ananth; Erion, Jack L; Breeman, Wouter A P; Vulto, Arnold G; Krenning, Eric P; de Jong, Marion

    2007-06-01

    Neurotensin (NT) receptors are overexpressed in different human tumors, such as human ductal pancreatic adenocarcinoma. New stable neurotensin analogs with high receptor affinity have been synthesized by replacing arginine residues with lysine and arginine derivatives. The aim of this study was to explore the biodistribution, tumor uptake, kidney localization, and stability characteristics of these new analogs in order to develop new diagnostic tools for exocrine pancreatic cancer. Four (111)In-labeled DTPA-chelated NT analogs and one (111)In-labeled DOTA-chelated NT analog were evaluated in NMRI nude mice bearing NT receptor-positive HT29 tumors. Experiments with a coinjection of unlabeled NT or lysine were performed to investigate receptor-mediated uptake and kidney protection, respectively. In addition, the in vivo serum stability of the most promising analog was analyzed. In the biodistribution study in mice, at 4 hours postinjection, a low percentage of the injected dose per gram (%ID/g) of tissue for all compounds was found in NT receptor-negative organs, such as the blood, spleen, pancreas, liver, muscle, and femur. A high uptake was found in the colon, intestine, kidneys, and in implanted HT29 tumors. The coinjection of excess unlabeled neurotensin significantly reduced tumor uptake, showing tumor uptake to be receptor-mediated. To a lesser extent, this was also observed for the colon, but not for other tissues. We concluded that DTPA-(Pip)Gly-Pro-(PipAm)Gly-Arg-Pro-Tyr-tBuGly-Leu-OH and the DOTA-linked counterpart have the most favorable biodistribution properties regarding tumor uptake.

  19. A high-resolution map of the chromosomal region surrounding the nude gene

    SciTech Connect

    Blackburn, C.C.; Griffith, J.; Morahan, G.

    1995-03-20

    The nude mutation produces the apparently disparate phenotypes of hairlessness and congenital thymic aplasia. These pleiotropic defects are the result of a single, autosomal recessive mutation that was previously mapped to a 9-cM region of murine chromosome 11 bounded by loci encoding the acetylcholine receptor P subunit and myeloperoxidase. In this study, exclusion mapping of a panel of congenic nude strains was used to place the nude locus between the microsatellite loci D11Nds1 and D11Mit8. The relative distance from nude to each of these loci was determined by analyzing a large segregating cross. Thus, nude lies 1.4 cM distal to D11Nds1 and is 0.5 cM proximal to D11Mit8. Mice that carried recombinational breakpoints between D11Nds1 and D11Mit8 were further analyzed at the loci Evi-2 and D11Mit34, which placed nu 0.2 cM proximal to these markers. D11Nds1 and Evi-2/D11Mit34 thus define the new proximal and distal boundaries, respectively, for the nu interval. We also report the typing of the above microsatellite markers in the AKXD, AKXL, BXD, CXB, and BXH recombinant inbred strains, which confirmed the relative order and separation of loci in this region. 47 refs., 3 figs., 1 tab.

  20. Induction of IgG in young nude mice by lipid A or thymus grafts

    PubMed Central

    1976-01-01

    Postnatal serum concentrations of IgG2a of paternal allotype, measured in congenitally thymusless nude mice, increase with kinetics and titers comparable to their normal congeneic counterparts. Lipid A, the mitogenic part of LPS, stimulates IgG synthesis in nude mice when it is given 7 days after birth. IgG concentrations at 15 days of age are 6- to 8-fold higher than in untreated control nudes; this is considerably lower, however, than in normal mice, which show up to 45-fold higher IgG2ab levels after lipid A treatment. A thymus graft from nearly congeneic donors of the same age, transplanted at 4 days after birth, also stimulates long-lasting IgG synthesis in the nude recipients. If the grafted nudes are injected with lipid A 3 days later, IgG synthesis is further stimulated 8- to 16-fold. The data are discussed in relation to the thymus dependency of IgG production and the conditions for lipid A stimulation. PMID:978133

  1. Induction of IgG in young nude mice by lipid A or thymus grafts.

    PubMed

    Kolb, C; Di Pauli, R; Weiler, E

    1976-10-01

    Postnatal serum concentrations of IgG2a of paternal allotype, measured in congenitally thymusless nude mice, increase with kinetics and titers comparable to their normal congeneic counterparts. Lipid A, the mitogenic part of LPS, stimulates IgG synthesis in nude mice when it is given 7 days after birth. IgG concentrations at 15 days of age are 6- to 8-fold higher than in untreated control nudes; this is considerably lower, however, than in normal mice, which show up to 45-fold higher IgG2ab levels after lipid A treatment. A thymus graft from nearly congeneic donors of the same age, transplanted at 4 days after birth, also stimulates long-lasting IgG synthesis in the nude recipients. If the grafted nudes are injected with lipid A 3 days later, IgG synthesis is further stimulated 8- to 16-fold. The data are discussed in relation to the thymus dependency of IgG production and the conditions for lipid A stimulation.

  2. Direct gaze of photographs of female nudes influences startle in men.

    PubMed

    Lass-Hennemann, Johanna; Schulz, André; Nees, Frauke; Blumenthal, Terry D; Schachinger, Hartmut

    2009-05-01

    Foreground presentation of photographs of opposite sex nudes lowers startle elicited by sudden acoustic stimuli. However, the impact of gaze direction of the presented nudes on this startle modulation has not been investigated. Theoretically, direct gaze of photographs of female nudes could either lead to a larger inhibition of the startle reaction due to a summating valence and arousal effect of direct eye contact, or lead to a smaller inhibition due to an attention capturing effect of the eyes. Two subsets of erotic photographs of female nudes (women looking directly at the observer vs. gazing away) and standard IAPS neutral pictures were viewed by 26 male volunteers, while startle eye blink responses to binaural bursts of white noise (50 ms, 105 dB) were recorded by EMG. Erotic pictures reduced startle eyeblink magnitude as compared to neutral pictures. Furthermore, erotic stimuli without direct gaze at the observer showed a greater startle eyeblink inhibition than erotic stimuli with direct gaze at the observer. Our data suggest that direct gaze of opposite sex nudes may direct attention to the face, thereby reducing the appetitive impact of an attractive body.

  3. Epidermal proliferation of nude mouse skin, pig skin, and pig skin grafts. Failure of nude mouse skin to respond to the tumor promoter 12- O-tetradecanoyl phorbol 13-acetate

    PubMed Central

    1980-01-01

    Human skin transplanted to nude mice offers a possible experimental system for the study of normal epidermal proliferation and differentiation, and for their pathological counterparts. Crucial to the development of such a system is the demonstration that such grafts retain the responsive features of donor skin. To document that donor proliferative characteristics are maintained in the grafts, a comparative analysis of agents that induce proliferation was made on skin of mice homozygous and heterozygous for nude, on pig skin, and on pig skin transplanted onto nude mice. A wave of epidermal proliferation could be induced in pig skin and pig skin grafted onto nude mice, but not in nude mouse skin after the topical application of 10 ng 12-O- tetradecanoyl phorbol 13-acetate (TPA). A 10-fold greater concentration of TPA or 5% croton oil induced proliferation in all species of epidermis studied. Mice, heterozygous for nude, showed a normal response to 10 ng TPA, suggesting that the ability to respond to TPA may be related, in part, to a recessive genetic trait. Nude mouse skin transplanted to a heterozygous littermate capable of responding to 10 ng TPA does not respond. These observations argue that: the graft retains its donor proliferative characteristics when transplanted to the nude, and the inability of the nude mouse to respond to lower doses of TPA may be related to absorption, the nude gene(s), or an inherent threshold to response. The lack of response to the promoter TPA provides a plausible explanation for the decreased incidence of tumors arising in nude mice during two-stage carcinogenesis experiments. PMID:7000965

  4. [Chemotherapy of yolk sac tumor heterotransplanted to nude mice (author's transl)].

    PubMed

    Sawada, M; Hayakawa, K; Matsui, Y; Nishiura, H; Okudaira, Y

    1980-10-01

    Chemotherapy of yolk sac tumor heterotransplanted to nude mice was studied. 1. Yolk sac tumor of the ovary taken from a 38-year -old woman was transplanted to BALB/c female nude mice. The transplantable tumor cells produce a solid tumor, designated as YST-1 tumor. The YST-1 tumor cells preserve the histological appearance of a human yolk sac tumor and produce x-fetoprotein. The tumors on passage 8 were used for experimental chemotherapy. 2. Anticancer drugs clinically known to be effective for ovarian cancer, such as Adriamycin, Carbazilquinone, 5-Fluorouracil, Cyclophosphamide, Mitomycin C, Chromomycin A3, Vinblastine and Bleomycin were administered intraperitoneally to tumor-bearing nude mice. Tumor size was measured two or three times a week during the course of experiments. Therapeutic effects were evaluated by tumor size and relative tumor size before and after experiments. Among these drugs, Vinblastine and Bleomycin combination showed the significant effect arresting the growth of YST-1 tumor.

  5. Complete suppression of in vivo growth of human leukemia cells by specific immunotoxins: nude mouse models

    SciTech Connect

    Hara, H.; Seon, B.K.

    1987-05-01

    In this study, immunotoxins containing monoclonal anti-human T-cell leukemia antibodies are shown to be capable of completely suppressing the tumor growth of human T-cell leukemia cells in vivo without any overt undersirable toxicity. These immunotoxins were prepared by conjugating ricin A chain (RA) with our monoclonal antibodies, SN1 and SN2, directed specifically to the human T-cell leukemia cell surface antigens TALLA and GP37, respectively. The authors have shown that these monoclonal antibodies are highly specific for human T-cell leukemia cells and do not react with various normal cells including normal T and B cells, thymocytes, and bone marrow cells. Ascitic and solid human T-cell leukemia cell tumors were generated in nude mice. The ascitic tumor was generated by transplanting Ichikawa cells (a human T-cell leukemia cell) i.p. into nude mice, whereas the solid tumor was generated by transplanting s.c. MOLT-4 cells (a human T-cell leukemia cell line) and x-irradiated human fibrosarcoma cells into x-irradiated nude mice. To investigate the efficacy of specific immunotoxins in suppression the in vivo growth of the ascitic tumor, they divided 40 nude mice that were injected with Ichikawa cells into four groups. None of the mice in group 4 that were treated with SN1-RA and SN2-RA showed any signs of a tumor or undesirable toxic effects for the 20 weeks that they were followed after the transplantation. Treatment with SN1-RA plus SN2-RA completely suppressed solid tumor growth in 4 of 10 nude mice carrying solid tumors and partially suppressed the tumor growth in the remaining 6 nude mice. These results strongly suggest that SN1-RA and SN2-RA may be useful for clinical treatment.

  6. Effect of steroidal and nonsteroidal antiestrogens on the growth of a tamoxifen-stimulated human endometrial carcinoma (EnCa101) in athymic mice.

    PubMed

    Gottardis, M M; Ricchio, M E; Satyaswaroop, P G; Jordan, V C

    1990-06-01

    Tamoxifen (TAM), a nonsteroidal antiestrogen, is used in the adjuvant treatment of breast cancer. Previous studies, however, have indicated that some human breast and endometrial tumors are stimulated to grow with TAM in the athymic mouse. One such TAM-stimulated tumor is the EnCa101 human endometrial adenocarcinoma. Our aim was to evaluate the ability of different doses of TAM or other nonsteroidal antiestrogens to stimulate the growth of EnCa101 tumors in athymic mice. Additionally we have evaluated less estrogenic antiestrogens (two steroidal antiestrogens, RU 39,411 and ICI 164,384, and two nonsteroidal antiestrogens, keoxifene and MER-25) for their ability to inhibit TAM-stimulated growth. All experiments were done in ovariectomized athymic mice transplanted in the axillary mammary fat with 1-mm3 pieces of EnCa101 tumor. Sustained release preparations (0.5-2.0-cm Silastic capsule or 5-mg TAM cholesterol pellet) of TAM caused similar tumor growth. The growth rate was not altered by an additional daily i.p. injection of 1 mg TAM in 0.1 ml peanut oil. A 3-mg TAM daily dose was toxic. Four weeks of treatment (100-micrograms s.c. injections, every other day) with nonsteroidal antiestrogens, trioxifene mesylate, enclomiphene, or nafoxidine stimulated tumor growth. However, keoxifene stimulated this tumor to a lesser degree than TAM and partially inhibited TAM-stimulated growth. ICI 164,384 showed no stimulatory activity (1-mg s.c. injections every other day) alone compared to controls but inhibited TAM-stimulated (0.25-cm Silastic capsule) growth. In a parallel experiment, RU 39,411 (1-mg s.c. injections every other day) stimulated EnCa101 to grow. In contrast when RU 39,411 was administered in a sustained release preparation (2.0-cm Silastic capsule) there was no stimulatory growth compared to controls. Additionally RU 39,411 inhibited TAM-stimulated growth, but the low-potency antiestrogen, MER-25, was less effective in this regard. These data suggest that less

  7. Serial transplantation of a human acute T lymphoblastic leukemia into nude mice.

    PubMed

    Martinotti, M G; Arione, R; Foà, R; Pegoraro, L; Jemma, C; Forni, G

    1986-12-31

    A human acute T lymphoblastic leukemia line (PF-382) was serially transplanted into nude mice. No takes were observed in untreated nude mice, whereas solid tumors were observed in splenectomized and total body, sublethally irradiated mice. The minimal tumor-inducing dose and the latency time remained unchanged after the third and fifth serial transplants. Moreover, leukemic cells recovered from the 8th in vivo passages displayed the same differentiation antigens and chromosomal markers as the in vitro PF-382 cell line used for the first transplant. This stable and well-characterized experimental system could be a new model for T-lymphocyte differentiation and immune-reactivity against human leukemias.

  8. 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

    SciTech Connect

    Rofstad, E.K.

    1989-06-15

    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.

  9. Human cord blood mononuclear cell transplantation for the treatment of premature ovarian failure in nude mice

    PubMed Central

    Dang, Jianhong; Jin, Zhijun; Liu, Xiaojun; Hu, Dian; Wang, Zhifeng

    2015-01-01

    Objective: This study explored the potential of human cord blood mononuclear cell (HCMNC) transplantation as a treatment for premature ovarian failure (POF) in a nude mouse model. Methods: Female nude mice were randomly divided into three groups; a normal control group (n = 35), a POF group (POF plus vehicle, n = 35) and a POF plus cell transplantation group (HCMNCs were implanted into the ovaries, n = 35). HCMNCs were isolated by Ficoll density gradient centrifugation and labeled with BrdU. Four weeks after transplantation, the nude mice were sacrificed to determine serum levels of E2, FSH and LH as indicators of ovarian function, and the ovaries were examined both histologically and immunochemically. Results: The transplanted HCMNCs survived in the transplantation group and were detected by BrdU. In the transplantation group, serum levels of E2 significantly increased while serum levels of FSH and LH significantly decreased compared to the POF control group. Additionally, the transplantation group had a recovery in follicle number. Conclusion: HCMNCs can be successfully transplanted into the ovaries of nude mice and can improve ovarian function in POF. PMID:26064319

  10. Effect of dietary selenium on T cell immunity and cancer xenograft in nude mice

    USDA-ARS?s Scientific Manuscript database

    Selenium is known to regulate carcinogenesis and immunity at nutritional and supranutritional levels. Because the immune system provides one of the main body defenses against cancer, we asked whether T cell immunity can modulate selenium chemoprevention. Twenty-four homozygous NU/J nude mice were fe...

  11. Color-Coded Imaging of Breast Cancer Metastatic Niche Formation in Nude Mice.

    PubMed

    Suetsugu, Atsushi; Momiyama, Masashi; Hiroshima, Yukihiko; Shimizu, Masahito; Saji, Shigetoyo; Moriwaki, Hisataka; Bouvet, Michael; Hoffman, Robert M

    2015-12-01

    We report here a color-coded imaging model in which metastatic niches in the lung and liver of breast cancer can be identified. The transgenic green fluorescent protein (GFP)-expressing nude mouse was used as the host. The GFP nude mouse expresses GFP in all organs. However, GFP expression is dim in the liver parenchymal cells. Mouse mammary tumor cells (MMT 060562) (MMT), expressing red fluorescent protein (RFP), were injected in the tail vein of GFP nude mice to produce experimental lung metastasis and in the spleen of GFP nude mice to establish a liver metastasis model. Niche formation in the lung and liver metastasis was observed using very high resolution imaging systems. In the lung, GFP host-mouse cells accumulated around as few as a single MMT-RFP cell. In addition, GFP host cells were observed to form circle-shaped niches in the lung even without RFP cancer cells, which was possibly a niche in which future metastasis could be formed. In the liver, as with the lung, GFP host cells could form circle-shaped niches. Liver and lung metastases were removed surgically and cultured in vitro. MMT-RFP cells and GFP host cells resembling cancer-associated fibroblasts (CAFs) were observed interacting, suggesting that CAFs could serve as a metastatic niche.

  12. Biokinetics of radiolabeled monoclonal antibodies in heterotransplanted nude rats: Evaluation of corrected specific tissue uptake

    SciTech Connect

    Ingvar, C.; Norrgren, K.; Strand, S.E.; Brodin, T.; Joensson, P.E.S.; Sjoegren, H.O. )

    1989-07-01

    A tumor model is presented to study the biokinetics and localization of radiolabeled monoclonal antibodies (MAb) in the nude rat (Rowett RNu/RNu) heterotransplanted with human melanoma metastases. The nude rat is larger, less sensitive, and lives longer than the nude mouse. It is, therefore, well suited for in vivo studies of tumor localization with radiolabeled monoclonal antibodies. The tumor-to-host weight ratio was closer to the human situation for the nude rat than for the mouse, and quantitative imaging could be performed with a parallel hole collimator. We followed the antibody biokinetics for as long as 8 days, with repeated blood sampling and imaging. Specific uptake of MAb was higher in tumor tissue than in all other tissues except blood. Initial high uptake was also recorded in the bone marrow. The lymph glands showed a slow uptake of specific and control antibody. A simple in vitro correction procedure is described to calculate the corrected specific tissue uptake (STUcorr) that takes the blood activity into account. Thus it was shown that 80% of the tissue uptake in the dissected liver at 30 hr was due to labeled antibodies circulating in the blood. The specific tissue uptake ratio of antibodies 96.5 and OKT3 (nonspecific control) was unity for all other organs except for tumor tissue, where the ratio was greater than two and even higher when correction for blood content of labeled antibody was made.

  13. Characteristics of Viruses Derived from Nude Mice with Persistent Measles Virus Infection

    PubMed Central

    Hashimoto, Koichi; Watanabe, Masahiro; Ohara, Shinichiro; Sato, Masatoki; Kawasaki, Yukihiko; Hashimoto, Yuko; Hosoya, Mitsuaki

    2013-01-01

    Measles virus (MV) isolates from patients with subacute sclerosing panencephalitis (SSPE) differ from wild-type MV virologically. However, few animal models have reported viruses with characteristics of the SSPE virus. The MV Edmonston strain was inoculated into the subarachnoid space of nude mice. All nude mice displayed weight loss and required euthanasia, with a mean survival duration of 73.2 days. The viral load in the brain was 4- to 400-fold higher than the inoculated load, and brain infection was confirmed by immunostaining. Gene sequencing of the viruses revealed that amino acid mutations occurred more frequently in matrix proteins. The most common mutation was a uridine-to-cytosine transition. The virus exhibited lower free virus particle formation ability than the Edmonston strain. When nude mice were challenged with 2 × 102 PFU of the brain-derived virus, the mean survival duration was 34.7 days, which was significantly shorter than that of the mice challenged with 4 × 104 PFU of the Edmonston strain (P < 0.01). This study indicated that MV in a nude mouse model of persistent infection exhibited characteristics of the SSPE virus. This model may prove useful in elucidating the pathogenic mechanism of SSPE and developing potential therapeutics. PMID:23345518

  14. [Transplantation and magnetic resonance imaging of transplantable human glioma tissue in the brain of nude mice].

    PubMed

    Li, Ru-Jun; Diao, Yi; Huang, Qiang; Shen, Jun-Kang; Lan, Qing

    2007-09-01

    In previous reports, orthotopic transplantation models of glioma were produced by injecting cell suspension into the brain of mice, which is complex, time-consuming, and nearly impossible to prepare in a large scale within a short period. This study was to establish human glioma orthotopic transplantation model in nude mice by transplanting tumor tissue in the brain, and investigate magnetic resonance imaging (MRI) of the transplanted tumors. Human glioma cells were injected subcutaneously into nude mice to form human glioma. The transplantable human glioma tissues (2 mm3) were put into trocar and directly injected into the caudate nucleus of nude mice. Thirty days later, the tumors were detected by 1.5T superconduct MR machine with micro-23 coil and measured by Dicomworks (V1.35) software. Tumor morphology was observed under light microscope with HE staining. Tumor volume was measured under stereomicroscope. The feasibility of measuring tumor volume according to MRI data was evaluated. MRI showed that in the 15 nude mice received orthotopic transplantation in the caudate nucleus, 14 developed glioma. Under microscope, glioma tissues were found at the same sites as where MRI indicated. Tumor volume was (23.45+/-11.64) mm3 as measured by MRI and (23.19+/-10.18) mm3 as detected under stereomicroscope (P>0.05). The successful rate of tumor model preparation was 93% (14/15). The successful rate of tumor imaging by MRI was 100% (14/14). Tissue quantitative transplantation via trocar is simple, time-saving, and easy to construct tumor model in a large scale with high successful rate. The 1.5T MR machine with micro-23 coil can be used to observe tumor position and size of orthotopic transplantation models of human glioma in nude mice.

  15. Visualization and body distribution of [¹³¹I]-herceptin in nude mice with BT-474 breast carcinoma.

    PubMed

    Yang, Z X; Cao, H; Xing, C G; Wei, S H; Jiang, G Q; Liu, Z L

    2014-08-29

    The study aimed to investigate the bio-distribution and radio-immuno-imaging features of [(131)I]-herceptin in nude mice with BT-474 breast carcinoma. [(131)I]-Herceptin was administrated by tail intravenous injection to the nude mice with BT-474 breast carcinoma. Radiocounting was performed at 4, 12, 24, 48, and 96 h after administration. The activity ratio in the tumor tissue and non-tumor tissue (T/NT) and the radiocounting percentage per gram tissue to the injected dose (%ID/g) were calculated. The nude mice with BT-474 breast carcinoma were also visualized continuously by single photon emission computed tomography at 2, 4, 8, 12, 24, 48, and 96 h after the injection of [(131)I]-herceptin. Nude mice with MDA-MB-231 used as the control group were subjected to the same analyses. Clear tumor images were obtained after the injection of [(131)I]-herceptin in nude mice with BT-474 breast carcinoma. The images were the clearest at 24 h after the injection and remained clear even at 96 h. The T/NT ratio and %ID/g in the tumor tissues of nude mice with BT-474 were both significantly higher than those of the control group (P < 0.01). [(131)I]-Herceptin displays tumors clearly in the nude mice with BT-474 and accumulates well in the tumor tissues.

  16. Antibody-dependent cellular cytotoxicity (K) and natural killing (NK) in B-suppressed germ-free nude rats.

    PubMed Central

    Chassoux, D; Kolb, J P; Bazin, H; MacLennan, I C

    1983-01-01

    The influence of the thymus and the possible requirement for surface immunoglobulin expression for the development of K and NK activity were assessed in rats. This species was chosen in preference to mice as they show good levels of K-cell activity. Studies were carried out in athymic (rnu/rnu) rats some of which were treated from birth with rabbit anti-rat IgM antibody to suppress B-cell development. The results indicate that normal levels of both K and NK activity develop in the spleens of 6-8-week-old athymic rats, which do not contain cells expressing surface membrane immunoglobulin. While K and NK cells show characteristics of the lymphoid lineage, neither the thymus nor surface membrane immunoglobulin expression appears to be required for development of normal levels of these cytolytic activities. PMID:6605300

  17. Human endodermal sinus tumour in nude mice and its markers for diagnosis and management.

    PubMed Central

    Takeuchi, T; Nakayasu, M; Hirohashi, S; Kameya, T; Kaneko, M; Yokomori, K; Tsuchida, Y

    1979-01-01

    Two human endodermal sinus tumours (yolk sac tumours) were transplanted successfully into nude mice. The transplanted tumours maintained not only morphological characters, such as Schiller-Duval bodies, but also the ability to synthesise alpha-fetoprotein, lactic dehydrogenase 1, liver and bone type alkaline phosphatase, and some human serum proteins. Since these tumours produced lactic dehydrogenase 1 but not the other four isozymes of lactic dehydrogenase, this isozyme, like alpha-fetoprotein, seems to be a good marker for the diagnosis and management of cases of endodermal sinus tumour. One of the two tumours produced another fetal antigen or carcinoembryonic antigen in addition to alpha-fetoprotein. These two endodermal sinus tumours, with their various markers in nude mice, will be useful in studies on diagnostic markers. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:91627

  18. Human Endometrial Adenocarcinoma Transplanted into Nude Mice: Growth Regulation by Estradiol

    NASA Astrophysics Data System (ADS)

    Satyaswaroop, P. G.; Zaino, R. J.; Mortel, R.

    1983-01-01

    A model for studying the growth of primary tumors of human endometrium and its regulation by 17β -estradiol has been developed in which ovariectomized nude mice are used as recipients. The receptors for sex steroids are maintained during serial transplantation of the tumor in this system. Although the rate of growth of receptor-negative endometrial tumors transplanted into ovariectomized nude mice is unaffected by the sustained presence or absence of estradiol, the growth of receptor-positive tumors is significantly increased by estradiol. Receptor-positive tumors treated with estradiol produced elevated concentrations of progesterone receptor. That the progesterone receptor is functional in this tumor is evident from the induction of estradiol 17β -dehydrogenase activity upon progestin administration. These findings are consistent with receptor-mediated regulation of growth of endometrial carcinoma.

  19. Survival of human parathyroid tissue xenotransplanted in nude mice after 9 to 55 months' cryopreservation.

    PubMed

    Smeds, S; Trulsson, L; Garovoy, M; Gumbert, M; Clark, O H

    1999-04-01

    Survival of human parathyroid tissue xenotransplanted after cryopreservation was studied. Peroperative biopsies from 26 patients were cryopreserved and xenotransplanted into nude mice after 9 to 55 months. At 8 to 12 weeks after transplantation, the morphology of the transplanted tissue was compared to that of the original tissue after thawing and before transplantation. Morphologically viable tissue was observed in 20 out of 26 nude mice (77%). Based on the morphological appearance, the parathyroid transplants were arranged into four "quality" groups. No correlation existed between the quality of the transplants and duration of storage, or between the age and sex of the patients. There was no correlation between initial clinical diagnosis or histopathological patterns (primary, secondary and tertiary hyperplasia [n=16], adenoma [n=9], one case undetermined) and transplant survival. After thawing and transplantation, all parathyroid grafts, except one, were morphologically either of the same or somewhat lower quality.

  20. Utilization of an antibody specific for human dystrophin to follow myoblast transplantation in nude mice.

    PubMed

    Huard, J; Tremblay, G; Verreault, S; Labrecque, C; Tremblay, J P

    1993-01-01

    Human myoblasts were transplanted in nude mice. The efficacy of these transplantations was analyzed using a monoclonal antibody (NCLDys3) specific for human dystrophin. This antibody did not reveal any dystrophin in nude mice that did not receive a human myoblast transplantation. However, about 30 days after a human myoblast transplantation, dystrophin-positive muscle fibers were observed. They were not abundant, and were present either in small clusters or isolated. This technique follows the fate of myoblast transplantation in animals that already have dystrophin, and distinguishes between new dystrophin-positive fibers due to the transplantation and the revertant fibers in mdx mice. Moreover, this technique does not require any labelling of the myoblasts before transplantation. It can also be used to detect dystrophin produced following the fusion of myoblasts transfected with the human dystrophin gene.

  1. Association of tumor growth on nude mice and poor clinical outcome in soft tissue sarcoma patients.

    PubMed

    Budach, W; Budach, V

    2001-09-01

    Permanent growth in nude mice (PGNM) may be associated with poor clinical outcome. We tested this hypothesis in a group of soft tissue sarcoma (STS) patients. Small chunks from fresh tumor biopsies of 81 patients with STS were transplanted subcutaneously into NMRI-nu/nu nude mice. Tumor cell lines exhibiting growth in nude mice for more than three tumor passages were considered as permanently established. Clinical outcome of all patients was monitored with a median follow-up of 38 months. 39/81 (48%) STSs exhibited PGNM. High grade, high S-phase proportion, and aneuploidy were significant predictors of PGNM. Overall survival (OS) at 3 years was 21% (+7% standard error of median) for STS patients with PGNM and 53% (+/-8%) for patients without PGNM (P<0.01). Considering only patients without distant metastasis at the time of biopsy (n = 49), 3-year-OS was 25% (+/-10%) and 71% (+/-9%) for STS with PGNM and without PGNM, respectively (P<0.01). In the univariate analysis, PGNM, aneuploidy high S-phase proportion, tumor location at the trunk, high tumor grade, and non-liposarcoma histology were associated with reduced survival time. In the multivariate analysis, aneuploidy and tumor location at the trunk were the only independent predictors of overall survival. Permanent growth of STS on nude mice is associated with poor clinical outcome in the univariate analysis, but is not an independent predictor of survival in the multivariate analysis due to a strong co-correlation to other known adverse prognostic factors.

  2. Induction of lymphomas on implantation of human oral squamous cell carcinomas in nude mice.

    PubMed

    Teni, T R; Saranath, D; Mahale, A M; Pai, S A; Ahire, S D; Ingle, A D

    2001-02-01

    Cancer cells from five oral cancer patients and pleomorphic adenoma cells from one individual were inoculated as single cell suspension into subcutis of 30 Swiss nude mice and tail vein of additional 30 mice. Further, tumor tissue pieces from three oral cancer patients were xenografted s.c. in 18 nude mice, and 10 mice were kept as controls. In animals implanted with tumor pieces, 7/18 (39%) mice, developed squamous cell carcinoma at the site of inoculation within 8-15 days, while tumors were not observed in mice inoculated with single cell suspension, up to 60/90 days. In 8/68 (12%) mice, white foci were observed in several tissues, with hepatomegaly and splenomegaly noted in 27/68 (39%) mice. Histopathological examination of various tissues revealed presence of large cell lymphoma in several organs in 14/68 (21%) mice. No regional or distant metastasis of the implanted oral tumor cells was detected. Mice injected with cells from pleomorphic adenoma, also demonstrated large cell lymphoma in 2/10 (20%) mice, whereas none of the 10 control animals showed any gross abnormalities or microscopic abnormalities in several organs. 2/16 (12%) lymphomas exhibited positive reaction with mouse B cell antibodies illustrating the murine origin of the lymphomas, and these were immunophenotyed as B cell lymphomas. The lymphomas were also examined with mouse T cell antibodies and none reacted positively with the mouse T cell antibodies. The lymphomas also failed to react with human T cell, B cell and human Leucocyte common antigen (LCA) antibodies, indicating that the induced lymphomas were not of human origin. The tumor specimens from seven of eight oral cancer patients and the pleomorphic adenoma patient induced lymphomas in nude mice. Thus it appears that xenografting oral tumor cells into nude mice may cause induction of the murine lymphomas, and this needs further investigation.

  3. Tumorigenicity assays in nude mice: analysis of an implanted gelatin-sponge method

    SciTech Connect

    Kraemer, P.M.; Travis, G.L.; Saunders, G.C.; Ray, F.A.; Stevenson, A.P.; Bame, K.; Cram, L.S.

    1982-01-01

    Gelatin sponges, preimplanted in nude mice for 10 days, were used for an improved assay for tumorigenicity of cultured cells. Cells inoculated through the skin into such sponges yielded tumors more rapidly and with greater frequency than with newly implanted sponges or into subcutaneous tissue. However, an unexpected loss of cells occurred in the first few days after implantation. This loss may be an important aspect of tumorigenicity assays of all kinds, and is readily studied with the sponge methods described.

  4. A new childhood T-cell lymphoma established in nude mice and in vitro.

    PubMed

    Arione, R; Jemma, C; Forni, M; Marchese, C; Benetton, G; Giubellino, C; Modesti, A; Martinotti, M G; di Montezemolo, L C; Musso, T

    1988-03-01

    A T-lymphoma cell line was established from a lymph node biopsy of a boy currently alive in complete remission. Neoplastic cells from this biopsy did not grow in vitro, whereas they formed a progressively growing s.c. tumor in splenectomized and sublethally irradiated nude mice and became serially transplantable in splenectomized and sublethally irradiated nude mice with a stable latency time. After the fourth transplant, cells were stored in liquid nitrogen and referred to as ST-4 cells. ST-4 cells display a membrane phenotype and a karyotype similar to that of the biopsy cells. After thawing, ST-4 cells grow both in splenectomized and sublethally irradiated nude mice and in vitro. They do not secrete interferon or interleukin 2, do not have natural killer activity, and do not respond to mitogen or alloantigen stimulation. The stable features of these T-lymphoma cells and the availability of normal autologous lymphocytes from the patient make this in vivo system quite unique and of importance for studies in tumor immunotherapy.

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

    PubMed Central

    Begum, Shahnaz; Lee, Mi Ra; Gu, Li Juan; Hossain, Md. Jamil; Kim, Hyun Kyoung; Sung, Chang Keun

    2014-01-01

    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. PMID:25478567

  6. Bone formation in vitro and in nude mice by human osteosarcoma cells.

    PubMed

    Ogose, A; Motoyama, T; Hotta, T; Watanabe, H; Takahashi, H E

    1995-01-01

    Osteosarcomas contain variable amounts of bony tissue, but the mechanism of bone formation by osteosarcoma is not well understood. While a number of cultured human osteosarcoma cell lines have been established, they are maintained by different media and differ qualitatively with regard to bone formation. We examined different media for their ability to support bone formation in vitro and found the alpha-modification of Eagle's minimal essential medium supplemented with beta glycerophosphate was best for this purpose, because it contained the proper calcium and phosphate concentrations. Subsequently, we compared seven human osteosarcoma cell lines under the same experimental conditions to clarify their ability to induce bone formation. NOS-1 cells most frequently exhibited features of bone formation in vitro and in nude mice. Collagen synthesis by tumour cells themselves seemed to be the most important factor for bone volume. However, even HuO9 cells, which lacked collagen synthesis and failed to form bone in vitro, successfully formed tumours containing bone in nude mice. Histological analysis of HuO9 cells in diffusion chambers implanted in nude mice and the findings of polymerase chain reaction indicated that the phenomenon was probably due to bone morphogenetic protein.

  7. Comparative hair restorer efficacy of medicinal herb on nude (Foxn1nu) mice.

    PubMed

    Begum, Shahnaz; Lee, Mi Ra; Gu, Li Juan; Hossain, Md Jamil; Kim, Hyun Kyoung; Sung, Chang Keun

    2014-01-01

    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.

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

    SciTech Connect

    Giavazzi, R.; Garofalo, A.; Bani, M.R.; Abbate, M.; Ghezzi, P.; Boraschi, D.; Mantovani, A.; Dejana, E. )

    1990-08-01

    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.

  9. [Establishment of a keloid model by transplanting human keloid onto the backs of nude mice].

    PubMed

    Philandrianos, C; Gonnelli, D; Andrac-Meyer, L; Bruno, M; Magalon, G; Mordon, S

    2014-08-01

    Keloid scar is a proliferative healing dysfunction formed by an excessive build-up of collagen fibers on the dermis. It is responsible of aesthetic and functional disabilities. There is no ideal treatment and recurrence occurs very often. Keloid scars occur only to human, that's why animal model needs to be made to study this pathology and new treatments. Few models have been described using human keloid scars implanted into subcutaneous tissue of nude mice or rat. To allow study of topical and laser treatment we have developed a new animal model using human keloid scar fragment with epidermal and dermal tissue implanted into back of nude mice like a full thickness skin graft. Keloid fragments from five donors have been grafted onto 40 nudes mice. Macroscopic and microscopic studies have been made at day 28, 56, 84 and 112. We observed integration of the fragments in all cases. Hyalinized collagen bundles were observed in all implant biopsies confirming the stability of the keloid architecture within 112 days. This model is easily reproducible and allows the study of topical treatment and laser due to the accessibility of the keloid. Copyright © 2012. Published by Elsevier Masson SAS.

  10. Scarless skin wound healing in FOXN1 deficient (nude) mice is associated with distinctive matrix metalloproteinase expression.

    PubMed

    Gawronska-Kozak, Barbara

    2011-05-01

    Similar to mammalian fetuses FOXN1 deficient (nude) mice are able to restore the structure and integrity of injured skin in a scarless healing process by mechanisms independent of the genetic background. Matrix metalloproteinases (MMPs) are required for regular skin wound healing and the distinctive pattern of their expression has been implicated to promote scarless healing. In this study, we analyzed the temporal and spatial expression patterns of these molecules during the incisional skin wounds in adult nude mice. Macroscopic and histological analyses of skin wounds revealed an accelerated wound healing process, minimal granulation tissue formation and markedly diminished scarring in nude mice. Quantitative RT-PCR (Mmp-2, -3, -8, -9, -10, -12, -13, -14 and Timp-1, -2, -3), Western blots (MMP-13) and gelatin zymography (MMP-9) revealed that MMP-9 and MMP-13 showed a unique, bimodal pattern of up-regulation during the early and late phases of wound healing in nude mice. Immunohistochemically MMP-9 and MMP-13 were generally detected in epidermis during the early phase and in dermis during the late (remodeling) phase. Consistent with these in vivo observations, dermal fibroblasts cultured from nude mice expressed higher levels of types I and III collagen, MMP-9 and MMP-13 mRNA levels and higher MMP enzyme activity than wild type controls. Collectively, these finding suggest that the bimodal pattern of MMP-9 and MMP-13 expression during skin repair process in nude mice could be a major component of their ability for scarless healing.

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

    PubMed Central

    Gawronska-Kozak, Barbara

    2011-01-01

    Similar to mammalian fetuses FOXN1 deficient (nude) mice are able to restore the structure and integrity of injured skin in a scarless healing process by mechanisms independent of the genetic background. Matrix metalloproteinases (MMPs) are required for regular skin wound healing and the distinctive pattern of their expression has been implicated to promote scarless healing. In this study, we analyzed the temporal and spatial expression patterns of these molecules during the incisional skin wounds in adult nude mice. Macroscopic and histological analyses of skin wounds revealed an accelerated wound healing process, minimal granulation tissue formation and markedly diminished scarring in nude mice. Quantitative RT-PCR (Mmp-2,-3,-8,-9,-10,-12,-13,-14 and Timp-1, -2, -3), Western blots (MMP-13) and gelatin zymography (MMP-9) revealed that MMP-9 and MMP-13 showed a unique, bimodal pattern of up-regulation during the early and late phases of wound healing in nude mice. Immunohistochemically MMP-9 and MMP-13 were generally detected in epidermis during the early phase and in dermis during the late (remodeling) phase. Consistent with these in vivo observations, dermal fibroblasts cultured from nude mice expressed higher levels of type I and III collagen, MMP-9 and MMP-13 mRNA levels and higher MMP enzyme activity than wild type controls. Collectively, these finding suggest that the bimodal pattern of MMP-9 and MMP-13 expression during skin repair process in nude mice could be a major component of their ability for scarless healing. PMID:21539913

  12. [Targeting therapy of magnetic doxorubicin liposome in nude mice bearing colon cancer].

    PubMed

    Zhou, Ping-hong; Yao, Li-qing; Qin, Xin-yu; Shen, Xi-zhong; Liu, Yi-shu; Lu, Wei-yue; Yao, Ming

    2003-12-10

    To investigate the effect of magnetic doxorubicin liposome (MDL) in the targeting treatment of nude mice bearing colon cancer. Human colon cancer line LoVo cells were implanted hypodermically into nude mouse. Two weeks after the mouse was killed and the tumor was taken out and cut into small pieces to be retransplanted into nude mice so as to establish an experimental model. MDL was prepared by reverse-phase evaporation method. The particle size and structure of MDL were evaluated. Eighteen nude mice with colon cancer were divided into 3 groups of 3 mice: free DOX group, MDL (-) group (no magnetic field was added to the tumor surface), and MDL (+) group (magnetic field with the strength of 4,500 G was added). DOX of the dosage of 5 mg/kg was injected through the caudal vein in these 3 groups. Then the mice were killed 30 minutes after. Fluorescence spectrophotometry was used to examine the concentrations of DOX in the tissues and plasma. Another 36 nude mice with colon cancer were divided into 6 groups of 6 mice: normal saline group (as controls), DOX group, blank liposome group, magnetic liposome group, MDL (-) group (non-magnetic alloy was implanted into the tumor), and MDL (+) group (rare earth magnet was implanted into the tumor). The body weight, longest diameter of tumor, and short diameter vertical to the longest diameter were calculated regularly. The mice were killed 11 days after. The tumors were taken out to undergo staining and light microscopy. Flow cytometry was used to examine the apoptosis of tumor cells. The particle size of MDL was 230 nm and the magnetic particles (Fe(3)O(4)) were evenly distributed within the liposome. The DOX concentration in tumor tissue of the MDL (+) group was remarkably higher than those of the DOX and MDL (-) groups (both P < 0.05). The DOX concentration in heart and kidney of the DOX group were higher than those of the other 2 groups, and the plasma DOX concentrations of the DOX group was significantly lower than those of

  13. Polyphenol-rich extract of Pimenta dioica berries (Allspice) kills breast cancer cells by autophagy and delays growth of triple negative breast cancer in athymic mice

    PubMed Central

    Zhang, Lei; Shamaladevi, Nagarajarao; Jayaprakasha, Guddadarangavvanahally K.; Patil, Bhimu S.; Lokeshwar, Bal L.

    2015-01-01

    Bioactive compounds from edible plants have limited efficacy in treating advanced cancers, but they have potential to increase the efficacy of chemotherapy drugs in a combined treatment. An aqueous extract of berries of Pimenta dioica (Allspice) shows promise as one such candidate for combination therapy or chemoprevention. An aqueous extract of Allspice (AAE) was tested against human breast cancer (BrCa) cells in vitro and in vivo. AAE reduced the viability and clonogenic growth of several types of BrCa cells (IC50 ≤ 100 μg/ml) with limited toxicity in non-tumorigenic, quiescent cells (IC50 >200 μg/ml). AAE induced cytotoxicity in BrCa was inconsistent with apoptosis, but was associated with increased levels of autophagy markers LC3B and LC3B-positive puncta. Silencing the expression of autophagy related genes (ATGs) prevented AAE-induced cell death. Further, AAE caused inhibition of Akt/mTOR signaling, and showed enhanced cytotoxicity when combined with rapamycin, a chemotherapy drug and an inhibitor of mTOR signaling. Oral administration (gavage) of AAE into athymic mice implanted with MDA-MB231 tumors inhibited tumor growth slightly but not significantly (mean decrease ~ 14%, p ≥ 0.20) if mice were gavaged post-tumor implant. Tumor growth showed a significant delay (38%) in tumor palpability and growth rate (time to reach tumor volume ≥ 1,000 mm3) when mice were pre-dosed with AAE for two weeks. Analysis of tumor tissues showed increased levels of LC3B in AAE treated tumors, indicating elevated autophagic tumor cell death in vivo in treated mice. These results demonstrate antitumor and chemo-preventive activity of AAE against BrCa and potential for adjuvant to mTOR inhibition. PMID:25945840

  14. Polyphenol-rich extract of Pimenta dioica berries (Allspice) kills breast cancer cells by autophagy and delays growth of triple negative breast cancer in athymic mice.

    PubMed

    Zhang, Lei; Shamaladevi, Nagarajarao; Jayaprakasha, Guddadarangavvanahally K; Patil, Bhimu S; Lokeshwar, Bal L

    2015-06-30

    Bioactive compounds from edible plants have limited efficacy in treating advanced cancers, but they have potential to increase the efficacy of chemotherapy drugs in a combined treatment. An aqueous extract of berries of Pimenta dioica (Allspice) shows promise as one such candidate for combination therapy or chemoprevention. An aqueous extract of Allspice (AAE) was tested against human breast cancer (BrCa) cells in vitro and in vivo. AAE reduced the viability and clonogenic growth of several types of BrCa cells (IC50 ≤ 100 μg/ml) with limited toxicity in non-tumorigenic, quiescent cells (IC50 >200 μg/ml). AAE induced cytotoxicity in BrCa was inconsistent with apoptosis, but was associated with increased levels of autophagy markers LC3B and LC3B-positive puncta. Silencing the expression of autophagy related genes (ATGs) prevented AAE-induced cell death. Further, AAE caused inhibition of Akt/mTOR signaling, and showed enhanced cytotoxicity when combined with rapamycin, a chemotherapy drug and an inhibitor of mTOR signaling. Oral administration (gavage) of AAE into athymic mice implanted with MDA-MB231 tumors inhibited tumor growth slightly but not significantly (mean decrease ~ 14%, p ≥ 0.20) if mice were gavaged post-tumor implant. Tumor growth showed a significant delay (38%) in tumor palpability and growth rate (time to reach tumor volume ≥ 1,000 mm3) when mice were pre-dosed with AAE for two weeks. Analysis of tumor tissues showed increased levels of LC3B in AAE treated tumors, indicating elevated autophagic tumor cell death in vivo in treated mice. These results demonstrate antitumor and chemo-preventive activity of AAE against BrCa and potential for adjuvant to mTOR inhibition.

  15. Colocalization of human papillomavirus type 11 E1[symbol: see text]E4 and L1 proteins in human foreskin implants grown in athymic mice.

    PubMed

    Brown, D R; Fan, L; Jones, J; Bryan, J

    1994-05-15

    The most abundant viral mRNA species in tissues infected with HPV 11 consists of two exons, joining a short segment of open reading frame (ORF) E1 to ORF E4, potentially encoding an protein of 10 kDa. E4 gene products have previously been identified by immunohistochemistry in human tissues infected with HPV 1 and HPV 16, and in HPV 11-infected raft cultures. The E1[symbol: see text]E4 mRNA is produced in abundance in HPV 11-infected human foreskin implants grown in athymic mice. In contrast, the L1 mRNA is present at low levels and appears late in the course of infection. To characterize the relationship of these proteins, polyclonal rabbit antisera were produced against bacterially expressed HPV 11 trpE/E1[symbol: see text]E4 and trpE/L1 fusion proteins and tested in an immunohistochemical assay of paraffin-embedded sections of HPV 11-infected human foreskin tissue fixed with 10% buffered formalin phosphate or zinc formalin. In sections fixed with either fixative, the anti-L1 serum stained nuclei of cells in the upper spinous and granular layers. In contrast, the anti-E1[symbol: see text]E4 serum stained the cell membrane and, to a lesser degree, the cytoplasm of cells in the upper spinous and granular layers of tissue fixed with zinc formalin, but not 10% buffered formalin phosphate. In sections treated with both the E1[symbol: see text]E4 and L1 antisera, cell membrane staining occurred in the same cells that exhibited nuclear staining. The HPV 11 E1[symbol: see text]E4 protein appears to be a cell membrane-associated protein. Expression of the HPV 11 E1[symbol: see text]E4 and L1 proteins may be influenced by similar factors in differentiating cells.

  16. [Effect of valproic acid against angiogenesis of Kasumi-1 xenograft tumor in nude mice].

    PubMed

    Wang, Li-Hong; Zhang, Zhi-Hua; Zhao, Lei; Zhu, Cui-Min; Zhao, Li-Shuang; Hao, Chang-Lai

    2013-02-01

    This study was aimed to investigate the effect of valproic acid (VPA), a histone deacetylase inhibitor, on angiogenesis of acute myeloid leukemia in vivo and vitro, and to explore its molecular mechanism. Human t (8;21) AML cell line Kasumi-1 cells were treated with VPA at different concentration for 3 d, the mRNA and protein expression levels of Ang1 and Ang2 were determined by semi-quantitative RT-PCR and Western blot respectively. Nude mice model with xenograft Kasumi-1 tumor was established by subcutaneous inoculation of Kasumi-1 cells. The CD34, Ang1 and Ang2 protein levels were analyzed by immunohistochemistry method. The mRNA and protein expression levels of Ang1, Ang2 and VEGF were determined by semi-quantitative RT-PCR and Western blot. The results showed that in vitro, VPA at 3 mmol/L downregulated the Ang mRNA relative expression level for Ang1 from 0.360 ± 0.116 to 0.040 ± 0.008, Ang2 from 0.540 ± 0.049 to 0.146 ± 0.038. The animal experiment further verified that VPA 500 mg/kg, ip, for 14 d, reduced the relative expression of Ang1, Ang2 and VEGF mRNA and proteins in Kasumi-1 tumor of nude mice, and reduced microvascular density in xenograft tumor of nude mice (8.470 ± 0.300 vs 2.600 ± 0.200). It is concluded that VPA significantly inhibits tumor angiogenesis through the regulation of angiopoietins, thereby inhibits the proliferation and metastasis of leukemia cells.

  17. [Establishment of subcutaneously transplanted and metastatic neuroblastoma models in nude mice].

    PubMed

    Lu, Hong-ting; Dong, Qian; Gao, Qiang; Hao, Xi-wei; Song, Hua; Zhao, Nan

    2010-04-01

    To establish a tumor-bearing nude mouse model of human neuroblastoma in order to study the mechanisms of neuroblastoma invasion and metastasis, and to investigate potential therapeutic modalities in the experimental animal models. A human neuroblastoma cell line was cultured in vitro. 1 x 10(7) cells undergoing exponential growth were collected in 0.1 ml of suspension and subcutaneously inoculated into the right flank next to the forelimb in nude mice. The biological characteristics of the developed tumors were observed, and histopathological and DNA microarray analyses were performed. The expressions of NSE in the subcutaneous tumor, metastatic tumor and the primary neuroblastoma tumor tissues from a pediatric patient were analyzed by immunohistochemistry. Tumors successfully grew in 36 out of 48 injected mice, with a total tumor-formation rate of 75.0%. Metastasis occurred in 10 cases, and the metastatic rate was 20.8%. Tumors in five injected mice grew locally without metastasis. These tumors had large volume and the tumor weight reached up to half of the body weight of the host animal. Four mice exhibited systemic metastasis without tumor growth at the primary inoculation site. There were six mice with locally growing tumor accompanied by metastasis. We have successfully established a human neuroblastoma xenograft model in nude mice with high tumor growth and metastatic rates. This model depicting the natural cell growth, local infiltration and distant metastasis characteristics of human neuroblastoma, providing an ideal animal model for in vivo studies of neuroblastoma. In addition, the results of this study indicate the heterogeneous nature of neuroblastoma, it may play an important role in metastasis of this tumor.

  18. Inhibitory effects of subcutaneous tumors in nude mice mediated by low-frequency ultrasound and microbubbles

    PubMed Central

    SHEN, ZHI-YONG; SHEN, E.; DIAO, XUE-HONG; BAI, WEN-KUN; ZENG, MIN-XIA; LUAN, YAN YAN; NAN, SHU-LIANG; LIN, YAN-DUAN; WEI, CONG; CHEN, LI; SUN, DI; HU, BING

    2014-01-01

    The aim of the present study was to investigate the sonication effects of 21-kHz ultrasound (US) with microbubbles (MBs) on the subcutaneous prostate tumors of nude mice. In total, 15 tumor-bearing nude mice were divided into three groups: The control group, the low-frequency US group and the US+MB group. The MBs used were from US contrast agent SonoVue. The parameters of the US were as follows: 21 kHz, 26 mW/cm2 and a 40% duty cycle (2 sec on, 3 sec off) for 3 min, once every other day for 2 weeks. Color Doppler flow imaging, hematoxylin and eosin (HE) staining, immunoblotting and transmission electron microscopy (TEM) were used to evaluate the results. Following 2 weeks of treatment, the blood flow signal disappeared in the US+MB group only, and the tumor size was smaller when compared with the control and US groups. For the immunoblotting, the intensity of cyclooxygenase-2 and vascular endothelial growth factor in the US+MB group was lower compared with the other two groups. Tumor necrosis was present and the nucleus disappeared upon HE staining in the US+MB group. Upon TEM analysis, increased cytoplasmic vacuolation and dilatation of the perinuclear cisternae of the tumor cells were found in the US+MB group. In the control and US groups, the tumors had intact vascular endothelia and vessel lumens. However, lumen occlusion of the vessels was observed in the US+MB group. In conclusion, 21-kHz low-intensity US with MBs may result in vessel occlusion and growth inhibitory effects in the subcutaneous tumors of nude mice. PMID:24765142

  19. Effect of curcumin on Bcl-2 and Bax expression in nude mice prostate cancer.

    PubMed

    Yang, Jiayi; Ning, Jianping; Peng, Linlin; He, Dan

    2015-01-01

    Prostate cancer is a common malignant tumor in urinary system. Curcumin has curative effect on many kinds of cancers and can inhibit prostate cancer (PC)-3 cells proliferation. This study aimed to explore the curcumin induced prostate cancer cell apoptosis and apoptosis related proteins Bcl-2 and Bax expression. PC-3 cells were injected subcutaneously to the nude mice to establish the tumor model. The nude mice were randomly divided into group C (normal saline), group B (6% polyethylene glycol and 6% anhydrous ethanol), group H, M, L (100 mg/kg, 50 mg/kg, and 25 mg/kg curcumin). The tumor volume was measured every 6 days to draw the tumor growth curve. The mice were killed at the 30(th) day after injection to weight the tumor. TUNEL assay was applied to determine cell apoptosis. Immunohistochemistry was used to detect Bcl-2 and Bax expression. The tumor volume and weight in group H, M, L were significantly lower than the control group (C, B) (P<0.05), and the inhibitory rate increased following the curcumin dose increase. Compared with the control group, Bcl-2 expression in group H, M, L gradually decreased, while Bax protein expression increased (P<0.05). The cell apoptosis rate showed no statistical difference between group B and C, while it increased in curcumin group H, M, and L (P<0.05). Curcumin could inhibit PC-3 growth, decrease tumor volume, reduce tumor weight, and induce cell apoptosis under the skin of nude mice by up-regulating Bax and down-regulating Bcl-2.

  20. Safety assessment of ovarian cryopreservation and transplantation in nude mice bearing human epithelial ovarian cancer.

    PubMed

    Zhu, Gen-Hai; Wang, Sheng-Tan; Yang, Zhao-Xin; Cai, Jun-Hong; Chen, Chun-Ying; Yao, Mao-Zhong; Hong, Lan; He, Guo-Li; Yang, Shu-Ying

    2012-01-01

    Nude mice with orthotopic transplantation of human ovarian epithelial cancer were used to investigate screening criteria for paraneoplastic normal ovarian tissue and the security of the freezing and thawing for ovarian tissue transplantation. Expression of CK-7, CA125, P53, survivin, MMP-2/TIMP- 2 in paraneoplastic normal ovarian tissues were detected by RT-PCR as well as immunohistochemistry. The tissues of the groups with all negative indicators of RT-PCR, all negative indicators of immunohistochemistry, negative expression of CK-7, CA125 and survivin, positive expression of CK-7, CA125 and survivin, cancer tissues and normal ovarian tissues of nude mice were used for freezing and thawing transplantation, to analyze overt and occult carcinogenesis rates after transplantation. When all indicators or the main indicators, CK-7, CA125 and survivin, were negative, tumorigenesis did not occur after transplantation. In addition the occult carcinogenesis rate was lower than in the group with positive expression of CK-7, CA125 and survivin (P<0.01). After subcutaneous and orthotopic transplantation of ovarian tissues, rates did not change (P>0.05). There was no statistical significance among rates after transplantation of ovarian tissues which were obtained under different severity conditions (P>0.05). Negative expression of CK-7, CA125 and survivin can be treated as screening criteria for security of ovarian tissues for transplantation. Immunohistochemical methods can be used as the primary detection approach. Both subcutaneous and orthotopic transplantation are safe. The initial severity does not affect the carcinogenesis rate after tissue transplantation. Freezing and thawing ovarian tissue transplantation in nude mice with human epithelial ovarian carcinoma is feasible and safe.

  1. Effect of curcumin on Bcl-2 and Bax expression in nude mice prostate cancer

    PubMed Central

    Yang, Jiayi; Ning, Jianping; Peng, Linlin; He, Dan

    2015-01-01

    Prostate cancer is a common malignant tumor in urinary system. Curcumin has curative effect on many kinds of cancers and can inhibit prostate cancer (PC)-3 cells proliferation. This study aimed to explore the curcumin induced prostate cancer cell apoptosis and apoptosis related proteins Bcl-2 and Bax expression. PC-3 cells were injected subcutaneously to the nude mice to establish the tumor model. The nude mice were randomly divided into group C (normal saline), group B (6% polyethylene glycol and 6% anhydrous ethanol), group H, M, L (100 mg/kg, 50 mg/kg, and 25 mg/kg curcumin). The tumor volume was measured every 6 days to draw the tumor growth curve. The mice were killed at the 30th day after injection to weight the tumor. TUNEL assay was applied to determine cell apoptosis. Immunohistochemistry was used to detect Bcl-2 and Bax expression. The tumor volume and weight in group H, M, L were significantly lower than the control group (C, B) (P<0.05), and the inhibitory rate increased following the curcumin dose increase. Compared with the control group, Bcl-2 expression in group H, M, L gradually decreased, while Bax protein expression increased (P<0.05). The cell apoptosis rate showed no statistical difference between group B and C, while it increased in curcumin group H, M, and L (P<0.05). Curcumin could inhibit PC-3 growth, decrease tumor volume, reduce tumor weight, and induce cell apoptosis under the skin of nude mice by up-regulating Bax and down-regulating Bcl-2. PMID:26464676

  2. STAT3 Knockdown Reduces Pancreatic Cancer Cell Invasiveness and Matrix Metalloproteinase-7 Expression in Nude Mice

    PubMed Central

    Huang, Ke jian; Wu, Wei dong; Jiang, Tao; Cao, Jun; Feng, Zhen zhong; Qiu, Zheng jun

    2011-01-01

    Aims Transducer and activator of transcription-3 (STAT3) plays an important role in tumor cell invasion and metastasis. The aim of the present study was to investigate the effects of STAT3 knockdown in nude mouse xenografts of pancreatic cancer cells and underlying gene expression. Methods A STAT3 shRNA lentiviral vector was constructed and infected into SW1990 cells. qRT-PCR and western immunoblot were performed to detect gene expression. Nude mouse xenograft assays were used to assess changes in phenotypes of these stable cells in vivo. HE staining was utilized to evaluate tumor cell invasion and immunohistochemistry was performed to analyze gene expression. Results STAT3 shRNA successfully silenced expression of STAT3 mRNA and protein in SW1990 cells compared to control cells. Growth rate of the STAT3-silenced tumor cells in nude mice was significantly reduced compared to in the control vector tumors and parental cells-generated tumors. Tumor invasion into the vessel and muscle were also suppressed in the STAT3-silenced tumors compared to controls. Collagen IV expression was complete and continuous surrounding the tumors of STAT3-silenced SW1990 cells, whereas collagen IV expression was incomplete and discontinuous surrounding the control tumors. Moreover, microvessel density was significantly lower in STAT3-silenced tumors than parental or control tumors of SW1990 cells. In addition, MMP-7 expression was reduced in STAT3-silenced tumors compared to parental SW1990 xenografts and controls. In contrast, expression of IL-1β and IgT7α was not altered. Conclusion These data clearly demonstrate that STAT3 plays an important role in regulation of tumor growth, invasion, and angiogenesis, which could be act by reducing MMP-7 expression in pancreatic cancer cells. PMID:21991388

  3. Exploring the frontier from the inside out: John Sloan's nude studies.

    PubMed

    Coco, J M

    1999-01-01

    The American realist artist John Sloan (1871-1951), a leading member of The Eight and the Ashcan School, is best known for his paintings and etchings of New York City life at the turn of the twentieth century--pictures that have endured as major documents in art history. Given the social nature of his early images, contemporaries were perplexed when Sloan became almost exclusively preoccupied with what was perhaps the most unpopular genre in American art--the female nude. Yet despite disapproval from his peers and lack of public interest, he continued to focus on nude studies for over twenty years, and created a series of unusual and disturbing images that so far have defied explanation. Formal analyses exist, but little has been written about the content of these pictures. My study bypasses the question of aesthetic quality that has troubled other art historians, and instead attempts to correlate these works with Sloan's personal life and his early career. When interpreted in the light of his history and his own words, these images reveal Sloan's intimate connection to his depicted female figures--a bond that emerges despite his attempt to maintain an objective distance from his subjects. My analysis is based on the work of D. W. Winnicott, who theorized that cultural production embodies our earliest, most profound relationship to our parents. As I will argue, the late nudes represent an intense period of mature, retrospective self-exploration. While this psychoanalytic investigation is certainly speculative, it is intended to open some possible new ways of understanding Sloan's representations of women.

  4. Establishment and characterization of a metastasis model of human gastric cancer in nude mice.

    PubMed

    Li, Kesheng; Du, Huifen; Lian, Xiaowen; Chai, Dandan; Li, Xinwen; Yang, Rong; Wang, Chunya

    2016-02-03

    A mouse model of metastasis of human gastric cancer is one of the most important tools for studying the biological mechanisms underlying human gastric cancer metastasis. In this paper, we established a mouse model of metastatic human gastric cancer in nude mice that has a higher rate of tumor formation and metastasis than existing models. To generate the mouse model of metastatic human gastric cancer, fresh tumor tissues from patients that have undergone surgery for gastric cancer were subcutaneously implanted in the right and left groins of nude mice. When the implanted tissue grew to 1 cubic centimeter, the mice were killed, and the tumor tissues were examined and resected. The tumor tissues were implanted into nude mice and subjected to pathological examination, immunohistochemical staining, and real-time PCR for cytokeratin 8/18 (CK8/18), E-cadherin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). The mice were also analyzed for metastasis in their peritoneum, abdominal cavity, and internal organs by histopathological examination. Tissues collected from these organs were examined for pathology. After ten generations of implantation, all mice developed tumor growth at the implanted position, 94% of the mice developed metastasis to the retroperitoneum and viscera. The implanted and metastatic tumor maintained the same histological features across all generations, and metastasis was observed in the esophagus, stomach, spleen, liver, kidney, adrenal, intestine, and pancreas. These metastatic tumors revealed no detectable expression of CK8/18, E-cadherin, VCAM-1, and ICAM-1. This model will serve as valuable tool for understanding the metastatic process of human gastric cancer.

  5. Extensive Hair Shaft Growth after Mouse Whisker Follicle Isolation, Cryopreservation and Transplantation in Nude Mice

    PubMed Central

    Cao, Wenluo; Li, Lingna; Tran, Benjamin; Kajiura, Satoshi; Amoh, Yasuyuki; Liu, Fang; Hoffman, Robert M.

    2015-01-01

    We previously demonstrated that whole hair follicles could be cryopreserved to maintain their stem-cells differentation potential. In the present study, we demonstrated that cryopreserved mouse whisker hair follicles maintain their hair growth potential. DMSO better cryopreserved mouse whisker follicles compared to glycerol. Cryopreserved hair follicles also maintained the hair follicle-associated-pluripotent (HAP) stem cells, evidenced by P75NTR expression. Subcutaneous transplantation of DMSO-cryopreserved hair follicles in nude mice resulted in extensive hair fiber growth over 8 weeks, indicating the functional recovery of hair shaft growth of cryopreserved hair follicles. PMID:26716690

  6. Gallbladder small cell carcinoma Xenograft established by serial transplantation in nude mice.

    PubMed

    Nishime, Chiyoko; Ohnishi, Yasuyuki; Suemizu, Hiroshi; Tamaoki, Norikazu; Suematsu, Makoto; Oida, Yasuhisa; Yamazaki, Hitoshi; Nakamura, Masato; Ueyama, Yoshito; Kijima, Hiroshi

    2006-01-01

    The GB-04-JCK xenograft line of human gallbladder small cell carcinoma was established in nude mice by serial transplantation. The xenotransplantability has been maintained for more than 20 years. The carcinoma cells grew in a solid-sheet pattern and were found to have hyperchromatic nuclei, finely dispersed chromatin and inconspicuous nucleoli in the primary gallbladder tumor, as well as in the established xenograft GB-04-JCK The carcinoma cells also had Grimelius argyrophil granules, electron-dense neuroendocrine granules bounded by a single membrane. The xenograft line retained histological and immunohistochemical characteristics of the primary gallbladder tumor and is the first reported xenotransplantable tumor of human gallbladder small cell carcinoma.

  7. Ultrasound images of implanted tumors in nude mice using Sono-CT correlated with MRI appearance

    NASA Astrophysics Data System (ADS)

    Freedman, Matthew T.; Sarcone, Anita; Pirollo, Kathleen F.; Lin, Chin-Shoou; Chang, Esther

    2001-05-01

    Monitoring the effect of novel cancer chemotherapeutic agents in nude mice is now commonly done by external direct measurement and by autopsy. The development of small animal imaging has focused on micro-MRI, micro-CT and micro-PET -- each a highly expensive and highly valuable method. Far less work has been done with ultrasound imaging. We wish to demonstrate a new method of ultrasound imaging of living mice named Sono-CTR, Sono-CTR provides a compound image by combining the images obtained by electronically directing the transducer to scan from multiple angles.

  8. Abnormal blood vessels formed by human liver cavernous hemangioma endothelial cells in nude mice are suitable for drug evaluation.

    PubMed

    Zhang, Wen-jian; Wu, Lian-qiu; Liu, Hong-lin; Ye, Li-ya; Xin, Yu-ling; Grau, Georges E; Lou, Jin-ning

    2009-12-01

    Cavernous hemangioma is vascular malformation with developmental aberrations. It was assumed that the abnormality of endothelial cells contributed greatly to the occurrence of cavernous hemangioma. In our previous study, we have found distinct characteristics of endothelial cells derived from human liver cavernous hemangioma (HCHEC). Here, we reported the abnormal vascular vessels formed by primary HCHEC in nude mice and that the drug podophyllotoxin can destroy HCHEC in vitro and in vivo. HCHEC was isolated from a human liver cavernous hemangioma specimen, and the HCHEC generated a red hemangioma-like mass 7 days after subcutaneously co-inoculating HCHEC and human liver cancer cells (Bel-7402) in nude mice. Lentiviral expression of GFP and immunohistochemistry for human CD31 was used to confirm that the HCHEC formed the blood vessels in nude mice. And the pathological features of vascular vessels formed by HCHEC were very similar to clinical cavernous hemangioma. In addition, by MTT assay, the drug podophyllotoxin was found inhibiting HCHEC viability, and by TUNEL and DNA ladder assays, podophyllotoxin was found inducing apoptosis of HCHEC. Moreover, podophyllotoxin was also effective for destroying the abnormal vascular vessels in the hemangioma-like mass in nude mice. In summary, the HCHEC can form abnormal blood vessels in nude mice, and we can evaluate drugs for cavernous hemangioma by using HCHEC in vitro and in vivo.

  9. Non-invasive fluorescent-protein imaging of orthotopic pancreatic-cancer-patient tumorgraft progression in nude mice.

    PubMed

    Suetsugu, Atsushi; Katz, Matthew; Fleming, Jason; Truty, Mark; Thomas, Ryan; Saji, Shigetoyo; Moriwaki, Hisataka; Bouvet, Michael; Hoffman, Robert M

    2012-08-01

    In order to individualize and therefore have more effective treatment for pancreatic cancer, we have developed a multicolor, imageable, orthotopic mouse model for individual patients with pancreatic cancer by passaging their tumors through transgenic nude mice expressing green fluorescent protein (GFP) and red fluorescent protein (RFP). The tumors acquired brightly fluorescent stroma from the transgenic host mice, which was stably associated with the tumors through multiple passages. In the present study, pancreatic cancer patient tumor specimens were initially established in NOD.CB17-Prkdc(scid)/NcrCrl (NOD/SCID) mice. The tumors were then passaged orthotopically into transgenic nude mice ubiquitously expressing GFP and subsequently to nude mice ubiquitously expressing RFP. The tumors, with very bright GFP and RFP stroma, were then orthotopically passaged to non-transgenic nude mice. It was possible to image the brightly fluorescent tumors non-invasively longitudinally as they progressed in the non-transgenic nude mice. This non-invasive imageable tumorgraft model will be valuable to screen for effective treatment options for individual patients with pancreatic cancer, as well as for the discovery of improved agents for this treatment-resistant disease.

  10. Human cancer xenografts in outbred nude mice can be confounded by polymorphisms in a modifier of tumorigenesis.

    PubMed

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

    2014-08-01

    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 heterogeneous for this polymorphic Pla2g2a allele. This heterogeneity even extends to mice obtained from a single commercial provider, which display mixed Pla2g2a genotypes. Notably, we demonstrated that the polymorphic Pla2g2a allele affects orthotopic xenograft establishment of human colon cancer cells in outbred nude mice. This finding establishes a non-cell-autonomous role for Pla2g2a in suppressing intestinal tumorigenesis. Using in vitro reporter assays and pharmacological inhibitors, we show promoter polymorphisms and nonsense-mediated RNA decay (NMD) as underlying mechanisms that lead to low Pla2g2a mRNA levels in tumor-sensitive mice. Together, this study provides mechanistic insight regarding Pla2g2a polymorphisms and demonstrates a non-cell-autonomous role for Pla2g2a in suppressing tumors. Moreover, our direct demonstration that mixed genetic backgrounds of outbred nude mice can significantly affect baseline tumorigenicity cautions against future use of outbred mice for tumor xenograft studies.

  11. Nutritional and supranutritional levels of selenate differentially suppress prostate tumor growth in adult but not young nude mice.

    PubMed

    Holmstrom, Alexandra; Wu, Ryan T Y; Zeng, Huawei; Lei, K Y; Cheng, Wen-Hsing

    2012-09-01

    The inhibitory effect of oral methylseleninic acid or methylselenocysteine administration on cancer cell xenograft development in nude mice is well characterized; however, less is known about the efficacy of selenate and age on selenium chemoprevention. In this study, we tested whether selenate and duration on diets would regulate prostate cancer xenograft in nude mice. Thirty-nine homozygous NU/J nude mice were fed a selenium-deficient, Torula yeast basal diet alone (Se-) or supplemented with 0.15 (Se) or 1.0 (Se+) mg selenium/kg (as Na₂SeO₄) for 6 months in Experiment 1 and for 4 weeks in Experiment 2, followed by a 47-day PC-3 prostate cancer cell xenograft on the designated diet. In Experiment 1, the Se- diet enhanced the initial tumor development on days 11-17, whereas the Se+ diet suppressed tumor growth on days 35-47 in adult nude mice. Tumors grown in Se- mice were loosely packed and showed increased necrosis and inflammation as compared to those in Se and Se+ mice. In Experiment 2, dietary selenium did not affect tumor development or histopathology throughout the time course. In both experiments, postmortem plasma selenium concentrations in Se and Se+ mice were comparable and were twofold greater than those in Se- mice. Taken together, dietary selenate at nutritional and supranutritional levels differentially inhibit tumor development in adult, but not young, nude mice engrafted with PC-3 prostate cancer cells.

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

    PubMed Central

    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 heterogeneous for this polymorphic Pla2g2a allele. This heterogeneity even extends to mice obtained from a single commercial provider, which display mixed Pla2g2a genotypes. Notably, we demonstrated that the polymorphic Pla2g2a allele affects orthotopic xenograft establishment of human colon cancer cells in outbred nude mice. This finding establishes a non-cell-autonomous role for Pla2g2a in suppressing intestinal tumorigenesis. Using in vitro reporter assays and pharmacological inhibitors, we show promoter polymorphisms and nonsense-mediated RNA decay (NMD) as underlying mechanisms that lead to low Pla2g2a mRNA levels in tumor-sensitive mice. Together, this study provides mechanistic insight regarding Pla2g2a polymorphisms and demonstrates a non-cell-autonomous role for Pla2g2a in suppressing tumors. Moreover, our direct demonstration that mixed genetic backgrounds of outbred nude mice can significantly affect baseline tumorigenicity cautions against future use of outbred mice for tumor xenograft studies. PMID:24913681

  13. Antibody repertoire against HIV-1 gp120 triggered in nude and normal mice by GM-CSF/gp120 immunization.

    PubMed

    del Real, G; Llorente, M; Lucas, P; Kremer, L; Torán, J L; Martínez-A, C

    1999-08-01

    Granulocyte-macrophage colony stimulating factor (GM-CSF) facilitates the induction of primary immune responses by activating and recruiting antigen-presenting cells (APC), which efficiently present antigen determinants to Th cells. We have derived a functional GM-CSF/gp120 chimeric protein that, following immunization in soluble, adjuvant-independent form in normal mice, triggers highly specific, high affinity anti-gp120 antibodies. In contrast, nude mice respond with mutated, polyreactive, low affinity antibodies that mature further and increase in affinity in T cell-reconstituted nude mice. Anti-gp120 antibody production in nude mice is mediated principally by GM-CSF/gp120-triggered IL-4 production, since neutralizing anti-IL-4 abrogates the in vivo response. The anti-gp120 antibody response in normal, nude and T cell-reconstituted nude mice is encoded at a remarkably high frequency by the VH81X and VH7183 genes, a family used notably during fetal life and, when expressed at the adult stage, associated with autoimmune disease. We conclude that HIV gp120 binds and selects a subpopulation of developing B cells expressing a set of VH genes associated with immunodeficiency and autoimmunity.

  14. Measuring Implicit Sexual Response Biases to Nude Male and Female Pictures in Androphilic and Gynephilic Men.

    PubMed

    Timmins, Liam; Barnes-Holmes, Dermot; Cullen, Claire

    2016-05-01

    Snowden, Wichter, and Gray (2008) demonstrated that an Implicit Association Test and a Priming Task both predicted the sexual orientation of gynephilic and androphilic men in terms of their attraction biases towards pictures of nude males and females. For both measures, relative bias scores were obtained, with no information on the separate response biases to each target gender. The present study sought to extend this research by assessing both relative and individual implicit biases using the Implicit Relational Assessment Procedure (IRAP). An explicit measure screened for men with androphilic (n = 16) or gynephilic (n = 16) orientations on the dimensions of "sexual attraction," "sexual behavior," "sexual fantasies," "hetero/gay lifestyle," and "self identification." The IRAP involved responding "True" or "False" to pictures of nude males and females as either attractive or unattractive. Participants were required to respond in a manner consistent with their reported sexual orientation for half of the IRAP's test blocks and inconsistent for the other half. Response latencies were recorded and analyzed. The IRAP revealed a non-orthogonal pattern of biases across the two groups and had an excellent ability to predict sexual orientation with areas under the curves of 1.0 for the relative bias score and .94 and .95 for the bias scores for the male and female pictures, respectively. Correlations between the IRAP and explicit measures of sexual orientation were consistently high. The findings support the IRAP as a potentially valuable tool in the study of sexual preferences.

  15. Folate antagonist, methotrexate induces neuronal differentiation of human embryonic stem cells transplanted into nude mouse retina.

    PubMed

    Hara, Akira; Taguchi, Ayako; Aoki, Hitomi; Hatano, Yuichiro; Niwa, Masayuki; Yamada, Yasuhiro; Kunisada, Takahiro

    2010-06-25

    Transplanted embryonic stem (ES) cells can be integrated into the retinas of adult mice as well-differentiated neuroretinal cells. However, the transplanted ES cells also have a tumorigenic activity as they have the ability for multipotent differentiation to various types of tissues. In the present study, human ES (hES) cells were transplanted into adult nude mouse retinas by intravitreal injections 20 h after intravitreal N-methyl-D-aspartate (NMDA) administration. After the transplantation of hES cells, the folate antagonist, methotrexate (MTX) was administrated in order to control the differentiation of the transplanted hES cells. Neuronal differentiation and teratogenic potential of hES cells were examined immunohistochemically 5 weeks after transplantation. The proliferative activity of transplanted cells was determined by both the mitotic index and the Ki-67 proliferative index. Disappearance of Oct-4-positive hES cells showing undifferentiated morphology was observed after intraperitoneal MTX treatment daily, for 15 days. Decreased mitotic and Ki-67 proliferative indices, and increased neuronal differentiation were detected in the surviving hES cells after the MTX treatment. These results suggest two important effects of intraperitoneal MTX treatment for hES cells transplanted into nude mouse retina: (1) MTX treatment following transplantation induces neuronal differentiation, and (2) MTX decreases proliferative activity and tumorigenic potential.

  16. Rapid deposition of amyloid in human islets transplanted into nude mice.

    PubMed

    Westermark, P; Eizirik, D L; Pipeleers, D G; Hellerström, C; Andersson, A

    1995-05-01

    Human islets of Langerhans were transplanted to the subcapsular space of the kidneys of nude mice which were either normoglycaemic or made diabetic with alloxan. After 2 weeks, the transplants were processed for light and electron microscopical analyses. In all transplants, islet amyloid polypeptide (IAPP)-positive cells were found with highest frequency in normoglycaemic animals. IAPP-positive amyloid was seen in 16 out of 22 transplants (73%), either by polarisation microscopy after Congo red staining or by immune electron microscopy. At variance with previous findings of amyloid deposits exclusively in the extracellular space of islets of non-insulin-dependent diabetic patients, the grafted islets contained intracellular amyloid deposits as well. There was no clear difference in occurrence of amyloid between diabetic and non-diabetic animals. The present study indicates that human islets transplanted into nude mice very soon present IAPP-positive amyloid deposits. This technique may provide a valuable model for studies of the pathogenesis of islet amyloid and its impact on islet cell function.

  17. Interaction of the heterozygous nude gene with the asplenia trait in mammary tumorigenesis

    PubMed Central

    1985-01-01

    The BALB/c mouse strain has been shown to contain endogenous mouse mammary tumor virus (MMTV) proviral sequences. However, no exogenous MMTV particles have been detected in their tissues. Female BALB/c mice from our colonies exhibit a very low incidence of spontaneous mammary tumors (SMT); less than 1% at up to 20 mo of age. Immunodeficient BALB/c mice heterozygous for the nude gene (nu/+, +/+), for the dominant hemimelia gene associated with asplenia (+/+, Dh/+), or for both traits (nu/+, Dh/+) have been examined for SMT incidence and the presence of MMTV proviruses. Based on restriction digestion with Eco RI, Bam HI, and Pst I, the immunodeficient mice have an MMTV provirus copy number and organization identical to the BALB/cCrgl strain. This MMTV DNA pattern is distinct from the MMTV proviruses in C3H/He, C57BL/6J and CBA/CaJ mice, which were parental strains of the immunodeficient mutants. Normal female BALB/c or BALB/c heterozygous for the asplenic trait do not develop significant numbers of SMT at up to 19 mo of age. In contrast, an incidence of 23.8% and 57.7% SMT was observed in BALB/c nu/+ heterozygotes, and in BALB/c nu/+, Dh/+ heterozygotes, respectively. These results indicate that agenesis of the spleen, concomitant with the presence of the heterozygous nude gene, contribute to a high incidence of SMT in the low-SMT BALB/c mouse strain. PMID:2982992

  18. 3-Bromopyruvate inhibits human gastric cancer tumor growth in nude mice via the inhibition of glycolysis.

    PubMed

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

    2015-02-01

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

  19. Effects of Tetrahydrocurcumin on Tumor Growth and Cellular Signaling in Cervical Cancer Xenografts in Nude Mice

    PubMed Central

    Yoysungnoen, Bhornprom; Bhattarakosol, Parvapan; Changtam, Chatchawan; Patumraj, Suthiluk

    2016-01-01

    Tetrahydrocurcumin (THC) is a stable metabolite of curcumin (CUR) in physiological systems. The mechanism underlying the anticancer effect of THC is not completely understood. In the present study, we investigated the effects of THC on tumor growth and cellular signaling in cervical cancer xenografts in nude mice. Cervical cancer cells (CaSki) were subcutaneously injected in nude mice to establish tumors. One month after the injection, mice were orally administered vehicle or 100, 300, and 500 mg/kg of THC daily for 30 consecutive days. Relative tumor volume (RTV) was measured every 3-4 days. COX-2, EGFR, p-ERK1&2, p-AKT, and Ki-67 expressions were measured by immunohistochemistry whereas cell apoptosis was detected by TUNELS method. THC treatments at the doses of 100, 300, and 500 mg/kg statistically retarded the RTV by 70.40%, 76.41%, and 77.93%, respectively. The CaSki + vehicle group also showed significantly increased COX-2, EGFR, p-ERK1&2, and p-AKT; however they were attenuated by all treatments with THC. Ki-67 overexpression and a decreasing of cell apoptosis were found in CaSki + vehicle group, but these findings were reversed after the THC treatments. PMID:26881213

  20. Effects of Tetrahydrocurcumin on Tumor Growth and Cellular Signaling in Cervical Cancer Xenografts in Nude Mice.

    PubMed

    Yoysungnoen, Bhornprom; Bhattarakosol, Parvapan; Changtam, Chatchawan; Patumraj, Suthiluk

    2016-01-01

    Tetrahydrocurcumin (THC) is a stable metabolite of curcumin (CUR) in physiological systems. The mechanism underlying the anticancer effect of THC is not completely understood. In the present study, we investigated the effects of THC on tumor growth and cellular signaling in cervical cancer xenografts in nude mice. Cervical cancer cells (CaSki) were subcutaneously injected in nude mice to establish tumors. One month after the injection, mice were orally administered vehicle or 100, 300, and 500 mg/kg of THC daily for 30 consecutive days. Relative tumor volume (RTV) was measured every 3-4 days. COX-2, EGFR, p-ERK1&2, p-AKT, and Ki-67 expressions were measured by immunohistochemistry whereas cell apoptosis was detected by TUNELS method. THC treatments at the doses of 100, 300, and 500 mg/kg statistically retarded the RTV by 70.40%, 76.41%, and 77.93%, respectively. The CaSki + vehicle group also showed significantly increased COX-2, EGFR, p-ERK1&2, and p-AKT; however they were attenuated by all treatments with THC. Ki-67 overexpression and a decreasing of cell apoptosis were found in CaSki + vehicle group, but these findings were reversed after the THC treatments.

  1. Therapeutic effect of a radiolabeled monoclonal antibody on human ovarian cancer xenograft in nude mice

    SciTech Connect

    Manetta, A.; Satyaswaroop, P.G.; Hamilton, T.; Ozols, R.; Mortel, R.

    1989-03-01

    The therapeutic value of 131I-OC125, a radiolabeled monoclonal antibody directed against a human ovarian tumor associated antigen CA125, was examined in an ascites forming intraperitoneal human ovarian carcinoma nude mouse model. Nude mice were injected intraperitoneally with NIH:OVCAR3 cells. Twenty-one days after tumor transplantation, groups of animals were injected intraperitoneally as follows: Group 1 with 200 microCi of 131I-OC125 (n = 20), Group 2 with 200 microCi of 131I (n = 17), Group 3 with 200 microCi of 131I-IgG (n = 21), Group 4 with 60 micrograms of OC125 (n = 18), and Group 5 was left untreated (n = 21). Survival of the tumor-bearing animals was used as the endpoint of the experiment. Mean survivals were found to be 52 +/- 18 days for the 131I-OC125 group, 53 +/- 16 days for the 131I-IgG group, 49 +/- 13 days for the 131I group, 47 +/- 24 days for the OC125 group, and 47 +/- 15 days for the untreated control. These results would indicate no therapeutic advantage of 131I-OC125 over controls in this animal model. However, other approaches using single as well as multiple radiolabeled monoclonal antibodies need to be tested in this model in order to definitely establish the efficacy of this treatment modality.

  2. [Reversal of multidrug resistance of MCF-7/ADR in nude mice by grape seed polyphenol].

    PubMed

    Zhang, Cui-Juan; Zhou, Geng-Yin; Li, Li; Ma, Li-Li; Gao, Peng; Li, Hong

    2004-07-07

    To study the reversing effect of Grape seed polyphenol (GSP) on multidrug resistance of MCF-7/ADR cell in vivo. The transplantable breast carcinoma cell line MCF-7/ADR model was established in BALB/C-nu/nu mice by subcutaneous implantation. Flow cytometry (FCM) was used to investigate the changes of Pgp expression and apoptosis rate after different drug treatment. GSP has some effect on inhibition of tumor growth (the rate of inhibition was 18.35%), and combined with adriamycin can significantly inhibit tumor growth in nude mice, 20 mg/kg GSP can effectively reverse the resistance of MCF-7/ADR cells to ADR in vivo, and the rate of inhibition was 54.64%. FCM results showed that the expression of Pgp was significantly decreased (32.03 +/- 2.09) After administration of GSP and ADR, there was distinct difference between it and control (55.13 +/- 2.12). The mean rate of apoptosis was 15.12% +/- 1.04%, and was significantly increased compared with control (9.07% +/- 0.43%), P < 0.05. GSP can effectively reversed the resistance of MCF-7/ADR cells in nude mice, the mechanism may be correlated with inhibition of Pgp expression and apoptosis.

  3. Beware of contaminating mouse cells in human xenografts from nude mice.

    PubMed

    Yang, J; Liu, A; Dougherty, C; Chen, X; Guzman, R; Nandi, S

    2000-01-01

    Human tumor xenografts in nude mice are widely utilized model system for the transplantation of human surgical specimens and human established cell lines. Gene expression studies are often carried out in these model systems. With an increasing use of PCR based analyses, the extreme sensitivity of this technique poses a serious challenge with regards to the extent of contaminating host mouse cells in the human tumor xenografts. These xenografts are never free of host cell contamination. We detected mouse estrogen receptor expression in several human tumor xenografts using RT-PCR demonstrating that precaution is necessary when utilizing PCR based analyses in human tumor xenografts. A cytologically based methodology which distinguishes human versus mouse cells will be more suitable for ER expression studies using human xenograft models. Both (1) in situ hybridization using human probe and (2) immunocytochemistry using a monoclonal antibody directed against human cytokeratin have been used successfully to distinguish human cells versus host mouse cells in human xenografts in nude mice. Immunostaining of ER can then be utilized to determine the expression pattern of ER in the transplanted human cells.

  4. Enhancing the survival of aspirated human fat injected into nude mice.

    PubMed

    Ullmann, Y; Hyams, M; Ramon, Y; Beach, D; Peled, I J; Lindenbaum, E S

    1998-06-01

    Injection of aspirated fat is now the most commonly used technique for the filling of depressed areas. Partial absorption of the injected fat is the main limitation of this procedure. Cariel T.M. is an enriched serum-free cell culture medium, its ability to enhance the survival of human aspirated fat grafts was investigated in the nude mouse model. A volume of 0.75-cc Cariel preprocessed fat was injected under the scalp skin of 16 nude mice in the experimental group, and the same volume of saline preprocessed fat was injected to 15 control group of mice. Significant maintenance of the weight, 46 percent in the experimental group compared with 29 percent in the control group (p < 0.008), and the volume, 44 percent in the experimental group compared with 31 percent in the control group (p < 0.026), was observed, after 15 weeks, in this newly used model. It seems that addition of the nutrients enriched with anabolic hormones enabled the survival and take of more adipose cells in the graft.

  5. ACTIVITY OF HOST-DERIVED T CELLS WHICH DIFFERENTIATE IN NUDE MICE GRAFTED WITH CO-ISOGENIC OR ALLOGENEIC THYMUSES

    PubMed Central

    Kindred, Berenice; Loor, Francis

    1974-01-01

    If nude mice are grafted with a neonatal thymus, host type precursor cells develop within the graft thymus and after about 6 wk the T-cell population of the thymus, spleen, and lymph nodes is of host type. However, immunological responsiveness produced in nude mice in this manner is incomplete: (a) the ability to react to T-cell mitogens in vitro is greater than in untreated nudes but lower than in normal mice; (b) the response to T-cell dependent antigens is less than normal; and (c) the rejection of skin grafts is slower than in normal animals. Whether host precursor cells which differentiate in an allogeneic thymus are able to reject skin grafts from thymus donor strain appears to depend on the strain combination used. PMID:4596513

  6. Activity of host-derived T cells which differentiate in nude mice grafted with co-isogenic or allogeneic thymuses.

    PubMed

    Kindred, B; Loor, F

    1974-05-01

    If nude mice are grafted with a neonatal thymus, host type precursor cells develop within the graft thymus and after about 6 wk the T-cell population of the thymus, spleen, and lymph nodes is of host type. However, immunological responsiveness produced in nude mice in this manner is incomplete: (a) the ability to react to T-cell mitogens in vitro is greater than in untreated nudes but lower than in normal mice; (b) the response to T-cell dependent antigens is less than normal; and (c) the rejection of skin grafts is slower than in normal animals. Whether host precursor cells which differentiate in an allogeneic thymus are able to reject skin grafts from thymus donor strain appears to depend on the strain combination used.

  7. Inhibition of Growth and Metastasis of Tumor in Nude Mice after Intraperitoneal Injection of Bevacizumab.

    PubMed

    Zhao, Ze-Xue; Li, Xiang; Liu, Wei-Dong; Liu, Xiao-Zhou; Wu, Su-Jia; Hu, Xiao-Hui

    2016-05-01

    To explore the inhibitory effect of bevacizumab, a vascular endothelial growth factor antibody, on angiogenesis in human osteosarcoma of nude mice. Twenty-one nude mice were inoculated with red fluorescent protein (RFP)-labeled human osteosarcoma cell line 143B-RFP, that is, clones that expressed RFP in the cytoplasm, and randomly assigned to one of three groups: G1 (Control group, injected with saline solution); G2 (intraperitoneal bevacizumab 2 mg/kg twice per week) and G3 (intraperitoneal bevacizumab 5 mg/kg, twice per week). The tumor-bearing mice were examined in a fluorescence light box that was illuminated periodically. The primary tumors were measured by fluorescence imaging weekly and their volumes calculated. The mean tumor volumes were significantly smaller in the G3 (186.4 ± 100.8 mm(3) ) than the control group (587.0 ± 406.8 mm(3) ) (P < 0.05) on Day 31, and again significantly smaller in the G3 (677.3 ± 461.9 mm(3) ) than the control group (3162.6 ± 1529.2 mm(3) ) on Day 38 (P < 0.01). The average tumor volume in the G2 group was 493.5 ± 425.4 mm(3) on Day 31 and 1870.1 ± 1524.8 mm(3) on Day 38. The effect on tumor volume was greater in the G3 than the G2 group. Three mice in the G2 group, four in the G3 group and four in the control group developed lung metastases that were confirmed by pathological examination; these differences were not statistically significant (P < 0.05). Bevacizumab exhibits strong antiangiogenesis activity in experimental osteosarcoma in a nude mouse model but does not influence the incidence of lung metastasis. Our findings may have considerable potential for the treatment of osteosarcoma. © 2016 The Authors. Orthopaedic Surgery Published by John Wiley & Sons Australia, Ltd and Chinese Orthopaedic Association.

  8. Optoacoustic system for 3D functional and molecular imaging in nude mice

    NASA Astrophysics Data System (ADS)

    Fronheiser, Matthew P.; Stein, Alan; Herzog, Don; Thompson, Scott; Liopo, Anton; Eghtedari, Mohammad; Motamedi, Massoud; Ermilov, Sergey; Conjusteau, Andre; Gharieb, Reda; Lacewell, Ron; Miller, Tom; Mehta, Ketan; Oraevsky, Alexander A.

    2008-02-01

    A three-dimensional laser optoacoustic imaging system was developed, which combines the advantages of optical spectroscopy and high resolution ultrasonic detection, to produce high contrast maps of optical absorbance in tissues. This system was tested in a nude mouse model of breast cancer and produced tissue images of tumors and vasculature. The imaging can utilize either optical properties of hemoglobin and oxyhemoglobin, which are the main endogenous tissue chromophores in the red and near-infrared spectral ranges, or exogenous contrast agent based on gold nanorods. Visualization of tissue molecules targeted by the contrast agent provides molecular information. Visulization of blood at multiple colors of light provides functional information on blood concentration and oxygen saturation. Optoacoustic imaging, using two or more laser illumination wavelengths, permits an assessment of the angiogenesis-related microvasculature, and thereby, an evaluation of the tumor stage and its metastatic potential. The optoacoustic imaging system was also used to generate molecular images of the malignancy-related receptors induced by the xenografts of BT474 mammary adenocarcinoma cells in nude mice. The development of the latter images was facilitated by the use of an optoacoustic contrast agent that utilizes gold nanorods conjugated to monoclonal antibody raised against HER2/neu antigens. These nanorods possess a very strong optical absorption peak that can be tuned in the near-infrared by changing their aspect ratio. The effective conversion of the optical energy into heat by the gold nanorods, followed by the thermal expansion of the surrounding water, makes these nanoparticles an effective optoacoustic contrast agent. Optical scattering methods and x-ray tomography may also benefit from the application of this contrast agent. Administration of the gold nanorod bioconjugates to mice resulted in an enhanced contrast of breast tumors relative the background of normal tissues

  9. Development of a nude mouse model to study human sebaceous gland physiology and pathophysiology.

    PubMed Central

    Petersen, M J; Zone, J J; Krueger, G G

    1984-01-01

    Study of human sebaceous gland physiology and pathophysiology is limited by lack of an adequate animal model. This study was designed to develop an animal model using human face skin grafted onto the nude mouse to study human sebaceous glands. Full-thickness human face skin was grafted onto 60 adult male nude mice. 4 wk after grafting, androgens, which are known to stimulate sebaceous glands, were administered to test the system. Androgens were administered to 21 animals by implanted catheters that were filled with testosterone (T) or dihydrotestosterone (DHT). Empty catheters were implanted in 15 control animals. Graft biopsies and blood for androgen levels were obtained at time 1 (pre-catheter) and time 2 (26 d after catheter implantation). Three assessments were made on each biopsy: sebaceous gland volume, using an image analyzing computer; sebaceous cell size; and sebaceous gland labeling index. 29 mice completed the study through time 2. In the androgen-treated group, T levels (nanogram per milliliter) five times increased to 4.92 +/- 0.35, and DHT levels (nanogram per milliliter) increased 50 times to 16.70. In the androgen-treated group, sebaceous gland volume (micron 3 X 10(-3) increased from 896 +/- 194 to 3,233 +/- 754 (P less than 0.001), sebaceous cell area (micron 2) increased from 167 +/- 12 to 243 +/- 19 (P less than 0.001), and labeling index (percentage) increased from 2.7 +/- 0.7 to 6.4 +/- 0.9 (P less than 0.01). In the control group, sebaceous gland volume fell from 1,070 +/- 393 to 417 +/- 99 (NS), sebaceous cell size remained the same, and the labeling index fell from 5.1 +/- 1.9 to 3.2 +/- 1.1. After androgen administration, Halowax N-34, a known comedogen, or its vehicle, was applied to 15 grafts for 2-6 wk. Twice as many microcomedones were seen in the Halowax-treated grafts, compared with vehicle-treated grafts at the end of this time period. No visible comedones were produced. This study demonstrated that: (a) human sebaceous glands can

  10. Mesenchymal stem cell-based NK4 gene therapy in nude mice bearing gastric cancer xenografts.

    PubMed

    Zhu, Yin; Cheng, Ming; Yang, Zhen; Zeng, Chun-Yan; Chen, Jiang; Xie, Yong; Luo, Shi-Wen; Zhang, Kun-He; Zhou, Shu-Feng; Lu, Nong-Hua

    2014-01-01

    Mesenchymal stem cells (MSCs) have been recognized as promising delivery vehicles for gene therapy of tumors. Gastric cancer is the third leading cause of worldwide cancer mortality, and novel treatment modalities are urgently needed. NK4 is an antagonist of hepatocyte growth factor receptors (Met) which are often aberrantly activated in gastric cancer and thus represent a useful candidate for targeted therapies. This study investigated MSC-delivered NK4 gene therapy in nude mice bearing gastric cancer xenografts. MSCs were transduced with lentiviral vectors carrying NK4 complementary DNA or enhanced green fluorescent protein (GFP). Such transduction did not change the phenotype of MSCs. Gastric cancer xenografts were established in BALB/C nude mice, and the mice were treated with phosphate-buffered saline (PBS), MSCs-GFP, Lenti-NK4, or MSCs-NK4. The tropism of MSCs toward gastric cancer cells was determined by an in vitro migration assay using MKN45 cells, GES-1 cells and human fibroblasts and their presence in tumor xenografts. Tumor growth, tumor cell apoptosis and intratumoral microvessel density of tumor tissue were measured in nude mice bearing gastric cancer xenografts treated with PBS, MSCs-GFP, Lenti-NK4, or MSCs-NK4 via tail vein injection. The results showed that MSCs migrated preferably to gastric cancer cells in vitro. Systemic MSCs-NK4 injection significantly suppressed the growth of gastric cancer xenografts. MSCs-NK4 migrated and accumulated in tumor tissues after systemic injection. The microvessel density of tumor xenografts was decreased, and tumor cellular apoptosis was significantly induced in the mice treated with MSCs-NK4 compared to control mice. These findings demonstrate that MSC-based NK4 gene therapy can obviously inhibit the growth of gastric cancer xenografts, and MSCs are a better vehicle for NK4 gene therapy than lentiviral vectors. Further studies are warranted to explore the efficacy and safety of the MSC-based NK4 gene therapy in

  11. Development of a nude mouse model to study human sebaceous gland physiology and pathophysiology.

    PubMed

    Petersen, M J; Zone, J J; Krueger, G G

    1984-10-01

    Study of human sebaceous gland physiology and pathophysiology is limited by lack of an adequate animal model. This study was designed to develop an animal model using human face skin grafted onto the nude mouse to study human sebaceous glands. Full-thickness human face skin was grafted onto 60 adult male nude mice. 4 wk after grafting, androgens, which are known to stimulate sebaceous glands, were administered to test the system. Androgens were administered to 21 animals by implanted catheters that were filled with testosterone (T) or dihydrotestosterone (DHT). Empty catheters were implanted in 15 control animals. Graft biopsies and blood for androgen levels were obtained at time 1 (pre-catheter) and time 2 (26 d after catheter implantation). Three assessments were made on each biopsy: sebaceous gland volume, using an image analyzing computer; sebaceous cell size; and sebaceous gland labeling index. 29 mice completed the study through time 2. In the androgen-treated group, T levels (nanogram per milliliter) five times increased to 4.92 +/- 0.35, and DHT levels (nanogram per milliliter) increased 50 times to 16.70. In the androgen-treated group, sebaceous gland volume (micron 3 X 10(-3) increased from 896 +/- 194 to 3,233 +/- 754 (P less than 0.001), sebaceous cell area (micron 2) increased from 167 +/- 12 to 243 +/- 19 (P less than 0.001), and labeling index (percentage) increased from 2.7 +/- 0.7 to 6.4 +/- 0.9 (P less than 0.01). In the control group, sebaceous gland volume fell from 1,070 +/- 393 to 417 +/- 99 (NS), sebaceous cell size remained the same, and the labeling index fell from 5.1 +/- 1.9 to 3.2 +/- 1.1. After androgen administration, Halowax N-34, a known comedogen, or its vehicle, was applied to 15 grafts for 2-6 wk. Twice as many microcomedones were seen in the Halowax-treated grafts, compared with vehicle-treated grafts at the end of this time period. No visible comedones were produced. This study demonstrated that: (a) human sebaceous glands can

  12. A nude rat model for neutron capture therapy of human intracerebral melanoma

    SciTech Connect

    Barth, R.F.; Matalka, K.Z.; Bailey, M.Q.; Staubus, A.E.; Soloway, A.H.; Moeschberger, M.L. ); Coderre, J.A. ); Rofstad, E.K. )

    1994-03-30

    The present study was carried out to determine the efficacy of Boron Neutron Capture Therapy (BNCT) for intracerebral melanoma using nude rats, the human melanoma cell line MRA 27, and boronophenylalanine as the capture agent. MRA 27 cells (2 [times] 10[sup 5]) were implanted intracerebrally, and 30 days later, 120 mg of [sup 10]B-L-BPA were injected intraperitoneally into nude rats. Thirty days following implantation, tumor bearing rats were irradiated at the Brookhaven Medical Research Reactor. Six hours following administration of BPA, tumor, blood, and normal brain boron-10 levels were 23.7, 9.4, and 8.4 [mu]g/g respectively. Median survival time of untreated rats was 44 days compared to 76 days and 93 days for those receiving physical doses of 2.73 Gy and 3.64 Gy, respectively. Rats that have received both [sup 10]B-BPA and physical doses of 1.82, 2.73, or 3.64 Gy had median survival times of 170, 182, and 262 days, respectively. Forty percent of rats that had received the highest tumor dose (10.1 Gy) survived for > 300 days and in a replicate experiment 21% of the rats were longterm survivors (>220 days). Animals that received 12 Gy in a single dose or 18 Gy fractionated (2 Gy [times] 9) of gamma photons from a [sup 137]Cs source had median survival times of 86 and 79 days, respectively, compared to 47 days for untreated animals. Histopathologic examination of the brains of longterm surviving rats, euthanized at 8 or 16 months following BNCT, showed no residual tumor, but dense accumulations of melanin laden macrophages and minimal gliosis were observed. Significant prolongations in median survival time were noted in nude rats with intracerebral human melanoma that had received BNCT, thereby suggesting therapeutic efficacy. Large animal studies should be carried out to further assess BNCT of intracerebral melanoma before any human trials are contemplated. 49 refs., 7 figs., 2 tabs.

  13. RNA interference of pax2 inhibits growth of transplanted human endometrial cancer cells in nude mice

    PubMed Central

    Zhang, Li-Ping; Shi, Xiao-Yan; Zhao, Chang-Yin; Liu, Yong-Zhen; Cheng, Ping

    2011-01-01

    The development of human endometrial carcinoma (HEC) is a complex pathologic process involves several oncogenes and tumor suppressor genes. The full-length paired-box gene 2 (pax2), a recently discovered Oncogene, promotes cell proliferation and growth and inhibits apoptosis of HEC cells. Here, we examined the effect of pax2 small interfering RNA (siRNA) on the growth of transplanted HEC cells in nude mice. The expression of Pax2 in 21 cases of normal endometrium and 38 cases of HEC was examined by immohistochemistry (IHC). HEC models were developed by subcutaneously transferring HEC cells into nude mice, followed by treatment with empty lentivirus vector, lentivirus vector-based pax2 siRNA, and phosphate buffered saline, respectively. Four weeks later, tumor size was measured, tumor inhibition rate was calculated, and histological analyses were conducted after staining with hematoxylin and eosin. The expression of Pax2 and Bcl-2 was detected by Western blot; proliferating cell nuclear antigen (PCNA) was detected by IHC. Significant differences were observed in the positive rate of Pax2 between normal endometrium and HEC (14.2% vs. 60.5%, P < 0.01). The expression index of Pax2 in well differentiated tumors was 1.88 ± 1.68, much lower than that in tumors of moderate (3.07 ± 1.96, P < 0.05) or poor differentiation (5.45 ± 2.76, P < 0.01). Tumor necrosis increased, nuclear basophilia stain decreased, tumor growth was inhibited, and PCNA, Pax2, and Bcl-2 expression was reduced in HEC models treated with pax2 siRNA. These results indicate that Pax2 expression is related to HEC tumor biology with the increased expression of Pax2 correlated to malignancy. pax2 siRNA down-regulates Pax2 expression and inhibits tumorigenesis of HEC in nude mice, possibly due to cell apoptosis and the inhibition of tumor proliferation induced by down-regulation of Bcl-2. PMID:21627862

  14. Coinfection of human foreskin fragments with multiple human papillomavirus types (HPV-11, -40, and -LVX82/MM7) produces regionally separate HPV infections within the same athymic mouse xenograft.

    PubMed Central

    Christensen, N D; Koltun, W A; Cladel, N M; Budgeon, L R; Reed, C A; Kreider, J W; Welsh, P A; Patrick, S D; Yang, H

    1997-01-01

    The athymic mouse xenograft system was used to prepare infectious stocks of two additional anogenital tissue-targeting human papillomaviruses (HPVs) in a manner similar to that for the development of infectious stocks of HPV-11. An anal condyloma from a transplant patient was used as material for extraction of infectious virus, and human foreskin fragments were incubated with the virus suspension and transplanted subrenally into athymic mice. Partial viral sequencing indicated that two rare HPV types (HPV-40 and HPVLVX82/MM7) were concurrently present in both the patient condyloma and the foreskin xenografts, and passage of both types was achieved as a mixed infection with HPV-40 predominating. Xenografts that developed from simultaneous infection of human foreskin fragments with HPV-11, -40, and -LVX82/MM7 virions produced regionally separate areas of HPV-11 and -40 infection as determined by in situ hybridization. In addition, in situ hybridization with HPV-40 and HPVLVX82/MM7 DNA probes demonstrated that both of these HPV types were present as adjacent but separate infections within the same anal condyloma of the transplant patient. These studies indicate that multiple HPV types can simultaneously infect genital tissue and that each HPV type predominantly maintains regional separation within the same papilloma. PMID:9311811

  15. Inhibition of the growth of human hepatocellular carcinoma in vitro and in athymic mice by a quinazoline inhibitor of thymidylate synthase, CB3717.

    PubMed Central

    Curtin, N. J.; Harris, A. L.; James, O. F.; Bassendine, M. F.

    1986-01-01

    Two human primary liver cancer cell-lines, PLC/PRF/5 and Hep 3B, grown both in vitro and as xenografts in nude mice were used to evaluate the chemotherapeutic potential of a new quinazoline antifolate CB3717. Xenograft growth rate was followed both by serial serum alphafoetoprotein (AFP) measurement and direct volume estimation. A dose regime of 200 mg CB3717 kg-1 body wt day-1 for 5 days caused a significant reduction in growth rate, as measured by relative serum AFP, of both xenografts; PLC/PRF/5 derived xenograft growth was also inhibited by 125 mg CB 3717 kg-1 day-1 for 5 days. Cell culture experiments showed that the ID50 for the cell lines fell within the range of serum CB3717 concentration achieved by a dose of 300 mg m-2 given to patients. Treatment with CB3717 stimulated the incorporation of exogenous thymidine into DNA by the tumour cells, presumably because of inhibition of the de novo pathway and reduction of endogenous thymidine triphosphate pools. These results suggest that CB3717 may be a useful new therapeutic agent in human primary liver cell carcinoma and that blocking the salvage pathway may further increase efficacy. PMID:3008799

  16. Tissue-Specific Expression of Herpes Simplex Virus Thymidine Kinase Gene Delivered by Adeno-Associated Virus Inhibits the Growth of Human Hepatocellular Carcinoma in Athymic Mice

    NASA Astrophysics Data System (ADS)

    Su, Hua; Lu, Ronghua; Chang, Judy C.; Kan, Yuet Wai

    1997-12-01

    About 70% of hepatocellular carcinomas are known to express α -fetoprotein, which is normally expressed in fetal but not in adult livers. To induce herpes simplex virus-thymidine kinase expression in these cancer cells, we constructed an adeno-associated viral vector containing the HSV-TK gene under the control of the α -fetoprotein enhancer and albumin promoter. We previously demonstrated in vitro that although this vector can transduce a variety of human cells, only transduced AFP and albumin-expressing hepatocellular carcinoma cell lines were sensitive to killing by ganciclovir (GCV). In the present study, we explored the effect of this vector on hepatocellular carcinoma cells in vivo. Subcutaneous tumors generated in nude mice by implanting hepatocellular carcinoma cells previously transduced with this vector shrank dramatically after treatment with GCV. Bystander effect was also observed on the tumors generated by mixing transduced and untransduced cells. To test whether the tumor cells can be transduced by the virus in vivo, we injected the recombinant adeno-associated virus into tumors generated by untransduced hepatocarcinoma cell line. Tumor growth were retarded after treatment with GCV. These experiments demonstrate the feasibility of in vivo transduction of tumor cell with rAAV.

  17. Analytical characterization of academic nude paintings by José Veloso Salgado.

    PubMed

    Cardeira, A M; Longelin, S; Costa, S; Candeias, A; Carvalho, M L; Manso, M

    2016-01-15

    This case study illustrates the analytical characterization of 12 academic nude paintings by Veloso Salgado, made between 1883 and 1893. The study was done with in situ methods (infrared reflectography and EDXRF) and benchtop equipment (Raman and FTIR microscopes and SEM-EDS). Infrared reflectography revealed underdrawings, painting style, execution method and retouched/restored areas. Analytical techniques allowed the identification of gypsum, lead white, barium white, zinc white, yellow ochre, chrome yellow, zinc yellow, vermilion, synthetic ultramarine blue, cerulean blue, Prussian blue, viridian, green earth, Paris green, red ochre, raw umber and lamp black. These results provide valuable information on Salgado's palette and his artistic production technique and allow the distinction between palettes used in Lisbon and Paris and consequently, technical interchanges between both Academies. Finally, this study intends to start a systematic analytical study of the Faculty of Fine Arts' collection, allowing the characterization of many other authors and their influences for the development of painting methodology in this Academy.

  18. Mueller matrix polarimetry for characterizing microstructural variation of nude mouse skin during tissue optical clearing.

    PubMed

    Chen, Dongsheng; Zeng, Nan; Xie, Qiaolin; He, Honghui; Tuchin, Valery V; Ma, Hui

    2017-08-01

    We investigate the polarization features corresponding to changes in the microstructure of nude mouse skin during immersion in a glycerol solution. By comparing the Mueller matrix imaging experiments and Monte Carlo simulations, we examine in detail how the Mueller matrix elements vary with the immersion time. The results indicate that the polarization features represented by Mueller matrix elements m22&m33&m44 and the absolute values of m34&m43 are sensitive to the immersion time. To gain a deeper insight on how the microstructures of the skin vary during the tissue optical clearing (TOC), we set up a sphere-cylinder birefringence model (SCBM) of the skin and carry on simulations corresponding to different TOC mechanisms. The good agreement between the experimental and simulated results confirm that Mueller matrix imaging combined with Monte Carlo simulation is potentially a powerful tool for revealing microscopic features of biological tissues.

  19. Transplantation of a cell line derived from a canine benign mixed mammary tumour into nude mice.

    PubMed

    Priosoeryanto, B P; Tateyama, S; Yamaguchi, R; Uchida, K

    1995-11-01

    The MCM-B2 canine mammary cell line was serially transplanted into nude mice. The tumour masses consisted of elongated pleomorphic cells of varying size in the first to third passages; oval cells, becoming rounder, in the sixth to eighth passages; and cord-like, glandular and duct-like structures with compact radiating projections in the ninth and tenth passages. Ultrastructural and immunohistochemical examination of round cells confirmed their epithelial cell nature, but the morphology of the elongated and oval cells was identical with that of the original cell line. The findings suggest that the MCM-B2 cell line is a multipotential stem cell or is derived from glandular differentiation of mammary gland.

  20. Analytical characterization of academic nude paintings by José Veloso Salgado

    NASA Astrophysics Data System (ADS)

    Cardeira, A. M.; Longelin, S.; Costa, S.; Candeias, A.; Carvalho, M. L.; Manso, M.

    2016-01-01

    This case study illustrates the analytical characterization of 12 academic nude paintings by Veloso Salgado, made between 1883 and 1893. The study was done with in situ methods (infrared reflectography and EDXRF) and benchtop equipment (Raman and FTIR microscopes and SEM-EDS). Infrared reflectography revealed underdrawings, painting style, execution method and retouched/restored areas. Analytical techniques allowed the identification of gypsum, lead white, barium white, zinc white, yellow ochre, chrome yellow, zinc yellow, vermilion, synthetic ultramarine blue, cerulean blue, Prussian blue, viridian, green earth, Paris green, red ochre, raw umber and lamp black. These results provide valuable information on Salgado's palette and his artistic production technique and allow the distinction between palettes used in Lisbon and Paris and consequently, technical interchanges between both Academies. Finally, this study intends to start a systematic analytical study of the Faculty of Fine Arts' collection, allowing the characterization of many other authors and their influences for the development of painting methodology in this Academy.

  1. Growth of human normal and neoplastic mammary tissues in the cleared mammary fat pad of the nude mouse.

    PubMed

    Outzen, H C; Custer, R P

    1975-12-01

    Dysplastic and malignant human breast tissues were grown successfully in the cleared mammary fat pads (CFP) of nude mice. The mammary fat pads were cleared while the mice were in a germfree isolator. Prepared mice were removed fron the germfree enviornment to facilitate transplantation of the human mammary tissue into their CFP and subsequently were maintained in sterile laminar flow racks.

  2. Different patterns of macrophage infiltration into allogeneic-murine and xenogeneic-human neoplasms growing in nude mice.

    PubMed Central

    Bucana, C. D.; Fabra, A.; Sanchez, R.; Fidler, I. J.

    1992-01-01

    This study determined the distribution pattern of tumor-associated macrophages (TAM) in murine and human neoplasms growing subcutaneously in nude mice. Seven different human neoplasms (cancers of the breast, kidney, colon, prostate, lung, and skin, and a melanoma) and five different murine neoplasms (carcinomas of the lung, colon, and kidney, melanoma, and fibrosarcoma) were injected into nude mice. The murine tumors also were injected into syngeneic mice. Tumor-associated macrophages in small and large tumors were studied immunohistochemically by the use of several antibodies, including the macrophage-specific F4/80. The pattern of TAM distribution differed between mouse and human tumors. Regardless of histologic classification, TAM were uniformly distributed throughout all the murine neoplasms growing in syngeneic or nude mice. In the human neoplasms, TAM were found on the periphery of the lesions and in association with fibrous septae. The distribution of TAM in murine and human tumors was associated with a pattern of vascularization as determined by antibodies to basement membrane collagen type IV. Because the pattern of TAM distribution in neoplasms influences their antitumor activity, the data question the validity of the nude mouse model for the study of macrophage infiltration into human neoplasms. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:1443054

  3. Alleviation of streptozotocin-induced diabetes in nude mice by stem cells derived from human first trimester umbilical cord.

    PubMed

    Cao, M; Zhang, J B; Dong, D D; Mou, Y; Li, K; Fang, J; Wang, Z Y; Chen, C; Zhao, J; Yie, S M

    2015-10-16

    Cells isolated from human first trimester umbilical cord perivascular layer (hFTM-PV) tissues display the pluripotent characteristics of stem cells. In this study, we examined whether hFTM-PV cells can differentiate into islet-like clusters (ILCs) in vitro, and whether transplantation of the hFTM-PV cells with and without differentiation in vitro can alleviate diabetes in nude mice. The hFTM-PV cells were differentiated into ILCs in vitro through a simple stepwise culture protocol. To examine the in vivo effects of the cells, the hFTM-PV cells with and without differentiation in vitro were transplanted into the abdominal cavity of nude mice with streptozotocin (STZ)-induced diabetes. Blood glucose levels, body weight, and the survival probability of the diabetic nude mice were then statistically analyzed. The hFTM-PV cells were successfully induced into ILCs that could release insulin in response to elevated concentrations of glucose in vitro. In transplantation experiments, we observed that mice transplanted with the undifferentiated hFTM-PV cells, embryonic body-like cell aggregations, or ILCs all demonstrated normalized hyperglycemia and showed improved survival rate compared with those without cell transplantation. The hFTM-PV cells have the ability to differentiate into ILCs in vitro and transplantations of undifferentiated and differentiated cells can alleviate STZ-induced diabetes in nude mice. This may offer a potential cell source for stem cell-based therapy for treating diabetes in the future.

  4. Knockdown of RhoA expression alters ovarian cancer biological behavior in vitro and in nude mice.

    PubMed

    Wang, Xiaoxia; Jiang, Wenyan; Kang, Jiali; Liu, Qicai; Nie, Miaoling

    2015-08-01

    RhoA regulates cell proliferation, migration, angiogenesis and gene expression. Altered RhoA activity contributes to cancer progression. The present study investigated the effects of RhoA knockdown on the regulation of ovarian cancer biological behavior in vitro and in nude mice. The expression of RhoA was knocked down using a lentivirus carrying RhoA short hairpin RNA (shRNA) in ovarian cancer cells and was confirmed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The altered ovarian cancer biological behaviors were assayed by cell viability, terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL), migration, invasion, and nude mice tumorigenicity assays, while the altered gene expression was detected by RT-qPCR and western blot analysis. The results showed that lentivirus-carrying RhoA shRNA significantly suppressed RhoA expression in ovarian cancer cells, which suppressed tumor cell viability, migration, invasion and adhesion in vitro. RhoA silencing also inhibited the tumorigenicity of ovarian cancer cells in nude mice, which was characterized by the suppression of tumor xenograft formation and growth and induction of tumor cell apoptosis. The results of the present study demonstrated that knockdown of RhoA expression had a significant antitumor effect on ovarian cancer cells in vitro and in nude mice, suggesting that RhoA may be a target for the development of a novel therapeutic strategy in the control of ovarian cancer.

  5. Astaxanthin Inhibits PC-3 Xenograft Prostate Tumor Growth in Nude Mice

    PubMed Central

    Ni, Xiaofeng; Yu, Haining; Wang, Shanshan; Zhang, Chengcheng; Shen, Shengrong

    2017-01-01

    Prostate cancer (PCa), the most common malignancy in men, is a major cause of cancer deaths. A better understanding of the mechanisms that drive tumor initiation and progression may identify actionable targets to improve treatment of this patient group. As a dietary carotenoid, astaxanthin has been demonstrated to exert beneficial effects against inflammation, cardiovascular disease, oxidative damage, or different cancer sites. This study used intragastric administration of astaxanthin to detect its role on tumor proliferation, apoptosis, microRNA (miRNA) overexpression, and microbacteria composition change by establishing androgen-independent PCa cell PC-3 xenograft nude mice. Nude mice were inoculated with androgen-independent prostate cancer PC-3 cells subcutaneously. The intervention was started when tumors reached 0.5–0.6 cm in diameter. Mice were intragastrically administered 100 mg/kg astaxanthin (HA), 25 mg/kg astaxanthin (LA), or olive oil (TC). The results showed that 100 mg/kg astaxanthin significantly inhibited tumor growth compared to the TC group, with an inhibitory rate of 41.7%. A decrease of Ki67 and proliferating cell nuclear antigen (PCNA) as well as an increase of cleaved caspase-3 were observed in HA-treated tumors, along with increasing apoptotic cells, obtained by TUNEL assay. The HA significantly elevated the levels of tumor suppressors miR-375 and miR-487b in tumor tissues and the amount of Lactobacillus sp. and Lachnospiraceae in mice stools, while there was no significant difference between LA and TC groups. These results provide a promising regimen to enhance the therapeutic effect in a dietary supplement manner. PMID:28282880

  6. Tumorigenesis and spontaneous metastasis by luciferase-labeled human xenograft osteosarcoma cells in nude mice.

    PubMed

    Du, Lin; Xu, Wen-ting; Fan, Qi-ming; Tu, Bing; Shen, Yang; Yan, Wei; Tang, Ting-ting; Wang, You

    2012-11-01

    Osteosarcoma (OS) is the most common primary malignant tumor of bone. Mouse models of human OS can invariably provide greater insight into the complex mechanisms that underlie the development and pathogenesis of this aggressive tumor. Bioluminescence technology favored tracing cancer cells in vivo. In this study, an OS model was described and evaluated using human OS cell line, Saos2, labeled with luciferase (Saos2-luc). Saos2 cells were infected by lentivirus loading a firefly luciferase gene. Luciferase expression of Saos2-luc cells was characterized both in vitro and in vivo. Specific biologic and oncologic features of Saos2-luc cells were analyzed. The OS was established as orthotopic xenografts in nude mice. Both orthotopic tumors and spontaneous lung metastasis were analyzed. Tumorigenesis and spontaneous lung metastasis in nude mice could be monitored in vivo through in vivo imaging system. The enhancement in proliferation, migration and invasion abilities and the attenuation in adhesion ability were observed in Saos2-luc cells compared with Saos2 cells. Furthermore, there were the up-regulation of Osteocalcin, CCR10, CXCR1 and ID1 and the down-regulation of ALP, collagen I, CCR1, CCR3, CXCR3, NID and N-cadherin in Saos2-luc cells compare to Saos2 cells. The rate of spontaneous lung metastasis in Saos2-luc cells was higher than that in Saos2 cells, although without significant difference. Lentivirus transfection may cause alteration of gene expression profiles and further biological functions. This model can be used in the elucidation of molecular mechanisms of tumorigenesis and the screening of new therapeutic agents.

  7. Primary tumorectomy promotes angiogenesis and pulmonary metastasis in osteosarcoma-bearing nude mice.

    PubMed

    Wang, Zhi-Yuan; Mei, Jiong; Gao, You-Shui; Ni, Ming; Yao, Bin

    2013-03-01

    To investigate the effect of primary tumorectomy on angiogenesis and pulmonary metastasis in osteosarcoma-bearing nude mice. Osteosarcoma was introduced to nude mice via subcutaneous injection of MG-63 cells. One hundred and eighty osteosarcoma-bearing mice were used equally in 3 parallel experiments. The effect of tumorectomy (TR) on the expression of vascular endothelial growth factor (VEGF) and endostatin was investigated by ELISA. Meanwhile, the effect on angiogenesis was evaluated by Matrigel plug assay, and pulmonary metastasis assessed by calculating the metastatic foci. Sham-operation (SO) and untreated (UT) groups served as controls. The VEGF (TR: 79.55 ± 7.82 pg/mL vs. SO: 110.01 ± 5.69 pg/mL, UT: 123.50 ± 10.41 pg/mL; p < 0.01) and endostatin (TR: 47.09 ± 6.22 ng/mL vs. SO: 117.64 ± 7.39 ng/mL, UT: 126.73 ± 6.55 ng/mL; p<0.01) were down-regulated significantly after tumorectomy, and angiogenesis was significantly promoted simultaneously. The incidence of pulmonary metastatic foci was 80.0% in the TR group, 40.0% in the SO group and 35.0% in the UT group. Primary tumorectomy can down-regulate the expression of VEGF and endostatin and promote angiogenesis which leads to the acceleration of pulmonary metastasis. These findings imply that anti-angiogenic treatment can be considered after primary tumorectomy.

  8. Therapeutic efficacy of astatine-211-labeled trastuzumab on radioresistant SKOV-3 tumors in nude mice.

    PubMed

    Palm, Stig; Bäck, Tom; Claesson, Ingela; Danielsson, Anna; Elgqvist, Jörgen; Frost, Sofia; Hultborn, Ragnar; Jensen, Holger; Lindegren, Sture; Jacobsson, Lars

    2007-10-01

    To investigate the potential use of astatine-211 (211At)-labeled trastuzumab for the treatment of HER-2-positive, radioresistant ovarian carcinoma. Four-week-old nude mice were inoculated intraperitoneally with 5 . 10(6) SKOV-3 cells in 0.4 mL saline on Day 0. The endpoint was the total tumor weight in each mouse on Day 63. Three experiments were performed in which the response to single-dose and fractionated treatment with unlabeled and 211At-labeled antibody was evaluated. Experiment 1 showed, for the same total amount of trastuzumab, a dose-response relationship between 211At activity (0-400 kBq on Day 7) and therapeutic efficacy (p = 0.001). The effect of varying the amount of unlabeled trastuzumab was studied in Experiment 2. All mice, except for the controls, received 400 kBq 211At-trastuzumab, and different groups received 5, 50, or 500 microg trastuzumab on Day 7. The increase from 5 to 50 microg trastuzumab reduced the tumors by 78% in weight. No tumors were present in mice given 500 microg trastuzumab. In Experiment 3, the effect of a fractionated treatment regimen was studied. Mice that received 100 kBq 211At-trastuzumab on Days 7 and 8 had a 42% smaller tumor burden than did controls. Groups of mice injected with 200 + 100 kBq on Days 7 and 21 and mice injected with 100 kBq on Days 7, 8, and 21 both had 24% less tumor weight than the corresponding controls. The combination of 500 microg trastuzumab and 400 kBq 211At-trastuzumab had the greatest effect, with complete eradication of the tumors in this nude mouse model.

  9. Therapeutic Efficacy of Astatine-211-Labeled Trastuzumab on Radioresistant SKOV-3 Tumors in Nude Mice

    SciTech Connect

    Palm, Stig Baeck, Tom; Claesson, Ingela; Danielsson, Anna; Elgqvist, Joergen; Frost, Sofia; Hultborn, Ragnar; Jensen, Holger; Lindegren, Sture; Jacobsson, Lars

    2007-10-01

    Purpose: To investigate the potential use of astatine-211 ({sup 211}At)-labeled trastuzumab for the treatment of HER-2-positive, radioresistant ovarian carcinoma. Methods and Materials: Four-week-old nude mice were inoculated intraperitoneally with 5 . 10{sup 6} SKOV-3 cells in 0.4 mL saline on Day 0. The endpoint was the total tumor weight in each mouse on Day 63. Three experiments were performed in which the response to single-dose and fractionated treatment with unlabeled and {sup 211}At-labeled antibody was evaluated. Results: Experiment 1 showed, for the same total amount of trastuzumab, a dose-response relationship between {sup 211}At activity (0-400 kBq on Day 7) and therapeutic efficacy (p = 0.001). The effect of varying the amount of unlabeled trastuzumab was studied in Experiment 2. All mice, except for the controls, received 400 kBq {sup 211}At-trastuzumab, and different groups received 5, 50, or 500 {mu}g trastuzumab on Day 7. The increase from 5 to 50 {mu}g trastuzumab reduced the tumors by 78% in weight. No tumors were present in mice given 500 {mu}g trastuzumab. In Experiment 3, the effect of a fractionated treatment regimen was studied. Mice that received 100 kBq {sup 211}At-trastuzumab on Days 7 and 8 had a 42% smaller tumor burden than did controls. Groups of mice injected with 200 + 100 kBq on Days 7 and 21 and mice injected with 100 kBq on Days 7, 8, and 21 both had 24% less tumor weight than the corresponding controls. Conclusion: The combination of 500 {mu}g trastuzumab and 400 kBq {sup 211}At-trastuzumab had the greatest effect, with complete eradication of the tumors in this nude mouse model.

  10. The Rac Inhibitor EHop-016 Inhibits Mammary Tumor Growth and Metastasis in a Nude Mouse Model

    PubMed Central

    Castillo-Pichardo, Linette; Humphries-Bickley, Tessa; De La Parra, Columba; Forestier-Roman, Ingrid; Martinez-Ferrer, Magaly; Hernandez, Eliud; Vlaar, Cornelis; Ferrer-Acosta, Yancy; Washington, Anthony V.; Cubano, Luis A.; Rodriguez-Orengo, Jose; Dharmawardhane, Suranganie

    2014-01-01

    Metastatic disease still lacks effective treatments, and remains the primary cause of cancer mortality. Therefore, there is a critical need to develop better strategies to inhibit metastatic cancer. The Rho family GTPase Rac is an ideal target for anti-metastatic cancer therapy, because Rac is a key molecular switch that is activated by a myriad of cell surface receptors to promote cancer cell migration/invasion and survival. Previously, we reported the design and development of EHop-016, a small molecule compound, which inhibits Rac activity of metastatic cancer cells with an IC50 of 1 μM. EHop-016 also inhibits the activity of the Rac downstream effector p21-activated kinase (PAK), lamellipodia extension, and cell migration in metastatic cancer cells. Herein, we tested the efficacy of EHop-016 in a nude mouse model of experimental metastasis, where EHop-016 administration at 25 mg/kg body weight (BW) significantly reduced mammary fat pad tumor growth, metastasis, and angiogenesis. As quantified by UPLC MS/MS, EHop-016 was detectable in the plasma of nude mice at 17 to 23 ng/ml levels at 12 h following intraperitoneal (i.p.) administration of 10 to 25 mg/kg BW EHop-016. The EHop-016 mediated inhibition of angiogenesis In Vivo was confirmed by immunohistochemistry of excised tumors and by In Vitro tube formation assays of endothelial cells. Moreover, EHop-016 affected cell viability by down-regulating Akt and Jun kinase activities and c-Myc and Cyclin D expression, as well as increasing caspase 3/7 activities in metastatic cancer cells. In conclusion, EHop-016 has potential as an anticancer compound to block cancer progression via multiple Rac-directed mechanisms. PMID:25389450

  11. Antitumor and antiangiogenic activities of curcumin in cervical cancer xenografts in nude mice.

    PubMed

    Yoysungnoen-Chintana, Pornphrom; Bhattarakosol, Parvapan; Patumraj, Suthiluk

    2014-01-01

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

  12. Intradermal injection of human adipose-derived stem cells accelerates skin wound healing in nude mice.

    PubMed

    Rodriguez, Jonathan; Boucher, Fabien; Lequeux, Charlotte; Josset-Lamaugarny, Audrey; Rouyer, Ondine; Ardisson, Orianne; Rutschi, Héléna; Sigaudo-Roussel, Dominique; Damour, Odile; Mojallal, Ali

    2015-12-08

    The use of stem cells from adipose tissue or adipose-derived stem cells (ASCs) in regenerative medicine could be an interesting alternative to bone marrow stem cells because they are easily accessible and available in large quantities. The aim of this study was to evaluate the potential effect of ASCs on the healing of 12 mm diameter-excisional wounds (around 110 mm(2)) in nude mice. Thirty nude mice underwent surgery to create one 12-mm excisional wound per mouse (spontaneous healing, n = 6; Cytocare® 532, n = 12; ASCs, n = 12). The Galiano wound model was chosen to avoid shrinkage and thus slow the spontaneous healing (SH) of mouse skin, making it closer to the physiology of human skin healing. Transparent dressings were used to enable daily healing time measurements to be taken. Immunohistochemistry, histological and blood perfusion analysis were carried out on the healed skin. The in vivo results showed the effectiveness of using ASCs on reducing the time needed for complete healing to 21.2 days for SH, 17.4 days for vehicle alone (Cytocare® 532) and 14.6 days with the addition of ASCs (p < 0.001). Moreover, cutaneous perfusion of the healed wound was significantly improved in ASC-treated mice compared to SH group, as shown by laser Doppler flowmetry and the quantitation of blood vessels using immunohistochemistry of αsmooth muscle actin. The tolerance and efficacy of cryopreserved ASCs to accelerate the complete closure of the wound by increasing the maturation of the skin and its blood perfusion, shows their therapeutic benefit in the wound healing context.

  13. Astaxanthin Inhibits PC-3 Xenograft Prostate Tumor Growth in Nude Mice.

    PubMed

    Ni, Xiaofeng; Yu, Haining; Wang, Shanshan; Zhang, Chengcheng; Shen, Shengrong

    2017-03-08

    Prostate cancer (PCa), the most common malignancy in men, is a major cause of cancer deaths. A better understanding of the mechanisms that drive tumor initiation and progression may identify actionable targets to improve treatment of this patient group. As a dietary carotenoid, astaxanthin has been demonstrated to exert beneficial effects against inflammation, cardiovascular disease, oxidative damage, or different cancer sites. This study used intragastric administration of astaxanthin to detect its role on tumor proliferation, apoptosis, microRNA (miRNA) overexpression, and microbacteria composition change by establishing androgen-independent PCa cell PC-3 xenograft nude mice. Nude mice were inoculated with androgen-independent prostate cancer PC-3 cells subcutaneously. The intervention was started when tumors reached 0.5-0.6 cm in diameter. Mice were intragastrically administered 100 mg/kg astaxanthin (HA), 25 mg/kg astaxanthin (LA), or olive oil (TC). The results showed that 100 mg/kg astaxanthin significantly inhibited tumor growth compared to the TC group, with an inhibitory rate of 41.7%. A decrease of Ki67 and proliferating cell nuclear antigen (PCNA) as well as an increase of cleaved caspase-3 were observed in HA-treated tumors, along with increasing apoptotic cells, obtained by TUNEL assay. The HA significantly elevated the levels of tumor suppressors miR-375 and miR-487b in tumor tissues and the amount of Lactobacillus sp. and Lachnospiraceae in mice stools, while there was no significant difference between LA and TC groups. These results provide a promising regimen to enhance the therapeutic effect in a dietary supplement manner.

  14. Human nerve xenografting in nude mouse: Experimental study of graft revascularization

    SciTech Connect

    Duprez, K.; Bour, C.; Merle, M.; Duprez, A. )

    1991-01-01

    In the nude mouse, the congenital absence of T lymphocytes makes it possible to implant human nerve grafts without rejection or iatrogenic modifications (by immunosuppression) of human and murine tissues. Medial antebrachial cutaneous nerves were harvested from human cadavers 1-18 hours after death. These nerve grafts were implanted using different techniques in nude mice. All the grafts were macroscopically and microscopically revascularized 3 days after implantation. The modifications in time of this vascularization could be studied with precision through the use of repeated biopsies. The absence of human blood group antigens on the neovessel endothelium suggested a murine origin for angiogenesis. In situ DNA hybridizations with human and mouse DNA confirmed this origin. The topography of the revascularization (maximal in the perineurium and endoneurium) and the almost complete absence of human cells other than Schwann cells in the grafts at the peak of angiogenesis (26 days after grafting) suggested that Schwann cells had a determining role in graft vascularization. The irradiation of the nerve grafts with a dose of 30 grays before implantation did not modify significantly their histologic appearance compared to the control group, whereas an irradiation of 60 grays led to massive lesions. The neurotization of murine axons led to chimerical structures of normal histologic appearance, with vascularization similar to that observed in nonneurotized nerves. Through chimerism (human Schwann cells, murine vessels and axons) this model makes it possible to dissociate the respective role of the host and of the nerve graft in angiogenesis and suggests the existence of growth factors produced by the human Schwann cells.

  15. Synthetic progestins induce growth and metastasis of BT-474 human breast cancer xenografts in nude mice

    PubMed Central

    Liang, Yayun; Benakanakere, Indira; Besch-Williford, Cynthia; Hyder, Ryyan S; Ellersieck, Mark R.; Hyder, Salman M

    2010-01-01

    Objective Previous studies showed that sequential exposure to estrogen and progesterone or medroxyprogesterone acetate (MPA) stimulates vascularization and promotes the progression of BT-474 and T47-D human breast cancer cell xenografts in nude mice (Liang et al, Cancer Res 2007, 67:9929). In this follow-up study, the effects of progesterone, MPA, norgestrel (N-EL) and norethindrone (N-ONE) on BT-474 xenograft tumors were compared in the context of several different hormonal environments. N-EL and N-ONE were included in the study since synthetic progestins vary considerably in their biological effects and the effects of these two progestins on the growth of human tumor xenografts are not known. Methods Estradiol-supplemented intact and ovariectomized Immunodeficient mice were implanted with BT-474 cells. Progestin pellets were implanted either simultaneously with estradiol pellets 2-days prior to tumor cell injection (i.e. combined), or 5-days following tumor cell injections (i.e. sequentially). Results Progestins stimulated the growth of BT-474 xenograft tumors independent of exposure timing and protocol, MPA stimulated the growth of BT-474 xenograft tumors in ovariectomized mice and progestins stimulated VEGF elaboration and increased tumor vascularity. Progestins also increased lymph node metastasis of BT-474 cells. Therefore, progestins, including N-EL and N-ONE, induce the progression of breast cancer xenografts in nude mice and promote tumor metastasis. Conclusions These observations suggests that women who ingest progestins for HT or oral contraception could be more at risk for developing breast cancer as a result of proliferation of existing latent tumor cells. Such risks should be considered in the clinical setting. PMID:20461021

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

    SciTech Connect

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

    1985-05-01

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

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

    PubMed

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

    2014-04-16

    The objective of this study was to explore the feasibility and methods of screening the residual normal ovarian tissue adjacent to orthotopic ovarian carcinomas in nude mice. Human epithelial ovarian cancer cells (OVCAR3) were subcutaneously implanted for a tumor source and ovarian orthotopic transplantation. The cancer tissue, proximal paraneoplastic tissue, middle paraneoplastic tissue, remote paraneoplastic tissue, and normal ovarian tissue were removed. CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was detected by reverse transcription polymerase chain reaction. We obtained 35 paraneoplastic residual ovarian tissues with normal biopsies from 40 cases of an orthotopic epithelial ovarian carcinoma model (87.5%). CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was lower in proximal paraneoplastic tissue than in cancer tissue (P < 0.05) and higher than in middle and remote paraneoplastic tissue (P < 0.01). There was no statistically significant difference between the expression of these genes in middle and proximal paraneoplastic tissue as well as among residual normal ovarian tissues with different severity (P > 0.05). In ovarian tissues of 20 normal nude mice, the expression of CK- 7, CA125, p53, survivin, MMP-2, and TIMP-2 was negative. Overall, the expression levels of CK-7, CA125, p53, survivin, MMP-2, TIMP-2, and other molecular markers showed a decreasing trend in the non-cancer tissue direction. The expression levels can be used as standards to screen residual normal ovarian tissue. We can obtain relatively safe normal ovarian tissues adjacent to epithelial ovarian cancer.

  18. Clonal dominance between subpopulations of mixed small cell lung cancer xenografts implanted ectopically in nude mice.

    PubMed

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

    1995-01-01

    Clonal evolution of neoplastic cells during solid tumour growth leads to the emergence of new tumour cell subpopulations with diverging phenotypic characteristics which may alter the behaviour of a malignant disease. Cellular interaction was studied in mixed xenografts in nude mice and during in vitro growth of two sets of small cell lung cancer (SCLC) subpopulations (54A, 54B and NYH, NYH2). The tumour cell lines differed in cellular DNA content enabling flow cytometric DNA analysis (FCM) to be used to monitor changes in the fractional composition of the mixed cell populations. The progeny clone 54B was found to dominate the parent 54A clone when grown as mixed subcutaneous xenografts in nude mice, whereas no dominance was exerted during in vitro growth. The in vivo dominance could not be explained by differences in growth kinetics between the two tumour cell lines, and the interaction was not dependent on 54B being in excess in mixed tumours. The dominance was dependent on close in vivo contact as no remote effect on the growth of 54A was found when the dominating 54B cells were growing in the opposite flank of tumour-bearing mice. Irradiation inactivated 54B cells were unable to exert the dominating effect, indicating that the interaction required viable and proliferating cells. Clonal dominance was not found in mixed NYH-NYH2 tumours indicating that the dominance mechanism(s) may not always be operational between subpopulations in heterogeneous tumours. Recognition of interaction between tumour cell populations may result in a better understanding of the behaviour of heterogeneous human malignancies.

  19. Intravenously Administered Alphavirus Vector VA7 Eradicates Orthotopic Human Glioma Xenografts in Nude Mice

    PubMed Central

    Ruotsalainen, Janne J.; Martikainen, Miika W.; Stanford, Marianne M.; McCart, J. Andrea; Bell, John C.; Hinkkanen, Ari E.

    2010-01-01

    Background VA7 is a neurotropic alphavirus vector based on an attenuated strain of Semliki Forest virus. We have previously shown that VA7 exhibits oncolytic activity against human melanoma xenografts in immunodeficient mice. The purpose of this study was to determine if intravenously administered VA7 would be effective against human glioma. Methodology/Principal Findings In vitro, U87, U251, and A172 human glioma cells were infected and killed by VA7-EGFP. In vivo, antiglioma activity of VA7 was tested in Balb/c nude mice using U87 cells stably expressing firefly luciferase in subcutaneous and orthotopic tumor models. Intravenously administered VA7-EGFP completely eradicated 100% of small and 50% of large subcutaneous U87Fluc tumors. A single intravenous injection of either VA7-EGFP or VA7 expressing Renilla luciferase (VA7-Rluc) into mice bearing orthotopic U87Fluc tumors caused a complete quenching of intracranial firefly bioluminescence and long-term survival in total 16 of 17 animals. In tumor-bearing mice injected with VA7-Rluc, transient intracranial and peripheral Renilla bioluminescence was observed. Virus was well tolerated and no damage to heart, liver, spleen, or brain was observed upon pathological assessment at three and ninety days post injection, despite detectable virus titers in these organs during the earlier time point. Conclusion VA7 vector is apathogenic and can enter and destroy brain tumors in nude mice when administered systemically. This study warrants further elucidation of the mechanism of tumor destruction and attenuation of the VA7 virus. PMID:20066051

  20. Nanomicellar TGX221 blocks xenograft tumor growth of prostate cancer in nude mice

    PubMed Central

    Chen, Ruibao; Zhao, Yunqi; Huang, Yan; Yang, Qiuhong; Zeng, Xing; Jiang, Wencong; Liu, Jihong; Thrasher, J. Brantley; Forrest, M. Laird; Li, Benyi

    2014-01-01

    Background Combination of androgen ablation along with early detection and surgery has made prostate cancer highly treatable at the initial stage. However, this cancer remains the second leading cause of cancer death among American men due to castration-resistant progression, suggesting that novel therapeutic agents are urgently needed for this life-threaten condition. Phosphatidylinositol 3-kinase p110β is a major cellular signaling molecule and has been identified as a critical factor in prostate cancer progression. In a recent report, we established a nanomicelle-based strategy to deliver p110β-specific inhibitor TGX221 to prostate cancer cells by conjugating the surface of nanomicelles with a RNA aptamer against prostate membrane specific antigen (PSMA) present in all clinical prostate cancers. In this study, we tested this nanomicellar TGX221 for its in vivo anti-tumor effect in mouse xenograft models. Methods Prostate cancer cell lines LAPC-4, LNCaP, C4-2 and 22RV1 were used to establish subcutaneous xenograft tumors in nude mice. Paraffin sections from xenograft tumor specimens were used in immunohistochemistry assays to detect AKT phosphorylation, cell proliferation marker Ki67 and PCNA, as well as BrdU incorporation. Quantitative PCR assay was conducted to determine PSA gene expression in xenograft tumors. Results Although systemic delivery of unconjugated TGX221 significantly reduced xenograft tumor growth in nude mice compared to solvent control, the nanomicellar TGX221 conjugates completely blocked tumor growth of xenografts derived from multiple prostate cancer cell lines. Further analyses revealed that AKT phosphorylation and cell proliferation indexes were dramatically reduced in xenograft tumors received nanomicellar TGX221 compared to xenograft tumors received unconjugated TGX221 treatment. There was no noticeable side effect by gross observation or at microscopic level of organ tissue section. Conclusion These data strongly suggest that prostate

  1. The Rac Inhibitor EHop-016 Inhibits Mammary Tumor Growth and Metastasis in a Nude Mouse Model.

    PubMed

    Castillo-Pichardo, Linette; Humphries-Bickley, Tessa; De La Parra, Columba; Forestier-Roman, Ingrid; Martinez-Ferrer, Magaly; Hernandez, Eliud; Vlaar, Cornelis; Ferrer-Acosta, Yancy; Washington, Anthony V; Cubano, Luis A; Rodriguez-Orengo, Jose; Dharmawardhane, Suranganie

    2014-10-01

    Metastatic disease still lacks effective treatments, and remains the primary cause of cancer mortality. Therefore, there is a critical need to develop better strategies to inhibit metastatic cancer. The Rho family GTPase Rac is an ideal target for anti-metastatic cancer therapy, because Rac is a key molecular switch that is activated by a myriad of cell surface receptors to promote cancer cell migration/invasion and survival. Previously, we reported the design and development of EHop-016, a small molecule compound, which inhibits Rac activity of metastatic cancer cells with an IC50 of 1 μM. EHop-016 also inhibits the activity of the Rac downstream effector p21-activated kinase (PAK), lamellipodia extension, and cell migration in metastatic cancer cells. Herein, we tested the efficacy of EHop-016 in a nude mouse model of experimental metastasis, where EHop-016 administration at 25 mg/kg body weight (BW) significantly reduced mammary fat pad tumor growth, metastasis, and angiogenesis. As quantified by UPLC MS/MS, EHop-016 was detectable in the plasma of nude mice at 17 to 23 ng/ml levels at 12 h following intraperitoneal (i.p.) administration of 10 to 25 mg/kg BW EHop-016. The EHop-016 mediated inhibition of angiogenesis In Vivo was confirmed by immunohistochemistry of excised tumors and by In Vitro tube formation assays of endothelial cells. Moreover, EHop-016 affected cell viability by down-regulating Akt and Jun kinase activities and c-Myc and Cyclin D expression, as well as increasing caspase 3/7 activities in metastatic cancer cells. In conclusion, EHop-016 has potential as an anticancer compound to block cancer progression via multiple Rac-directed mechanisms.

  2. Effects and mechanisms of silibinin on human hepatocellular carcinoma xenografts in nude mice

    PubMed Central

    Cui, Wei; Gu, Fan; Hu, Ke-Qin

    2009-01-01

    AIM: To investigate the in vivo effects and mechanisms of silibinin on the growth of hepatocellular carcinoma (HCC) xenografts in nude mice. METHODS: Nude mice bearing HuH7 xenografts were used to assess the anti-HCC effects and mechanisms of silibinin. RESULTS: Silibinin resulted in a potent dose-dependent reduction of HuH7 xenografts in association with a significant decrease in Ki-67 and α-fetoprotein production, nuclear NF-κB content, polo-like kinase 1, Rb phosphorylation, and E2F1/DP1 complex, but increased p27/CDK4 complex and checkpoint kinase 1 expression, suggesting that the in vivo effects of silibinin are mediated by inhibiting G1-S transition of the cell cycle. Silibinin-induced apoptosis of HuH7 xenografts was associated with inhibited survivin phosphorylation. Silibinin-reduced growth of HuH7 xenografts was associated with decreased p-ERK, increased PTEN expression and the activity of silibinin was correlated with decreased p-Akt production, indicating involvement of PTEN/PI3K/Akt and ERK pathways in its in vivo anti-HCC effects. Silibinin-reduced growth of HuH7 xenografts was also associated with a significant increase in AC-H3 and AC-H4 expression and the production of superoxide dismutase (SOD)-1. CONCLUSION: Silibinin reduces HCC xenograft growth through the inhibition of cell proliferation, cell cycle progression and PTEN/P-Akt and ERK signaling, inducing cell apoptosis, and increasing histone acetylation and SOD-1 expression. PMID:19399925

  3. Inhibition of SRC tyrosine kinase as treatment for human pancreatic cancer growing orthotopically in nude mice.

    PubMed

    Yezhelyev, Maksim V; Koehl, Gudrun; Guba, Markus; Brabletz, Thomas; Jauch, Karl-Walter; Ryan, Anderson; Barge, Alan; Green, Tim; Fennell, Michael; Bruns, Christiane J

    2004-12-01

    The Src family comprises a family of nonreceptor intracellular tyrosine kinases that mediate a variety of cellular pathways. Src kinases are overexpressed in a variety of human tumors, including cancer of the colon, breast, and pancreas, and they are an integral part of tumor cell signaling pathways associated with migration, proliferation, adhesion, and angiogenesis. We investigated whether the blockade of Src kinase by daily oral administration of the novel Src tyrosine kinase inhibitor AZM475271 [kindly provided by AstraZeneca (Macclesfield, United Kingdom)], alone or in combination with intraperitoneal gemcitabine, can inhibit growth and metastasis of orthotopically implanted human pancreatic carcinoma cells in nude mice. Treatment with AZM475271 alone reduced the primary pancreatic tumor volume by approximately 40%, whereas AZM475271 plus gemcitabine reduced tumor volume by 90%. Furthermore, treatment with AZM475271 and gemcitabine significantly reduced metastasis: none of eight animals who received the combination treatment had lymph node or liver metastases, compared with five of five and three of five animals, respectively, in the control group (P = 0.001). Src inhibition by AZM475271 (alone or with gemcitabine) was associated with significantly reduced tumor cell proliferation, decreased tumor microvessel density, and increased apoptosis in vivo. Moreover, these effects were all significantly increased when gemcitabine was combined with AZM475271 compared with gemcitabine alone. Src inhibition by AZM475271, either alone or in combination with gemcitabine, demonstrated significant antitumor and antimetastatic activity in an orthotopic nude mouse model for human pancreatic cancer. The combination of AZM475271 with gemcitabine sensitized tumor cells to the cytotoxic effect of gemcitabine.

  4. Growth and fertilization of porcine fetal oocytes grafted under the renal capsules of nude mice.

    PubMed

    Kaneko, Hiroyuki; Kikuchi, Kazuhiro; Noguchi, Junko

    2016-10-15

    The fetal ovary contains a larger pool of oocytes than the adult ovary, but utilization of the fetal oocytes of large animals has hardly been examined. In this study, we investigated the developmental competence of oocytes grown in host mice harboring ovarian grafts obtained from fetal pigs. Ovarian fragments from fetuses at 55, 70, and 90 days postartificial insemination (dpi) were grafted into ovariectomized nude mice (Crlj:CD1-Foxn1(nu); 55-, 70- and 90-dpi groups, respectively). For comparison, ovarian fragments from 20-day postpartum (dpp) piglets were also grafted (20-dpp group). About 60 days after detection of vaginal opening, the mice were given 62.5 U/mL porcine FSH for 13 days by infusion to enhance their follicular development. In the fetal ovaries before grafting, the percentage of germ cells in primordial follicles (termed primordial oocytes) relative to the total number of germ cells was 0.06% at 55 dpi, 2.4% at 70 dpi, and 7.2% at 90 dpi, but the majority was contained within egg nests. At 20 dpp, primordial oocytes accounted for 91.7% of the total number of germ cells and the rest were mostly in primary follicles. After FSH stimulation of host mice, formation of antral follicles was promoted in the grafts of the 70- and 90-dpi groups as well as the 20-dpp group, but a very small number of antral follicles developed in the 55-dpi group consistent with the lowest (P < 0.05) levels of circulating inhibin in that group. The mean number of full-sized oocytes with meiotic competence recovered per mouse was 6.0 in the 70-dpi, 18.0 in the 90-dpi, and 21.2 in the 20-dpp groups, whereas virtually no oocytes were recovered from mice in the 55-dpi group. Moreover, the mature oocytes in the 70- and 90-dpi groups were fertilized in vitro, as shown by formation of male and female pronuclei, but the percentage of oocytes penetrated by sperm was low in the 70- (49%) and 90-dpi (29%) groups as compared with the 20-dpp group (88%). These results clearly

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

    PubMed Central

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

    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-labeled biotinylated 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 McAb-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 non-treated group, treated groups with and without avidin chase showed significant

  6. Intracranial elimination of human glioblastoma brain tumors in nude rats using the bispecific ligand-directed toxin, DTEGF13 and convection enhanced delivery.

    PubMed

    Oh, Seunguk; Ohlfest, John R; Todhunter, Deborah A; Vallera, Vincent D; Hall, Walter A; Chen, Hua; Vallera, Daniel A

    2009-12-01

    A bispecific ligand-directed toxin (BLT) consisting of human interleukin-13, epithelial growth factor, and the first 389 amino acids of diphtheria toxin was assembled in order to target human glioblastoma. In vitro, DTEGF13 selectively killed the human glioblastoma cell line U87-luc as well as other human glioblastomas. DTEGF13 fulfilled the requirement of a successful BLT by having greater activity than either of its monospecific counterparts or their mixture proving it necessary to have both ligands on the same single chain molecule. Aggressive brain tumors established intracranially (IC) in nude rats with U87 glioma genetically marked with a firefly luciferase reporter gene were treated with two injections of DTEGF13 using convection enhanced delivery resulting in tumor eradication in 50% of the rats which survived with tumor free status at least 110 days post tumor inoculation. An irrelevant BLT control did not protect establishing specificity. The bispecific DTEGF13 MTD dose was measured at 2 microg/injection or 0.5 microg/kg and toxicity studies indicated safety in this dose. Combination of monospecific DTEGF and DTIL13 did not inhibit tumor growth. ELISA assay indicated that anti-DT antibodies were not generated in normal immunocompetent rats given identical intracranial DTEGF13 therapy. Thus, DTEGF13 is safe and efficacious as an alternative drug for glioblastoma therapy and warrants further study.

  7. Establishment and characterization of a new human oestradiol- and progesterone-receptor-positive mammary carcinoma serially transplantable in nude mice.

    PubMed

    Naundorf, H; Fichtner, I; Büttner, B; Frege, J

    1992-01-01

    A human mammary carcinoma originating from a postmenopausal patient was successfully transplanted into nude mice. According to the adopted criteria the tumour proved to be oestradiol- and progesterone-receptor-positive. Histological studies of the patient tumour revealed a ductal invasive mammary carcinoma with 80% tubular growth pattern. Following transplantation the adenoid structures decreased to 30%; the mitosis rate and grade of malignancy increased. Treatment of the nude mice with 20 micrograms oestradiol benzoate/mouse caused a loss of the oestradiol receptor of the mammary carcinoma. The mammary carcinoma 3366 can be used for testing of antineoplastic substances, antihormones and for studies in regard to down-regulation or blocking of hormone receptors and possible consequences for therapies.

  8. Imaging exosome transfer from breast cancer cells to stroma at metastatic sites in orthotopic nude-mouse models.

    PubMed

    Suetsugu, Atsushi; Honma, Kimi; Saji, Shigetoyo; Moriwaki, Hisataka; Ochiya, Takahiro; Hoffman, Robert M

    2013-03-01

    Exosomes play an important role in cell-to-cell communication to promote tumor metastasis. In order to image the fate of cancer-cell-derived exosomes in orthotopic nude mouse models of breast cancer, we used green fluorescent protein (GFP)-tagged CD63, which is a general marker of exosomes. Breast cancer cells transferred their own exosomes to other cancer cells and normal lung tissue cells in culture. In orthotopic nude-mouse models, breast cancer cells secreted exosomes into the tumor microenvironment. Tumor-derived exosomes were incorporated into tumor-associated cells as well as circulating in the blood of mice with breast cancer metastases. These results suggest that tumor-derived exosomes may contribute to forming a niche to promote tumor growth and metastasis. Our results demonstrate the usefulness of GFP imaging to investigate the role of exosomes in cancer metastasis.

  9. Paracoccidioides brasiliensis infection in nude mice: studies with isolates differing in virulence and definition of their T cell-dependent and T cell-independent components.

    PubMed

    Burger, E; Vaz, C C; Sano, A; Calich, V L; Singer-Vermes, L M; Xidieh, C F; Kashino, S S; Nishimura, K; Miyaji, M

    1996-10-01

    Athymic and euthymic BALB/c mice infected with highly (Pb18) or slightly (Pb265) virulent Paracoccidioides brasiliensis isolates were compared regarding mortality, presence of viable yeasts, specific immunoglobulin M (IgM) and IgG titers, and the antigen recognition patterns of these antibodies. Isolate Pb18 caused a more severe disease in athymic mice, as supported by higher number of infected organs and shorter survival times. These animals, however, were resistant to Pb265 infection. High titers of antibodies were found only in euthymic mice, seven weeks after Pb18 infection. At this time, euthymic animals presented IgG antibodies to numerous protein bands that were not detected at four weeks postinfection or after Pb265 inoculation. In contrast, antibodies from athymic mice always reacted with few antigen bands. Although the majority of P. brasiliensis antigens are T cell-dependent, the immunodominant gp43 and also the 41.5- and 27.5-kD antigens are here, for the first time, characterized as T cell-independent antigens of P. brasiliensis.

  10. Inhibition of human pancreatic cancer growth in nude mice by boron neutron capture therapy.

    PubMed

    Yanagië, H; Tomita, T; Kobayashi, H; Fujii, Y; Nonaka, Y; Saegusa, Y; Hasumi, K; Eriguchi, M; Kobayashi, T; Ono, K

    1997-01-01

    Immunoliposomes were prepared by conjugating anti-carcinoembryonic antigen (CEA) monoclonal antibody with liposomes containing [10B]compound. These immunoliposomes were shown to bind selectively to human pancreatic carcinoma cells (AsPC-1) bearing CEA on their surface. The cytotoxic effects of locally injected [10B]compound, multilamellar liposomes containing [10B]compound or [10B]immunoliposomes (anti-CEA) on human pancreatic carcinoma xenografts in nude mice were evaluated with thermal neutron irradiation. After thermal neutron irradiation of mice injected with [10B]solution, 10B-containing liposomes or [10B]immunoliposomes, AsPC-1 tumour growth was suppressed relative to controls. Injection of [10B]immunoliposomes caused the greatest tumour suppression with thermal neutron irradiation in vivo. Histopathologically, hyalinization and necrosis were found in 10B-treated tumours, while tumour tissue injected with saline or saline-containing immunoliposomes showed neither destruction nor necrosis. These results suggest that intratumoral injection of boronated immunoliposomes can increase the retention of 10B atoms by tumour cells, causing tumour growth suppression in vivo upon thermal neutron irradiation. Boron neutron capture therapy (BNCT) with intratumoral injection of immunoliposomes is able to destroy malignant cells in the marginal portion between normal tissues and cancer tissues from the side of 4He generation.

  11. Xenotransplantation of testicular tissue into nude mice can be used for detecting leukemic cell contamination.

    PubMed

    Hou, Mi; Andersson, Margareta; Eksborg, Staffan; Söder, Olle; Jahnukainen, Kirsi

    2007-07-01

    Xeno-grafting of testicular tissue may allow viable gamete maturation. This would be beneficial for prepubertal cancer patients in that it may allow restoration of fertility without the risk of a cancer relapse. However it is unknown whether cancer cells in the testicular graft can transmit the malignancy into the host animal and also if gametes can be retrieved from testicular grafts that are contaminated with malignant cells. Rat T-cell leukemia was employed as the source of leukemic lymphoblasts and testicular tissue. This was injected i.p. (lymphoblasts) or grafted s.c. (fresh or cryopreserved testicular tissue) into the back skin of intact nude mice. To simulate clinical autografting, testicular tissue was also transplanted into healthy piebald variegated (PVG) rats. 50-70% of the mice, receiving 200 or 6000 leukemic lymphoblasts, developed terminal leukemia. All mice, grafted with either fresh or cryopreserved testicular tissue from leukemic donor, developed generalized leukemia and/or local tumors. All syngenic PVG rats, treated in the same manner, died of generalized leukemia. In all of the retrieved leukemic grafts, rat spermatogenesis was destroyed and only leukemic infiltration was detected. Grafting testicular tissue contaminated with leukemic cells led to tumor growth at the injection site without potential to differentiate germline stem cells into gametes. Xenografting could provide a novel functional strategy for simultaneous detection of malignant cell contamination and spermatogonial potential in testicular xenografts collected for fertility preservation.

  12. Fluorescence-Guided Surgery Improves Outcome in an Orthotopic Osteosarcoma Nude-Mouse Model

    PubMed Central

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

    2014-01-01

    In order to develop a model for fluorescence-guided surgery (FGS), 143B human osteosarcoma cells expressing red fluorescent protein (RFP) cells were injected into the intramedullary cavity of the tibia in nude mice. The fluorescent area of residual tumors after bright-light surgery (BLS) and FGS was 10.2 ± 2.4 mm2 and 0.1 ± 0.1 mm2, respectively (p < 0.001). The BLS-treated mice and BLS+cisplatinum (CDDP)-treated mice had significant recurrence. In contrast, the FGS mice and FGS+CDDP mice had very little recurring tumor growth. Disease-free survival (DFS) in the BLS-, BLS+CDDP-, FGS-, and FGS+CDDP-treated mice were 12.5%, 37.5%, 75.0%, and 87.5%, respectively. The FGS-treated mice had a significantly higher DFS rate than the BLS-treated mice (p = 0.021). The FGS+CDDP-treated mice had significantly higher DFS rate than the BLS+CDDP-treated mice (p = 0.043). Although chemotherapy significantly reduced multiple metastases (p = 0.033), there was no significant correlation between FGS and lung metastasis. FGS significantly reduced the recurrence of the tumor but did not reduce lung metastasis. The combination of FGS and adjuvant CDDP reduced tumor recurrence and prevented multiple metastases. FGS and adjuvant chemotherapy should be performed as early as possible in the disease to prevent both recurrence and metastatic development. PMID:25138581

  13. Topical cyclosporin induces hair growth in human split skin grafted onto nude mice.

    PubMed

    Gilhar, A; Etzioni, A; Moscona, R

    1991-01-01

    Previously we observed that systemic CyA induces hair growth in an experimental model of human scalp skin graft transplanted onto nude mice. In the present study we investigated the role of topical CyA in the murine transplantation model, using human split-thickness skin grafts (HSTSG). Ten mice grafted with 1-mm-thick skin and another 10 mice grafted with 0.4-mm-thick skin were treated topically with CyA in olive oil. Ten other mice, treated with olive oil only, served as a control group. At the end of the study we observed hair growth only on the grafted skin of the CyA-treated group. Four out of 10 grafts showed hair growth in each of the groups. Quantitative analysis of transverse sections of cylindrical punch biopsy specimens of HSTSG before transplantation revealed anagen follicles, including small ones and telogen/catagen follicles, whereas specimens after skin transplantation showed terminal follicles mostly in the anagen phase. The present study provides further support to previous observations regarding the beneficial effect of CyA on hair growth.

  14. Impairment of glucose-induced insulin secretion in human pancreatic islets transplanted to diabetic nude mice.

    PubMed

    Jansson, L; Eizirik, D L; Pipeleers, D G; Borg, L A; Hellerström, C; Andersson, A

    1995-08-01

    Hyperglycemia-induced beta-cell dysfunction may be an important component in the pathogenesis of non-insulin-dependent diabetes mellitus. However, most available data in this field were obtained from rodent islets. To investigate the relevance of this hypothesis for human beta-cells in vivo, human pancreatic islets were transplanted under the renal capsule of nude mice. Experimental groups were chosen so that grafted islets were exposed to either hyper- or normoglycemia or combinations of these for 4 or 6 wk. Grafts of normoglycemic recipients responded with an increased insulin release to a glucose stimulus during perfusion, whereas grafts of hyperglycemic recipients failed to respond to glucose. The insulin content of the grafts in the latter groups was only 10% of those observed in controls. Recipients initially hyperglycemic (4 wk), followed by 2 wk of normoglycemia regained a normal graft insulin content, but a decreased insulin response to glucose remained. No ultrastructural signs of beta-cell damage were observed, with the exception of increased glycogen deposits in animals hyperglycemic at the time of killing. It is concluded that prolonged exposure to a diabetic environment induces a long-term secretory defect in human beta-cells, which is not dependent on the size of the islet insulin stores.

  15. Impairment of glucose-induced insulin secretion in human pancreatic islets transplanted to diabetic nude mice.

    PubMed Central

    Jansson, L; Eizirik, D L; Pipeleers, D G; Borg, L A; Hellerström, C; Andersson, A

    1995-01-01

    Hyperglycemia-induced beta-cell dysfunction may be an important component in the pathogenesis of non-insulin-dependent diabetes mellitus. However, most available data in this field were obtained from rodent islets. To investigate the relevance of this hypothesis for human beta-cells in vivo, human pancreatic islets were transplanted under the renal capsule of nude mice. Experimental groups were chosen so that grafted islets were exposed to either hyper- or normoglycemia or combinations of these for 4 or 6 wk. Grafts of normoglycemic recipients responded with an increased insulin release to a glucose stimulus during perfusion, whereas grafts of hyperglycemic recipients failed to respond to glucose. The insulin content of the grafts in the latter groups was only 10% of those observed in controls. Recipients initially hyperglycemic (4 wk), followed by 2 wk of normoglycemia regained a normal graft insulin content, but a decreased insulin response to glucose remained. No ultrastructural signs of beta-cell damage were observed, with the exception of increased glycogen deposits in animals hyperglycemic at the time of killing. It is concluded that prolonged exposure to a diabetic environment induces a long-term secretory defect in human beta-cells, which is not dependent on the size of the islet insulin stores. Images PMID:7635965

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

    PubMed

    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.

  17. Microcirculation of human pancreatic islets transplanted under the renal capsule of nude mice.

    PubMed

    Jansson, L; Tyrberg, B; Carlsson, P O; Nordin, A; Andersson, A; Källskog O

    2001-08-27

    The aim was to measure the capillary blood pressure in transplanted human islets. Human islets were isolated at the Central Unit of the beta-cell Transplant in Brussels, Belgium. After transport to our laboratory, the islets were implanted under the renal capsule of normoglycemic nude mice. Two weeks later the capillary and venous blood pressures in the islet graft and adjacent renal parenchyma were measured with a micropuncture technique. Capillary blood pressure was approximately 5-8 mmHg in both graft and renal capillaries: twice as high as in native islets. Venous blood pressures were similar (4-5 mmHg) in the veins draining the graft and in the renal interlobular veins. All veins leading from the graft emptied into the renal parenchyma, that is, into interlobular veins. The capillary hypertension seen in transplanted human islets is probably necessary to secure adequate drainage through the renal veins. Whether this contributes to the poor results of long-term islet graft survival is unknown.

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

    PubMed

    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

    2008-09-02

    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.

  19. Inhibition of human pancreatic cancer growth in nude mice by boron neutron capture therapy.

    PubMed Central

    Yanagië, H.; Tomita, T.; Kobayashi, H.; Fujii, Y.; Nonaka, Y.; Saegusa, Y.; Hasumi, K.; Eriguchi, M.; Kobayashi, T.; Ono, K.

    1997-01-01

    Immunoliposomes were prepared by conjugating anti-carcinoembryonic antigen (CEA) monoclonal antibody with liposomes containing [10B]compound. These immunoliposomes were shown to bind selectively to human pancreatic carcinoma cells (AsPC-1) bearing CEA on their surface. The cytotoxic effects of locally injected [10B]compound, multilamellar liposomes containing [10B]compound or [10B]immunoliposomes (anti-CEA) on human pancreatic carcinoma xenografts in nude mice were evaluated with thermal neutron irradiation. After thermal neutron irradiation of mice injected with [10B]solution, 10B-containing liposomes or [10B]immunoliposomes, AsPC-1 tumour growth was suppressed relative to controls. Injection of [10B]immunoliposomes caused the greatest tumour suppression with thermal neutron irradiation in vivo. Histopathologically, hyalinization and necrosis were found in 10B-treated tumours, while tumour tissue injected with saline or saline-containing immunoliposomes showed neither destruction nor necrosis. These results suggest that intratumoral injection of boronated immunoliposomes can increase the retention of 10B atoms by tumour cells, causing tumour growth suppression in vivo upon thermal neutron irradiation. Boron neutron capture therapy (BNCT) with intratumoral injection of immunoliposomes is able to destroy malignant cells in the marginal portion between normal tissues and cancer tissues from the side of 4He generation. Images Figure 2 PMID:9043021

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

    PubMed

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

    2017-02-01

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

  1. Tumor lipids and liver lipid metabolism in the model human lung carcinoma/nude mice.

    PubMed

    de Antueno, R J; Niedfeld, G; De Tomás, M E; Mercuri, O F; Quintans, C

    1987-06-01

    Tumor lipids were studied in the experimental model Human Lung Carcinoma/nude mice as well as the effect of this human neoplasm on the host liver lipid metabolism. Fatty acid profiles from tumoral lipids revealed the loss of specificity for fatty acid composition in triglycerides. Host liver fatty acid composition and cholesterol metabolism were affected by the implanted human lung tissue. A noticeable increase ratio between saturated/unsaturated fatty acids was observed in host liver fatty acid phospholipids (1.17 +/- 0.17) in comparison to control liver (0.84 +/- 0.04). Cholesterol synthesis was assessed "in vivo" by means of [14C]acetate incorporation. The specific radioactivity of [14C] cholesterol was increased by a factor of about 6 in host liver as compared with control liver. This observation along with the marked decrease in the cholesterol content of host liver and the hypocholesterolemia detected in the host mice led us to suggest an increase in the liver cholesterol catabolism promoted by the presence of the tumor.

  2. Carbonate ion-enriched hot spring water promotes skin wound healing in nude rats.

    PubMed

    Liang, Jingyan; Kang, Dedong; Wang, Yingge; Yu, Ying; Fan, Jianglin; Takashi, En

    2015-01-01

    Hot spring or hot spa bathing (Onsen) is a traditional therapy for the treatment of certain ailments. There is a common belief that hot spring bathing has therapeutic effects for wound healing, yet the underlying molecular mechanisms remain unclear. To examine this hypothesis, we investigated the effects of Nagano hot spring water (rich in carbonate ion, 42°C) on the healing process of the skin using a nude rat skin wound model. We found that hot spring bathing led to an enhanced healing speed compared to both the unbathed and hot-water (42°C) control groups. Histologically, the hot spring water group showed increased vessel density and reduced inflammatory cells in the granulation tissue of the wound area. Real-time RT-PCR analysis along with zymography revealed that the wound area of the hot spring water group exhibited a higher expression of matrix metalloproteinases-2 and -9 compared to the two other control groups. Furthermore, we found that the enhanced wound healing process induced by the carbonate ion-enriched hot spring water was mediated by thermal insulation and moisture maintenance. Our results provide the evidence that carbonate ion-enriched hot spring water is beneficial for the treatment of skin wounds.

  3. Analyzing visual enjoyment of color: using female nude digital Image as example

    NASA Astrophysics Data System (ADS)

    Chin, Sin-Ho

    2014-04-01

    This research adopts three primary colors and their three mixed colors as main color hue variances by changing the background of a female nude digital image. The color saturation variation is selected to 9S as high saturation and 3S as low saturation of PCCS. And the color tone elements are adopted in 3.5 as low brightness, 5.5 as medium brightness for primary color, and 7.5 as low brightness. The water-color brush stroke used for two female body digital images which consisting of a visual pleasant image with elegant posture and another unpleasant image with stiff body language, is to add the visual intimacy. Results show the brightness of color is the main factor impacting visual enjoyment, followed by saturation. Explicitly, high-brightness with high saturation gains the highest rate of enjoyment, high-saturation medium brightness (primary color) the second, and high-brightness with low saturation the third, and low-brightness with low saturation the least.

  4. [Amphiregulin antisense RNA expression inhibits angiogenesis of human breast cancer in nude mice].

    PubMed

    Ma, Lin; Serova, Maria; Podgorniak, Marie Pierre; Berthois, Yolande; Mourah, Samia; Calvo, Fabien

    2005-09-01

    To investigate the anti-angiogenic effect of amphiregulin (AR) antisense RNA expression in breast cancer. Human AR cDNA antisense plasmid was transfected into NS2T2A1 cells (a human breast cancer cell line). Two selected clones expressed AR antisense RNA (AR AS1 and AR AS3 cell lines) in which AR protein expression was reduced. Control cell line NS2T2A1 V was obtained by empty vector transfection. These cells were injected subcutaneously into nude mice. The effects of conditioned media on proliferation of human microvascular endothelial cells (HMEC) were evaluated and VEGF secreted by the cells was measured by ELISA method. In tumor tissues, VEGF expression levels were measured by quantitative RT-PCR, and CD31-immunostaining was used for intra-tumoral vascular quantification. The proliferation index of HMEC cells grown in conditioned media with AR AS1 and AR AS3 was significantly reduced in comparison with that of control cells, accompanied by a decreased VEGF secretion. In tumors derived from AR AS1 and AR AS3 cells, intra-tumoral vascularization was reduced to about 50% of that derived from control cell line, accompanied with a decrease of VEGF expression. Amphiregulin antisense RNA expression inhibits efficiently the angiogenesis in breast cancer, suggesting this growth factor could represent a novel therapeutic target in breast cancer.

  5. In vivo optical imaging of bacterial infection and antibiotic response in intact nude mice

    NASA Astrophysics Data System (ADS)

    Xiong, Tao; Chen, Yanping; Chu, Jun; Zhang, Zhihong; Liu, Bifeng; Luo, Qingming

    2005-03-01

    We describe imaging the luminance of red fluorescent protein (DsRed2)-expressing bacteria from outside intact infected animals. This simple, nonintrusive technique can show in great detail the temporal behavior of the infectious process. Fluorescence stereo microscope, laser and cooled CCD are expensive to many institutes, we set up an inexpensive compact whole-body fluorescent imaging tool, which consisted of a digital camera, fluorescence filters and a mercury 50-W lamp power supply as excitation light source. The bacteria, expressing the DsRed2, are sufficiently bright as to be clearly visible from outside the infected animal and recorded with simple equipment. Introduced bacteria were observed in the abdomen. Instantaneous real-time images of the infectious process were acquired by using a digital camera by simply illuminating nude mice with mercury lamp. The development of infection over 48 hours and its regression after kanamycin treatment were visualized by whole-body imaging. The DsRed2 was excited directly by mercury lamp with EF500/50 nm band-pass filter and fluorescence was recorded by digital camera with CB580 nm long-pass filter. By this easy operation tool, the authors imaged, in real time, fluorescent tumors growing in live mice. The imaging system is external and noninvasive. For one year our experiments suggested the imaging scheme was feasible, which affords a powerful approach to visualizing the infection process.

  6. In vivo cultivation of human articular chondrocytes in a nude mouse-based contained defect organ culture model.

    PubMed

    Mueller-Rath, R; Gavénis, K; Gravius, S; Andereya, S; Mumme, T; Schneider, U

    2007-01-01

    The nude mouse model is an established method to cultivate and investigate tissue engineered cartilage analogues under in vivo conditions. One limitation of this common approach is the lack of appropriate surrounding articular tissues. Thus the bonding capacity of cartilage repair tissue cannot be evaluated. Widely applied surgical techniques in cartilage repair such as conventional and three-dimensional autologous chondrocyte implantation (ACI) based on a collagen gel matrix cannot be included into nude mouse studies, since their application require a contained defect. The aim of this study is to apply an organ culture defect model for the in vivo cultivation of different cell-matrix-constructs. Cartilage defects were created on osteochondral specimens which had been harvested from 10 human knee joints during total knee replacement. Autologous chondrocytes were isolated from the cartilage samples and cultivated in monolayer until passage 2. On each osteochondral block defects were treated either by conventional ACI or a collagen gel seeded with autologous chondrocytes, including a defect left empty as a control. The samples were implanted into the subcutaneous pouches of nude mice and cultivated for six weeks. After retrieval, the specimens were examined histologically, immunohistochemically and by cell morphology quantification. In both, ACI and collagen gel based defect treatment, a repair tissue was formed, which filled the defect and bonded to the adjacent tissues. The repair tissue was immature with low production of collagen type II. In both groups redifferentiation of chondrocytes remained incomplete. Different appearances of interface zones between the repair tissue and the adjacent cartilage were found. The presented contained defect organ culture model offers the possibility to directly compare different types of clinically applied biologic cartilage repair techniques using human articular tissues in a nude mouse model.

  7. Quantitation of ceramides in nude mouse skin by normal-phase liquid chromatography and atmospheric pressure chemical ionization mass spectrometry.

    PubMed

    Liou, Yi-Bo; Sheu, Ming-Thau; Liu, Der-Zen; Lin, Shan-Yang; Ho, Hsiu-O

    2010-06-01

    A sensitive and accurate normal-phase liquid chromatography and atmospheric pressure chemical ionization mass spectrometry (LC-APCI-MS) method for determining the standard ceramide [NS] (Cer[NS]) was developed and validated so as to improve the traditional thin-layer chromatography (TLC) technique and LC-electrospray ionization (ESI)-MS method to profile and quantify ceramides in nude mouse skin. Normal-phase LC-APCI-MS was optimized to separate the nine classes of ceramides presented in the stratum corneum (SC) of nude mouse skin. A normal-phase silica column eluted with the gradient system from heptane:acetone/butanol (90:10, v/v) of 75:25 to 100% acetone/butanol (90:10, v/v) (with each solvent containing 0.1% [v/v] triethylamine and 0.1% [v/v] formic acid) at a flow rate of 0.8 ml/min was found to be optimal for analyzing standard Cer[NS]. The analysis of Cer[NS] was validated and employed as the standard for constructing a calibration curve to quantitate all classes of ceramides. This method was applied to profile the classes and contents of ceramides in the SC of nude mouse skin and proved to be workable. It was concluded that this improved method can be used to directly detect and quantify all classes of ceramides in the SC of nude mouse skin and that it is more convenient and labor-saving than the traditional TLC method.

  8. Inhibition by an angiogenesis inhibitor, TNP-470, of the growth of a human hepatoblastoma heterotransplanted into nude mice.

    PubMed

    Matsusaka, S; Nakasho, K; Terada, N; Sugihara, A; Tsujimura, T; Takanashi, T; Uematsu, K; Okamoto, E; Toyosaka, A

    2000-08-01

    The effect of TNP-470, an angiogenesis inhibitor, on the growth of a hepatoblastoma transplanted into nude mice was examined. A hepatoblastoma obtained from a 3-year-old girl was serially transplanted into nude mice subcutaneously, and the transplant tumors of the seventh and eighth generations were used for experiments. Expression of various markers in the tumors was examined immunohistochemically. TNP-470 was injected subcutaneously every other day into tumor-bearing mice from 3 weeks after tumor transplantation. The proliferation of tumor cells and endothelial cells was estimated by means of the bromodeoxyuridine labeling index. The original hepatoblastoma showed the histology of the epithelial type, consisting of both the fetal and embryonal subtypes and was positively stained with anti-alpha-fetoprotein (AFP), anti-cytokeratin-19 and polyclonal anticarcinoembryonic antigen antibodies, and an antihuman hepatocyte antibody (hepatocyte paraffin 1). The transplant tumors consisted of solid nests of tumor cells with numerous vascular lakes of various sizes, and showed positive staining with all antibodies that reacted positively with the original hepatoblastoma. Injections of TNP-470 at the doses of 15 mg and 30 mg/kg body weight suppressed the tumor growth and the increase in the serum level of AFP dose dependently. Injections of TNP-470 also suppressed the proliferation of tumor cells and endothelial cells in the tumors. Hepatoblastomas maintained in nude mice retained the immunohistochemical characteristics of the original hepatoblastoma, and TNP-470 suppressed the growth of hepatoblastomas transplanted into nude mice. TNP-470 may be worth investigating further as to its usefulness as a therapy for hepatoblastomas.

  9. A metastatic nude-mouse model of human pancreatic cancer constructed orthotopically with histologically intact patient specimens.

    PubMed Central

    Fu, X; Guadagni, F; Hoffman, R M

    1992-01-01

    Pancreatic cancer is one of the most intractable and least understood of all human cancers. Pancreatic cancers is the fourth-leading cause of cancer-related mortality in the United States with less than 2% of the patients surviving for 5 yr. In an effort to help develop more effective treatment modalities for pancreatic cancer and improve detection, we report an animal model for individual human pancreatic-cancer patients. The model involves orthotopic transplantation of histologically intact pancreatic-cancer specimens to the nude-mouse pancreas, which can result in models that resemble the clinical picture including (i) extensive local tumor growth, (ii) extension of the locally growing human pancreatic cancer to the nude-mouse stomach and duodenum, (iii) metastases of the human pancreatic tumor to the nude-mouse liver and regional lymph nodes, and (iv) distant metastases of the human pancreatic tumor to the nude-mouse adrenal gland, diaphragm, and mediastinal lymph nodes. In a series of five patient cases, a 100% take rate has been demonstrated, and of 17 mice transplanted, 15 supported tumor growth. Immunohistochemical analysis of the antigenic phenotype of the transplanted human pancreatic tumors showed a similar pattern of expression of two different human tumor-associated antigens, such as tumor-associated glycoprotein 72 and carcinoembryonic antigen in the transplanted tumors when compared with the original surgical biopsy, suggesting similarity between the two. This model should, therefore, prove valuable for treatment evaluation of individual cancer patients, as well as for evaluation of experimental treatment modalities for this disease. Images PMID:1608975

  10. Enhanced delivery of paclitaxel liposomes using focused ultrasound with microbubbles for treating nude mice bearing intracranial glioblastoma xenografts.

    PubMed

    Shen, Yuanyuan; Pi, Zhaoke; Yan, Fei; Yeh, Chih-Kuang; Zeng, Xiaojun; Diao, Xianfen; Hu, Yaxin; Chen, Siping; Chen, Xin; Zheng, Hairong

    2017-01-01

    Paclitaxel liposomes (PTX-LIPO) are a clinically promising antineoplastic drug formulation for the treatment of various extracranial cancers, excluding glioblastoma. A main reason for this is the presence of the blood-brain barrier (BBB) or blood-tumor barrier (BTB), preventing liposomal drugs from crossing at a therapeutically meaningful level. Focused ultrasound (FUS) in conjunction with microbubbles (MBs) has been suggested in many studies to be an effective approach to increase the BBB or BTB permeability. In this study, we investigated the feasibility of enhancing the delivery of PTX-LIPO in intracranial glioblastoma-bearing nude mice using pulsed low-intensity FUS exposure in the presence of MBs. Our results showed that the delivery efficiency of PTX-LIPO could be effectively improved in terms of the penetration of both the BBB in vitro and BTB in vivo by pulsed FUS sonication with a 10 ms pulse length and 1 Hz pulse repetition frequency at 0.64 MPa peak-rarefactional pressure in the presence of MBs. Quantitative analysis showed that a 2-fold higher drug concentration had accumulated in the glioblastoma 3 h after FUS treatment, with 7.20±1.18 µg PTX per g glioma tissue. Longitudinal magnetic resonance imaging analysis illustrated that the intracranial glioblastoma progression in nude mice treated with PTX-LIPO delivered via FUS with MBs was suppressed consistently for 4 weeks compared to the untreated group. The medium survival time of these tumor-bearing nude mice was significantly prolonged by 20.8%, compared to the untreated nude mice. Immunohistochemical analysis further confirmed the antiproliferation effect and cell apoptosis induction. Our study demonstrated that noninvasive low-intensity FUS with MBs can be used as an effective approach to deliver PTX-LIPO in order to improve their chemotherapy efficacy toward glioblastoma.

  11. [99mTc-octreotide receptor scintigraphy in NCI-H446 small cell lung cancer nude mice model].

    PubMed

    Li, Chao; Zuo, Shuyao; Wang, Xufu; Liu, Xinfeng; Wang, Guoming; Wu, Fengyu

    2015-01-01

    For highly aggressive small cell lung cancer (SCLC), early diagnosis is important 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, difficult 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. The aim of this study is to observe the biodistribution and metabolism of 99mTc-octreotide in normal and the human SCLC bearing nude mice. Dynamic and static scintigraphy at 0.5 h, 2 h, 3 h, 4 h were performed in both normal and tumor bearing nude mice after intravenous injection of 99mTc-octreotide. The technique of drawing region of interest (ROI) was used to obtain the averaged pixel counts and the activity-time (A-T) curve of brain, heart, lung, liver, kidney, tumor, respectively. ① The 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. The 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). The radioactivity of tumor was lower than liver, and similar with the lung. The curve of tumor showed a radioactivity peak at 2 min-3 min postinjection. 99mTc-octreotide receptor imaging on nude mice bearing SCLC shares high positive rate, especially at 3 h postinjection.

  12. Mechanisms of defective glucose-induced insulin release in human pancreatic islets transplanted to diabetic nude mice.

    PubMed

    Eizirik, D L; Jansson, L; Flodström, M; Hellerström, C; Andersson, A

    1997-08-01

    We have previously observed that human islets, transplanted under the kidney capsule of hyperglycemic nude mice, show a longlasting impairment in glucose-induced insulin release. To investigate the cause(s) of this phenomenon, we transplanted human islets into normoglycemic or alloxan-diabetic nude mice for a 4- to 6-week period. In a third experimental group, aimed at evaluating reversibility of hyperglycemia effects, diabetic nude mice bearing a human islet graft were cured by a second intrasplenic transplant of mouse islets, and the human islets were exposed to a further 2 weeks of normoglycemia. Four to 6 weeks of hyperglycemia induced a severe impairment of glucose- and arginine-induced insulin release, as demonstrated by perfusion of the graft-bearing kidney. This defective release was not restored by a subsequent 2-week period of normoglycemia, and it was accompanied by normal (pro)insulin biosynthesis, glucose oxidation, and expression of insulin messenger RNA. Taken together with our previous study, these observations indicate that impaired glucose metabolism, depletion of insulin messenger RNA, decreased (pro)insulin biosynthesis, increased glycogen accumulation, and depletion of insulin reserves cannot explain the deleterious effects of the diabetic state on human islet insulin release. This, and the similar inhibition of glucose- and arginine-induced insulin release, suggest that prolonged hyperglycemia may exert its deleterious effect on insulin release at a step distal to closure of ATP-sensitive K-channels.

  13. Serum CEA levels in patients with gastric carcinoma correlate with the tumorigenicity of their xenografts in nude mice.

    PubMed

    Kiyama, T; Onda, M; Tokunaga, A; Okuda, T; Mizutani, T; Yoshiyuki, T; Shimizu, Y; Nishi, K; Matsukura, N; Tanaka, N

    1991-01-01

    We examined the correlation among preoperative serum carcinoembryonic antigen (CEA) levels, staining properties of the tumors by CEA immunohistochemistry and the tumorigenicity of their xenografts in nude mice, in 28 patients with gastric cancer. Eleven (40 per cent) of them were positive for serum CEA (greater than or equal to 2.5 ng/ml) and seven (25 per cent) of the xenografts were tumorigenic in nude mice. All the tumorigenic cases were positive for serum CEA (p less than 0.001) and the mean value of the serum CEA level in the patients with tumorigenic neoplasms was 20.8 ng/ml, being significantly higher than that (1.4 ng/ml) in the patients with non-tumorigenic neoplasms (p less than 0.001). Twenty-five of the 28 carcinomas (89 per cent) were positive for CEA staining in their cancer cells by the ABC method and CEA localization correlated with tumorigenicity (p less than 0.05). These results suggest that the serum CEA level in patients is correlated with the tumorigenicity of their gastric carcinoma xenografts in nude mice and may account for the poor prognosis of patients with high serum CEA.

  14. The growth of glioblastoma orthotopic xenografts in nude mice is directly correlated with impaired object recognition memory.

    PubMed

    Wasilewska-Sampaio, Ana Paula; Santos, Tiago G; Lopes, Marilene Hohmuth; Cammarota, Martin; Martins, Vilma Regina

    2014-01-17

    Cognitive dysfunction is found in patients with brain tumors and there is a need to determine whether it can be replicated in an experimental model. In the present study, the object recognition (OR) paradigm was used to investigate cognitive performance in nude mice, which represent one of the most important animal models available to study human tumors in vivo. Mice with orthotopic xenografts of the human U87MG glioblastoma cell line were trained at 9, 14, and 18days (D9, D14, and D18, respectively) after implantation of 5×10(5) cells. At D9, the mice showed normal behavior when tested 90min or 24h after training and compared to control nude mice. Animals at D14 were still able to discriminate between familiar and novel objects, but exhibited a lower performance than animals at D9. Total impairment in the OR memory was observed when animals were evaluated on D18. These alterations were detected earlier than any other clinical symptoms, which were observed only 22-24days after tumor implantation. There was a significant correlation between the discrimination index (d2) and time after tumor implantation as well as between d2 and tumor volume. These data indicate that the OR task is a robust test to identify early behavior alterations caused by glioblastoma in nude mice. In addition, these results suggest that OR task can be a reliable tool to test the efficacy of new therapies against these tumors.

  15. Determination of transdermal sildenafil in nude mouse skin by reversed-phase high-performance liquid chromatography.

    PubMed

    Lia, J; Chang, T W

    2001-12-25

    A simple and sensitive high-performance liquid chromatographic method was developed for the determination of sildenafil transdermal permeation of nude mouse skin. A reversed-phase column with UV detection at 224 nm was used for chromatographic separation. The mobile phase consisted of 32% acetonitrile with 0.2% phosphoric acid in water at pH 5.3 adjusted with 10 M NaOH with the flow-rate set at 1.0 ml/min. The limit of quantitation achieved was 5 ng/ml, and the calibration curve showed good linearity over the concentration range of 5-500 ng/ml. The relative standard deviations of within- and between-day analyses were all within 15%. Sildenafil was found to be stable between pH 3 and 12 during 24-h incubation with skin. After transdermal administration of 15.8 microg/ml of sildenafil to nude mouse skin, it was detected as early as 15 min. The transport amount of sildenafil could be quantitated and, at pH 8-11, had the highest permeation rate in nude mouse skin.

  16. POOR MOBILIZATION IN T CELL-DEFICIENT NUDE MICE IS EXPLAINED BY DEFECTVE ACTIVATION OF GRANULOCYTES AND MONOCYTES

    PubMed Central

    Wysoczynski, Marcin; Adamiak, Mateusz; Suszynska, Malwina; Abdel-Latif, Ahmed; Ratajczak, Janina; Ratajczak, Mariusz Z.

    2017-01-01

    It has been reported that both SCID mice and SCID patients mobilize hematopoietic stem/progenitor cells (HSPCs) poorly in response to granulocyte colony stimulating factor (G-CSF). This defect has been proposed to result from a lack of naturally occurring IgM immunoglobulins to trigger activation of the complement cascade (ComC) and release of C5 cleavage fragments crucial in the mobilization process. However, SCID individuals also have T cell deficiency, and T cells have been shown to modulate trafficking of HSPCs. To learn more about the role of T lymphocytes, we performed mobilization studies in T lymphocyte-deficient nude mice and found that these mice respond poorly to G-CSF and zymosan but are normal mobilizers in response to AMD3100. Since nude mice have normal levels of IgM immunoglobulins in peripheral blood and may activate the ComC, we focused on the potential involvement of Gr1+ granulocytes and monocytes, which show defective maturation in these animals. Using a nude mouse mobilization model, we found further support for the proposition that proper function of Gr1+ cells is crucial for optimal mobilization of HSPCs. PMID:27436627

  17. Radiation Protection

    MedlinePlus

    ... EPA United States Environmental Protection Agency Search Search Radiation Protection Share Facebook Twitter Google+ Pinterest Contact Us Radiation Protection Document Library View and download EPA radiation ...

  18. Bone regeneration by nanohydroxyapatite/chitosan/poly(lactide-co-glycolide) scaffolds seeded with human umbilical cord mesenchymal stem cells in the calvarial defects of the nude mice.

    PubMed

    Wang, Fei; Su, Xiao-Xia; Guo, Yu-Cheng; Li, Ang; Zhang, Yin-Cheng; Zhou, Hong; Qiao, Hu; Guan, Li-Min; Zou, Min; Si, Xin-Qin

    2015-01-01

    In the preliminary study, we have found an excellent osteogenic property of nanohydroxyapatite/chitosan/poly(lactide-co-glycolide) (nHA/CS/PLGA) scaffolds seeded with human umbilical cord mesenchymal stem cells (hUCMSCs) in vitro and subcutaneously in the nude mice. The aim of this study was to further evaluate the osteogenic capacity of nHA/CS/PLGA scaffolds seeded with hUCMSCs in the calvarial defects of the nude mice. Totally 108 nude mice were included and divided into 6 groups: PLGA scaffolds + hUCMSCs; nHA/PLGA scaffolds + hUCMSCs; CS/PLGA scaffolds + hUCMSCs; nHA/CS/PLGA scaffolds + hUCMSCs; nHA/CS/PLGA scaffolds without seeding; the control group (no scaffolds) (n = 18). The scaffolds were implanted into the calvarial defects of nude mice. The amount of new bones was evaluated by fluorescence labeling, H&E staining, and Van Gieson staining at 4 and 8 weeks, respectively. The results demonstrated that the amount of new bones was significantly increased in the group of nHA/CS/PLGA scaffolds seeded with hUCMSCs (p < 0.01). On the basis of previous studies in vitro and in subcutaneous implantation of the nude mice, the results revealed that the nHA and CS also enhanced the bone regeneration by nHA/CS/PLGA scaffolds seeded with hUCMSCs in the calvarial defects of the nude mice at early stage.

  19. Bone Regeneration by Nanohydroxyapatite/Chitosan/Poly(lactide-co-glycolide) Scaffolds Seeded with Human Umbilical Cord Mesenchymal Stem Cells in the Calvarial Defects of the Nude Mice

    PubMed Central

    Wang, Fei; Su, Xiao-Xia; Guo, Yu-Cheng; Li, Ang; Zhang, Yin-Cheng; Zhou, Hong; Qiao, Hu; Guan, Li-Min; Zou, Min; Si, Xin-Qin

    2015-01-01

    In the preliminary study, we have found an excellent osteogenic property of nanohydroxyapatite/chitosan/poly(lactide-co-glycolide) (nHA/CS/PLGA) scaffolds seeded with human umbilical cord mesenchymal stem cells (hUCMSCs) in vitro and subcutaneously in the nude mice. The aim of this study was to further evaluate the osteogenic capacity of nHA/CS/PLGA scaffolds seeded with hUCMSCs in the calvarial defects of the nude mice. Totally 108 nude mice were included and divided into 6 groups: PLGA scaffolds + hUCMSCs; nHA/PLGA scaffolds + hUCMSCs; CS/PLGA scaffolds + hUCMSCs; nHA/CS/PLGA scaffolds + hUCMSCs; nHA/CS/PLGA scaffolds without seeding; the control group (no scaffolds) (n = 18). The scaffolds were implanted into the calvarial defects of nude mice. The amount of new bones was evaluated by fluorescence labeling, H&E staining, and Van Gieson staining at 4 and 8 weeks, respectively. The results demonstrated that the amount of new bones was significantly increased in the group of nHA/CS/PLGA scaffolds seeded with hUCMSCs (p < 0.01). On the basis of previous studies in vitro and in subcutaneous implantation of the nude mice, the results revealed that the nHA and CS also enhanced the bone regeneration by nHA/CS/PLGA scaffolds seeded with hUCMSCs in the calvarial defects of the nude mice at early stage. PMID:26550565

  20. Overexpression of caudal-related homeobox transcription factor 2 inhibits the growth of transplanted colorectal tumors in nude mice.

    PubMed

    Zheng, Jian-Bao; Qiao, Li-Na; Sun, Xue-Jun; Qi, Jie; Ren, Hai-Liang; Wei, Guang-Bing; Zhou, Pei-Hua; Yao, Jian-Feng; Zhang, Li; Jia, Peng-Bo

    2015-09-01

    Caudal‑related homeobox transcription factor 2 (CDX2) is a transcription factor, which is specifically expressed in the adult intestine. It is essential for the development and homeostasis of the intestinal epithelium and its functions as a tumor suppressor have been demonstrated in the adult colon. The present study aimed to examine the inhibitory effects of the overexpression of CDX2 on subcutaneously‑transplanted tumors, derived from LoVo colon cancer cells, in nude mice, and to provide experimental evidence for the biotherapy of colon cancer. A pEGFP‑C1‑CDX2 eukaryotic expression vector was transfected into the LoVo cells via lipofection, and LoVo cells stably‑expressing CDX2 (pEGFP‑C1‑CDX2 cells) were obtained using G418 selection. A nude mouse subcutaneously‑transplanted tumor model was established by inoculating the nude mice with the pEGFP‑C1‑CDX2 cells, and the effects of overexpression of CDX2 on transplanted tumor growth in the LoVo cells were observed. Western blotting results demonstrated that the protein expression of CDX2 in the LoVo cells was higher in the pEGFP‑C1‑CDX2 cell group, compared with that in the pEGFP‑C1 cell group and the untreated cell group. At 20 days post‑inoculation with either pEGFP‑C1‑CDX2 or pEGFP‑C1, the transplanted tumor masses were significantly lower in the pEGFP‑C1‑CDX2 group, compared with those in the pEGFP‑C1 and untreated groups. Immunohistochemistry revealed that the expression levels of CDX2 and matrix metalloproteinase‑2 (MMP‑2) were detected in each group, and the protein expression of CDX2 was increased in the tumor tissues from the nude mice in the pEGFP‑C1‑CDX2 group. However the expression of MMP‑2 was downregulated in the tumor tissues of the nude mice in the pEGFP‑C1‑CDX2 group. Taken together, these data suggested that pEGFP‑C1‑CDX2 cells exhibited suppressed tumor growth in vivo. Overexpression of CDX2 was observed in transplanted tumors in the p

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

    PubMed Central

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

    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-2 and 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-2 and bax by immunohistoch-emical 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, 1000 mg/kg and 1500 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, 1000 mg/kg resveratrol, and 1500 mg/kg resveratrol was 13.68±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, 1500 mg/kg DMSO, 500 mg/kg resveratrol, 1000 mg/kg resveratrol, and

  2. Syzygium campanulatum korth methanolic extract inhibits angiogenesis and tumor growth in nude mice

    PubMed Central

    2013-01-01

    Background Syzygium campanulatum Korth (Myrtaceae) is an evergreen shrub rich in phenolics, flavonoid antioxidants, and betulinic acid. This study sought to investigate antiangiogenic and anti-colon cancer effects of S.C. standardized methanolic extract. Methods Betulinic acid was isolated from methanolic extract by crystallization and chromatography techniques. S.C. methanolic extract was analyzed by UV-Vis spectrophotometry, FTIR, LC-MS, and HPLC. Antiangiogenic effect was studied on rat aortic rings, matrigel tube formation, cell proliferation and migration, and expression of vascular endothelial growth factor (VEGF). Antitumor effect was studied using a subcutaneous tumor model of HCT 116 colorectal carcinoma cells established in nude mice. Results Analysis by HPLC, LC-MS and FTIR confirm presence of betulinic acid in S.C. methanolic extract. Quantitative analysis by HPLC indicates presence of betulinic acid in S.C. extract at 5.42 ± 0.09% (w/w). Antiangiogenesis study showed potent inhibition of microvessels outgrowth in rat aortic rings, and studies on normal and cancer cells did not show any significant cytotoxic effect. Antiangiogenic effect was further confirmed by inhibition of tube formation on matrigel matrix that involves human endothelial cells (IC50 = 17.6 ± 2.9 μg/ml). S.C. extract also inhibited migration of endothelial cells and suppressed expression of VEGF. In vivo antiangiogenic study showed inhibition of new blood vessels in chicken embryo chorioallantoic membrane (CAM), and in vivo antitumor study showed significant inhibition of tumor growth due to reduction of intratumor blood vessels and induction of cell death. Conclusion Collectively, our results indicate S. campanulatum as antiangiogenic and antitumor candidate, and a new source of betulinic acid. PMID:23842450

  3. Systemic interleukin 2 therapy for human prostate tumors in a nude mouse model.

    PubMed

    Triest, J A; Grignon, D J; Cher, M L; Kocheril, S V; Montecillo, E J; Talati, B; Tekyi-Mensah, S; Pontes, J E; Hillman, G G

    1998-08-01

    Once the regional lymph nodes become involved in prostate carcinoma, 85% of patients develop distant metastases within 5 years, and metastatic disease is difficult to treat. We have investigated the effect of systemic interleukin 2 (IL-2) treatment on metastatic prostate carcinoma using a xenograft tumor model. Cells from a PC-3/IF cell line, produced by intrafemoral injection of human PC-3 prostate carcinoma cells, were injected in the prostate of Balb/c nude mice. Prostate tumors and para-aortic lymph nodes were resected, and tumor cells were recultured and passaged in the prostate in vivo to produce new cell lines. On day 6 following prostatic injection of these cell lines, mice were treated with i.p. injections of IL-2 at 25,000-50,000 units/ day for 5 consecutive days. The effect of IL-2 on tumor progression was assessed, and histological studies were performed on prostate tumor and lymph node sections. The tumor cell lines generated by serial prostate injection were tumorigenic and metastasized to regional para-aortic lymph nodes. Tumors of 0.4 cm were obtained by day 16 and grew to 1-1.5 cm by day 40 with metastasis to para-aortic lymph nodes. Following two to three weekly courses of 5 days of 25,000-40,000 units/day of IL-2, the growth of prostate tumors was inhibited by 94%. Higher doses of 50,000 units/ day were toxic. Histologically, prostate sections showed vascular damage manifested by multifocal hemorrhages and an influx of lymphocytes and polymorphonuclear cells into disintegrating tumors and areas of necrosis containing numerous apoptotic cells. In contrast to control mice, para-aortic lymph nodes were not enlarged in responding mice. These findings suggest that systemic IL-2 therapy can induce an antitumor response in prostate tumors and control their growth and metastasis.

  4. Assessment of Viability of Human Fat Injection into Nude Mice with Micro-Computed Tomography

    PubMed Central

    Chung, Michael T.; McArdle, Adrian; Senarath-Yapa, Kshemendra; Zielins, Elizabeth R.; Tevlin, Ruth; Duldulao, Christopher R.; Walmsley, Graham G.; Wearda, Taylor; Marecic, Owen; Longaker, Michael T.; Wan, Derrick C.

    2015-01-01

    Lipotransfer is a vital tool in the surgeon’s armamentarium for the treatment of soft tissue deficits of throughout the body. Fat is the ideal soft tissue filler as it is readily available, easily obtained, inexpensive, and inherently biocompatible.1 However, despite its burgeoning popularity, fat grafting is hampered by unpredictable results and variable graft survival, with published retention rates ranging anywhere from 10-80%. 1-3 To facilitate investigations on fat grafting, we have therefore developed an animal model that allows for real-time analysis of injected fat volume retention. Briefly, a small cut is made in the scalp of a CD-1 nude mouse and 200-400 µl of processed lipoaspirate is placed over the skull. The scalp is chosen as the recipient site because of its absence of native subcutaneous fat, and because of the excellent background contrast provided by the calvarium, which aids in the analysis process. Micro-computed tomography (micro-CT) is used to scan the graft at baseline and every two weeks thereafter. The CT images are reconstructed, and an imaging software is used to quantify graft volumes. Traditionally, techniques to assess fat graft volume have necessitated euthanizing the study animal to provide just a single assessment of graft weight and volume by physical measurement ex vivo. Biochemical and histological comparisons have likewise required the study animal to be euthanized. This described imaging technique offers the advantage of visualizing and objectively quantifying volume at multiple time points after initial grafting without having to sacrifice the study animal. The technique is limited by the size of the graft able to be injected as larger grafts risk skin and fat necrosis. This method has utility for all studies evaluating fat graft viability and volume retention. It is particularly well-suited to providing a visual representation of fat grafts and following changes in volume over time. PMID:25590561

  5. [Effects of primary tumor excision on angiogenesis and pulmonary metastasis in osteosarcoma-bearing nude mice].

    PubMed

    Mei, Jiong; Ni, Ming; Chen, Yan-xi; Yao, Bin; Gao, You-shui; Yu, Xiu-mao; Wang, Zhi-yuan

    2009-04-01

    To investigate the effects of primary tumor excision on osteosarcoma angiogenesis and pulmonary metastasis, and explore its possible mechanism and clinical significance. The tumor-bearing nude mice were constructed by injection of human osteosarcoma cell suspension, and divided into primary tumor resection, amputation and normal groups. The level of VEGF and endostatin was examined by ELISA assay. The hemoglobin content in Matrigel pellets was measured with HiCN method. Pulmonary metastasis was detected with dilated-squash technique and immunohistochemical staining. The serum VEGF and endostatin level was significantly decreased in the primary tumor excision group compared with that in the normal and control groups after operation, but endostatin decreased more prominently [VEGF: (71.43 +/- 9.15) pg/ml vs. (115.81 +/- 4.38) pg/ml, (111.68 +/- 12.26) pg/ml, P < 0.01; ES: (40.77 +/- 5.41) ng/ml vs. (123.18 +/- 5.94) ng/ml, (128.06 +/- 4.52) ng/ml, P < 0.01]. The HB contents in Matrigel pellets increased in the primary tumor excision group compared with that in normal and control groups [(36.55 +/- 2.35) g/L vs. (16.84 +/- 1.15) g/L, (16.29 +/- 1.10) g/L, P < 0.01]. The rate of pulmonary metastasis in tumor excision group was much higher than that in the un-excised groups (80.0% vs. 40.0% and 35.0%, P < 0.05). The excision of primary tumor can promote osteosarcoma angiogenesis and pulmonary metastasis, so anti-angiogenic treatment after operation has instructive clinical significance in preventing tumor metastasis.

  6. Fluorescence-guided surgery improves outcome in an orthotopic osteosarcoma nude-mouse model.

    PubMed

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

    2014-12-01

    In order to develop a model for fluorescence-guided surgery (FGS), 143B human osteosarcoma cells expressing red fluorescent protein (RFP) were injected into the intramedullary cavity of the tibia in nude mice. The fluorescent areas of residual tumors after bright-light surgery (BLS) and FGS were 10.2 ± 2.4 mm(2) and 0.1 ± 0.1 mm(2) , respectively (p<0.001). The BLS-treated mice and BLS+cisplatinum (CDDP)-treated mice had significant recurrence. In contrast, the FGS mice and FGS+CDDP mice had very little recurring tumor growth. Disease-free survival (DFS) in the BLS-, BLS+CDDP-, FGS-, and FGS+CDDP-treated mice was 12.5%, 37.5%, 75.0%, and 87.5%, respectively. The FGS-treated mice had a significantly higher DFS rate than the BLS-treated mice (p=0.021). The FGS+CDDP-treated mice had significantly higher DFS rate than the BLS+CDDP-treated mice (p=0.043). Although chemotherapy significantly reduced multiple metastases (p=0.033), there was no significant correlation between FGS and lung metastasis. FGS significantly reduced the recurrence of the primary tumor but did not reduce lung metastasis. The combination of FGS and adjuvant CDDP reduced tumor recurrence and prevented multiple metastases. FGS and adjuvant chemotherapy should be performed as early as possible in the disease to prevent both recurrence and metastatic development. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  7. In vivo potentiation of radiation response by topotecan in human rhabdomyosarcoma xenografted into nude mice.

    PubMed

    Chastagner, P; Merlin, J L; Marchal, C; Hoffstetter, S; Barberi-Heyob, M; Vassal, G; Duprez, A

    2000-08-01

    The lack of new highly efficacious drugs for cancer treatment promotes the search for innovative therapeutic modalities. The authors reported the results leading to the definition of parameters needed to demonstrate a possible radiopotentiation by topotecan (TPT) on two representative human rhabdomyosarcomas (RMSs) xenografted into nude mice. Experimental studies of radiopotentiation with different doses of topotecan showed that concomitant association of topotecan and RT for 5 consecutive days provided a synergistic therapeutic effect. Response rates were statistically higher with the radiochemotherapeutic combination (P < 0.001). Efficacy enhancement factors of this combination compared with the sum of the antitumoral activity of these treatments separately administrated were 1.54 and 1.60, respectively, on both rhabdomyosarcomas. Moreover, the efficiency of the combination of radiotherapy at the dose of 20 Gy with topotecan (12.5 mg/kg) was not statistically different from that of radiotherapy at the dose of 40 Gy. According to microscopy results, the analyses performed at different periods after topotecan treatment alone, radiotherapy alone, and their combination seemed to show that tumoral repopulation by malignant cells is as fast as the dose of radiotherapy and/or topotecan is low. Furthermore, lesions observed with the dose of 40 Gy were similar to those obtained with the association of topotecan at the dose of 12.5 mg/kg and radiotherapy at the dose of 20 Gy. In conclusion, all clinical and pathological results are consistent with a radiopotentiation effect of topotecan on the two xenografted human rhabdomyosarcomas and are currently leading to the design of clinical studies.

  8. Chondrocytic differentiation of peripheral neuroectodermal tumor cell line in nude mouse xenograft.

    PubMed

    Goji, J; Sano, K; Nakamura, H; Ito, H

    1992-08-01

    We have established a cell line (KU-SN) from a peripheral neuroectodermal tumor originating in the left scapula of a 4-year-old girl. The original tumor was immunoreactive with antibodies for neurofilament proteins, neuron-specific enolase, vimentin, S100 protein, and beta 2-microglobulin. Dense core granules, 50-150 nm in diameter, were identified by electron microscopy. The cell line was established from tumor cells in metastatic lung fluid. KU-SN cells were immunoreactive with the antibodies for neurofilament proteins, vimentin, neuron-specific enolase, S100 protein, glial fibrillary acidic protein, cytokeratin, and carcinoembryonic antigen. Besides these neuronal features, KU-SN cells express type 2 collagen and insulin-like growth factor 1 receptor. The addition of insulin-like growth factor 1 (100 ng/ml) increased the growth rate of KU-SN cells 2.1-fold over control. Some cells were positive for Alcian blue and alkaline phosphatase staining. Cytogenetic analysis of KU-SN cells disclosed a reciprocal chromosomal translocation [t(11,22)]. Northern blot analysis of KU-SN cells demonstrated amplified expression of the c-myc gene but not the N-myc gene. When tumor cells were transplanted into nude mice, cartilage was formed. The cartilage was immunoreactive with the antibody for HLA-ABC, indicating that it was derived from the tumor cells, not from mouse tissue. Chondrocytic differentiation was not observed in xenografts of Ewing's sarcoma cell lines SK-ES or RD-ES or the peripheral neuroectodermal tumor cell line SK-N-MC. These results indicate that KU-SN cells represent primitive neural crest cells having the potential for chondrocytic differentiation.

  9. Surveillance of systemic trafficking of macrophages induced by UHMWPE particles in nude mice by noninvasive imaging.

    PubMed

    Ren, Pei-Gen; Huang, Zhinong; Ma, Ting; Biswal, Sandip; Smith, Robert L; Goodman, Stuart B

    2010-09-01

    Macrophages constitute a major part of the cell response to wear particles produced at articulating and nonarticulating interfaces of joint replacements. This foreign body reaction can result in periprosthetic osteolysis and implant loosening. We demonstrate that ultra-high molecular weight polyethylene (UHMWPE) particles induce systemic trafficking of macrophages by noninvasive in vivo imaging and immunohistochemistry. The distal femora of nude mice were injected with 60 mg/mL UHMWPE suspension or saline alone. Reporter RAW264.7 macrophages that stably expressed the bioluminescent reporter gene and the fluorescence reporter gene were injected intravenously. Bioluminescence imaging was performed using an in vivo imaging system immediately after macrophage injection and at 2-day intervals. Compared with the nonoperated contralateral femora, at day 4, 6, and 8, the bioluminescent signal of femora containing UHMWPE suspension increased 1.30 +/- 0.09-, 2.36 +/- 0.92-, and 10.32 +/- 7.61-fold, respectively. The values at same time points for saline-injected control group were 1.08 +/- 0.07-, 1.14 +/- 0.27-, and 1.14 +/- 0.35-fold, respectively. The relative bioluminescence of the UHMWPE group was higher at all postinjection days and significantly greater than the saline group at day 8 (p < 0.05). Histological analysis confirmed the presence of reporter macrophages within the medullary canal of mice with implanted UHMWPE particles. The presence of UHMWPE particles induced enhanced bone remodeling activity. Clinically relevant UHMWPE particles stimulated the systemic recruitment of macrophages during an early time course using the murine femoral implant model. Interference with systemic macrophage trafficking may potentially mitigate UHMWPE particle-induced periprosthetic osteolysis.

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

    NASA Astrophysics Data System (ADS)

    Bose, Satya Ranjan

    2000-06-01

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

  11. Effects of Spectral Transmittance through Standard Laboratory Cages on Circadian Metabolism and Physiology in Nude Rats

    PubMed Central

    Dauchy, Robert T; Dauchy, Erin M; Hanifin, John P; Gauthreaux, Sheena L; Mao, Lulu; Belancio, Victoria P; Ooms, Tara G; Dupepe, Lynell M; Jablonski, Michael R; Warfield, Benjamin; Wren, Melissa A; Brainard, George C; Hill, Steven M; Blask, David E

    2013-01-01

    Light is potent in circadian, neuroendocrine, and neurobehavioral regulation, thereby having profound influence on the health and wellbeing of all mammals, including laboratory animals. We hypothesized that the spectral quality of light transmitted through colored compared with clear standard rodent cages alters circadian production of melatonin and temporal coordination of normal metabolic and physiologic activities. Female nude rats (Hsd:RH-Foxn1rnu; n = 6 per group) were maintained on a 12:12-h light:dark regimen (300 lx; lights on, 0600) in standard translucent clear, amber, or blue rodent cages; intensity and duration of lighting were identical for all groups. Rats were assessed for arterial blood levels of pO2 and pCO2, melatonin, total fatty acid, glucose, lactic acid, insulin, leptin, and corticosterone concentrations at 6 circadian time points. Normal circadian rhythms of arterial blood pO2 and pCO2 were different in rats housed in cages that were blue compared with amber or clear. Plasma melatonin levels (mean ± 1 SD) were low (1.0 ± 0.2 pg/mL) during the light phase in all groups but higher at nighttime in rats in blue cages (928.2 ± 39.5 pg/mL) compared with amber (256.8 ± 6.6 pg/mL) and clear (154.8 ± 9.3 pg/mL) cages. Plasma daily rhythms of total fatty acid, glucose, lactic acid, leptin, insulin, and corticosterone were disrupted in rats housed in blue or amber compared with clear cages. Temporal coordination of circadian rhythms of physiology and metabolism can be altered markedly by changes in the spectral quality of light transmitted through colored standard rodent cages. PMID:23562097

  12. Monoclonal antibody-targeted radiotherapy of renal cell carcinoma using a nude mouse model

    SciTech Connect

    Chiou, R.K.; Vessella, R.L.; Limas, C.; Shafer, R.B.; Elson, M.K.; Arfman, E.W.; Lange, P.H.

    1988-05-01

    Radiation dosimetry and monoclonal antibody (MAB)-targeted radiotherapy studies were performed to evaluate the feasibility of using tumor-preferential MAB as targeting agents for internal radiotherapy of renal cell carcinoma (RCC). Two human RCC xenograft lines, TK-177G and TK-82, were established in nude mice and studied using MAB A6H as a targeting agent. This MAB has previously demonstrated excellent in vivo localization to RCC xenografts. Two doses of A6H (13 to 19 micrograms) labeled with iodine 131 (110 to 130 microCi) caused the tumor to regress or arrested the tumor growth in both xenografts. Similar doses (18 to 43 micrograms; 120 microCi) of /sup 131/I-labeled control MAB AFP-22 or of unlabeled A6H did not inhibit tumor growth. While most mice in the control groups had tumors greater than 250 mg in weight by day 43, none of the tumors in mice treated with /sup 131/I-labeled A6H grew to that size during the 3-month observation period. Sequential computerized scintigraphy was used to calculate the amount of radioisotope localized in tumor versus normal mouse tissue. Therapeutic doses of /sup 131/I-labeled A6H delivered a median calculated radiation dose of 38 cGy/microCi (range, 28 to 57) injected dose to RCC xenografts, and a median of 0.9 cGy/microCi to normal mouse tissues. These findings suggest that A6H is able to target radioisotopes highly specifically to RCC and achieve a therapeutic effect in the experimental setting.

  13. Follicular development in cryopreserved Common Wombat ovarian tissue xenografted to Nude rats.

    PubMed

    Wolvekamp, M C; Cleary, M L; Cox, S L; Shaw, J M; Jenkin, G; Trounson, A O

    2001-01-31

    The Northern Hairy-nosed Wombat (Lasiorhinus krefftii) is a highly endangered marsupial species and every possible option for sustaining the species needs to be explored. One important approach may be the development of assisted reproductive technologies in the non-endangered Common Wombat (Vombatus ursinus) and Southern Hairy-nosed Wombat (Lasiorhinus latifrons) for application in breeding the Northern Hairy-nosed Wombat. In this study, it was examined whether cryopreserved Wombat ovarian tissue would develop following xenografting to immunologically deficient rats. Ovarian tissue was collected from Common Wombats (n = 3) and cryopreserved as small cortical pieces. After thawing the cortical pieces were grafted underneath the kidney capsule of Nude rats (n = 16). The grafts were recovered at 2, 4, and 10 weeks after transplantation and their gross and histological appearance investigated. Two weeks after grafting (n = 2), the tissue was revascularized and healthy primordial follicles were present. At week 4 (n = 2), some follicular development was present. At week 10, six rats received human chorionic gonadotrophin (hCG) to trigger follicle and oocyte maturation while another six rats were not given any treatment. The administration of hCG did not induce preovulatory follicles and oocyte maturation although type 5 follicles were present in ovarian tissue collected 10 weeks posttransplantation in both treated and untreated groups. This study demonstrates for the first time that Wombat ovarian tissue can survive and function when grafted into immunocompromized rats and that Wombat ovarian follicles can be recruited to growth and development in an ovarian xenograft. This model system has the potential to produce mature oocytes from endangered species for use in assisted reproductive technologies such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and mature oocytes from non-endangered species for nuclear transfer which may be necessary for

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

    NASA Astrophysics Data System (ADS)

    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.

  15. Myxoma virus therapy for human embryonal rhabdomyosarcoma in a nude mouse model.

    PubMed

    Kinn, Veronica G; Hilgenberg, Valerie A; MacNeill, Amy L

    2016-01-01

    Rhabdomyosarcoma (RMS) is a devastating tumor of young people that is difficult to cure. To determine if oncolytic virus therapy can improve outcomes in individuals with RMS, myxoma virus expressing a red fluorescent protein (MYXV-red) was evaluated for antitumoral effects using a murine model of RMS. Fluorescent protein was expressed in four RMS cell lines inoculated with MYXV-red, indicating that these cells were semipermissive to MYXV infection. MYXV-red replication and cytopathic effects were further evaluated using human embryonal RMS (CCL-136) cells. Logarithmic growth of MYXV-red and significant cell death were observed 72 hours after inoculation with MYXV. The oncolytic effects of MYXV-red were then studied in nude mice that were injected subcutaneously with CCL-136 cells to establish RMS xenografts. Once tumors measured 5 mm in diameter, mice were treated with multiple intratumoral injections of MXYV-red or saline. The average final tumor volume and rate of tumor growth were significantly decreased, and median survival time was significantly increased in MYXV-red-treated mice (P-values =0.0416, 0.0037, and 0.0004, respectively). Histologic sections of MYXV-red-treated tumors showed increased inflammation compared to saline-treated tumors (P-value =0.0002). In conclusion, MXYV-red treatment of RMS tumors was successful in individual mice as it resulted in decreased tumor burden in eight of eleven mice with nearly complete tumor remission in five of eleven mice. These data hold promise that MYXV-red treatment may be beneficial for people suffering from RMS. To our knowledge, this is the first report of successful treatment of RMS tumors using an oncolytic poxvirus.

  16. Myxoma virus therapy for human embryonal rhabdomyosarcoma in a nude mouse model

    PubMed Central

    Kinn, Veronica G; Hilgenberg, Valerie A; MacNeill, Amy L

    2016-01-01

    Rhabdomyosarcoma (RMS) is a devastating tumor of young people that is difficult to cure. To determine if oncolytic virus therapy can improve outcomes in individuals with RMS, myxoma virus expressing a red fluorescent protein (MYXV-red) was evaluated for antitumoral effects using a murine model of RMS. Fluorescent protein was expressed in four RMS cell lines inoculated with MYXV-red, indicating that these cells were semipermissive to MYXV infection. MYXV-red replication and cytopathic effects were further evaluated using human embryonal RMS (CCL-136) cells. Logarithmic growth of MYXV-red and significant cell death were observed 72 hours after inoculation with MYXV. The oncolytic effects of MYXV-red were then studied in nude mice that were injected subcutaneously with CCL-136 cells to establish RMS xenografts. Once tumors measured 5 mm in diameter, mice were treated with multiple intratumoral injections of MXYV-red or saline. The average final tumor volume and rate of tumor growth were significantly decreased, and median survival time was significantly increased in MYXV-red-treated mice (P-values =0.0416, 0.0037, and 0.0004, respectively). Histologic sections of MYXV-red-treated tumors showed increased inflammation compared to saline-treated tumors (P-value =0.0002). In conclusion, MXYV-red treatment of RMS tumors was successful in individual mice as it resulted in decreased tumor burden in eight of eleven mice with nearly complete tumor remission in five of eleven mice. These data hold promise that MYXV-red treatment may be beneficial for people suffering from RMS. To our knowledge, this is the first report of successful treatment of RMS tumors using an oncolytic poxvirus. PMID:27579297

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

    PubMed Central

    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

  18. Syzygium campanulatum korth methanolic extract inhibits angiogenesis and tumor growth in nude mice.

    PubMed

    Aisha, Abdalrahim F A; Ismail, Zhari; Abu-Salah, Khalid M; Siddiqui, Jamshed M; Ghafar, Gheniya; Abdul Majid, Amin Malik Shah

    2013-07-11

    Syzygium campanulatum Korth (Myrtaceae) is an evergreen shrub rich in phenolics, flavonoid antioxidants, and betulinic acid. This study sought to investigate antiangiogenic and anti-colon cancer effects of S.C. standardized methanolic extract. Betulinic acid was isolated from methanolic extract by crystallization and chromatography techniques. S.C. methanolic extract was analyzed by UV-Vis spectrophotometry, FTIR, LC-MS, and HPLC. Antiangiogenic effect was studied on rat aortic rings, matrigel tube formation, cell proliferation and migration, and expression of vascular endothelial growth factor (VEGF). Antitumor effect was studied using a subcutaneous tumor model of HCT 116 colorectal carcinoma cells established in nude mice. Analysis by HPLC, LC-MS and FTIR confirm presence of betulinic acid in S.C. methanolic extract. Quantitative analysis by HPLC indicates presence of betulinic acid in S.C. extract at 5.42 ± 0.09% (w/w). Antiangiogenesis study showed potent inhibition of microvessels outgrowth in rat aortic rings, and studies on normal and cancer cells did not show any significant cytotoxic effect. Antiangiogenic effect was further confirmed by inhibition of tube formation on matrigel matrix that involves human endothelial cells (IC50 = 17.6 ± 2.9 μg/ml). S.C. extract also inhibited migration of endothelial cells and suppressed expression of VEGF. In vivo antiangiogenic study showed inhibition of new blood vessels in chicken embryo chorioallantoic membrane (CAM), and in vivo antitumor study showed significant inhibition of tumor growth due to reduction of intratumor blood vessels and induction of cell death. Collectively, our results indicate S. campanulatum as antiangiogenic and antitumor candidate, and a new source of betulinic acid.

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

    PubMed

    Ricard, Clement; Fernandez, Manuel; Requardt, Herwig; Wion, Didier; Vial, Jean Claude; Segebarth, Christoph; van der Sanden, Boudewijn

    2013-09-01

    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. Antiangiogenic effect of propranolol on the growth of the neuroblastoma xenografts in nude mice.

    PubMed

    Xu, Ting; Xiao, Xianmin; Zheng, Shan; Zheng, Jicui; Zhu, Haitao; Ji, Yi; Yang, Shaobo

    2013-12-01

    Propranolol has been reported to display an antiangiogenic effect on infantile hemangiomas and also some adult cancers. Little is known, however, about whether propranolol has such effect on pediatric malignancies. Nude mice bearing BE(2) C neuroblastoma xenografts were injected intraperitoneally with propranolol and divided into groups of PROP-2 (n=11), -5 (n=11), and -10 (n=10) according to the treating dosages of 2, 5, and 10 mg kg(-1) day(-1), respectively. The tumor volume and body weight were recorded every other day. All mice were sacrificed on day 9, and the levels of angiogenic factors were measured in harvested xenografts by immunohistochemistry and western blotting. The tumor volume and weight of PROP-2 (0.72±0.28 cm(3), 0.59±0.21 g) and PROP-5 (0.81±0.35 cm(3), 0.61±0.25 g) were significantly decreased when compared with those of CTL (1.22±0.58 cm(3), 0.93±0.15 g; P<0.01). The tumor microvessel density (MVD) scores that PROP-2, -5, and -10 groups had (49.28±17.53, 52.45±17.11, and 51.09±13.18 pixels per picture, respectively) were lower than those from the control group (65.29±17.33 pixels per picture, P<0.01). Furthermore, vascular endothelial growth factor (VEGF), metalloproteinase-2 (MMP-2), and metalloproteinase-9 (MMP-9) levels were significantly lower in the groups with propranolol treated dosage of 5 and 10 mg kg(-1)day(-1) than in the control group. Propranolol can exhibit an inhibitory effect on the tumor growth and angiogenic factors expression in neuroblastoma xenografts, which may provide some knowledge to the role of β-blockers in the management of NB. © 2013.

  1. The effect of Setarud (IMODTM) on angiogenesis in transplanted human ovarian tissue to nude mice

    PubMed Central

    Hormozi, Maryam; Talebi, Saeed; Khorram Khorshid, Hamid Reza; Zarnani, Amir-Hassan; Kamali, Koorosh; Jeddi-Tehrani, Mahmood; Soltangoraee, Haleh; Akhondi, Mohammad Mehdi

    2015-01-01

    Background: One of the promising methods in fertility preservation among women with cancer is cryopreservation of ovarian cortex but there are many drawbacks such as apoptosis and considerable reduction of follicular density in the transplanted ovary. One solution to reduce ischemic damage is enhancing angiogenesis after transplantation of ovarian cortex tissue. Objective: The aim of this study was to investigate the effect of Setarud, on angiogenesis in transplanted human ovarian tissue. Materials and Methods: In this case control study, twenty four nude mice were implanted subcutaneously, with human ovarian tissues, from four women. The mice were randomly divided into two groups (n=12): the experimental group was treated with Setarud, while control group received only vehicle. Each group was divided into three subgroups (n=4) based on the graft recovery days post transplantation (PT). The transplanted fragments were removed on days 2, 7, and 30 PT and the expression of Angiopoietin-1, Angiopoietin-2, and Vascular endothelial growth factor at both gene and protein levels and vascular density were studied in the grafted ovarian tissues. Results: On the 2nd and 7th day PT, the level of Angiopoietin-1 gene expression in case group was significantly lower than that in control group, while the opposite results were obtained for Angiopoietin-2 and Vascular endothelial growth factor. These results were also confirmed at the protein level. The density of vessels in Setarud group elevated significantly on day 7 PT compared to pre-treatment state. Conclusion: Our results showed that administration of Setarud may stimulates angiogenesis in transplanted human ovarian tissues, although further researches are needed before a clear judgment is made. PMID:26644788

  2. Chronopharmacodynamics and mechanisms of antitumor effect induced by erlotinib in xenograft-bearing nude mice.

    PubMed

    Lin, Pingping; An, Fengmei; Xu, Xia; Zhao, Liyan; Liu, Liang; Liu, Ning; Wang, Peipei; Liu, Jiao; Wang, Le; Li, Mingchun

    2015-05-01

    Receptor tyrosine kinases, mediators of a variety of critical cellular functions, contribute to tumor progression and metastasis. The epidermal growth factor receptor (EGFR), a member of the receptor tyrosine kinase family, is ubiquitously expressed on the surface of mammalian cells. Erlotinib hydrochloride (Tarceva) can inhibit the intracellular phosphorylation of tyrosine kinases. To investigate the influence of dosing time on the ability of erlotinib to inhibit tumor growth and the underlying molecular mechanisms via the PI3K/AKT and ERK/MAPK pathway, we established nude mice HCC827 tumor xenografts models. The tumor-bearing mice were housed 3-4 per cage under standardized light/dark cycle conditions (lights on at 07:00 h, off at 19:00 h) with food and water ad libitum. The mice were randomly divided into erlotinib treated groups and control groups, gavaged with erlotinib and vehicle respectively at 6 different time points for 21 days. To draw tumor growth curves, the tumor volume was measured every three days. After the mice were sacrificed, the tumor masses of each group were removed and weighed. The relative protein expression levels of p-EGFR, p-AKT and p-MAPK were assayed at 4 h after erlotinib or vehicle gavage by Western blot analysis. The antitumor effect of erlotinib presented diurnal rhythmicity. The growth of HCC827 xenograft was more potently inhibited by erlotinib in the early light phase than in the early dark phase (p < 0.05). The inhibitory effect of erlotinib on phosphorylation of EGFR, AKT and MAPK varied with its administration time. The results indicate that the antitumor effect of erlotinib is more potent when the drug was administered when the activities of EGFR and its downstream factors increased. Our findings may provide a clue to optimize the dosing schedule of erlotinib. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Hiwi knockdown inhibits the growth of lung cancer in nude mice.

    PubMed

    Liang, Dong; Dong, Min; Hu, Lin-Jie; Fang, Ze-Hui; Xu, Xia; Shi, En-Hui; Yang, Yi-Ju

    2013-01-01

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

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

    PubMed

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

    2009-03-07

    To study the action of aminoguanidine on pancreatic cancer xenografts in relation to cell proliferation, apoptosis, redox status and vascularization. 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 vivo in both groups. Tumors were excised and ex vivo 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. 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. The antitumoral action of aminoguanidine is associated with decreased cell proliferation, reduced angiogenesis, and reduced expression of antioxidant enzymes.

  5. Eliminating established tumor in nu/nu nude mice by a TRAIL-armed oncolytic adenovirus

    PubMed Central

    Dong, Fengqin; Wang, Li; Davis, John J.; Hu, Wenxian; Zhang, Lidong; Guo, Wei; Teraishi, Fuminori; Ji, Lin; Fang, Bingliang

    2006-01-01

    Purpose The tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) and oncolytic viruses have recently been investigated extensively for cancer therapy. However, preclinical and clinical studies have revealed that their clinical application is hampered by either weak anticancer activity or systemic toxicity. We examined whether the weaknesses of the two strategies can be overcome by integrating the TRAIL gene into an oncolytic vector. Experimental Design We constructed a TRAIL-expressing oncolytic adenovector designated Ad/TRAIL-E1. The expression of both the TRAIL and viral E1A genes is under the control of a synthetic promoter consisting of sequences from the human telomerase reverse transcriptase promoter and a minimal cytomegalovirus early promoter. The transgene expression, apoptosis induction, viral replication, antitumor activity and toxicity of Ad/TRAIL-E1 were determined in vitro and in vivo in comparison with control vectors. Results Ad/TRAIL-E1 elicited enhanced viral replication and/or stronger oncolytic effect in vitro in various human cancer cell lines than a TRAIL-expressing replication-defective adenovector or an oncolytic adenovector expressing green fluorescent protein. Intralesional administration of Ad/TRAIL-E1 eliminated all subcutaneous xenograft tumors established from a human non-small cell lung cancer cell line, H1299, on nu/nu nude mice, resulting in long-term tumor-free survival. Furthermore, we found no treatment-related toxicity. Conclusions Viral replication and antitumor activity of oncolytic adenovirus can be enhanced by the TRAIL gene and Ad/TRAIL-E1 could become a potent therapeutic agent for cancer therapy. PMID:16951242

  6. Compact whole-body fluorescent imaging of nude mice bearing EGFP expressing tumor

    NASA Astrophysics Data System (ADS)

    Chen, Yanping; Xiong, Tao; Chu, Jun; Yu, Li; Zeng, Shaoqun; Luo, Qingming

    2005-01-01

    Issue of tumor has been a hotspot of current medicine. It is important for tumor research to detect tumors bearing in animal models easily, fast, repetitively and noninvasivly. Many researchers have paid their increasing interests on the detecting. Some contrast agents, such as green fluorescent protein (GFP) and Discosoma red fluorescent protein (Dsred) were applied to enhance image quality. Three main kinds of imaging scheme were adopted to visualize fluorescent protein expressing tumors in vivo. These schemes based on fluorescence stereo microscope, cooled charge-coupled-device (CCD) or camera as imaging set, and laser or mercury lamp as excitation light source. Fluorescence stereo microscope, laser and cooled CCD are expensive to many institutes. The authors set up an inexpensive compact whole-body fluorescent imaging tool, which consisted of a Kodak digital camera (model DC290), fluorescence filters(B and G2;HB Optical, Shenyang, Liaoning, P.R. China) and a mercury 50-W lamp power supply (U-LH50HG;Olympus Optical, Japan) as excitation light source. The EGFP was excited directly by mercury lamp with D455/70 nm band-pass filter and fluorescence was recorded by digital camera with 520nm long-pass filter. By this easy operation tool, the authors imaged, in real time, fluorescent tumors growing in live mice. The imaging system is external and noninvasive. For half a year our experiments suggested the imaging scheme was feasible. Whole-body fluorescence optical imaging for fluorescent expressing tumors in nude mouse is an ideal tool for antitumor, antimetastatic, and antiangiogenesis drug screening.

  7. Effects of herbal medicine on human uterine tumor-bearing nude mice

    PubMed Central

    Ohh, Mi Hyang; Kim, Seong Jin; Han, Jong Kwon; Pak, Sok Cheon; Chee, Kew-mahn

    2016-01-01

    Aim: Uterine leiomyomas are the most common benign uterine neoplasms associated with significant morbidity. Herbal formulas capable of restoring yin-yang balance by dispersing blood stasis may be useful for managing fibroid symptoms. Materials and Methods: In this study, the antitumor properties of three herbs viz., Trogopterus xanthipes Milen-Edwards, Paeonia lactiflora Pallas, and Ulmus davidiana Planch were evaluated in nude mice injected intravenously with human malignant myomas. Tumor fragments were xenografted subcutaneously through a flank incision in female mice. The mice entered the study for 8 weeks when their tumors reached the threshold volume (260 mm3). The mice were randomly allocated to receive subcutaneous injections of normal saline (Group 1; negative control), P. lactiflora Pallas (Group 2), U. davidiana Planch (Group 3), T. xanthipes Milen-Edwards (Group 4), and intravenous injections of paclitaxel (Group 5; positive control). The weight and tumor volume were measured, followed by histopathology. Results: A few cases of abdominal distention and death were observed in the negative control group. Furthermore, a considerable enlargement of the liver and spleen was observed in the negative control group at autopsy with a gradual increase in body weight during the experiment. The mean tumor volume which increased in negative control mice reduced in mice treated with herbal remedies or paclitaxel from day 14 onwards (P < 0.05). The degree of necrosis and apoptosis induction from herbal treatments was similar to that of paclitaxel. Conclusion: Collectively, three herbs viz., T. xanthipes Milen-Edwards, P. lactiflora Pallas, and U. davidiana Planch were able to induce necrosis and apoptosis of uterine leiomyoma cells, proving antitumor properties against uterine fibroids. PMID:27757274

  8. Conjugated eicosapentaenoic acid (EPA) inhibits transplanted tumor growth via membrane lipid peroxidation in nude mice.

    PubMed

    Tsuzuki, Tsuyoshi; Igarashi, Miki; Miyazawa, Teruo

    2004-05-01

    Both conjugated linoleic acid (CLA) and eicosapentaenoic acid (EPA) have an antitumor effect. Hence, we hypothesized that a combination of conjugated double bonds and an (n-3) highly unsaturated fatty acid would produce stronger bioactivity. To verify the antitumor effect of conjugated EPA (CEPA), we transplanted DLD-1 human colon tumor cells into nude mice, and compared the tumor growth between CEPA-fed mice and CLA- and EPA-fed mice. After tumor cell inoculation, mice were assigned to 1 of 4 groups (control, CLA, EPA, and CEPA) consisting of 10 mice each. The control group received only safflower oil fatty acids, whereas the remaining groups received a mixture of safflower oil fatty acids and 20 g/100 g of total fatty acids as CLA, EPA, or CEPA. Mice were fed once every 2 d for 4 wk at a dose of 50 mg/mouse at each feeding. After 4 wk, tumor growth in CEPA-fed mice was significantly suppressed, compared with that in CLA- (P < 0.005) and EPA-fed mice (P < 0.001). DNA fragmentation in the tumor tissues of the CEPA-fed mice occurred more frequently than in the CLA- (P < 0.001) and EPA-fed mice (P < 0.001), suggesting that CEPA induced apoptosis in the tumor tissues. To further investigate the mechanism, the level of oxidative stress in the tumor tissues was determined. The CEPA-fed mice showed significant lipid peroxidation, compared with the CLA- (P < 0.001) and EPA-fed mice (P < 0.001). Therefore, we verified that CEPA has a stronger in vivo antitumor effect than EPA and CLA, and that CEPA acts through induction of apoptosis via lipid peroxidation.

  9. STAT1 is overexpressed in tumors selected for radioresistance and confers protection from radiation in transduced sensitive cells

    PubMed Central

    Khodarev, Nikolai N.; Beckett, Michael; Labay, Edwardine; Darga, Thomas; Roizman, Bernard; Weichselbaum, Ralph R.

    2004-01-01

    Nu61, a radiation-resistant human tumor xenograft, was selected from a parental radiosensitive tumor SCC-61 by eight serial cycles of passage in athymic nude mice and in vivo irradiation. Replicate DNA array experiments identified 52 genes differentially expressed in nu61 tumors compared with SCC-61 tumors. Of these, 19 genes were in the IFN-signaling pathway and moreover, 25 of the 52 genes were inducible by IFN in the nu61 cell line. Among the genes involved in IFN signaling, STAT1α and STAT1β were the most highly overexpressed in nu61 compared to SCC-61. STAT1α and STAT1β cDNAs were cloned and stably transfected into SCC-61 tumor cells. Clones of SCC-61 tumor cells transfected with vectors expressing STAT1α and STAT1β demonstrated radioprotection after exposure to 3 Gy (P < 0.038). The results indicate that radioresistance acquired during radiotherapy treatment may account for some treatment failures and demonstrate an association of acquired tumor radioresistance with up-regulation of components of the IFN-related signaling pathway. PMID:14755057

  10. Immune responses in mice against herpes simplex virus: mechanisms of protection against facial and ganglionic infections.

    PubMed Central

    Zweerink, H J; Martinez, D; Lynch, R J; Stanton, L W

    1981-01-01

    We performed experiments with mice to determine the nature of the immune response(s) that prevents primary infections of the skin and the trigeminal ganglia with herpes simplex virus. Immunization with infectious herpes simplex virus, inactivated virus, or material enriched for viral glycoproteins protected hairless mice against primary facial and ganglionic infections. Live and inactivated viruses induced neutralizing antibodies, whereas glycoprotein material did not. Instead, glycoprotein material induced antibodies that were largely directed against two glycopolypeptides with molecular weights of 120,000 to 130,000. Hairless mice immunized with glycoprotein material responded faster than control mice in the synthesis of neutralizing antibodies after challenge with infectious virus. Congenital athymic BALB/c (nu/nu) mice were protected against primary facial infections after immunization with glycoprotein material, but glycoprotein-specific antibodies were not induced. Images PMID:6260662

  11. Organ specific Gst-pi expression of the metastatic androgen independent prostate cancer cells in nude mice.

    PubMed

    Naiki, Taku; Asamoto, Makoto; Toyoda-Hokaiwado, Naomi; Naiki-Ito, Aya; Tozawa, Keiichi; Kohri, Kenjiro; Takahashi, Satoru; Shirai, Tomoyuki

    2012-04-01

    Elucidating the mechanisms of metastasis in prostate cancer, particularly to the bone, is a major issue for treatment of this malignancy. We previously reported that an androgen-independent variant had higher expression of glutathione S-transferase pi (Gst-pi) compared with a parent androgen-dependent transplantable rat prostate carcinoma which was established from the transgenic rat for adenocarcinoma of the prostate (TRAP). A new cell line, PCai1, was established from the androgen-independent tumor and investigated its metastatic potential in nude mice. The tumorigenesis of PCai1 cells in vivo was studied by subcutaneous transplantations into nude mice. The growth in the microenvironment of the prostate was studied by orthotopic transplantation of PCai1 cells into nude mice. The metastatic potential of PCai1 cells was studied by tail vein injections. Effects of Gst-pi knocked down were analysis in PCai1 cells. PCai1 frequently formed metastatic lesions in the lung and lymph nodes after orthotopic implantation in the prostate. Intravenous injections of PCai1, metastasis to lung and bone were obvious. PCai1 had strong expression for Gst-pi, therefore we tried knocked down Gst-pi. Gst-pi-siRNA in vitro significantly suppressed cell proliferation rate. In addition, high levels of intracellular reactive oxygen species (ROS) were recognized in the Gst-pi knockout. Gst-pi expression of the prostate cancers are dependent on metastatic site, and that Gst-pi has an important role in adapting prostate cancer for growth and metastasis involving an alteration of ROS signals. Copyright © 2011 Wiley Periodicals, Inc.

  12. Lovastatin, a cholesterol biosynthesis inhibitor, inhibits the growth of human H-ras oncogene transformed cells in nude mice.

    PubMed

    Sebti, S M; Tkalcevic, G T; Jani, J P

    1991-05-01

    Post-translational modification of oncogenic p21ras proteins with farnesyl, a lipid intermediate in cholesterol biosynthesis, is required for p21ras membrane association and for the ability of p21ras to transform cultured cells. We have tested the ability of lovastatin, a specific inhibitor of cholesterol biosynthesis, to inhibit the growth of ras oncogene-transformed cells in vivo. Balb/c mouse 3T3 cells, transfected with H-ras oncogene from human EJ bladder carcinoma, were highly tumorigenic in nude mice. Immunoprecipitation studies with transformed EJ cells showed that lovastatin (1-100 microM) inhibited p21ras membrane association in a concentration-dependent manner and that a 10 microM concentration reduced the amount of p21ras bound to the membrane by 50%. Lovastatin also inhibited EJ cell growth in a concentration range that closely paralleled that required for inhibition of p21ras membrane association. Treatment of nude mice bearing subcutaneous (s.c.) EJ tumors with lovastatin (50 mg/kg) significantly inhibited the abilities of these tumors to grow as early as four days and, by day 12, the lovastatin treated group of animals had tumors with an average size that was 3-fold smaller than those in the saline treated group. Western blotting studies showed that lovastatin (50 mg/kg) was also able to inhibit p21ras membrane association in EJ tumors implanted s.c. in nude mice. These results demonstrate that lovastatin, an inhibitor of cholesterol biosynthesis, inhibited in vivo tumor growth of H-ras oncogene transformed cells. The results also suggest that inhibition of p21ras membrane association, an essential step in ras oncogene neoplastic transformation, is one mechanism by which lovastatin may express its antitumor activity.

  13. ‘Obligate’ anaerobic Salmonella strain YB1 suppresses liver tumor growth and metastasis in nude mice

    PubMed Central

    Li, Chang-Xian; Yu, Bin; Shi, Lei; Geng, Wei; Lin, Qiu-Bin; Ling, Chang-Chun; Yang, Mei; Ng, Kevin T. P.; Huang, Jian-Dong; Man, Kwan

    2017-01-01

    The antitumor properties of bacteria have been demonstrated over the past decades. However, the efficacy is limited and unclear. Furthermore, systemic infection remains a serious concern in bacteria treatment. In this study, the effect of YB1, a rationally designed ‘obligate’ anaerobic Salmonella typhimurium strain, on liver tumor growth and metastasis in a nude mouse orthotopic liver tumor model was investigated. The orthotopic liver tumor model was established in nude mice using the hepatocellular carcinoma cell line MHCC-97L. Two weeks after orthotopic liver tumor implantation, YB1, SL7207 and saline were respectively administered through the tail vein of the mice. Longitudinal monitoring of tumor growth and metastasis was performed using Xenogen IVIS, and direct measurements of tumor volume were taken 3 weeks after treatment. In vitro, MHCC-97L and PLC cells were incubated with YB1 or SL7207 under anaerobic conditions. YB1 was observed to invade tumor cells and induce tumor cell apoptosis and death. The results revealed that all mice in the YB1 group were alive 3 weeks after YB1 injection while all mice in the SL7207 group died within 11 days of the SL7207 injection. The body weight decreased by ~9% on day 1 after YB1 injection and but subsequently recovered. Liver tumor growth and metastases were significantly inhibited following YB1 treatment. By contrast to the control group, a large number of Gr1-positive cells were detected on days 1 to 21 following YB1 treatment. Furthermore, YB1 also effectively invaded tumor cells and induced tumor cell apoptosis and death. In conclusion, YB1 suppressed liver tumor growth and metastasis in a nude mice liver tumor model. The potential mechanism may be through enhancing innate immune response and inducing tumor cell apoptosis and cell death. PMID:28123538

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

    PubMed

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

    2017-02-15

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

  15. Using X-ray in-line phase-contrast imaging for the investigation of nude mouse hepatic tumors.

    PubMed

    Tao, Qiang; Li, Dongyue; Zhang, Lu; Luo, Shuqian

    2012-01-01

    The purpose of this paper is to report the noninvasive imaging of hepatic tumors without contrast agents. Both normal tissues and tumor tissues can be detected, and tumor tissues in different stages can be classified quantitatively. We implanted BEL-7402 human hepatocellular carcinoma cells into the livers of nude mice and then imaged the livers using X-ray in-line phase-contrast imaging (ILPCI). The projection images' texture feature based on gray level co-occurrence matrix (GLCM) and dual-tree complex wavelet transforms (DTCWT) were extracted to discriminate normal tissues and tumor tissues. Different stages of hepatic tumors were classified using support vector machines (SVM). Images of livers from nude mice sacrificed 6 days after inoculation with cancer cells show diffuse distribution of the tumor tissue, but images of livers from nude mice sacrificed 9, 12, or 15 days after inoculation with cancer cells show necrotic lumps in the tumor tissue. The results of the principal component analysis (PCA) of the texture features based on GLCM of normal regions were positive, but those of tumor regions were negative. The results of PCA of the texture features based on DTCWT of normal regions were greater than those of tumor regions. The values of the texture features in low-frequency coefficient images increased monotonically with the growth of the tumors. Different stages of liver tumors can be classified using SVM, and the accuracy is 83.33%. Noninvasive and micron-scale imaging can be achieved by X-ray ILPCI. We can observe hepatic tumors and small vessels from the phase-contrast images. This new imaging approach for hepatic cancer is effective and has potential use in the early detection and classification of hepatic tumors.

  16. Photodynamic activity of BAM-SiPc, an unsymmetrical bisamino silicon(IV) phthalocyanine, in tumour-bearing nude mice

    PubMed Central

    Leung, S C H; Lo, P-C; Ng, D K P; Liu, W-K; Fung, K-P; Fong, W-P

    2008-01-01

    Background and purpose Ever since the discovery of photodynamic therapy, there has been a continuous search for more potent photosensitizers. Towards that end, we have synthesized a number of novel phthalocyanine derivatives. The unsymmetrical bisamino silicon(IV) phthalocyanine BAM-SiPc is one of the most potent compounds. In in vitro cell culture, it exhibits high phototoxicity against a number of cancer cell lines. Experimental approach In the present investigation, the in vivo effect of BAM-SiPc was studied in the tumour-bearing nude mice model. The biodistribution of BAM-SiPc was followed to evaluate its tumour selectivity and rate of clearance. The tumour volume in the hepatocarcinoma HepG2- and the colorectal adenocarcinoma HT29-bearing nude mice was measured after photodynamic therapy. The level of intrinsic toxicity induced was also investigated. Finally, the metabolism of BAM-SiPc in the ‘normal' WRL68 liver cells and the hepatocarcinoma HepG2 cells was compared. Key results The results not only showed significant tumour regression of HepG2 and growth inhibition of HT29 in the tumour-bearing nude mice, but also no apparent hepatic or cardiac injury with the protocol used. Histological analyses showed that apoptosis was induced in the solid tumour. BAM-SiPc could be metabolized by WRL68 liver cells but not by the hepatocarcinoma HepG2 cells. Unfortunately, BAM-SiPc did not show any specific targeting towards the tumour tissue. Conclusions and implications The efficiency of BAM-SiPc in inhibiting tumour growth makes it a good candidate for further evaluation. Enhancement of its uptake in tumour tissue by conjugation with biomolecules is currently under investigation. PMID:18332853

  17. Antitumor effect of microbubbles enhanced by low frequency ultrasound cavitation on prostate carcinoma xenografts in nude mice

    PubMed Central

    WANG, YU; HU, BING; DIAO, XUEHONG; ZHANG, JIZHEN

    2012-01-01

    The aim of this study was to investigate the antitumor effect induced by low frequency (20 kHz) ultrasound (US) radiation combined with intravenous injection of microbubbles (Mbs) on prostate carcinoma Du145 xenografts in nude mice. Du145 prostate tumors were percutaneously implanted in 40 nude mice, which were randomly divided into 4 groups (n=10 each): US+Mbs, US, Mbs and control groups. The mice in the US+Mbs group were treated with 20 kHz, 200 mW/cm2 US radiation and with 0.2 ml Mbs injected intravenously. Mice in the US and Mbs groups were only treated with US radiation and injection of Mbs, respectively. Tumors were measured with sonography, and the ratio of antitumor growth was calculated. The mice were sacrificed 14 days after treatment. Specimens of the tumor tissues were observed pathologically using light microscopy and transmission electron microscopy. Microvessel density and the average optical density of vascular endothelial growth factor were compared among groups by immunohistochemistry. The average gross tumor volume of the US+Mbs group was significantly reduced compared with the other groups following treatment (P<0.05). The ratio of the antitumor growth in the US+Mbs group was significantly greater than that of the US and Mbs group (P<0.05). Histological examination showed signs of tumor cell injury in the US+Mbs group. Examination by electron microscopy revealed vessel injury in the endothelium in the tumors treated with US+Mbs. Microvessel density and the average optical density of vascular endothelial growth factor in the US+Mbs group were significantly less than that of other groups (P<0.05). In conclusion, low frequency US of 20 kHz radiation combined with Mbs may be used to inhibit the growth of human prostate carcinoma xenografts in nude mice, and the effect is likely realized through microvessel destruction caused by cavitation. PMID:22969866

  18. Antitumor effect of microbubbles enhanced by low frequency ultrasound cavitation on prostate carcinoma xenografts in nude mice.

    PubMed

    Wang, Yu; Hu, Bing; Diao, Xuehong; Zhang, Jizhen

    2012-02-01

    The aim of this study was to investigate the antitumor effect induced by low frequency (20 kHz) ultrasound (US) radiation combined with intravenous injection of microbubbles (Mbs) on prostate carcinoma Du145 xenografts in nude mice. Du145 prostate tumors were percutaneously implanted in 40 nude mice, which were randomly divided into 4 groups (n=10 each): US+Mbs, US, Mbs and control groups. The mice in the US+Mbs group were treated with 20 kHz, 200 mW/cm(2) US radiation and with 0.2 ml Mbs injected intravenously. Mice in the US and Mbs groups were only treated with US radiation and injection of Mbs, respectively. Tumors were measured with sonography, and the ratio of antitumor growth was calculated. The mice were sacrificed 14 days after treatment. Specimens of the tumor tissues were observed pathologically using light microscopy and transmission electron microscopy. Microvessel density and the average optical density of vascular endothelial growth factor were compared among groups by immunohistochemistry. The average gross tumor volume of the US+Mbs group was significantly reduced compared with the other groups following treatment (P<0.05). The ratio of the antitumor growth in the US+Mbs group was significantly greater than that of the US and Mbs group (P<0.05). Histological examination showed signs of tumor cell injury in the US+Mbs group. Examination by electron microscopy revealed vessel injury in the endothelium in the tumors treated with US+Mbs. Microvessel density and the average optical density of vascular endothelial growth factor in the US+Mbs group were significantly less than that of other groups (P<0.05). In conclusion, low frequency US of 20 kHz radiation combined with Mbs may be used to inhibit the growth of human prostate carcinoma xenografts in nude mice, and the effect is likely realized through microvessel destruction caused by cavitation.

  19. Epidermal growth factor inhibits radioiodine uptake but stimulates deoxyribonucleic acid synthesis in newborn rat thyroids grown in nude mice

    SciTech Connect

    Ozawa, S.; Spaulding, S.W. )

    1990-08-01

    We have studied the effect of altering the level of circulating epidermal growth factor (EGF) on the function and growth of newborn rat thyroids transplanted into nude mice. Preliminary studies confirmed that sialoadenectomy reduced circulating EGF levels in nude mice (from 0.17 +/- 0.02 to 0.09 +/- 0.02 ng/ml), and that ip injection of 5 micrograms EGF raised EGF levels (the peak level of 91.7 +/- 3.3 ng/ml was achieved at 30 min, with a subsequent half-life of about 1 h). The radioiodine uptake by newborn rat thyroid transplants in the sialoadenectomized and sham-operated animals correlated inversely with the circulating EGF levels determined when the mice were killed (r = -0.99). Low-dose TSH treatment (0.1 microU/day) generally stimulated the radioiodine uptake, but high-dose TSH groups (100 microU/day) were not significantly different from the control group. The 5-day nuclear (3H)thymidine labeling index was 6.8 +/- 0.5% IN newborn rat thyroid transplants grown in sialoadenectomized animals, 13.1 +/- 0.3% in sham-operated animals, and 16.8 +/- 0.5% in nude mice receiving 5 micrograms EGF ip daily. In general, both low-dose and high-dose TSH promoted DNA synthesis under low EGF conditions but were ineffective in the presence of higher levels of EGF. Adult rat thyroid transplants showed no significant responses. Although sialoadenectomy may alter other factors besides EGF, it appears that changes in the levels of circulating EGF within the physiological range affect the function and growth of newborn rat thyroid transplants. Circulating EGF may play a role in thyroid maturation and may also be involved in the regulation of thyroid function throughout life.

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

    SciTech Connect

    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. )

    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.

  1. siRNA blocking the RAS signalling pathway and inhibits the growth of oesophageal squamous cell carcinoma in nude mice.

    PubMed

    Wang, Xinjie; Zheng, Yuling; Fan, Qingxia; Zhang, Xudong; Shi, Yonggang

    2014-12-01

    The aim of this study was to study RAS-siRNA blocking RAS pathway and suppressing cell growth in human oesophageal squamous cell carcinoma in nude mice. The methods in this study was to construct RAS-siRNA expression vector, establish 40 oesophageal squamous cell carcinoma xenograft animal models and divided them into five groups: control group, siRNA control group, RAS-siRNA group, paclitaxel group and RAS-siRNA and paclitaxel group. We observed tumour growth in nude mice, studied histology by HE staining, tumour growth inhibition by TUNEL assay and detected the RAS, MAPK and cyclin D1 protein expression by immunohistochemistry and western blot. We have obtained the following results: (i) successfully established animal models; (ii) nude mice in each group after treatment inhibited tumour volume was significantly reduced compared with the control group (p < 0.05); (iii) compared with the control group, the number of apoptotic cells were significantly increased in the siRNA control group and the RAS-siRNA group, and the number of apoptosis cells in the paclitaxel and RAS-siRNA group is significantly most than the paclitaxel group and RAS-siRNA group (p < 0.05); and (iv) after treatment, RAS, MAPK and cyclin D1 expression in five groups was decreasing gradually. After adding paclitaxel, the protein expression in the paclitaxel and RAS-siRNA group was significantly lower than that of paclitaxel group, negative control and paclitaxel group (p < 0.05). We therefore conclude that RAS-siRNA can block the RAS signal transduction pathway, reduce the activity of tumour cells, arrest tumour cell cycle, promote apoptosis, inhibit cell proliferation and increase tumour cell sensitivity to chemotherapeutic drugs.

  2. Hair Follicle Generation by Injections of Adult Human Follicular Epithelial and Dermal Papilla Cells into Nude Mice.

    PubMed

    Nilforoushzadeh, Mohammadali; Rahimi Jameh, Elham; Jaffary, Fariba; Abolhasani, Ehsan; Keshtmand, Gelavizh; Zarkob, Hajar; Mohammadi, Parvaneh; Aghdami, Nasser

    2017-01-01

    Dermal papilla and hair epithelial stem cells regulate hair formation and the growth cycle. Damage to or loss of these cells can cause hair loss. Although several studies claim to reconstitute hairs using rodent cells in an animal model, additional research is needed to develop a stable human hair follicle reconstitution protocol. In this study, we have evaluated hair induction by injecting adult cultured human dermal papilla cells and a mixture of hair epithelial and dermal papilla cells in a mouse model. In this experimental study, discarded human scalp skins were used to obtain dermal papilla and hair epithelial cells. After separation, cells were cultured and assessed for their characteristics. We randomly allocated 15 C57BL/6 nude mice into three groups that received injections in their dorsal skin. The first group received cultured dermal papilla cells, the second group received a mixture of cultured epithelial and dermal papilla cells, and the third group (control) received a placebo [phosphate-buffered saline (PBS-)]. Histopathologic examination of the injection sites showed evidence of hair growth in samples that received cells compared with the control group. However, the group that received epithelial and dermal papilla cells had visible evidence of hair growth. PKH tracing confirmed the presence of transplanted cells in the new hair. Our data showed that injection of a combination of adult human cultured dermal papilla and epithelial cells could induce hair growth in nude mice. This study emphasized that the combination of human adult cultured dermal papilla and epithelial cells could induce new hair in nude mice.

  3. Hair Follicle Generation by Injections of Adult Human Follicular Epithelial and Dermal Papilla Cells into Nude Mice

    PubMed Central

    Nilforoushzadeh, Mohammadali; Rahimi Jameh, Elham; Jaffary, Fariba; Abolhasani, Ehsan; Keshtmand, Gelavizh; Zarkob, Hajar; Mohammadi, Parvaneh; Aghdami, Nasser

    2017-01-01

    Objective Dermal papilla and hair epithelial stem cells regulate hair formation and the growth cycle. Damage to or loss of these cells can cause hair loss. Although several studies claim to reconstitute hairs using rodent cells in an animal model, additional research is needed to develop a stable human hair follicle reconstitution protocol. In this study, we have evaluated hair induction by injecting adult cultured human dermal papilla cells and a mixture of hair epithelial and dermal papilla cells in a mouse model. Materials and Methods In this experimental study, discarded human scalp skins were used to obtain dermal papilla and hair epithelial cells. After separation, cells were cultured and assessed for their characteristics. We randomly allocated 15 C57BL/6 nude mice into three groups that received injections in their dorsal skin. The first group received cultured dermal papilla cells, the second group received a mixture of cultured epithelial and dermal papilla cells, and the third group (control) received a placebo [phosphate-buffered saline (PBS-)]. Results Histopathologic examination of the injection sites showed evidence of hair growth in samples that received cells compared with the control group. However, the group that received epithelial and dermal papilla cells had visible evidence of hair growth. PKH tracing confirmed the presence of transplanted cells in the new hair. Conclusion Our data showed that injection of a combination of adult human cultured dermal papilla and epithelial cells could induce hair growth in nude mice. This study emphasized that the combination of human adult cultured dermal papilla and epithelial cells could induce new hair in nude mice. PMID:28670518

  4. In vivo regulation of murine hair growth: insights from grafting defined cell populations onto nude mice.

    PubMed

    Lichti, U; Weinberg, W C; Goodman, L; Ledbetter, S; Dooley, T; Morgan, D; Yuspa, S H

    1993-07-01

    The nude mouse graft model for testing the hair-forming ability of selected cell populations has considerable potential for providing insights into factors that are important for hair follicle development and proper hair formation. We have developed a minimal component system consisting of immature hair follicle buds from newborn pigmented C57BL/6 mice and adenovirus E1A-immortalized rat vibrissa dermal papilla cells. Hair follicle buds contribute to formation of hairless skin when grafted alone or with Swiss 3T3 cells, but produce densely haired skin when grafted with a fresh dermal cell preparation. The fresh dermal cell preparation represents the single cell fraction after hair follicles have been removed from a collagenase digest of newborn mouse dermis. It provides dermal papilla cells, fibroblasts, and possibly other important growth factor-producing cell types. Rat vibrissa dermal papilla cells supported dense hair growth at early passage in culture but progressively lost this potential during repeated passage in culture. Of 19 E1A-immortalized, clonally derived rat vibrissa dermal papilla cell lines, the four most positive clones supported hair growth to the extent of approximately 200 to 300 hairs per 1-2 cm2 graft area. The remaining clones were moderately positive (five clones), weakly positive (three clones), or negative (seven clones). Swiss 3T3 cells prevented contraction of the graft area but did not appear to affect the number of hairs in the graft site produced by dermal papilla cells plus hair follicle buds alone. The relatively low hair density (estimated 1-5% of normal) resulting from grafts of hair follicle buds with the most positive of the immortalized dermal papilla cell clones compared to fresh dermal cells suggests that optimal reconstitution of hair growth requires some function of dermal papilla cells partially lost during the immortalization process and possibly the contribution of other cell types present in the fresh dermal cell

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

    PubMed

    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

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

    PubMed

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

    2005-06-01

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

  7. Killing effects of Huaier Granule combined with DC-CIK on nude mice transplanted with colon carcinoma cell line.

    PubMed

    Sun, Wen-Wen; Dou, Jin-Xia; Zhang, Lin; Qiao, Li-Kui; Shen, Na; Zhao, Qiang; Gao, Wen-Yuan

    2017-07-11

    This study aims to compare the efficacy of different treatments for nude mice transplanted with HT-29 colon carcinoma cell line. BalB/C nude mice were transplanted with HT-29 colon carcinoma cell line and randomly divided into four groups, with 5 mice in each group: blank control group, DC-CIK group, Huaier Granule group, and Huaier Granule group combined with DC-CIK group (combined treatment group). For DC-CIK group and combined treatment group, 1×106 DC-CIK cells were injected via the tail vein 4 days after transplantation. The injection was performed twice weekly for a total of 2 weeks. For Huaier Granule group and combined treatment group, Huaier Granule was administered at the dose of 20 g/60 g, by dissolving 20 g of Huaier granules in 600 ml of pure water. Intragastric administration of 0.2 ml of granules was performed once daily for 3 weeks. For the blank control group, equal volume of normal saline was given. Tumor size and body weight of nude mice were measured every 2 days during the 3-week treatment. The mice were sacrificed at the end of treatment to harvest tumors. Key genes of the signaling pathway were detected by RT-PCR. At the end of treatment, mice in combined treatment group, DC-CIK group and Huaier Granule group remained stable emotionally with normal mobility and water and food intake. However, in the blank control group, the mobility was restricted starting from the third week and the mice were on the verge of dying. The expression of PI3KR1, Akt, Wnt1, CTTNB1, Notch1, Notch2 and Notch3 genes were all downregulated significantly in the combined treatment group compared with DC-CIK group and Huaier Granule group (P<0.05). Therefore, the combined treatment of Huaier Granule combined with DC-CIK achieved the best effect in nude mice transplanted with HT-29 colon carcinoma cell line.

  8. Growth inhibitory effects and molecular mechanisms of crotoxin treatment in esophageal Eca-109 cells and transplanted tumors in nude mice

    PubMed Central

    He, Jing-kang; Wu, Xiang-sheng; Wang, Yan; Han, Rong; Qin, Zheng-hong; Xie, Yan

    2013-01-01

    Aim: To investigate the antitumor actions of the Crotalus durissus neurotoxin (crotoxin) on human esophageal carcinoma (Eca-109) cells in vitro and transplanted esophageal Eca-109 tumors in nude mice. Methods: The growth-inhibitory effect was analyzed in Eca-109 cells using MTT assay. Cell morphology changes in nuclei were observed using Hoechst 33342 staining, while apoptosis and cell cycle distribution were examined by flow cytometry. RT-PCR was used to measure the Bcl-2, p15, and caspase-3 p17 gene expression levels. A tumor transplantation model was established by inoculation of Eca-109 cells were into female Balb/c nude mice. Crotoxin (25, 50, and 100 mg/kg) was subcutaneously injected into the transplanted tumors every 2 d for a total of 10 injections. Tumor size and weight were measured. Bcl-2, p15, and caspase-3 p17 protein expression in transplanted tumors was analyzed using Western blotting. Results: Crotoxin (25, 50, and 100 μg/mL) inhibited the growth of Eca-109 cells in a dose-dependent manner with inhibition rates of 22.9%, 35.8%, and 57.2%, respectively. Hoechst 33342 staining revealed apoptotic cells with pyknotic nuclear chromatin after crotoxin treatment. In Eca-109 cells, crotoxin induced apoptosis and G1 block, significantly upregulated the expression of p15 and caspase-3 p17 genes and downregulated the expression of Bcl-2 gene. Furthermore, crotoxin inhibited the growth of Eca-109 tumors in nude mice in a dose-dependent manner. Western blotting showed that crotoxin increased p15 and caspase-3 p17 protein levels and reduced Bcl-2 protein level in tumor specimens. Conclusion: Crotoxin inhibits the growth of Eca-109 cells in vitro via apoptosis induction and G1 block. Local administration of crotoxin inhibits the growth of subcutaneously transplanted Eca-109 cells in nude mice, possibly via increasing p15 and caspase-3 p17 protein expression and reducing Bcl-2 protein expression. PMID:23202800

  9. Comparative study of Mitsuda reaction to nude mouse and armadillo lepromin preparations using nine-banded armadillos.

    PubMed

    Job, C K; Truman, R W

    2000-03-01

    In 14 nine-banded armadillos the Mitsuda response to nude mouse-derived lepromin (lepromin-nu/nu) was compared to that of armadillo-derived lepromin (lepromin-A) by injecting the reagents intradermally into either side of the abdomen of the animal and examining the biopsies from the sites after 12 days. The histopathologic responses to both antigens were found to be similar, whether the animal was Mitsuda-negative (lepromatous) or Mitsuda-positive (tuberculoid). It is pointed out that armadillos are good experimental models for leprosy, and their use can replace humans in experimental studies.

  10. Isolation and purification of psoralen and isopsoralen and their efficacy and safety in the treatment of osteosarcoma in nude rats.

    PubMed

    Lu, Honghui; Zhang, Lihai; Liu, Daohong; Tang, Peifu; Song, Feixiang

    2014-09-01

    Modern studies have shown that psoralen has a significant inhibitory effect on tumor growth in a variety of animals and humans. To obtain coumarin compounds - psoralen and isopsoralen - from traditional Chinese medicine Psoralea corylifolia L. using chromatographic techniques and isolation and purification methods, and to observe the transplanted tumor growth inhibitory effects and adverse reactions of psoralen and isopsoralen in nude rats with osteosarcoma. Dried ripe fruits of Psoralea corylifolia L. were taken as the raw material to prepare crude extract of Psoralea corylifolia L. by ethanol reflux method. Column chromatography was used to isolate the crude extract; compounds were structurally identified based on (1)H-NMR, (13)C-NMR spectra, the two compounds were identified as psoralen andisopsoralen, and their contents were 99.7% and 99.6, respectively. Nude rat model of osteosarcoma was established; the rats were randomized into: normal saline group, psoralen low- and high-dose groups, isopsoralen low- and high-dose groups, and cisplatin group. Osteosarcoma volume and weight inhibition rates in nude rats in each group were observed; radioimmunoassay was used to determine the serum alkaline phosphatase activity; peripheral blood cell and bone marrow nucleated cell counts were determined; light microscopy was used to observe heart, liver, spleen, lung, kidney, and tumor histopathology; and electron microscopy was used to observe the fine structure of tumor cells. Tumor volume inhibition rates were 43.75% and 40.18%, respectively, in the psoralen and isopsoralen low-dose groups, and tumor weight inhibition rates were 38.83% and 37.77%. Tumor volume inhibition rates were 67.86% and 66.96%, respectively, in the psoralen and isopsoralen high-dose groups, and tumor weight inhibition rates were 49.47% and 47.87%. Psoralen and ispsoralen markedly lowered serum AKP level. Psoralen and isopsoralen induced apoptosis or necrosis of osteosarcoma. After administration of

  11. Effects of low-frequency ultrasound and microbubbles on angiogenesis-associated proteins in subcutaneous tumors of nude mice.

    PubMed

    Shen, Zhi-Yong; Shen, E; Zhang, Ji-Zhen; Bai, Wen-Kun; Wang, Yu; Yang, Shao-Lin; Nan, Shu-Liang; Lin, Yan-Duan; Li, Yi; Hu, Bing

    2013-08-01

    It has been shown that 1 and 3 MHz low-intensity ultrasound was able to affect the fragile and leaky angiogenic blood vessels in a tumor. However, the biological effects of 21 kHz low-intensity ultrasound on tumors remain unclear. The aim of the present study was to explore the effects of 21 kHz ultrasound with microbubbles on the regulation of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) and apoptosis in subcutaneous prostate tumors in nude mice. The study included three parts, each with 20 tumor-bearing nude mice. Twenty nude mice were divided into four groups: control (sham treatment), microbubble ultrasound contrast agent (UCA), low-frequency ultrasound (US) and US+UCA groups. The UCA used was a microbubble contrast agent (SonoVue). The parameter of ultrasound: 21 kHz, an intensity of 26 mW/cm2, 40% duty cycle (on 2 sec, off 3 sec), 3 min, once every other day for 2 weeks. In the first study, all subcutaneous tumors were examined by contrast-enhanced ultrasonography (CEUS) at the initiation and completion of the experiments. Peak intensity (PI), time to peak intensity (TTP) and area under the curve (AUC) on the time intensity curve (TIC) were analyzed. In the second study, the intensity of VEGF and COX-2 protein expression in the vascular endothelium and cytoplasm was evaluated using immunohistochemistry and laser confocal microscopy. In the third study, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay was used for the evaluation of cell apoptosis in tumor tissues. The tumor cells and vasculature were examined by transmission electron microscopy (TEM). Only in the US+UCA group, PI and AUC decreased. The intensity of COX-2 and VEGF in the US+UCA group in immunohistochemical staining and laser confocal microscopy was lower compared to that of the other three groups. More cell apoptosis was found in the US+UCA group compared to the other 3 groups. In the control, UCA and US groups, the tumors

  12. Killing effects of Huaier Granule combined with DC-CIK on nude mice transplanted with colon carcinoma cell line

    PubMed Central

    Zhang, Lin; Qiao, Li-Kui; Shen, Na; Zhao, Qiang; Gao, Wen-Yuan

    2017-01-01

    This study aims to compare the efficacy of different treatments for nude mice transplanted with HT-29 colon carcinoma cell line. BalB/C nude mice were transplanted with HT-29 colon carcinoma cell line and randomly divided into four groups, with 5 mice in each group: blank control group, DC-CIK group, Huaier Granule group, and Huaier Granule group combined with DC-CIK group (combined treatment group). For DC-CIK group and combined treatment group, 1×106 DC-CIK cells were injected via the tail vein 4 days after transplantation. The injection was performed twice weekly for a total of 2 weeks. For Huaier Granule group and combined treatment group, Huaier Granule was administered at the dose of 20 g/60 g, by dissolving 20 g of Huaier granules in 600 ml of pure water. Intragastric administration of 0.2 ml of granules was performed once daily for 3 weeks. For the blank control group, equal volume of normal saline was given. Tumor size and body weight of nude mice were measured every 2 days during the 3-week treatment. The mice were sacrificed at the end of treatment to harvest tumors. Key genes of the signaling pathway were detected by RT-PCR. At the end of treatment, mice in combined treatment group, DC-CIK group and Huaier Granule group remained stable emotionally with normal mobility and water and food intake. However, in the blank control group, the mobility was restricted starting from the third week and the mice were on the verge of dying. The expression of PI3KR1, Akt, Wnt1, CTTNB1, Notch1, Notch2 and Notch3 genes were all downregulated significantly in the combined treatment group compared with DC-CIK group and Huaier Granule group (P<0.05). Therefore, the combined treatment of Huaier Granule combined with DC-CIK achieved the best effect in nude mice transplanted with HT-29 colon carcinoma cell line. PMID:28537906

  13. [Evaluation of combination chemotherapy with 5-FU, CDDP and CPT-11 for human gastric carcinoma transplanted into nude mice - comparative study of in vivo chemosensitivity test].

    PubMed

    Kanamori, Noriaki; Fujii, Masashi; Kochi, Mitsugu; Kaiga, Teruo; Takahashi, Tohru; Takayama, Tadatoshi

    2007-06-01

    We performed in vivo chemosensitivity tests on human gastric carcinoma. To evaluate the efficacy of some combined chemotherapy for human gastric carcinoma maintained in the subcutaneous space in nude mice, we designed the following six experimental groups: 1) 5-FU group, 2) CDDP group, 3) CPT-11 group, 4) combined therapy group of 5-FU and CDDP, 5) combined therapy group of 5-FU and CPT-11, and 6) combined therapy group of CPT-11 and CDDP. An in vivo nude mice assay was performed. Histopathological changes of the tumors in nude mice, treated with anti-cancer agents,were also evaluated and compared to the results of the nude mice assay. Based on histopathological grading,the true positive rate of the nude mice assay was 0%, the true negative rate was 83.3%, and the accuracy rate was 83.3%. CPT-11 appeared to be highly efficacious when given in combination with CDDP in human gastric cancer cell lines. These results suggest that combination chemotherapy with CPT-11 and CDDP is clinically effective for gastric cancer patients.

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

    SciTech Connect

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

    1990-06-01

    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 engraftment of allogeneic T-cell-depleted bone marrow is T-cell dependent. To ensure engraftment, a large inoculum of nude bone marrow must be supplemented with a trace number of donor T cells, whereas a small bone marrow dose from nude donors requires a much larger number of T cells for engraftment. Marked enhancement of donor type chimerism was also found when F1 thymocytes were added to nude bone marrow cells, indicating that the enhancement of bone marrow engraftment by T cells is not only mediated by alloreactivity against residual host cells but may rather be generated by growth factors, the release of which may require specific interactions between T cells and stem cells or between T cells and bone marrow stroma cells.

  15. [Influence of MSA on cell growth and spontaneousn metastasis of L9981-Luc lung cancer transplanted model in nude mice by bioluminescence imaging].

    PubMed

    Ren, Yuanrong; Wang, Yuli; Liu, Hongyu; Yan, Huiqin; Chen, Jun; Hou, Mei; Li, Weimin; Fan, Yaguang; Zhou, Qinghua

    2013-02-01

    Methylseleninic acid (MSA) is an artificially developed selenium compound. It has been proven that MSA could inhibit growth and metastasis on many tumor cells. This study investigated whether MSA has an impact on the growth and metastasis of L9981-Luc lung cancer transplanted model in nude mice or not. A transplantated tumor model was established in nude mice. Fifteen nude mice were randomly divided into three groups: the control group treated with normal saline (0.2 mL/d), the MSA group treated with MSA solution (0.2 mL), and the cisplatin (DDP) group injected intraperitoneally with DDP (4 mg/kg/w). Inhibition of MSA on tumor growth and tumor metastasis was observed using the IVIS Imaging System 200 Series. A significant difference was obserced in the primary tumor bioluminescence among the three groups (P=0.002) on 21 days post-inoculation. Primary tumor bioluminescence in the DDP group (P=0.001) and in the MSA group (P=0.031) was significantly lower than that in the control group (P=0.001). No significant difference in the metastasis bioluminescence of the thoracic area was indicated among the three groups (P>0.05). MSA can inhibit the growth of planted tumor of transgenic lung cancer cell lines L9981-Luc in nude mice. MSA may also suppress the distant metastasis of the transplanted tumor of transgenic lung cancer cell lines L9981-Luc in nude mice.

  16. Protection against Acute Hepatocellular Injury Afforded by Liver Fibrosis Is Independent of T Lymphocytes

    PubMed Central

    Lacoste, Benoit; Raymond, Valérie-Ann; Lapierre, Pascal; Bilodeau, Marc

    2016-01-01

    Collagen produced during the process of liver fibrosis can induce a hepatocellular protective response through ERK1 signalling. However, the influence of T cells and associated cytokine production on this protection is unknown. In addition, athymic mice are frequently used in hepatocellular carcinoma xenograft experiments but current methods limit our ability to study the impact of liver fibrosis in this setting due to high mortality. Therefore, a mouse model of liver fibrosis lacking T cells was developed using Foxn1 nu/nu mice and progressive oral administration of thioacetamide (TAA) [0.01–0.02%] in drinking water. Fibrosis developed over a period of 16 weeks (alpha-SMA positive area: 20.0 ± 2.2%, preCol1a1 mRNA expression: 11.7 ± 4.1 fold changes, hydroxyproline content: 1041.2 ± 77μg/g of liver) at levels comparable to that of BALB/c mice that received intraperitoneal TAA injections [200 μg/g of body weight (bw)] (alpha-SMA positive area: 20.9 ± 2.9%, preCol1a1 mRNA expression: 13.1 ± 2.3 fold changes, hydroxyproline content: 931.6 ± 14.8μg/g of liver). No mortality was observed. Athymic mice showed phosphorylation of ERK1/2 during fibrogenesis (control 0.03 ± 0.01 vs 16 weeks 0.22 ± 0.06AU; P<0.05). The fibrosis-induced hepatoprotection against cytotoxic agents, as assessed histologically and by serum AST levels, was not affected by the absence of circulating T cells (anti-Fas JO2 [0.5μg/g bw] for 6h (fibrotic 4665 ± 2596 vs non-fibrotic 13953 ± 2260 U/L; P<0.05), APAP [750 mg/kg bw] for 6 hours (fibrotic 292 ± 66 U/L vs non-fibrotic 4086 ± 2205; P<0.01) and CCl4 [0.5mL/Kg bw] for 24h (fibrotic 888 ± 268 vs non-fibrotic 15673 ± 2782 U/L; P<0.001)). In conclusion, liver fibrosis can be induced in athymic Foxn1 nu/nu mice without early mortality. Liver fibrosis leads to ERK1/2 phosphorylation. Finally, circulating T lymphocytes and associated cytokines are not involved in the hepatocellular protection afforded by liver fibrosis. PMID

  17. [Immunoradionuclide localization of human neuroblastoma xenografted in nude mice using anti-GD2 labelled with I125].

    PubMed

    Perdereau, B; Barbaroux, C; Michon, J; Fridman, W H; Rosin, N; Validire, P; Zucker, J M; Manil, L

    1994-07-01

    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 IgG3: BW704, 7A4, 60C3, and the IgG1 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 gramme. These results let us hope that these antibodies could also provide highly contrasted images in humans and could open the way for therapeutic applications.

  18. Cytokine mRNA expression in normal skin of various age populations before and after engraftment onto nude mice.

    PubMed

    Gilhar, A; Ullmann, Y; Shalagino, R; Weisinger, G

    1998-01-01

    Whether the impact of skin biological age on cytokine expression is a result of this tissue's proliferation potential or not is an important issue in dermatology. We investigated these questions by monitoring cytokine marker mRNA expression from human skin samples from healthy groups of individuals. The skin samples studied represented three age groups: fetal (17-21 weeks), young (18-35 years) and aged (76-88 years). Furthermore, upon skin transplantation of tissue from different age groups onto nude mice, we investigated whether cytokine marker RNA levels would change or normalize. Interestingly, both TNF-alpha and P53 mRNA showed a similar pattern of expression. Both were significantly higher in fetal skin (p < 0.0001 and p < 0.05, respectively), and no difference was noted between aged versus young skin. In contrast to this, IL1-alpha mRNA was expressed at its lowest and highest levels in fetal and young skin, respectively. Following skin transplantation, cytokines and P53 mRNA expression were normalized to similar levels in all age groups. This study implies that when cytokine expression was determined directly at the mRNA level, post-natal expression was not significantly different at either age group. Furthermore, it seems that the environmental conditions surrounding the grafted human skin found on nude mice encouraged normalization of donor cytokine expression.

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

    PubMed Central

    Zhuang, Lei; Steinberg, Florian; Trueb, Beat

    2016-01-01

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

  20. Generation and characterization of human monoclonal antibody HMD4 against ovarian carcinoma and the study of radioimmunoimaging in nude mice

    SciTech Connect

    Qian, H.N.; Cui, H.; Feng, J.; Fu, T.Y.; Wei, P.; Fu, Z.Y. )

    1990-01-01

    Lymphocytes from regional lymph nodes of patients with ovarian carcinoma were immortalized by fusing them with a nonsecreting cell line of murine myeloma (Sp2/0-Ag14). By early cloning and recloning a hybrid cell line, named HMD4, was established. It has secreted human IgG for more than 15 months stably. Chromosome analysis corresponded with the characterization of human-mouse hybridoma. Large quantities of ascites were obtained after hybrid cells injection into the primed nude mice. Human IgG of light chain was detected and purified from the ascites. Twenty-six of 43 (60.5%) epithelial ovarian cancers were positively stained with HMD4 by ABC immunoperoxidase methods while nonepithelial ovarian cancers and almost all benign tumors and normal tissues were negative. The molecular weight of the antigen recognized by HMD4 was 55KDa determined by Western blotting. 131I labeled HMD4 was administered intraperitoneally to nude mice bearing human ovarian epithelial adenocarcinoma; 131I labeled normal human IgG and normal murine IgG were used as controls. Measurements of T/NT and T/B ratios of 131I-HMD4 were done. Radioimaging showed HMD4 clearly localized on tumor regions at 48 and 72 hours and the biodistribution and metabolism of the labeled HMD4 corresponded with the images. The above results indicate that HMD4 was specific to ovarian carcinoma, a hopeful clue for clinical applications.

  1. Stat3 enhances the growth of LNCaP human prostate cancer cells in intact and castrated male nude mice.

    PubMed

    DeMiguel, Fernando; Lee, Soo Ok; Lou, Wei; Xiao, Xiao; Pflug, Beth R; Nelson, Joel B; Gao, Allen C

    2002-07-01

    Prostate cancer frequently progresses from an initial androgen dependence to androgen independence, rendering the only effective androgen ablation therapy useless. The mechanism underlying the androgen-independent progression is unknown. Stat3, a member of the family of signal transducers and activators of transcription, is activated in numerous cancers, including prostate. This study is to investigate the role of Stat3 activation in the growth of prostate cancer cells. A constitutively active Stat3 was ectopically expressed in androgen-sensitive LNCaP prostate cancer cells and resulting stable clones expressing activated Stat3 were isolated. The effect of Stat3 activation on LNCaP cell growth in response to androgen in vitro and in vivo was examined. We show that the levels of activated Stat3 are associated with the progression of androgen-independent prostate cancer. Activation of Stat3 in androgen-sensitive LNCaP prostate cancer cells results in enhancement of tumor growth in both intact and castrated male nude mice and enhances androgen receptor-mediated prostate specific antigen expression. These findings demonstrate that intracellular signaling mediated by Stat3 can enhance the growth of androgen-sensitive human LNCaP prostate cancer cells in both intact and castrated male nude mice. Copyright 2002 Wiley-Liss, Inc.

  2. Vulnerable but aloof versus naughty and nice: contrasting the presentation of male and female nude models in Viva and Playboy.

    PubMed

    Beggan, James K; Vencill, Jennifer A; Garos, Sheila

    2014-01-01

    The current research examined contested meanings of nudity by comparing images of nude men and women that appeared in Viva, a 1970s women's magazine founded with the intention of foregrounding male nudity, to corresponding issues of Playboy. A major difference was obtained between male models and Playboy Playmates regarding direction of gaze and nudity. Although gaze aversion is often interpreted as a sign of submission and direct gaze is seen as a dominance cue, men in Viva displayed a high level of gaze aversion and women in Playboy often gazed directly at the camera, especially when their pubic area was exposed. Additional content analysis examined the personality characteristics attributed to male models in Viva and Playmates in Playboy in their biographical sketches. In Viva, men were presented as possessing "bad boy" traits that may have been intended to compensate for the loss of power associated with male nudity. Playmates could be viewed as being naughty (by virtue of posing nude) and nice in the characterization of their personalities.

  3. Pulmonary metastases of the A549-derived lung adenocarcinoma tumors growing in nude mice. A multiple case study.

    PubMed

    Jakubowska, Monika; Sniegocka, Martyna; Podgórska, Ewa; Michalczyk-Wetula, Dominika; Urbanska, Krystyna; Susz, Anna; Fiedor, Leszek; Pyka, Janusz; Płonka, Przemysław M

    2013-01-01

    Lung adenocarcinoma is a leading human malignancy with fatal prognosis. Ninety percent of the deaths, however, are caused by metastases. The model of subcutaneous tumor xenograft in nude mice was adopted to study the growth of control and photodynamically treated tumors derived from the human A549 lung adenocarcinoma cell line. As a side-result of the primary studies, observations on the metastasis of these tumors to the murine lungs were collected, and reported in the present paper. The metastasizing primary tumors were drained by a prominent number of lymphatic vessels. The metastatic tissue revealed the morphology of well-differentiated or trans-differentiated adenocarcinoma. Further histological and histochemical analyses demonstrated the presence of golden-brown granules in the metastatic tissue, similar to these found in the tumor tissue. In contrast to the primary tumors, the electron paramagnetic resonance spectroscopy revealed no nitric oxide - hemoglobin complexes (a source of intense paramagnetic signals), in the metastases. No metastases were found in other murine organs; however, white infarctions were identified in a single liver. Taken together, the A549-derived tumors growing subcutaneously in nude mice can metastasize and grow on site in the pulmonary tissue. Thus, they can represent an alternative for the model of induced metastatic nodule formation, following intravenous administration of the cancerous cells.

  4. Failure-to-Thrive Syndrome Associated with Tumor Formation by Madin–Darby Canine Kidney Cells in Newborn Nude Mice

    PubMed Central

    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

    2013-01-01

    Tumors that formed in newborn nude mice that were inoculated with 107 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 = 102.8 to 107.5); 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

  5. Growth and metastasis of human bladder cancer xenografts in the bladder of nude rats. A model for intravesical radioimmunotherapy.

    PubMed

    Russell, P J; Ho Shon, I; Boniface, G R; Izard, M E; Philips, J; Raghavan, D; Walker, K Z

    1991-01-01

    A potentially useful therapeutic approach to the treatment of human bladder cancer is intravesical therapy with radiolabelled monoclonal antibodies (MAbs). We have established an animal model to study this approach. Inoculation of cloned 2B8 cells derived from the human bladder cancer cell line, UCRU-BL-17, into the bladder wall of nude rats pre-irradiated with 900 rads, resulted in local tumour growth in 39/40 (97.5%) animals, with invasion or metastases to distant organs in 25% of cases. Both the bladder tumours and the metastases were morphologically similar to the original biopsy sample from which the cell line, UCRU-BL-17, was established. The cells were of human origin, as shown by expression of HLA antigens, Alu probing, and cytogenetic analysis. Preliminary studies indicated that i.p. injection of anti-human bladder cancer monoclonal antibody (MAb), BLCA-38, radiolabelled with either iodine 131 or samarium 153 (153Sm), resulted in tumour localisation, with tumour-to-blood ratios of 5.04 (131I), and 4.3 and 3.1 (153Sm) respectively. We now aim to examine the efficacy of the intravesical route for radioimmunotherapy in the nude rat model. This model will also serve for preclinical studies on the efficacy of systemically injected radioimmunoconjugates for control of metastatic growth.

  6. Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats

    PubMed Central

    Curtis, Ryan C.; Custis, James T.; Ehrhart, Nicole P.; Ehrhart, E. J.; Condon, Keith W.; Gookin, Sara E.; Donahue, Seth W.

    2016-01-01

    Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma. PMID:27332712

  7. Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

    PubMed

    Curtis, Ryan C; Custis, James T; Ehrhart, Nicole P; Ehrhart, E J; Condon, Keith W; Gookin, Sara E; Donahue, Seth W

    2016-01-01

    Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma.

  8. Susceptibility of Anopheles quadrimaculatus (Diptera: Culicidae) to subperiodic Brugia malayi and Brugia pahangi (Nematoda: Filarioidea) adapted to nude mice and jirds.

    PubMed

    Nayar, J K; Knight, J W; Vickery, A C

    1990-05-01

    Anopheles quadrimaculatus and Aedes aegypti (Black-eyed Liverpool strain) were fed on jirds and nude mice (jird-jird infection, jird-mouse infection, and mouse-jird infection) infected with subperiodic Brugia malayi and B. pahangi. Microfilariae of B. malayi from jird-mouse and mouse-jird infections developed normally in An. quadrimaculatus, whereas those from jird-jird infections did not develop. Microfilariae of both species from jirds and nude mice developed normally in Ae. aegypti and those of B. pahangi developed normally in An. quadrimaculatus. It is suggested that microfilariae from nude mice are modified physiologically, immunologically, or both so that they can develop in refractory An. quadrimaculatus, thus indicating that susceptibility and refractoriness of An. quadrimaculatus to B. malayi also is influenced by factors relating to the vertebrate host in addition to mosquito genetic factors.

  9. [Effects of intratumoral injection of microspheres containing cobra venom cytotoxin on transplanted human hepatoma in nude mice].

    PubMed

    Wang, Yan; Lin, Li-wu; Chen, Zhi-kui; Xue, En-sheng; Lin, Xiao-dong; Yu, Li-Yun; Lin, Zhen-hu

    2009-09-01

    To evaluate the safety and efficacy of intratumoral injection of polylactic-co-glycolic acid (PLGA) microspheres containing cobra venom cytotoxin in nude mice with transplanted human hepatoma. Cytotoxic activity of cytotoxin from cobra venom was determined by using methyl thiazolyl tetrazolium method in vitro. Microspheres containing cobra venom cytotoxin were prepared with a double emulsion-solvent evaporation method. Forty BALB/c nude mice were inoculated subcutaneously in right flank with hepatoma BEL-7404 cells. Thirty-two mice whose tumor size reached about 1.0 cm in diameter, were randomly assigned into normal saline group, blank microsphers group, cytotoxin group and cytotoxin-PLGA group. Nude mice were intratumorally injected with normal saline, blank microspheres, cytotoxin or cytotoxin-PLGA microspheres respectively. Internal echo characteristics and blood flow of tumors were observed by high-frequency ultrasound every week after treatment. Twenty-six days after treatment, the tumors were removed to calculate the inhibition rate of tumor growth. The tumor, heart, liver and kidney tissues were obtained for histopathological examination. The cytotoxin separated and purified from crude cobra venom caused intense cytotoxic effects to the BEL-7404 cells in vitro. The diameter of PLGA microspheres containing cobra venom cytotoxin was about (34.45+/-9.85)microm. Encapsulation rate was up to (78.13+/-8.92)%, and cumulative amount of cobra venom cytotoxin released from the PLGA microspheres in vitro during 30 days was up to 84.3%. After intratumoral injection, tumor volumes and weights in the cytotoxin-PLGA group were lower than those in the normal saline group, with a tumor growth inhibition rate of 52.36%. Observed under a light microscope, most tumor tissues were necrotic. No obvious morphological change could be seen on the liver, kidney and heart tissues. The above findings indicate that intratumoral injection of cytotoxin-PLGA microspheres has strong

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

    PubMed Central

    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 in the control diet mice. The final average tumor size in the walnut-diet animals was roughly one-fourth the average size of the prostate tumors in the mice that ate the control diet. PMID:23758186

  11. Structure, growth and cell proliferation of human osteosarcoma and malignant fibrous histiocytoma xenografts in serial transplantation in nude mice.

    PubMed

    Broströ