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Sample records for mice bearing sarcoma-180

  1. A Comparative Study of the effects of Vitamins C and E in the Development of Sarcoma 180 in Mice

    PubMed Central

    Paiva, Gerson S.; Taft, Carlton A.; Carvalho, Marcos C.; de Souza, Ivone A.; da Silva, Elisângela C. Barbosa; Cavalcanti, Karen P.; L. Jr., Ronaldo F.; De la Cruz, Neil M.

    2013-01-01

    In this work we have investigated the effects of vitamins C and E on tumors via the mice xenotransplant model of sarcoma 180 (S180) in vivo. The experimental results suggest that dosages of 100 mg/kg vitamin C and 400 mg/kg vitamin E yields a great inhibitory behavior on tumors. PMID:24312142

  2. Inhibitory effect of orally-administered sulfated polysaccharide ascophyllan isolated from ascophyllum nodosum on the growth of sarcoma-180 solid tumor in mice.

    PubMed

    Jiang, Zedong; Abu, Ryogo; Isaka, Shogo; Nakazono, Satoru; Ueno, Mikinori; Okimura, Takasi; Yamaguchi, Kenichi; Oda, Tatsuya

    2014-04-01

    We evaluated the antitumor activity of crude extract and ascophyllan prepared from Ascophyllum nodosum in sarcoma-180 solid tumor-bearing mice with continuous intraperitoneal (i.p.) administration at a dose of 50 mg/kg body weight/day or oral administration at a dose of 500 mg/kg body weight/day. Ascophyllan and crude extract administered via the oral route showed greater antitumor effects than via i.p. route, and the tumor sizes in mice treated with ascopyllan and crude extract were reduced by a mean of 68.7±6.8% and 42.4±24.8% by the oral route, and 41.4±16.1% and 13.6±20.6% by i.p. route compared to control mice. Splenic natural killer cell activity in the mice treated with ascophyllan and crude extract by i.p. route was significantly enhanced, while only a slight increase of this activity was observed in orally-treated mice. Furthermore, increase in spleen weight of tumor-bearing mice was slightly suppressed by oral administration of ascophyllan, whereas i.p. administration resulted in further enlargement. Analysis of serum cytokines revealed that oral treatment with ascophyllan resulted in significant increase of tumor necrosis factor-α and interleukin-12 levels. Since ascophyllan showed no direct cytotoxic effect on sarcoma-180 cells, orally-administered ascophyllan is suggested to exhibit its antitumor activity through the activation of the host immune system. PMID:24692695

  3. Cytotoxicity of aniline mustard glucuronide alone or in a combination with glucose in Walker cells in culture and sarcoma-180 tumour bearing animals.

    PubMed

    Deliconstantinos, G; Ramantanis, G; Todorou, D K

    1983-01-01

    The effect of aniline mustard glucuronide (AMG), p-hydroxyaniline mustard (HAM), and aniline mustard (AM), on Walker ascites tumour cells in vitro showed that AM in about 80 times more toxic than its glucuronide but HAM is at least 800 times more toxic. A non toxic dose of AMG became completely lethal to Walker tumour cells in vitro, if bovine liver beta-glucuronidase was added to the incubation medium. Prior treatment of Walker tumour cells in vitro with glucose, increased the breakdown of AMG to HAM within the intact cells, while a non-toxic dose of the glucuronide became completely lethal to cells pretreated with glucose. The administration of AMG in combination with glucose to animals bearing the highly resistant to alkylating agents Sarcoma-180 tumour, increased the toxicity of the glucuronide but produced a slight effect on tumour growth. Glucose administration in Sarcoma-180 and ADJ/PC6 tumour bearing animals did not alter the tumour intracellular pH determined in vivo indirectly from the distribution of the weak non-metabolizable organic acid 5,5-dimethyl-2,4-oxazolinedione (DMO) between intra- and extra-cellular water. The present data suggest that the combination of aniline mustard glucuronide with glucose, could be effective in those tumours which have a high beta-glucuronidase activity and a lower tumour intracellular pH could be induced by glucose.

  4. High dose concentration administration of ascorbic acid inhibits tumor growth in BALB/C mice implanted with sarcoma 180 cancer cells via the restriction of angiogenesis

    PubMed Central

    Yeom, Chang-Hwan; Lee, Gunsup; Park, Jin-Hee; Yu, Jaelim; Park, Seyeon; Yi, Sang-Yeop; Lee, Hye Ree; Hong, Young Seon; Yang, Joosung; Lee, Sukchan

    2009-01-01

    To test the carcinostatic effects of ascorbic acid, we challenged the mice of seven experimental groups with 1.7 × 10-4 mol high dose concentration ascorbic acid after intraperitoneal administrating them with sarcoma S-180 cells. The survival rate was increased by 20% in the group that received high dose concentration ascorbic acid, compared to the control. The highest survival rate was observed in the group in which 1.7 × 10-4 mol ascorbic acid had been continuously injected before and after the induction of cancer cells, rather than just after the induction of cancer cells. The expression of three angiogenesis-related genes was inhibited by 0.3 times in bFGF, 7 times in VEGF and 4 times in MMP2 of the groups with higher survival rates. Biopsy Results, gene expression studies, and wound healing analysis in vivo and in vitro suggested that the carcinostatic effect induced by high dose concentration ascorbic acid occurred through inhibition of angiogenesis. PMID:19671184

  5. Comparative Antitumor Activity of Different Solvent Fractions from an Auricularia auricula-judae Ethanol Extract in P388D1 and Sarcoma 180 Cells

    PubMed Central

    Reza, Ahsanur; Choi, Myung-Jin; Damte, Dereje; Jo, Woo-Sik; Lee, Seung-Jin; Lee, Joong-Su

    2011-01-01

    The objective of this study was to evaluate and compare the antitumor activity of different solvent fractions (ethanol, dichloromethane, ethyl acetate, butanol and water) of the Auricularia auricula-judae 70% ethanol extract on the P388D1 macrophage and sarcoma 180 cells. A dose-dependent antitumor activity of each solvent fraction (from 0.01 mg/ml to 0.3 mg/ml) was shown against both cell types. These cytotoxic effects of all the tested fractions were confirmed on the MTT and SRB assays, without statistical differences each other. IC50 value of dichloromethane fraction was 94.2 μg/ml against sarcoma 180 cells lower than any other solvent fractions. The potent antitumor effect of the dichloromethane (DCM) fraction was also found against solid tumor in BALB/c mice. The splenomegaly and higher splenic index were found in tumor-bearing mice, with the DCM fraction returning to the negative control values. Thus, the results indicated the dichloromethane fraction may have potential ingredients as antitumor candidates. PMID:24278555

  6. Changes in the template activity of chromatin isolated from sarcoma-180 ascites cells treated with mitomycin C and gamma irradiation in vivo.

    PubMed

    Karuri, A; Mukherji, S

    1989-01-01

    The murine ascites sarcoma 180 cells were used to test the in vivo effectiveness of mitomycin C (MMC) and gamma-radiation applied in combination. The action of intraperitoneal administration of MMC and/or whole-body gamma irradiation on sarcoma 180 tumor bearing Swiss albino mice was investigated by studying the template activity of isolated tumor chromatin. The Km value for transcription of 10 Gy-irradiated chromatin was found to decrease with time implying an increase in the template efficiency with respect to that of the unirradiated control. Maximum decrease in Km was observed after 24 h of irradiation. MMC treatment (7 mg/kg body weight of mouse) for 18 h resulted in an inhibition of the transcription rate. Severe inhibition in the template activity was found when cells were subjected to MMC treatment 18 h prior to irradiation with 10 Gy. Susceptibility of tumor chromatin to DNase II followed the same pattern as observed in the case of transcription indicating structural alteration of the treated chromatin. The data showed that DNA damage and its consequences produced in the ascites cells by prior treatment of MMC were not repaired during the 18 h period after which the application of radiation enhanced cytotoxicity.

  7. Activation of antitumor immune responses by Ganoderma formosanum polysaccharides in tumor-bearing mice.

    PubMed

    Wang, Cheng-Li; Lu, Chiu-Ying; Hsueh, Ying-Chao; Liu, Wen-Hsiung; Chen, Chun-Jen

    2014-11-01

    Fungi of the genus Ganoderma are basidiomycetes that have been used as traditional medicine in Asia and have been shown to exhibit various pharmacological activities. We recently found that PS-F2, a polysaccharide fraction purified from the submerged culture broth of Ganoderma formosanum, stimulates the maturation of dendritic cells and primes a T helper 1 (Th1)-polarized adaptive immune response in vivo. In this study, we investigated whether the immune adjuvant function of PS-F2 can stimulate antitumor immune responses in tumor-bearing mice. Continuous intraperitoneal or oral administration of PS-F2 effectively suppressed the growth of colon 26 (C26) adenocarcinoma, B16 melanoma, and sarcoma 180 (S180) tumor cells in mice without adverse effects on the animals' health. PS-F2 did not cause direct cytotoxicity on tumor cells, and it lost the antitumor effect in mice with severe combined immunodeficiency (SCID). CD4(+) T cells, CD8(+) T cells, and serum from PS-F2-treated tumor-bearing mice all exhibited antitumor activities when adoptively transferred to naïve animals, indicating that PS-F2 treatment stimulates tumor-specific cellular and humoral immune responses. These data demonstrate that continuous administration of G. formosanum polysaccharide PS-F2 can activate host immune responses against ongoing tumor growth, suggesting that PS-F2 can potentially be developed into a preventive/therapeutic agent for cancer immunotherapy.

  8. Sonodynamically-induced cytotoxicity by rose bengal derivative and microbubbles in isolated sarcoma 180 cells

    NASA Astrophysics Data System (ADS)

    Sugita, Nami; Hosokawa, Mami; Sunaga, Naoki; Iwase, Yumiko; Yumita, Nagahiko; Ikeda, Toshihiko; Umemura, Shin-ichiro

    2015-07-01

    It is known that the combination of ultrasound and sonodynamic sensitizer (SDS) is effective in noninvasive tumor treatment, referred to as sonodynamic therapy (SDT). Microbubbles have been used in ultrasound therapy as well. The purpose of this paper is to clarify the effect of microbubbles on SDT. Sarcoma 180 cells were suspended in air-saturated phosphate-buffered saline and exposed to ultrasound with the SDS rose bengal derivative (RBD) in standing wave mode in the presence and absence of microbubbles [sonazoid (SZ)]. The ultrasonically induced cytotoxicity with RBD and SZ was about 20 times higher than without either, and about 80% of the SZ microbubbles were destructed by ultrasonic exposure in as short as five seconds. Since microbubbles induce significant cytotoxicity even with short duration, low intensity ultrasound, the application of microbubbles in SDT shows promise in anti-tumor treatment.

  9. Antitumor and immunomodulatory effects of weikangfu granule compound in tumor-bearing mice

    PubMed Central

    Nie, Xiaohua; Shi, Baojun; Ding, Yuting; Tao, Wenyi

    2006-01-01

    Background: Weikangfu granule compound (WKC) is a drug preparation based on a clinical prescription drug, Weikangfu-tang, which has been found to have therapeutic effects on gastric cancer. WKC comprises 7 components, including polysaccharides, saponin, flavonoids, and essential oil. Objective: The purpose of this study was to assess the antitumor and immunomodulatory effects of WKC in a tumor-bearing rodent model. Methods: Male and female Kuming mice weighing ∼20 g were subcutaneously implanted with sarcoma 180 (S180) tumor cells and randomly assigned to 1 of 5 treatment groups: oral WKC 175, 350, or 525 mg/kg·d, isotonic saline (negative control), or intraperitoneal cyclophosphamide 25 mg/kg·d (positive control). All treatments were administered daily for 10 days. After euthanization on day 11, the mice, tumors, and spleens were weighed. Lymphocyte proliferation and cytotoxic T lymphocyte (CTL) activity were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cellular viability assay method. Macrophage phagocytosis was identified using a yeast test. Results: Fifty mice were included in the study (10 mice were assigned to each group). The tumors of the mice administered WKC 175, 350, and 525 mg/kg·d were significantly regressed, as determined using MICs, compared with those in the negative-control group (P<0.05, P<0.01, and P<0.01, respectively), and the inhibitory rates were 30.43%, 46.72%, and 54.35%, respectively. Compared with those in the negative-control group, CTL activities and lymphocyte proliferations in the presence of concanavalin A were significantly greater in the WKC-treated groups at all doses (CTL activities: P<0.05, P<0.01, and P<0.01, respectively; lymphocyte proliferations: P<0.05, P<0.01, and P<0.01, respectively). In the groups receiving WKC 175, 350, and 525 mg/kg·d, the phagocytic rates were 1.5- to 2.0-fold those in the negative-control group (P<0.05, P<0.01, and P<0.01, respectively). In the groups

  10. Immunomodulatory and antitumour effects of abnormal Savda Munziq on S180 tumour-bearing mice

    PubMed Central

    2012-01-01

    Background Abnormal Savda Munziq (ASMq), a traditional uyghur medicine, has shown anti-tumour properties in vitro. This study attempts to confirm these effects in vivo and measure effects on the immune system. Methods Kunming mice transplanted with Sarcoma 180 cells were treated with ASMq (2–8 g/kg/day) by intra-gastric administration compared to model and cyclophosphamide (20 mg/kg/day). After the 14th day post tumour implant, thymus, liver, spleen and tumours were removed, weighed, and processed for histopathological analysis. Blood samples were also taken for haematological and biochemical analyses including TNF-α , IL-1 β and IL-2. Splenic lymphocyte function was measured with MTT; lymphocyte subpopulations were measured by flow cytometry. Results ASMq treated animals had reduced tumour volume compared to model and increased concentrations of TNF-α, IL-1β and IL-2 compared to untreated and to cyclophosphamide-treated animals. No histopathological alterations were observed. The absence of viable S180 cells and the presence of necrotic cells and granulation tissue were observed in tumour tissue of treated animals. The effect on T lymphocytes was unclear. Conclusions ASMq confirmed in vivo anti-tumour effects observed in vitro, which may be at least in part mediated by increased immune activity. PMID:22978453

  11. Metabolomic profiling of tumor-bearing mice.

    PubMed

    Wettersten, Hiromi I; Ganti, Sheila; Weiss, Robert H

    2014-01-01

    Metabolomics is one of the newcomers among the "omics" techniques, perhaps also constituting the most relevant for the study of pathophysiological conditions. Metabolomics may indeed yield not only disease-specific biomarkers but also profound insights into the etiology and progression of a variety of human disorders. Various metabolomic approaches are currently available to study oncogenesis and tumor progression in vivo, in murine tumor models. Many of these models rely on the xenograft of human cancer cells into immunocompromised mice. Understanding how the metabolism of these cells evolves in vivo is critical to evaluate the actual pertinence of xenograft models to human pathology. Here, we discuss various tumor xenograft models and methods for their metabolomic profiling to provide a short guide to investigators interested in this field of research. PMID:24924138

  12. Metabolomic profiling of tumor-bearing mice.

    PubMed

    Wettersten, Hiromi I; Ganti, Sheila; Weiss, Robert H

    2014-01-01

    Metabolomics is one of the newcomers among the "omics" techniques, perhaps also constituting the most relevant for the study of pathophysiological conditions. Metabolomics may indeed yield not only disease-specific biomarkers but also profound insights into the etiology and progression of a variety of human disorders. Various metabolomic approaches are currently available to study oncogenesis and tumor progression in vivo, in murine tumor models. Many of these models rely on the xenograft of human cancer cells into immunocompromised mice. Understanding how the metabolism of these cells evolves in vivo is critical to evaluate the actual pertinence of xenograft models to human pathology. Here, we discuss various tumor xenograft models and methods for their metabolomic profiling to provide a short guide to investigators interested in this field of research.

  13. In vitro translation of oogenetic messenger RNA of sea urchin eggs and picornavirus RNA with a cell-free system from sarcoma 180.

    PubMed

    Jenkins, N; Taylor, M W; Raff, R A

    1973-12-01

    A cell-free protein-synthesizing system prepared from mouse sarcoma 180 was characterized by use of RNA from mengo virus and sea urchin egg. In the presence of exogenous mammalian transfer RNA, total sea urchin egg RNA and mengo RNA direct incorporation of [(3)H]leucine into acid-insoluble material. The system is extremely efficient in that a stimulation of 100-times over background can be obtained. Studies with formylmethionyl-transfer RNA, as well as with inhibitors of initiation, indicate that multiple initiation occurs; further, 85-90% of all chains made in vitro are subsequently released from ribosomes. An average translation time of 3.5 min was determined with messenger RNA of sea urchin egg, and product analysis indicates that high-molecular-weight products (greater than 50,000 molecular weight) are being made in vitro. Sequences of sea urchin egg RNA containing poly(A) act as messenger RNA.

  14. Induction of hepatic metallothionein I in tumour-bearing mice.

    PubMed

    Kloth, D M; Chin, J L; Cherian, M G

    1995-04-01

    Metallothionein (MT) is an intracellular metal-binding protein which has been implicated in various biological roles, including heavy-metal detoxification and zinc and copper homeostasis, and has putative antioxidant properties. High levels of MT have been detected in certain human tumours, but its functions are unclear. The presence of tumour may cause stress conditions along with alterations in host metabolism, such as the redistribution of metals and, subsequently, in changes in hepatic MT isoforms. The distribution of basal levels of MT-1 and MT-11 isoforms in livers of different strains of mice and their induction in mice inoculated with tumour cells are investigated. While Balb-c, C57/BL and CD1 mice strains had an equal distribution of both hepatic MT isoforms, MT-I and MT-II. In addition, MT-I was the predominant isoform synthesised (> 88%) in the livers of all strains of mice at 24 h after injection with either cadmium or zinc salts. After inoculation with human testicular T7800 or T7799 tumour cells, the major form of MT induced in the livers of nude (nu/nu) mice was Zn-MT-I, and its concentration was positively correlated with the size of the inoculated tumours (r2 = 0.85). A similar positive relation was found in the livers of Balb-c mice inoculated with MM45T mouse bladder tumour cells (r2 = 0.96). Following surgical removal of T7800 tumour, hepatic MT concentrations returned to basal values. There was an increase in plasma MT levels in tumour-bearing mice and it was positively correlated with the increase in hepatic MT levels. These results demonstrate a specific increase in hepatic MT-I isoform in tumour-bearing mice, and this may be due to a generalised stress during tumour growth. PMID:7710933

  15. VEGF expression in hepatectomized tumor-bearing mice.

    PubMed

    Andrini, L; Blanco, A Fernandez; Inda, A; García, M; Garcia, A; Errecalde, A

    2011-01-01

    The experiments were designed in order to study the VEGF expression in intact (group I), hepatectomized (group II), and hepatectomized-tumor bearing mice (group III) throughout one complete circadian time span. Adult male mice were used for the VEGF expression study. The statistical analysis was performed using analysis of variance (ANOVA). The results showed statistical differences in the VEGF expression between groups I and II, but the most significant differences were found between groups I and III. In conclusion, these expressions have a circadian rhythm in all groups; moreover, in group III, this expression was higher and appeared before than in the others.

  16. Amino acid metabolism in tumour-bearing mice.

    PubMed Central

    Rivera, S; Azcón-Bieto, J; López-Soriano, F J; Miralpeix, M; Argilés, J M

    1988-01-01

    Mice bearing the Lewis lung carcinoma showed a high tumour glutaminase activity and significantly higher concentrations of most amino acids than in both the liver and the skeletal muscle of the host. Tumour tissue slices showed a marked preference for glutamine, especially for oxidation of its skeleton to CO2. It is proposed that the metabolism of this particular carcinoma is focused on amino acid degradation, glutamine being its preferred substrate. PMID:3342022

  17. Antitumorigenic potential of linalool is accompanied by modulation of oxidative stress: an in vivo study in sarcoma-180 solid tumor model.

    PubMed

    Jana, Samarjit; Patra, Kartick; Sarkar, Shehnaz; Jana, Jagannath; Mukherjee, Gopeswar; Bhattacharjee, Shamee; Mandal, Deba Prasad

    2014-01-01

    Coriander, used as a common food seasoning, contains linalool as the main constituent of its essential oil. In this study, we tested the effect of linalool vis-à-vis that of a conventional chemotherapeutic drug, cyclophosphamide, against solid S-180 tumor-bearing Swiss albino mice. Tumor volume, cell count, cell cycle phase distribution, apoptosis, and proliferation markers indicate that linalool has potent antitumor activity. In vitro and in vivo data suggest that induction of oxidative stress might be responsible for the anticancer effect of linalool. However, interestingly, unlike cyclophosphamide, linalool did not induce myelosuppression or hepatotoxicity in mice as evident from bone marrow cell count, status of hepatic oxidative stress/antioxidant enzymes, and histopathology. Thus, linalool exerted prooxidant effect in tumor tissue and an antioxidant effect in liver. This is also supported by the expression of Nrf-2 and p21, which are considered to be important players in response to oxidative stress. Moreover, administration of linalool modulated the proliferation of spleen cells in tumor-bearing mice challenged with lipopolysaccharide. Finally, the detection of linalool in sera and tumor tissues by HPLC confirmed its bioavailability. In conclusion, linalool showed differential cytotoxicity towards tumor and normal cells in contrast to cyclophosphamide, which is uniformly toxic to both.

  18. Chlorpromazine distribution in hamsters and mice bearing transplantable melanoma

    SciTech Connect

    Fairchild, R.G.; Greenberg, D.; Watts, K.P.; Packer, S.; Atkins, H.L.; Som, P.; Hannon, S.J.; Brill, A.B.; Fand, I.; McNally, W.P.

    1982-02-01

    Chlorpromazine (CPZ) distribution was measured in tissues of Syrian golden hamsters bearing Greene melanoma and in BALB/c mice bearing Harding-Passey melanoma. Distribution was evaluated as a function of time (0.5 to 14 days) and as a function of single and multiple doses (up to five) of from 5 to 50 mg CPZ per kg body weight. Routes of administration (i.p., i.v., p.o.) were compared. The physiological behavior of CPZ is of interest as it is used extensively as a tranquilizing drug (Thorazine). Further, since CPZ binds to the pigment melanin, the possibility exists of using CPZ to transport diagnostic or therapeutic agents to melanoma. It was found that, at 2 days postinjection, tumor/tissue concentration ratios exceeded 10 for metabolizing organs, such as liver, and 100 for background tissues, such as blood and muscle. Absolute concentrations of CPZ in tumor exceeding 100 ..mu..g CPZ per g tumor were obtained with both single and multiple doses. This selective high concentration in tumor would make CPZ an ideal vehicle for the transport of boron to tumor for use in neutron capture therapy via the /sup 10/B(n,..cap alpha..)/sup 7/Li reaction.

  19. Extracellular polysaccharide production by a strain of Pleurotus djamor isolated in the south of Brazil and antitumor activity on Sarcoma 180

    PubMed Central

    Borges, Gisele Martini; De Barba, Fabiana Figueredo Molin; Schiebelbein, Ana Paula; Pereira, Bruna Parmezzani; Chaves, Mariane Bonatti; Silveira, Marcia Luciane Lange; Pinho, Mauro Souza Leite; Furlan, Sandra Aparecida; Wisbeck, Elisabeth

    2013-01-01

    Polysaccharides with medicinal properties can be obtained from fruiting bodies, mycelium and culture broth of several fungus species. This work was carried out in batch culture using a stirred tank reactor with two different initial glucose concentrations (40–50 g/L) and pH values (3.0–4.0) to enhance extracellular polysaccharides production by Pleurotus djamor UNIVILLE 001 and evaluate antitumor effect of intraperitonial administration of Pleurotus djamor extract on sarcoma 180 animal model. According to factorial design, the low pH value (pH 3.0) led to a gain of 1.6 g/L on the extracellular polysaccharide concentration, while glucose concentration in the tested range had no significant effect on the concentration of polysaccharide. With 40 g/L initial glucose concentration and pH 3.0, it was observed that yield factor of extracellular polysaccharide on substrate (YP/S = 0.072) and maximum extracellular polysaccharide productivity (QPmax = 11.26 mg/L.h) were about 188% and 321% respectively higher than those obtained in the experiment performed at pH 4.0. Under these conditions, the highest values of the yield factor of biomass on substrate (YX/S = 0.24) and maximal biomass productivity (QXmax = 32.2 mg/L.h) were also reached. In tumor response study, mean tumor volume on the 21th day was 35.3 cm3 in untreated group and 1.6 cm3 in treated group (p = 0.05) with a tumor inhibition rate of 94%. These impressive results suggests an inhibitory effect of P.djamor extract on cancer cells. PMID:24688493

  20. [Effect of fluoropyrimidine, drugs of tegafur and UFT on transplanted tumor in liver-damaged mice].

    PubMed

    Aoike, A; Hosokawa, T; Koyama, K; Rokutan, K; Nishi, Y; Yoshida, A; Nakamura, K; Kawai, K

    1988-10-01

    1-(2-Tetrahydrofuryl)-5-fluorouracil (FT) and UFT are masked compounds of 5-fluorouracil (5-FU) and considered to be gradually metabolized and converted to 5-FU in the liver. Therefore, it is important clinically to classify whether or not these anti-cancer drugs are effective in individuals with liver diseases. BALB/c mice were injected 4 ml/kg of 10% CCl4 intraperitoneally twice a week for two months to induce liver damage. On the 49th day after starting of giving CCl4, mouse sarcoma 180 was transplanted to the right thigh of mice and from the next day 5-FU (10, 20, 30 mg/kg/day), FT (50, 100, 200 mg/kg/day), UFT (10, 20, 30 mg/kg/day) or physiological saline solution for control were orally administered daily for 7 days. On the 61st day, all mice were sacrificed and the weight of excised tumor was measured to judge the effect of anti-cancer drugs. Dose-dependent effect of 5-FU was observed in the liver-damaged mice. FT was more effective in liver-damaged mice than control. It was assumed that the suppression of 5-FU decomposition was due to the insufficient liver function. Effect of UFT was similar in liver-damaged mice to control. These data show that the effects of FT and UFT were not reduced in tumor-bearing mice by liver damage.

  1. Effect of N-acetylchitohexaose against Candida albicans infection of tumor-bearing mice.

    PubMed

    Kobayashi, M; Watanabe, T; Suzuki, S; Suzuki, M

    1990-01-01

    A water-soluble oligosaccharide, N-acetylchitohexaose (NACOS-6), was able to enhance the protective effect against Candida albicans infection in mice during the early phase of tumor-bearing. A significant decrease in the number of C. albicans cells in the kidneys of NACOS-6-treated tumor-bearing mice was observed 8 days after the fungal infection, or 15 days after the tumor transplantation. The candidacidal activity of polymorphonuclear leukocytes from NACOS-6-treated tumor-bearing mice did not differ from that of NACOS-6-untreated tumor-bearing mice. On the other hand, the candidacidal activities of both macrophages and T lymphocytes increased following administration of NACOS-6 in the early phase of tumor-bearing. The culture supernatant of T lymphocytes from NACOS-6-treated tumor-bearing mice also potentiated the candidacidal activity of casein-induced macrophages. An enhancement of natural killer cell activity of splenic lymphocytes obtained from NACOS-6-treated tumor-bearing mice was also observed.

  2. Curcumin reduces trabecular and cortical bone in naive and Lewis lung carcinoma-bearing mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study investigated the effects of dietary supplementation with curcumin on bone microstructural changes in female C57BL/6 mice in the presence or absence of Lewis lung carcinoma. Morphometric analysis showed that in tumor-bearing mice curcumin at 2% and 4% dietary levels (w/w) significa...

  3. Down-regulation of interleukin 1 production by macrophages of sarcoma-bearing mice.

    PubMed

    Moldawer, L L; Lonnroth, C; Mizel, S B; Lundholm, K G

    1987-06-15

    Peritoneal macrophages from mice bearing a transplantable methylcholanthrene-induced sarcoma produced progressively less IL 1 as tumor burden increased. The loss of activity was not explained by the production of any inhibitor of the mouse thymocyte comitogen bioassay. Immune precipitation with a polyclonal antibody confirmed the decline in IL 1 appearance. Although tumor-bearing animals lost approximately 17% of their carcass mass, the reduced production of IL 1 was not satisfactorily explained by coexistent malnutrition, since similarly depleted non-tumor-bearing mice were capable of producing IL 1. In addition to an altered IL 1 production by macrophages of tumor-bearing mice, SDS-polyacrylamide gel electrophoresis and autoradiography revealed that the pattern of secretory protein synthesis from LPS-stimulated and unstimulated peritoneal macrophages differed between tumor-bearing and control animals. Administration of LPS to tumor-bearing mice early after tumor transplantation resulted in reduced tumor growth and prevented the down-regulation of in vitro IL 1 production by peritoneal macrophages. These findings demonstrate a specific defect in IL 1 production associated with increasing tumor burden. Further studies are required to determine whether this defect in IL 1 synthesis contributes to the increased tumor growth.

  4. Antitumor Efficacy and Mechanism in Hepatoma H22-Bearing Mice of Brucea javanica Oil

    PubMed Central

    Shi, Wen-Rong; Liu, Yan; Wang, Xiao-Ting; Huang, Qiong-Ying; Cai, Xue-Rong; Wu, Shao-Rong

    2015-01-01

    Brucea javanica is a traditional herbal medicine in China, and its antitumor activities are of research interest. Brucea javanica oil, extracted with ether and refined with 10% ethyl alcohol from Brucea javanica seed, was used to treat hepatoma H22-bearing mice in this study. The antitumor effect and probable mechanisms of the extracted Brucea javanica oil were studied in H22-bearing mice by WBC count, GOT, GPT levels, and western blotting. The H22 tumor inhibition ratio of 0.5, 1, and 1.5 g/kg bw Brucea javanica oil were 15.64%, 23.87%, and 38.27%. Brucea javanica oil could inhibit the involution of thymus induced by H22 tumor-bearing, but it could not inhibit the augmentation of spleen and liver. Brucea javanica oil could decrease the levels of WBC count and GOT and GPT in H22-bearing mice. The protein levels of GAPDH, Akt, TGF-β1, and α-SMA in tumor tissues decreased after being treated with Brucea javanica oil. Disturbing energy metabolism and neoplastic hyperplasia controlled by Akt and immunoregulation activity were its probable antitumor mechanisms in hepatoma H22-bearing mice. PMID:26508976

  5. Curcumin reduces trabecular and cortical bone in naive and lewis lung carcinoma-bearing mice.

    PubMed

    Yan, Lin; Yee, John A; Cao, Jay

    2013-08-01

    The present study investigated the effects of curcumin on bone microstructure in non-tumor-bearing and Lewis lung carcinoma-(LLC)-bearing female C57BL/6 mice. Morphometric analysis showed that dietary supplementation with curcumin (2% or 4%) significantly reduced the bone volume to total volume ratio, connectivity density and trabecular number, and significantly increased the structure model index (an indicator of the plate- and rod-like geometry of trabecular structure) and trabecular separation in vertebral bodies compared to controls in both non-tumor-bearing and LLC-bearing mice. Similar changes in trabecular bone were observed in the femoral bone in curcumin-fed mice. Curcumin significantly reduced the cortical bone area to total area ratio and cortical thickness in femoral mid-shaft, but not in vertebral bodies, in both non-tumor-bearing and LLC-bearing mice. Curcumin feeding reduced plasma concentrations of osteocalcin and increased tartrate-resistant acid phosphate 5b in mice regardless of the presence of LLC, indicating that curcumin disrupts the balance of bone remodeling. Our results demonstrated that curcumin reduced the trabecular bone volume and cortical bone density. The skeleton is a favored site of metastasis for many types of cancers, and curcumin has been investigated in clinical trials in patients with cancer for its chemopreventive effects. Our results suggest the possibility of a combined effect of cancer-induced osteolysis and curcumin-stimulated bone loss in patients using curcumin. The assessment of bone structural changes should be considered for those who participate in curcumin clinical trials to determine its effects on skeleton health, particularly for those with advanced malignancies.

  6. Dietary Supplementation with Isoflavones Prevents Muscle Wasting in Tumor-Bearing Mice.

    PubMed

    Hirasaka, Katsuya; Saito, Shinobu; Yamaguchi, Saki; Miyazaki, Riho; Wang, Yao; Haruna, Marie; Taniyama, Shigeto; Higashitani, Atsushi; Terao, Junji; Nikawa, Takeshi; Tachibana, Katsuyasu

    2016-01-01

    Proinflammatory cytokines contribute to the progression of muscle wasting caused by ubiquitin-proteasome-dependent proteolysis. We have previously demonstrated that isoflavones, such as genistein and daidzein, prevent TNF-α-induced muscle atrophy in C2C12 myotubes. In this study, we examined the effect of dietary flavonoids on the wasting of muscle. Mice were divided into the following four groups: vehicle-injected (control) mice fed the normal diet (CN); tumor-bearing mice fed the normal diet (TN); control mice fed the isoflavone diet (CI); and tumor-bearing mice fed the isoflavone diet (TI). There were no significant differences in the intake of food or body weight gain among these four groups. The wet weight and myofiber size of gastrocnemius muscle in TN significantly decreased, compared with those in CN. Interestingly, the wet weight and myofiber size of gastrocnemius muscle in TI were nearly the same as those in CN and CI, although isoflavone supplementation did not affect the increased tumor mass or concentrations of proinflammatory cytokines, such as TNF-α and IL-6, in the blood. Moreover, increased expression of muscle-specific ubiquitin ligase genes encoding MAFbx/Atrogin-1 and MuRF1 in the skeletal muscle of TN was significantly inhibited by the supplementation of isoflavones. In parallel with the expression of muscle-specific ubiquitin ligases, dietary isoflavones significantly suppressed phosphorylation of ERK in tumor-bearing mice. These results suggest that dietary isoflavones improve muscle wasting in tumor-bearing mice via the ERK signaling pathway mediated-suppression of ubiquitin ligases in muscle cells. PMID:27465724

  7. HemoHIM enhances the therapeutic efficacy of ionizing radiation treatment in tumor-bearing mice.

    PubMed

    Park, Hae-Ran; Ju, Eun-Jin; Jo, Sung-Kee; Jung, Uhee; Kim, Sung-Ho

    2010-02-01

    Although radiotherapy is commonly used for a variety of cancers, radiotherapy alone does not achieve a satisfactory therapeutic outcome. In this study, we examined the possibility that HemoHIM can enhance the anticancer effects of ionizing radiation (IR) in melanoma-bearing mice. The HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs-Angelica Radix, Cnidium Rhizoma, and Paeonia Radix. Anticancer effects of HemoHIM were evaluated in melanoma-bearing mice exposed to IR. IR treatment (5 Gy at 7 days after melanoma cell injection) reduced the weight of the solid tumors, and HemoHIM supplementation with IR enhanced the decreases in tumor weight (P < .03). In the melanoma-bearing mice treated with IR, HemoHIM administration also increased the activity of natural killer cells and cytotoxic T cells, although the proportions of these cells in spleen were not different. In addition, HemoHIM administration increased the interleukin-2 and tumor necrosis factor-alpha secretion from lymphocytes stimulated with concanavalin A, which seemed to contribute to the enhanced efficacy of HemoHIM in tumor-bearing mice treated with IR. In conclusion, HemoHIM may be a beneficial supplement during radiotherapy for enhancing the antitumor efficacy. PMID:20136435

  8. Antitumor Effect of Zhihuang Fuzheng Soft Capsules on Tumor-Bearing Mice

    PubMed Central

    Bao, Yanyan; Pan, Xin; Jin, Yahong; Gao, Yingjie; Cui, Xiaolan

    2016-01-01

    Chinese medicines (CMs) have been shown to have some advantages in preventing and controlling tumors. In this study, we investigated the antitumor effect of ZFSC by establishing a mouse model of HT-1080, A-549, and HCT-8 tumors. The result showed that tumor volumes of HT-1080 tumor-bearing nude mice in ZFSC low, medium, and high dose groups were lower significantly compared to the model group, and the high dose ZFSC showed the best antitumor effect. Tumor volumes of A-549 tumor-bearing nude mice in ZFSC low, medium, and high dose groups were lower significantly compared to the model group and showed a good dose-response relationship. There was no significant effect on human colon cancer, although inhibition trends disappeared in the bar chart. In order to verify the immunomodulatory effect of ZFSC, ELISA was used to analyze serums IL-2, TNF-α, and IFN in spleens. The results showed that ZFSC could enhance the immune function of tumor-bearing mice. ZFSC reduced IFN-γ and TNF-α content in the serum of HT-1080 tumor-bearing mice and inhibit PD1 and PDL1 and suggested that the antitumor mechanism of ZFSC on human fibrosarcoma could be attributed to inhibition of the PDL1/PD1 pathway. PMID:27493673

  9. Anergy-like immunosuppression in mice bearing pulmonary foreign-body granulomatous inflammation.

    PubMed Central

    Allred, D. C.; Kobayashi, K.; Yoshida, T.

    1985-01-01

    Pulmonary granulomas were induced in BALB/c mice by the intratracheal injection of insoluble polymerized dextran and latex microparticles. Very large granulomas developed around dextran beads, which reached peak intensity within 2-3 days and rapidly declined in size thereafter. Latex beads generated small stable lesions. The involvement of cell-mediated immunity could not be demonstrated in the inflammatory responses induced by either type of bead. Antigen-induced delayed type hypersensitivity (DTH) and mitogen-induced DTH-like footpad reactions were markedly suppressed in immunized mice bearing early dextran granulomas. Mitogen-induced DTH-like footpad reactions were suppressed in unimmunized animals bearing early dextran foreign-body granulomas. Antigen- and mitogen-induced footpad swelling recovered to normal levels as dextran granulomas diminished in size. No suppression of these footpad reactions was observed in mice bearing small latex foreign-body granulomas. The intraperitoneal injection of aqueous extracts prepared from the lungs of unimmunized donor animals bearing early dextran foreign-body granulomas could partially transfer suppression of mitogen DTH-like footpad responses to normal mice. These results suggest that cells within large, nonimmunologic lung granulomas produce a soluble factor which participates in the expression of anergy-like immunosuppression. Images Figure 2 PMID:3907366

  10. HemoHIM enhances the therapeutic efficacy of ionizing radiation treatment in tumor-bearing mice.

    PubMed

    Park, Hae-Ran; Ju, Eun-Jin; Jo, Sung-Kee; Jung, Uhee; Kim, Sung-Ho

    2010-02-01

    Although radiotherapy is commonly used for a variety of cancers, radiotherapy alone does not achieve a satisfactory therapeutic outcome. In this study, we examined the possibility that HemoHIM can enhance the anticancer effects of ionizing radiation (IR) in melanoma-bearing mice. The HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs-Angelica Radix, Cnidium Rhizoma, and Paeonia Radix. Anticancer effects of HemoHIM were evaluated in melanoma-bearing mice exposed to IR. IR treatment (5 Gy at 7 days after melanoma cell injection) reduced the weight of the solid tumors, and HemoHIM supplementation with IR enhanced the decreases in tumor weight (P < .03). In the melanoma-bearing mice treated with IR, HemoHIM administration also increased the activity of natural killer cells and cytotoxic T cells, although the proportions of these cells in spleen were not different. In addition, HemoHIM administration increased the interleukin-2 and tumor necrosis factor-alpha secretion from lymphocytes stimulated with concanavalin A, which seemed to contribute to the enhanced efficacy of HemoHIM in tumor-bearing mice treated with IR. In conclusion, HemoHIM may be a beneficial supplement during radiotherapy for enhancing the antitumor efficacy.

  11. Epidermal growth factor prolongs survival time of tumor-bearing mice.

    PubMed

    Amagase, H; Tamura, K; Okuhira, M; Kakimoto, M; Amano, H; Hashimoto, K; Fuwa, T; Tsukagoshi, S

    1990-05-01

    We observed that human epidermal growth factor (hEGF) alone prolonged the survival time of mice bearing various murine syngeneic tumors as well as athymic nude mice bearing human xenografts. No changes in the subcutaneous solid tumor mass volume were observed. Prolongation of survival time by hEGF was observed in mice bearing murine epidermoid carcinoma (BSC) and human gastric carcinoma (KATO III), but not in murine epidermoid carcinoma (KLN205) or human epidermoid carcinoma (A431). Human tumor cells such as A431, KATO III, and murine tumor cells, KLN205, BSC had roughly 2 X 10(6), 3 X 10(4), 1.3 X 10(3) and 1 X 10(3) EGF receptors/cell, respectively. Although KLN205 and BSC tumor cells maintained nearly the same number of EGF receptors, the effects of hEGF were very different. Although A431 tumor cells had nearly 100 times more receptors than KATO III cells, the prolongation of survival time of mice bearing A431 by hEGF was no better than that of mice bearing KATO III. Accordingly, it appears that this prolongation of survival time by hEGF is independent of the number of EGF receptors on tumor cells. In addition, hEGF was shown to inhibit experimental pulmonary metastasis of murine BSC tumor, but was ineffective with murine KLN205 tumor. These results suggest that prolongation of survival time by hEGF may result from the inhibition of tumor cell metastasis and EGF may play a role in preventing the metastasis of certain malignant neoplasms unrelated to its effects through the EGF receptor on tumor cells.

  12. Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice

    PubMed Central

    2009-01-01

    Background Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. Methods HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of 3 edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Anticancer effects of HemoHIM with cisplatin were evaluated in melanoma-bearing mice. We used a Cr51-release assay to measure the activity of NK/Tc cell and ELISA to evaluate the production of cytokines. Results In melanoma-bearing mice, cisplatin (4 mg/kg B.W.) reduced the size and weight of the solid tumors, and HemoHIM supplementation with cisplatin enhanced the decrease of both the tumor size (p < 0.1) and weight (p < 0.1). HemoHIM itself did not inhibit melanoma cell growth in vitro, and did not disturb the effects of cisplatin in vitro. However HemoHIM administration enhanced both NK cell and Tc cell activity in mice. Interestingly, HemoHIM increased the proportion of NK cells in the spleen. In melanoma-bearing mice treated with cisplatin, HemoHIM administration also increased the activity of NK cells and Tc cells and the IL-2 and IFN-γ secretion from splenocytes, which seemed to contribute to the enhanced efficacy of cisplatin by HemoHIM. Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction. Conclusion HemoHIM may be a beneficial supplement during cisplatin chemotherapy for enhancing the anti-tumor efficacy and reducing the toxicity of cisplatin. PMID:19292900

  13. Analysis of splenic Gr-1int immature myeloid cells in tumor-bearing mice.

    PubMed

    Yamamoto, Yoshiko; Ishigaki, Hirohito; Ishida, Hideaki; Itoh, Yasushi; Noda, Yoichi; Ogasawara, Kazumasa

    2008-01-01

    It is known that the number of ImC, expressing myeloid markers, CD11b and Gr-1, increase with tumor growth and ImC play a role in the escape of tumor cells from immunosurveillance in tumor-bearing mice and cancer patients. However, the mechanisms by which ImC suppress immune responses in tumor-bearing mice have not been completely elucidated. In the present study, we investigated the function of splenic ImC freshly isolated from tumor-bearing mice and splenic ImC differentiated in vitro by GM-CSF. Freshly isolated splenic ImC were divided into two groups depending on Gr-1 expression, Gr-1 high (Gr-1hi) and intermediate (Gr-1int). Freshly isolated splenic Gr-1int ImC, but not Gr-1hi ImC, from tumor-bearing mice reduced production of IFN-gamma in CD8+ T cells, but neither splenic Gr-1int ImC nor Gr-1hi ImC isolated from naive mice did. Both Gr-1int and Gr-1hi ImC differentiated in vitro by GM-CSF inhibited production of IFN-gamma in both CD8+ and CD4+ T cells. In addition, the differentiated Gr-1int ImC, one-third of which were CD11c+F4/80+ cells, and their culture supernatants suppressed proliferative responses of T cells stimulated by CD3 ligation, but the differentiated Gr-1hi ImC and their culture supernatants did not. These results suggest that Gr-1int ImC are altered to immune-suppressive cells in tumor circumstances and that they are differentiated by GM-CSF progressively into CD11c+F4/80+ cells with further suppressive activity against T cells.

  14. Pharmacokinetics of Polymersomes Composed of Poly(Butadiene-Ethylene Oxide); Healthy versus Tumor-Bearing Mice.

    PubMed

    Wang, G; de Kruijff, R M; Abou, D; Ramos, N; Mendes, E; Franken, L E; Wolterbeek, H T; Denkova, A G

    2016-02-01

    Vesicles composed of block copolymers (i.e., polymersomes) are one of the most versatile nano-carriers for medical purposes due to their tuneable physicochemical properties and the possibility to encapsulate simultaneously hydrophobic and hydrophilic substances, allowing, for instance, the combination of therapy and imaging. In cancer treatment, these vesicles need to remain long enough in the blood stream to be sufficiently taken up by tumors. Here, we have investigated the biodistribution and the pharmacokinetics of polymersomes, composed of poly(butadiene-b-ethylene oxide) having dimensions around 80 nm. The polymersomes have been radiolabeled with ¹¹¹In via the so-called active loading method achieving a loading efficiency of 92.9 ± 0.9% with radionuclide retention in mouse serum of more than 95% at 24 h. The optimized ¹¹¹In containing polymersomes have been intravenously administered in healthy and tumor bearing mice for pharmacokinetic determination using microSPECT (Single Photon Emission Computed Tomography). In healthy mice these polymersomes have been found to exhibit relatively long blood circulation (> 6 h), low liver uptake (6 ± 1.5%ID/g, 48 h p.i.) and elevated spleen uptake (188 ± 30%ID/g). The blood circulation in tumor bearing mice is dramatically reduced (< 1.5 h) most likely due to elevated splenic filtration, clearly indicating the importance of in vivo studies in diseased mice. Finally, the polymersomes have been injected subcutaneously in tumor bearing mice revealing retention of 77% in the mice, primarily accumulated at the site of injection, up to 48 hours after administration.

  15. CCR4 is critically involved in effective antitumor immunity in mice bearing intradermal B16 melanoma.

    PubMed

    Matsuo, Kazuhiko; Itoh, Tatsuki; Koyama, Atsushi; Imamura, Reira; Kawai, Shiori; Nishiwaki, Keiji; Oiso, Naoki; Kawada, Akira; Yoshie, Osamu; Nakayama, Takashi

    2016-08-01

    CCR4 is a major chemokine receptor expressed by Treg cells and Th17 cells. While Treg cells are known to suppress antitumor immunity, Th17 cells have recently been shown to enhance the induction of antitumor cytotoxic T lymphocytes. Here, CCR4-deficient mice displayed enhanced tumor growth upon intradermal inoculation of B16-F10 melanoma cells. In CCR4-deficient mice, while IFN-γ+CD8+ effector T cells were decreased in tumor sites, IFN-γ+CD8+ T cells and Th17 cells were decreased in regional lymph nodes. In wild-type mice, CD4+IL-17A+ cells, which were identified as CCR4+CD44+ memory Th17, were found to be clustered around dendritic cells expressing MDC/CCL22, a ligand for CCR4, in regional lymph nodes. Compound 22, a CCR4 antagonist, also enhanced tumor growth and decreased Th17 cells in regional lymph nodes in tumor-bearing mice treated with Dacarbazine. In contrast, CCR6 deficiency did not affect the tumor growth and the numbers of Th17 cells in regional lymph nodes. These findings indicate that CCR4 is critically involved in regional lymph node DC-Th17 cell interactions that are necessary for Th17 cell-mediated induction of antitumor CD8+ effector T cells in mice bearing B16 melanoma. PMID:27132989

  16. Inhibitory efficacy of the quantified prunellae spica extract on H22 tumor bearing mice

    NASA Astrophysics Data System (ADS)

    Wang, Zhi-ping; Chen, Tong-sheng

    2013-02-01

    Hepatocarcinoma, a malignant cancer, threaten human life badly. It is a current issue to seek the effective natural remedy from plant to treat cancer due to the resistence of the advanced hepatocarcinoma to chemotherapy. In this report, we assessed the antitumor activity of a prunellae spica aqueous extract (PSE) in vitro and in vivo. PSE was quantified by HPLC and UV. MTT assay showed that PSE did not effectively inhibit the growth of H22 cells. The in vivo anti-tumor activity was assessed by using the mice bearing H22 tumor. In vivo studies showed the higher antitumor efficacy of PSE without significant side effect assessed by the reduced tumor weight, and the extended survival time of the mice bearing H22 solid and ascites tumor. Collectively, PSE is a promising Chinese medicinal herb for treating hepatocarcinoma.

  17. Pharmacokinetics of Ro 03-8799 in mice bearing melanosarcoma: comparison with tumors without melanin

    SciTech Connect

    Laurent, F.; Canal, P.; Soula, G.

    1989-04-01

    The pharmacokinetics of Ro 03-8799 has been studied in melanic and non-melanic tumor bearing mice after iv administration of 150 mg/kg. The peak concentration in B16 melanosarcoma tumor reached 152 micrograms/g, that is 7.6-fold higher than the plasma concentration at the same time. This concentration is 3-times greater than that obtained in the tumor of mice bearing non-melanic sarcoma (DB16) or Lewis lung carcinoma (3LL). The exposure of B16 tumor (AUC) is respectively 15-times and 11-times higher than the 3LL and the DB16 ones. These experimental data confirm that this 2-nitro-imidazol compound has an important affinity for melanin and suggest that it might be used as a radiosensitizer for the treatment of malignant melanoma.

  18. Radioprotection of normal tissues in tumor-bearing mice by troxerutin.

    PubMed

    Maurya, Dharmendra Kumar; Salvi, Veena Prakash; Krishnan Nair, Cherupally Krishnan

    2004-06-01

    The flavanoid derivative troxerutin, used clinically for treating venous disorders, protected biomembranes and cellular DNA against the deleterious effects of gamma-radiation. The peroxidation of lipids (measured as thiobarbituric acid-reacting substances, or TBARS) in rat liver microsomal and mitochondrial membranes resulting from gamma-irradiation up to doses of 500 Gy in vitro was prevented by 0.2 mM troxerutin. The administration of troxerutin (175 mg/kg body weight) to tumor-bearing mice by ip one hour prior to 4 Gy whole-body gamma-irradiation significantly decreased the radiation-induced peroxidation of lipids in tissues such as liver and spleen, but there was no reduction of lipid peroxidation in tumor. The effect of troxerutin in gamma-radiation-induced DNA strand breaks in different tissues of tumor-bearing mice was studied by comet assay. The administration of troxerutin to tumor-bearing animals protected cellular DNA against radiation-induced strand breaks. This was evidenced from decreases in comet tail length, tail moment, and percent of DNA in the tails in cells of normal tissues such as blood leukocytes and bone marrow, and these parameters were not altered in cells of fibrosarcoma tumor. The results revealed that troxerutin could preferentially protect normal tissues against radiation-induced damages in tumor-bearing animals.

  19. Administration of polysaccharide from Panax notoginseng prolonged the survival of H22 tumor-bearing mice

    PubMed Central

    Li, Huaiyu; Gu, Longlong; Zhong, Yuanyuan; Chen, Yajuan; Zhang, Lei; Zhang, Annie R; Sobol, Robert W; Chen, Tong; Li, Jianfeng

    2016-01-01

    Background Polysaccharides from various sources are being considered potential sources for the treatment of liver cancer. The aim of this study was to investigate the impact of polysaccharide isolated from Panax notoginseng (PPN) on the proliferation of H22 liver cancer cells and the survival of the tumor-bearing mice transplanted with H22 cells. Materials and methods Polysaccharide from PPN was added to the culture medium of mouse hepatoma H22 cells at different doses. Cell proliferation was assayed with a standard MTT assay. Survival rates of tumor-bearing mice were recorded. Peripheral blood lymphocytes were assayed by flow cytometry. Serum interleukin-2 levels in peripheral blood were measured by enzyme-linked immunosorbent assay. Results Polysaccharide from PPN inhibited the growth of H22 cells and significantly prolonged the survival of tumor-bearing mice. The increase in activated CD4+ T-cells and the elevation of serum interleukin-2 may contribute to the antitumor activity of PPN. Conclusion PPN has potential antitumor activity for the treatment of liver cancer. PMID:27354815

  20. Liver membrane proteome glycosylation changes in mice bearing an extra-hepatic tumor.

    PubMed

    Lee, Albert; Chick, Joel M; Kolarich, Daniel; Haynes, Paul A; Robertson, Graham R; Tsoli, Maria; Jankova, Lucy; Clarke, Stephen J; Packer, Nicolle H; Baker, Mark S

    2011-09-01

    Cancer is well known to be associated with alterations in membrane protein glycosylation (Bird, N. C., Mangnall, D., and Majeed, A. W. (2006) Biology of colorectal liver metastases: A review. J. Surg. Oncol. 94, 68-80; Dimitroff, C. J., Pera, P., Dall'Olio, F., Matta, K. L., Chandrasekaran, E. V., Lau, J. T., and Bernacki, R. J. (1999) Cell surface n-acetylneuraminic acid alpha2,3-galactoside-dependent intercellular adhesion of human colon cancer cells. Biochem. Biophys. Res. Commun. 256, 631-636; and Arcinas, A., Yen, T. Y., Kebebew, E., and Macher, B. A. (2009) Cell surface and secreted protein profiles of human thyroid cancer cell lines reveal distinct glycoprotein patterns. J. Proteome Res. 8, 3958-3968). Equally, it has been well established that tumor-associated inflammation through the release of pro-inflammatory cytokines is a common cause of reduced hepatic drug metabolism and increased toxicity in advanced cancer patients being treated with cytotoxic chemotherapies. However, little is known about the impact of bearing a tumor (and downstream effects like inflammation) on liver membrane protein glycosylation. In this study, proteomic and glycomic analyses were used in combination to determine whether liver membrane protein glycosylation was affected in mice bearing the Engelbreth-Holm Swarm sarcoma. Peptide IPG-IEF and label-free quantitation determined that many enzymes involved in the protein glycosylation pathway specifically; mannosidases (Man1a-I, Man1b-I and Man2a-I), mannoside N-acetylglucosaminyltransferases (Mgat-I and Mgat-II), galactosyltransferases (B3GalT-VII, B4GalT-I, B4GalT-III, C1GalT-I, C1GalT-II, and GalNT-I), and sialyltransferases (ST3Gal-I, ST6Gal-I, and ST6GalNAc-VI) were up-regulated in all livers of tumor-bearing mice (n = 3) compared with nontumor bearing controls (n = 3). In addition, many cell surface lectins: Sialoadhesin-1 (Siglec-1), C-type lectin family 4f (Kupffer cell receptor), and Galactose-binding lectin 9 (Galectin-9

  1. [Competitive effect of PSK against the immunosuppressive effect induced in the sera of mice bearing syngeneic tumors].

    PubMed

    Matsunaga, K; Morita, I; Oguchi, Y; Fujii, T; Yoshikumi, C; Nomoto, K

    1986-12-01

    PSK is a protein-bound polysaccharide prepared from cultured mycelium of Coriolus versicolor. The appearance of an immunosuppressive effect in sera of tumor-bearing mice and its elimination by oral administration of PSK were investigated using an in vitro assay of blastoid transformation of normal spleen cells in response to PHA. (1) An inhibitory effect appeared in sera of X5563 plasmacytoma-bearing mice, while a facilitating effect was noted in sera of MH134 hepatoma- and MM 102 mammary tumor-bearing mice. (2) The presence of both an inhibitory and a facilitating factor was shown by Sephacryl gel fractionation. (3) Oral administration of PSK resulted in the elimination of the inhibitory effect from sera of X5563-bearing mice. The facilitating effect of sera from MH134-bearing mice was augmented by PSK administration, but that in sera from MM102-bearing mice was not influenced by such treatment. The summarized effects of these factors may be expressed as various types of effects in serum and PSK may be effective in the elimination of a suppressive factor from such sera.

  2. Toxicity Profiles In Vivo in Mice and Antitumour Activity in Tumour-Bearing Mice of Di- and Triorganotin Compounds

    PubMed Central

    Willem, R.; Dalil, H.; de Vos, D.; Kuiper, C. M.; Peters, G. J.

    1998-01-01

    The in vivo toxicity profiles in mice and the antitumour activity in tumour bearing mice were screened for four di-n-butyltin and five triorganotin carboxylates, di-n-butyltin diterebate (5), bis(phenylacetate) (6), bis(deoxycholate) (7), bis(lithocholate) (8), tri-n-butyltin terebate (9), cinnamate (10), and triphenyltin terebate (11). At their maximum tolerated dosis (MTD), no antitumour effect (T/C ~1) was observed for the compounds 5, 7, 9, 10 and 11. The compounds 6 (T/C = 0.51) and 8 (T/C = 0.42) showed clear antitumour activity after single dose administration and might therefore be of interest for further antitumour activity studies. PMID:18475827

  3. Modulation of primary antibody response by protein A in tumor bearing mice.

    PubMed

    Zaidi, S I; Singh, K P; Raisuddin, S; Jafri, A; Saxena, A K; Choudhary, S; Ray, P K

    1995-11-01

    Protein A (PA) is a cell wall glycoprotein of Staphylococcus aureus Cowan I, which possess a number of immunomodulatory and antitumor properties. We have previously shown that PA suppresses the anti-sheep erythrocyte primary antibody response in normal mice. The present investigation evaluates the effect of protein A on the anti-sheep erythrocyte primary antibody response in tumor-bearing mice. The primary antibody response in tumor-bearing mice immunized with sheep red blood cells (SRBC) was suppressed by the intraperitoneal administration of PA in a dose-dependent fashion. The plaque forming cell (PFC) assay was used to assess this response. Maximum suppression of the PFC response was observed at 12 micrograms PA/animal (p < 0.001) and could be observed at doses as low as 1 microgram PA/animal (p < 0.01). The amount of suppression was proportional to the number of PA doses administered. In addition this effect was critically dependent on the timing of PA administration. PA showed no significant effect on PFC when injected after immunization, but it produced pronounced suppression when injected prior to the immunization with SRBC. Maximum suppression of the PFC response was observed when PA was administered one day before the antigen challenge. PA also reduced splenic localization of 51Cr labeled SRBC to 42% (p < 0.01). The altered localization of antigen in spleen may be responsible for reduced PFC response in tumor-bearing mice. Depletion of B-lymphocyte is reported to exhibit tumor inhibition. Therefore, we propose that the suppression of the primary antibody response by PA helps in tumor regression by reducing the soluble immunosuppressive immune complexes. PMID:8537611

  4. Cancer-induced anorexia in tumor-bearing mice is dependent on cyclooxygenase-1.

    PubMed

    Ruud, Johan; Nilsson, Anna; Engström Ruud, Linda; Wang, Wenhua; Nilsberth, Camilla; Iresjö, Britt-Marie; Lundholm, Kent; Engblom, David; Blomqvist, Anders

    2013-03-01

    It is well-established that prostaglandins (PGs) affect tumorigenesis, and evidence indicates that PGs also are important for the reduced food intake and body weight loss, the anorexia-cachexia syndrome, in malignant cancer. However, the identity of the PGs and the PG producing cyclooxygenase (COX) species responsible for cancer anorexia-cachexia is unknown. Here, we addressed this issue by transplanting mice with a tumor that elicits anorexia. Meal pattern analysis revealed that the anorexia in the tumor-bearing mice was due to decreased meal frequency. Treatment with a non-selective COX inhibitor attenuated the anorexia, and also tumor growth. When given at manifest anorexia, non-selective COX-inhibitors restored appetite and prevented body weight loss without affecting tumor size. Despite COX-2 induction in the cerebral blood vessels of tumor-bearing mice, a selective COX-2 inhibitor had no effect on the anorexia, whereas selective COX-1 inhibition delayed its onset. Tumor growth was associated with robust increase of PGE(2) levels in plasma - a response blocked both by non-selective COX-inhibition and by selective COX-1 inhibition, but not by COX-2 inhibition. However, there was no increase in PGE(2)-levels in the cerebrospinal fluid. Neutralization of plasma PGE(2) with specific antibodies did not ameliorate the anorexia, and genetic deletion of microsomal PGE synthase-1 (mPGES-1) affected neither anorexia nor tumor growth. Furthermore, tumor-bearing mice lacking EP(4) receptors selectively in the nervous system developed anorexia. These observations suggest that COX-enzymes, most likely COX-1, are involved in cancer-elicited anorexia and weight loss, but that these phenomena occur independently of host mPGES-1, PGE(2) and neuronal EP(4) signaling.

  5. Insulin-tumour interrelationship in EL4 lymphoma or thymoma-bearing mice. I. Alloxan-diabetic or non-diabetic mice.

    PubMed Central

    Yam, D.; Zilberstein, A.; Fink, A.; Nir, I.

    1990-01-01

    A study has been carried out in which a comparison was made between EL4 lymphoma (assumed to be an insulin-producing secreting tumour) and thymoma (an insulin-dependent tumour). Tumour development and incidence, 3H-thymidine incorporation and insulin content in tumours, the host's food intake, blood insulin, glucose and cholesterol were determined in non-diabetic and alloxan-diabetic mice. Whereas no significant differences were observed between the diabetic and non-diabetic EL4 tumour-bearing mice, the diabetic, thymoma tumour-bearing mice showed reduced tumour growth and lower tumour incidence as compared with their non-diabetic counterparts. Insulin administration to diabetic tumour bearing mice, enhanced 3H-thymidine incorporation in the thymoma tumour cells only, and the insulin content of the EL4 tumours was found to be higher than that of the thymoma tumours. Rapid diabetes remission was observed in the diabetic, EL4 tumour-bearing mice as compared with the thymoma tumour-bearing mice. PMID:2186773

  6. Radioprotection by Macerated Extract of Nigella sativa in Normal Tissues of Fibrosarcoma Bearing Mice.

    PubMed

    Velho-Pereira, Reelma; Kumar, A; Pandey, B N; Mishra, K P; Jagtap, Aarti G

    2012-09-01

    The current study was undertaken to study the effect of a macerated extract of Nigella sativa seeds in normal as well as in tumour bearing mice against gamma radiation-induced cellular damage to normal tissues. This was done to mimic the clinical setting where in, normal tissues of cancer patients undergoing radiotherapy are exposed to the deleterious effects of radiation. The protection of cellular DNA was analysed in peripheral blood leucocytes of whole body irradiated mice following pretreatment with macerated extract of Nigella sativa seeds (100 mg/kg), using alkaline comet assay, and also estimating biochemical and blood parameters such as levels of antioxidant enzymes superoxide dismutase and catalase, thiobarbituric acid reactive substances and protein oxidation in organs such as spleen, liver, brain and intestine haemoglobin and total leucocyte count, respectively. The results showed that the macerated extract of Nigella sativa seeds protected the liver, spleen, brain and intestines both in normal as well as tumour bearing mice. This study concludes that macerated extract of Nigella sativa seeds has protective effects against radiation-induced damage and biochemical alterations which could be attributed to the ability to scavenge free radicals and its antioxidant properties. Hence macerated extract of Nigella sativa seeds, could be used in combination with radiation to protect against oxidative stress in normal tissues and improving the quality of life of cancer patients by mitigating unwanted side effects of radiation in normal tissues.

  7. UHPLC-MS-based metabolomics analysis on mice bearing neoplasm (H22) for hispidulin.

    PubMed

    Li, Fuqiang; Li, Xiang; Miao, Yunjie; Shan, Chenxiao; Yuan, Fei; Ma, Chengyao; Wang, Qiwen; Chen, Jianwei; Chen, Yong

    2016-06-01

    Although some physiological and pathological function parameters of hepatitis and liver cancer have been investigated in relation to hispidulin (5,7,4'-trihydroxy-6-methoxyflavone), the changes of small metabolites in biofluids have been reported rarely. Recent research has shown that metabolic profiling with ultra-high-performance liquid chromatography coupled to quadrupole time of flight mass spectrometry (UHPLC-QTOF/MS) coupled with multivariate statistical analysis provides a good understanding of hispidulin effects on mice vaccinated intraperitoneally with H22 tumor cells. Twenty-five potential biomarkers, up- or down-regulated (P<0.05 or 0.01), were identified, and 17 metabolic pathways were constructed. These potential biomarkers underpin the metabolic pathways, which are disturbed in the mice bearing neoplasm (H22). These pathways include pantothenate and CoA biosynthesis; glycine, serine and threonine metabolism; nicotinate and nicotinamide metabolism; steroid hormone biosynthesis; pyrimidine metabolism; and glyoxylate and dicarboxylate metabolism. Furthermore, 4-phosphopantothenoylcysteine, glycine, niacinamide, cortisol, uracil and 5-thymidylic acid are potential biomarkers that may explain the link between hispidulin and the metabolism of mice bearing neoplasm (H22). Most of the potential biomarkers related to the function of TCA (tricarboxylic acid cycle). The rise of potential biomarkers in the drug groups promoted the up-regulation of TCA cycle compared with the model group. PMID:27077962

  8. Radioprotection by Macerated Extract of Nigella sativa in Normal Tissues of Fibrosarcoma Bearing Mice

    PubMed Central

    Velho-Pereira, Reelma; Kumar, A.; Pandey, B. N.; Mishra, K. P.; Jagtap, Aarti G.

    2012-01-01

    The current study was undertaken to study the effect of a macerated extract of Nigella sativa seeds in normal as well as in tumour bearing mice against gamma radiation-induced cellular damage to normal tissues. This was done to mimic the clinical setting where in, normal tissues of cancer patients undergoing radiotherapy are exposed to the deleterious effects of radiation. The protection of cellular DNA was analysed in peripheral blood leucocytes of whole body irradiated mice following pretreatment with macerated extract of Nigella sativa seeds (100 mg/kg), using alkaline comet assay, and also estimating biochemical and blood parameters such as levels of antioxidant enzymes superoxide dismutase and catalase, thiobarbituric acid reactive substances and protein oxidation in organs such as spleen, liver, brain and intestine haemoglobin and total leucocyte count, respectively. The results showed that the macerated extract of Nigella sativa seeds protected the liver, spleen, brain and intestines both in normal as well as tumour bearing mice. This study concludes that macerated extract of Nigella sativa seeds has protective effects against radiation-induced damage and biochemical alterations which could be attributed to the ability to scavenge free radicals and its antioxidant properties. Hence macerated extract of Nigella sativa seeds, could be used in combination with radiation to protect against oxidative stress in normal tissues and improving the quality of life of cancer patients by mitigating unwanted side effects of radiation in normal tissues. PMID:23716868

  9. Enhanced thermal stability of lysosomal beta-D-galactosidase in parenchymal cells of tumour bearing mice.

    PubMed Central

    Lenti, L.; Lipari, M.; Lombardi, D.; Zicari, A.; Dotta, A.; Pontieri, G. M.

    1986-01-01

    The thermal stability of the enzyme beta-D-galactosidase varies among different organs in normal C57Bl/6 mice, and increases in the same organs in mice with Lewis Lung carcinoma. Thermal stability of this enzyme is also increased by treatment of the mice with cell-free extracts of tumour cells or with inflammatory compounds such as carrageenan or orosomucoid. After desialylation, orosomucoid more effectively increases the heat stability of the enzyme. By contrast talc, which has no galactosyl groups, is without effect on the stability of the enzyme in vivo. Macrophages of tumour bearing mice release into the culture medium a more heat resistant enzyme than macrophages from control mice. In both cases the heat resistance of the secreted enzyme is higher when fetal calf serum is present in the culture medium. Bovine serum does not modify the thermal stability of beta-D-galactosidase in this system. Incubation of lysosomal fractions of various organs with the synthetic beta-D-galactosidase substrate, p-nitrophenyl-galactopyranoside, also strongly increases the heat resistance of the enzyme. The results suggest that one factor influencing the heat resistance of this enzyme may be complex formation between the enzyme and its substrates, an example of substrate protection of the enzyme. This may not be the only factor involved in enzyme stabilization in vivo. PMID:3099822

  10. Isotype profiles of anti-influenza antibodies in mice bearing the xid defect

    SciTech Connect

    Reale, M.A.; Bona, C.A.; Schulman, J.L.

    1985-02-01

    The humoral response to influenza A/PR8 virus was examined in the CAB/N and C/sub 3/J.xid strains of mice, both of which bear an X-linked genetic defect (xid), and in strains lacking this defect. Hemagglutination-inhibiting antibody titers and measurement of virus-specific antibodies by solid-phase radioimmunoassay indicated that the xid defect does not impair the production of an adequate anti-influenza antibody response. However, investigation of the isotopes of PR8 virus-specific antibodies disclosed a relative decrease in the levels of IgG3 and IgG1 in the xid-bearing strains. This was observed after both intraperitoneal immunization and aerosol infection. The isotope differences were not reflected in the susceptibility of these strains to influenza virus infection.

  11. Lowering photosensitizer doses and increasing fluences induce apoptosis in tumor bearing mice.

    PubMed

    Haedicke, Katja; Graefe, Susanna; Teichgraeber, Ulf; Hilger, Ingrid

    2016-07-01

    The objective of this study was to determine an optimal dose of photodynamic therapy (PDT) for inducing apoptotic tumor cells in vivo. In this context, mice bearing human tongue-squamous epithelium carcinomas were treated with various photosensitizer concentrations and fluences. Tumor apoptosis was imaged after 2 days via a self-designed DY-734-annexin V probe using near-infrared fluorescence (NIRF) optical imaging. Apoptosis was verified ex vivo via TUNEL staining. Apoptotic tumor cells were detected in vivo at a dose of 40 µg photosensitizer and a fluency of 100 J/cm(2). This is the lowest photosensitizer dose reported so far. PMID:27446695

  12. I-fibrinogen as an oncophilic radiodiagnostic agent: distribution kinetics in tumour-bearing mice.

    PubMed Central

    Krohn, K. A.; DeNardo, S. J.; Wheeler, D. W.; DeNardo, G. L.

    1977-01-01

    Fibrinogen radioiodinated by the iodine monochloride method was tested as a tumour radiodiagnostic agent in mice. The I-fibrinogen cleared from the blood of tumour-bearing mice more rapidly than from that of normal mice, but it cleared from the whole body more slowly, suggesting it accumulated in a substantial tumour-related compartment in the abnormal mice. The tumour concentration steadily increased for 4 h after injection, at which time it reached a peak concentration of 11-4% of the injected dose/g. This concentration was higher than the peak concentration for Ga-citrate (not reached until 24 h) or any other oncophilic radiopharmaceutical tested in this tumour model. The early accumulation is consistent with the use of 123I as a tracer label for fibrinogen. A combination of the large tumour concentration of I-fibrinogen, an increased catabolic rate induced by chemical modification, and the exceptional nuclear properties of 123I for scintigraphic imaging, could lead to a very useful radiodiagnostic procedure for cancer. Images Fig. 2 PMID:911661

  13. Tetrandrine Suppresses Cancer Angiogenesis and Metastasis in 4T1 Tumor Bearing Mice

    PubMed Central

    Gao, Jian-Li; He, Tong-Chuan; He, Kai; Chen, Su-Hong; Lv, Gui-Yuan

    2013-01-01

    Metastasis remains the most deadly aspect of cancer and still evades direct treatment. Thus, there is a great need to develop new treatment regimens to suppress tumor cells that have escaped surgical removal or that may have already disseminated. We have found that tetrandrine (TET) exhibits anticolon cancer activity. Here, we investigate the inhibition effect of TET to breast cancer metastasis, angiogenesis and its molecular basis underlying TET's anticancer activity. We compare TET with chemotherapy drug doxorubicin in 4T1 tumor bearing BALB/c mice model and find that TET exhibits an anticancer metastatic and antiangiogenic activities better than those of doxorubicin. The lung metastatic sites were decreased by TET, which is confirmed by bioluminescence imaging in vivo. On the other hand, laser doppler perfusion imaging (LDI) was used for measuring the blood flow of tumor in 4T1-tumor bearing mice. As a result, the local blood perfusion of tumor was markedly decreased by TET after 3 weeks. Mechanistically, TET treatment leads to a decrease in p-ERK level and an increase in NF-κB levels in HUVECs. TET also regulated metastatic and angiogenic related proteins, including vascular endothelial growth factor, hypoxia-inducible factor-1α, integrin β5, endothelial cell specific molecule-1, and intercellular adhesion molecule-1 in vivo. PMID:23762115

  14. 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

  15. 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

  16. DNA synthesis in tongue keratinocytes of hepatectomized and tumor-bearing mice.

    PubMed

    García, M N; Andrini, L B; Errecalde, A L; Barbeito, C G

    2006-11-01

    Tongue keratinocytes have high S-phase and mitotic indices with evident circadian variation. Transplanted tumors modify the intensity and temporal structure of the S-phase index in cell populations in tumor-bearing animals; also, partial hepatectomy changes the concentrations of substances involved in cellular proliferation, leading to compensatory liver hyperplasia. The aim of our study was to analyze the interaction between tumor growth and the liver regeneration that follows partial hepatectomy, and the effects of both these processes on lingual keratinocytes. We used 380 adult male mice divided into six groups: tumor-free and tumor-bearing mice without surgery, with sham hepatectomy, and with partial hepatectomy. Each group was divided into six subgroups, which were killed at 4-h intervals until a circadian cycle was completed (from 26 until 50h post-surgery in the operated animals). Each animal was injected with 5-bromodeoxyuridine (50mg/kg) 1h before it was killed, and tongue samples were obtained and processed for histology. The sections were placed on silanized slides and incubated with the primary antibody Bu 20a (1/100 dilution). The reaction was developed using diaminobenzidine and staining was detected visually. SIs were measured as the number of labeled nuclei per thousand cells. The mean+/-S.E. of each group was calculated. Differences among experimental groups were analyzed by ANOVA and the Student-Newman-Keuls Multiple Comparisons Test. The results show that the presence of a tumor alters the normal circadian curve of SI in lingual keratinocytes, irrespective of whether the mice underwent surgery. This finding has to be considered in drug treatments for neoplasms and in experiments related to growth.

  17. Protective effect of genistein on radiation-induced intestinal injury in tumor bearing mice

    PubMed Central

    2013-01-01

    Background Radiation therapy is the most widely used treatment for cancer, but it causes the side effect of mucositis due to intestinal damage. We examined the protective effect of genistein in tumor-bearing mice after abdominal irradiation by evaluation of apoptosis and intestinal morphological changes. Methods Mouse colon cancer CT26 cells were subcutaneously injected at the flank of BALB/c mice to generate tumors. The tumor-bearing mice were treated with abdominal radiation at 5 and 10 Gy, and with genistein at 200 mg/kg body weight per day for 1 d before radiation. The changes in intestinal histology were evaluated 12 h and 3.5 d after irradiation. To assess the effect of the combination treatment on the cancer growth, the tumor volume was determined at sacrifice before tumor overgrowth occurred. Results Genistein significantly decreased the number of apoptotic nuclei compared with that in the irradiation group 12 h after 5 Gy irradiation. Evaluation of histological changes showed that genistein ameliorated intestinal morphological changes such as decreased crypt survival, villus shortening, and increased length of the basal lamina 3.5 d after 10 Gy irradiation. Moreover, the genistein-treated group exhibited more Ki-67-positive proliferating cells in the jejunum than the irradiated control group, and crypt depths were greater in the genistein-treated group than in the irradiated control group. The mean weight of the CT26 tumors was reduced in the group treated with genistein and radiation compared with the control group. Conclusion Genistein had a protective effect on intestinal damage induced by irradiation and delayed tumor growth. These results suggest that genistein is a useful candidate for preventing radiotherapy-induced intestinal damage in cancer patients. PMID:23672582

  18. Identification of tissue sites for increased albumin degradation in sarcoma-bearing mice

    SciTech Connect

    Andersson, C.; Iresjoe, B.M.L.; Lundholm, K. )

    1991-02-01

    Plasma albumin concentration declines in both experimental and clinical cancer. Previous investigations have demonstrated that this is partly explained by increased breakdown of albumin. The present study has identified the tissue sites for increased albumin degradation in a nonmetastasizing sarcoma mouse (C57/BL6J) model. Results have been compared to nontumor-bearing animals either freely fed or food restricted (pair-weighed) so that their body composition was similar to tumor-bearing animals. Tumor-bearing mice had increased albumin degradation (0.13 +/- 0.02 mg/hr/g bw) compared to both freely fed (0.09 +/- 0.007) and pair-weighed control animals (0.05 +/- 0.008). Radioactivity from circulating (3H)raffine aldehyde labeled albumin appeared with maximum peak values in lysosomes isolated from both tumor and nontumor tissues at 48 hr following iv injection. The intralysosomal accumulation of radioactivity was two- to threefold higher in tumor tissue compared to liver tissue, although the specific activity of protease(s) for albumin degradation measured in vitro was not higher in tumor tissue (30.4 +/- 3.6 mg/hr/g tissue) compared to normal liver tissue (36.9 +/- 1.7). Accounting for the entire tumor the proteolytic capacity for albumin breakdown was however much larger in the tumor (161.6 +/- 32.6 mg/organ) compared to both normal liver (37.5 +/- 2.3) and tumor-host liver (56.4 +/- 2.8). Pepstatin inhibited 78 +/- 6% of the proteolytic activity in the tumor measured by 125I-labeled undenatured mouse albumin as the substrate. Leupeptin inhibited 49 +/- 6%. There was a significantly decreased breakdown of albumin in both skeletal muscles and the gastrointestinal tract from tumor-bearing animals.

  19. Antioxidative function and biodistribution of [Gd@C82(OH)22]n nanoparticles in tumor-bearing mice.

    PubMed

    Wang, Jiangxue; Chen, Chunying; Li, Bai; Yu, Hongwei; Zhao, Yuliang; Sun, Jin; Li, Yufeng; Xing, Gengmei; Yuan, Hui; Tang, Jun; Chen, Zhen; Meng, Huan; Gao, Yuxi; Ye, Chang; Chai, Zhifang; Zhu, Chuanfeng; Ma, Baocheng; Fang, Xiaohong; Wan, Lijun

    2006-03-14

    Oxidative stress is considered to be one of the important mechanisms involved in carcinogenesis. In our previous study, gadolinium endohedral metallofullerenol ([Gd@C82(OH)22]n nanoparticles) have shown high inhibitory activity on hepatoma cell (H22) growth in mice. To explore the antioxidative functions of nanoparticles, we investigated the biodistribution of [Gd@C82(OH)22]n nanoparticles, the changes of blood coagulation profiles, the metabolism of reactive oxygen species (ROS) in the tumor-bearing mice as well as the possible relationships between nanoparticles treatment and ROS production in this paper. The activities of hepatic superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione S-transferase (GST) and catalase (CAT) as well as the levels of reduced glutathione (GSH), protein-bound thiols and malondialdehyde (MDA) were compared between the tumor-bearing mice and normal mice. Transplanted tumors were grown in mice by subcutaneous injection of murine hepatoma cells in the mice. The comparison of the above parameters between nanoparticles and cyclophosphamide (CTX) therapy were also investigated. [Gd@C82(OH)22]n administration can efficiently restore the damaged liver and kidney of the tumor-bearing mice. All the activities of enzymes and other parameters related to oxidative stress were reduced after [Gd@C82(OH)22]n treatment and tended closely to the normal levels. The results suggest that [Gd@C82(OH)22]n nanoparticle treatment could regulate ROS production in vivo.

  20. Metabolic shifts induced by human H460 cells in tumor-bearing mice.

    PubMed

    Liu, Linsheng; Wang, Yaqiong; Zheng, Tian; Cao, Bei; Li, Mengjie; Shi, Jian; Aa, Nan; Wang, Xinwen; Zhao, Chunyan; Aa, Jiye; Wang, Guangji

    2016-03-01

    Tumor markers are most popularly used in diagnosis of various cancers clinically. However, the confounding factors of individual background diversities, such as genetics, food preferences, living styles, physical exercises, etc., greatly challenge the identification of tumor markers. Study of the metabolic impact of inoculated tumors on model animals can facilitate the identification of metabolomic markers relevant to tumor insult. In this study, serum metabolites from nude mice (n = 14) inoculated with human H460 cells (human nonsmall cell lung carcinoma) were profiled using gas chromatography time-of-flight mass spectrometry. The mice with inoculated tumors showed an obviously different metabolic pattern from the control; identification of the discriminatory metabolites suggested the metabolic perturbation of free fatty acids, amino acids, glycolysis and tricarboxylic acid (TCA) cycle turnover. The significantly decreased TCA intermediates, free fatty acids, 3-hydroxybutyric acid and fluctuating amino acids (t-test, p < 0.05) in serum of tumor-bearing mice characterized the metabolic impact of local inoculated H460 tumor cells on the whole system. This indicates that they are candidate metabolomic markers for translational study of lung cancer, clinically. PMID:26147780

  1. Antitumor effect of vitamin D-binding protein-derived macrophage activating factor on Ehrlich ascites tumor-bearing mice.

    PubMed

    Koga, Y; Naraparaju, V R; Yamamoto, N

    1999-01-01

    Cancerous cells secrete alpha-N-acetylgalactosaminidase (NaGalase) into the blood stream, resulting in deglycosylation of serum vitamin D3-binding protein (known as Gc protein), which is a precursor for macrophage activating factor (MAF). Incubation of Gc protein with immobilized beta-galactosidase and sialidase generates the most potent macrophage activating factor (designated GcMAF). Administration of GcMAF to cancer-bearing hosts can bypass the inactivated MAF precursor and act directly on macrophages for efficient activation. Therapeutic effects of GcMAF on Ehrlich ascites tumor-bearing mice were assessed by survival time and serum NaGalase activity, because serum NaGalase activity was proportional to tumor burden. A single administration of GcMAF (100 pg/mouse) to eight mice on the same day after transplantation of the tumor (5 x 10(5) cells) showed a mean survival time of 21 +/- 3 days for seven mice, with one mouse surviving more than 60 days, whereas tumor-bearing controls had a mean survival time of 13 +/- 2 days. Six of the eight mice that received two GcMAF administrations, at Day 0 and Day 4 after transplantation, survived up to 31 +/- 4 days whereas, the remaining two mice survived for more than 60 days. Further, six of the eight mice that received three GcMAF administrations with 4-day intervals showed an extended survival of at least 60 days, and serum NaGalase levels were as low as those of control mice throughout the survival period. The cure with subthreshold GcMAF-treatments (administered once or twice) of tumor-bearing mice appeared to be a consequence of sustained macrophage activation by inflammation resulting from the macrophage-mediated tumoricidal process. Therefore, a protracted macrophage activation induced by a few administrations of minute amounts of GcMAF eradicated the murine ascites tumor. PMID:9893164

  2. Preliminary pharmacokinetics of PEGylated oxaliplatin polylactic acid nanoparticles in rabbits and tumor-bearing mice.

    PubMed

    Wei, Haitian; Xu, Lisa; Sun, Yong; Li, Gaohong; Cui, Zhaoyuan; Yan, Guowen; Chen, Qian; Yin, Hongli; Ma, Chao

    2015-01-01

    To testify the targeting effect of PEGylated Oxaliplatin polylactic acid (OP-PEG-PLA) nanoparticles (NPs), we studied drug concentration in rabbit plasma and tissue distribution in tumor-bearing mice. Concentration of nanoparticle colloidal solution was performed with dialysis. Qualities of enriched NPs were characterized by particle size and drug content. OP concentration in samples was detected using ICP-MS. Compared to OP solution groups, OP concentration of NPs groups increased in the tumor (p < 0.05) and decreased in the kidney and heart (p < 0.05). Compared to OP-PLA NPs groups, OP concentration of OP-PEG-PLA NPs groups increased in the tumor and decreased in the liver and lung (p < 0.05). The concentrated OP-PEG-PLA NPs are good in clinical application and tumor delivery.

  3. 1H-NMR METABONOMICS ANALYSIS OF SERA DIFFERENTIATES BETWEEN MAMMARY TUMOR-BEARING MICE AND HEALTHY CONTROLS

    EPA Science Inventory

    Global analysis of 1H-NMR spectra of serum is an appealing approach for the rapid detection of cancer. To evaluate the usefulness of this method in distinguishing between mammary tumor-bearing mice and healthy controls, we conducted 1H-NMR metabonomic analyses on serum samples ob...

  4. Study on the effect of polysaccharides from Solanum nigrum Linne on cellular immune function in tumour-bearing mice.

    PubMed

    Chen, Hai; Qi, Xiaodong

    2013-01-01

    We investigated the anti-tumour effect of polysaccharides from Solanum nigrum Linne, and its relationship with the immune function of tumour-bearing organisms. MTT assay was used to observe the effect of different doses of polysaccharides from Solanum nigrum Linne on proliferation of lymphocytes in tumour-bearing mice. ELISA assay was also used to detect the levels of IL-2 in mice, and a laser scanning confocal microscope was used to detect the effect of polysaccharides from Solanum nigrum Linne on intralymphocytic free calcium ion concentration in tumour-bearing mice. Different doses of polysaccharides from Solanum nigrum Linne significantly inhibited the growth of mouse H22 solid tumours, improved the survival time of tumour-bearing mice, increased the proliferation of lymphocytes, elevated the levels of IL-2, and increased the concentration of calcium ions in the lymphocytes. Polysaccharides from Solanum nigrum Linne have certain anti-tumour effect, which is related with the cellular immune function that regulates the body. PMID:24146499

  5. Anticancer activity of cationic porphyrins in melanoma tumour-bearing mice and mechanistic in vitro studies

    PubMed Central

    2014-01-01

    Background Porphyrin TMPyP4 (P4) and its C14H28-alkyl derivative (C14) are G-quadruplex binders and singlet oxygen (1O2) generators. In contrast, TMPyP2 (P2) produces 1O2 but it is not a G-quadruplex binder. As their photosensitizing activity is currently undefined, we report in this study their efficacy against a melanoma skin tumour and describe an in vitro mechanistic study which gives insights into their anticancer activity. Methods Uptake and antiproliferative activity of photoactivated P2, P4 and C14 have been investigated in murine melanoma B78-H1 cells by FACS, clonogenic and migration assays. Apoptosis was investigated by PARP-1 cleavage and annexin-propidium iodide assays. Biodistribution and in vivo anticancer activity were tested in melanoma tumour-bearing mice. Porphyrin binding and photocleavage of G-rich mRNA regions were investigated by electrophoresis and RT-PCR. Porphyrin effect on ERK pathway was explored by Western blots. Results Thanks to its higher lipophylicity C14 was taken up by murine melanoma B78-H1 cells up to 30-fold more efficiently than P4. When photoactivated (7.2 J/cm2) in B78-H1 melanoma cells, P4 and C14, but not control P2, caused a strong inhibition of metabolic activity, clonogenic growth and cell migration. Biodistribution studies on melanoma tumour-bearing mice showed that P4 and C14 localize in the tumour. Upon irradiation (660 nm, 193 J/cm2), P4 and C14 retarded tumour growth and increased the median survival time of the treated mice by ~50% (P <0.01 by ANOVA), whereas porphyrin P2 did not. The light-dependent mechanism mediated by P4 and C14 is likely due to the binding to and photocleavage of G-rich quadruplex-forming sequences within the 5′-untranslated regions of the mitogenic ras genes. This causes a decrease of RAS protein and inhibition of downstream ERK pathway, which stimulates proliferation. Annexin V/propidium iodide and PARP-1 cleavage assays showed that the porphyrins arrested tumour growth by apoptosis

  6. Growth hormone releasing peptide 2 reverses anorexia associated with chemotherapy with 5-fluoruracil in colon cancer cell-bearing mice.

    PubMed

    Perboni, Simona; Bowers, Cyril; Kojima, Shinya; Asakawa, Akihiro; Inui, Akio

    2008-11-01

    The cancer-associated anorexia-cachexia syndrome is observed in 80% of patients with advanced-stage cancer, and is one of the major obstacles in chemotherapy. Ghrelin is a orexigenic hormone that has been proposed to prevent anorexia. Aim of the study was to determine whether the addition of the ghrelin agonist growth hormone releasing peptide 2 (GHRP-2) to cytotoxic therapy with 5-fluoruracil (5-FU) prevents the anorexia associated with chemotherapy in cancer cachectic mice. Thirty-three BALB/c female tumour-bearing mice were randomized to receive a solution containing: (a) placebo; (b) GHRP-2; (c) 5-FU; or (d) 5-FU+GHRP-2. Ten BALB/c no tumour-bearing mice received placebo solution. Food intake and survival were checked. Six hours after the drug injection the cumulative food intake was significantly increased in mice treated with the combination of 5-FU+GHRP-2 versus the 5-FU alone (P=0.0096). On day 3, the cumulative food intake of mice treated with GHRP-2, 5-FU and 5-FU+GHRP-2 significantly increased compared with naive and vehicle groups (P=0.0007, P=0.0038 and P=0.0166, respectively). The median survival time was longer in 5-FU+GHRP-2 treated mice than in those with 5-FU, although it was not significant (18 d versus 15.5 d, P=0.7). For the first time, we demonstrated that the addition of GHRP-2 to cytotoxic therapy with 5-FU improved appetite in tumour-bearing mice with anorexia/cachexia syndrome in early stage. These data suggest that GHRP-2 may improve the efficacy of therapy and the quality of life of cancer patients thank to the amelioration of their nutritional state.

  7. Discoidal Porous Silicon Particles: Fabrication and Biodistribution in Breast Cancer Bearing Mice

    PubMed Central

    Chiappini, Ciro; Srinivasan, Srimeenakshi; Alexander, Jenolyn F.; Yokoi, Kenji; Ferrari, Mauro; Decuzzi, Paolo

    2012-01-01

    Porous silicon (pSi) is emerging as a promising material in the development of nanovectors for the systemic delivery of therapeutic and imaging agents. The integration of photolithographic patterning, typical of the semiconductor industry, with electrochemical silicon etching provides a highly flexible strategy to fabricate monodisperse and precisely tailored nanovectors. Here, a microfabrication strategy for direct lithographic patterning of discoidal pSi particles is presented that enables precise and independent control over particle size, shape, and porous structure. Discoidal pSi nanovectors with diameters ranging from 500 to 2600 nm, heights from 200 to 700 nm, pore sizes from 5 to 150 nm, and porosities from 40 to 90% are demonstrated. The degradation in serum, interaction with immune and endothelial cells in vitro, and biodistribution in mice bearing breast tumors are assessed for two discoidal nanovectors with sizes of 600 nm × 400 nm and 1000 nm × 400 nm. It is shown that both particle types are degraded after 24 h of continuous gentle agitation in serum, do not stimulate cytokine release from macrophages or affect endothelial cell viability, and accumulate up to about 10% of the injected dose per gram tissue in orthotopic murine models of breast cancer. The accumulation of the discoidal pSi nanovectors into the breast tumor mass is found to be up to five times higher than for spherical silica beads with similar diameters. PMID:23227000

  8. Comparative activation states of tumor-associated and peritoneal macrophages from mice bearing an induced fibrosarcoma.

    PubMed

    Valdez, J C; de Alderete, N; Meson, O E; Sirena, A; Perdigon, G

    1990-11-01

    Balb/c mice bearing a methylcholanthrene-induced fibrosarcoma were used to compare the activation levels of tumor-associated and peritoneal macrophages. Two stages of tumor growth were examined, namely "small" and "large" tumors, with average diameters of 10 and 30 mm, respectively. The activation state, determined by measurement of both phagocytic index and beta-glucuronidase content, was found to be markedly higher in tumor-associated macrophages than in their peritoneal counterparts and it was, in addition, independent of tumor progression. The percentage of tumor-associated macrophages, which were detected on the basis of Fc receptor expression, remained constant in the growing neoplasm, at approximately 23% of total cell population. None of these parameters were affected by inoculation with an immunopotentiating dose of heat-killed Candida albicans which, on the other hand, seemed not to alter the course of the tumor. These data suggest that within the tumor microenvironment macrophages would somehow be maintained at a constant proportion and at a highly activated state, while outside the tumor they would be at a lower activation level. Our results also suggest that TAM would not possess antitumor activity in vivo, although we have found this activity in vitro.

  9. Citrus unshiu peel extract alleviates cancer-induced weight loss in mice bearing CT-26 adenocarcinoma

    PubMed Central

    Kim, Aeyung; Im, Minju; Gu, Min Jung; Ma, Jin Yeul

    2016-01-01

    Skeletal muscle atrophy is a critical feature of cancer-induced cachexia, caused by pro-cachectic factors secreted by host cells and tumor cells. Therefore, blockade of these factors has considered a reasonable target for pharmacological and nutritional interventions to prevent skeletal muscle loss under cancer-induced cachexia. Citrus unshiu peel (CUP) has been used for treating the common cold, dyspepsia, and bronchial discomfort and reported to have pharmacological activities against inflammation, allergy, diabetes, and viral infection. In the present study, we observed that daily oral administration of water extract of CUP (WCUP) to male BALB/c mice bearing CT-26 adenocarcinoma remarkably reduced the losses in final body weight, carcass weight, gastrocnemius muscle, epididymal adipose tissue, and hemoglobin (Hb), compared with saline treatment. The levels of serum IL-6 and muscle-specific E3 ligases elevated by tumor burden were also considerably reduced by WCUP administration. In an in vitro experiment, WCUP efficiently suppressed the production of pro-cachectic cytokines in immune cells as well as cancer cells. In addition, WCUP treatment attenuated C2C12 skeletal muscle cell atrophy caused by cancer cells. These findings collectively suggest that WCUP is beneficial as a nutritional supplement for the management of cancer patients with severe weight loss. PMID:27064118

  10. Delivery of methoxymorpholinyl doxorubicin by interleukin 2-activated NK cells: effect in mice bearing hepatic metastases

    PubMed Central

    Quintieri, L; Rosato, A; Amboldi, N; Vizler, C; Ballinari, D; Zanovello, P; Collavo, D

    1999-01-01

    The possibility of using interleukin 2 (IL-2)-activated natural killer cells (A-NK) to carry methoxymorpholinyl doxorubicin (MMDX; PNU 152243) to liver-infiltrating tumours was explored in mice bearing 2-day established M5076 reticulum cell sarcoma hepatic metastases. In vitro, MMDX was 5.5-fold more potent than doxorubicin against M5076 tumour cells. MMDX uptake by A-NK cells correlated linearly with drug concentration in the incubation medium [correlation coefficient (r) = 0.999]; furthermore, as MMDX incorporation was readily reproducible in different experiments, the amount of drug delivered by A-NK cells could be modulated. In vivo experiments showed that intravenous (i.v.) injection of MMDX-loaded A-NK cells exerted a greater therapeutic effect than equivalent or even higher doses of free drug. The increase in lifespan (ILS) following A-NK cell delivery of 53 μg kg−1 MMDX, a dosage that is ineffective when administered in free form, was similar to that observed in response to 92 μg kg−1 free drug, a dosage close to the 10% lethal dose (ILS 42% vs. 38% respectively). These results correlated with pharmacokinetic studies showing that MMDX encapsulation in A-NK cells strongly modifies its organ distribution and targets it to tissues in which IL-2 activated lymphocytes are preferentially entrapped after i.v. injection. © 1999 Cancer Research Campaign PMID:10098738

  11. Comparative activation states of tumor-associated and peritoneal macrophages from mice bearing an induced fibrosarcoma.

    PubMed

    Valdez, J C; de Alderete, N; Meson, O E; Sirena, A; Perdigon, G

    1990-11-01

    Balb/c mice bearing a methylcholanthrene-induced fibrosarcoma were used to compare the activation levels of tumor-associated and peritoneal macrophages. Two stages of tumor growth were examined, namely "small" and "large" tumors, with average diameters of 10 and 30 mm, respectively. The activation state, determined by measurement of both phagocytic index and beta-glucuronidase content, was found to be markedly higher in tumor-associated macrophages than in their peritoneal counterparts and it was, in addition, independent of tumor progression. The percentage of tumor-associated macrophages, which were detected on the basis of Fc receptor expression, remained constant in the growing neoplasm, at approximately 23% of total cell population. None of these parameters were affected by inoculation with an immunopotentiating dose of heat-killed Candida albicans which, on the other hand, seemed not to alter the course of the tumor. These data suggest that within the tumor microenvironment macrophages would somehow be maintained at a constant proportion and at a highly activated state, while outside the tumor they would be at a lower activation level. Our results also suggest that TAM would not possess antitumor activity in vivo, although we have found this activity in vitro. PMID:2099903

  12. Increased survival of tumor-bearing mice by the delta opioid SNC 80.

    PubMed

    Gomez-Flores, Ricardo; Caballero-Hernández, Diana; Tamez-Guerra, Reyes; Rodríguez-Padilla, Cristina; Tamez-Guerra, Patricia; Rice, Kenner C; Hicks, Mary E; Weber, Richard J

    2005-01-01

    Opioids represent a major source of relief from pain. However, opioid abuse may cause immunosuppression and cancer. We have recently reported results on novel non-peptidic delta- and mu-selective opioids that induced immunopotentiation of T cell and macrophage functions in vitro and ex vivo. In the present study, the effects of the delta-opioid receptor agonist and potent analgesic (+)-4-((alpha R)-alpha-((2S, 5R)-4-allyl-2, 5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N, N-diethyl-benzamide (SNC80) on in vitro and in vivo tumor cell growth were investigated using the L5178Y-R murine model. SNC80 marginally, but significantly (p < 0.05), inhibited (up to 14%) the in vitro growth of L5178Y-R tumor cells. However, in vivo intratumor administration of SNC80 (2 and 4 mg/kg) reduced up to 60% L5178Y-R tumor-bearing Balb/c mice death, and significantly (p < 0.05) reduced tumor weights (up to 73% reduction) in these animals. This study may support the evaluation of SNC80 in preclinical and clinical studies.

  13. Perinatal lethal osteogenesis imperfecta in transgenic mice bearing an engineered mutant pro-alpha 1(I) collagen gene.

    PubMed

    Stacey, A; Bateman, J; Choi, T; Mascara, T; Cole, W; Jaenisch, R

    1988-03-10

    Substitutions of single glycine residues of alpha 1(I) collagen have previously been associated with the inherited disease osteogenesis imperfecta type II. Transgenic mice bearing a mutant alpha 1(I) collagen gene into which specific glycine substitutions have been engineered show a dominant lethal phenotype characteristic of the human disease, and demonstrate that as little as 10% mutant gene expression can disrupt normal collagen function.

  14. Cyclophosphamide-induced appearance of immunopotentiating T-cells in the spleens of mice bearing a large MOPC-315 tumor.

    PubMed

    Ye, Q W; Mokyr, M B

    1984-09-01

    Following low-dose cyclophosphamide (CY) therapy (15 mg/kg) of mice bearing a large MOPC-315 tumor, the suppressive activity of their Sephadex G-10-adherent spleen cells (primarily macrophages) is overcome. Accordingly, when Sephadex G-10-adherent spleen cells from CY-treated tumor-bearing mice are added to the in vitro immunization culture of normal spleen cells, they do not suppress but actually bring about the generation of an augmented level of antitumor cytotoxicity. The ability to enhance the generation of antitumor cytotoxicity appears in the Sephadex G-10-adherent spleen cell population by Day 5 post-CY therapy of tumor-bearing mice and persists for at least 55 days; no such immunopotentiation is observed following administration of a low dose of CY to normal mice. In order for the immunopotentiating cells from CY-treated tumor-bearing mice to be effective in enhancing the generation of antitumor cytotoxicity, they must be added to the immunization culture of normal spleen cells no later than Day 3 (out of the 5 days) post-culture initiation. The CY-induced immunopotentiating activity resides in the T-cells, as is evident from the following observations. The immunopotentiating activity was abolished when the Sephadex G-10-adherent spleen cell population from CY-treated tumor-bearing mice was depleted of T-cells by anti-Thy 1.2 plus complement but not when this adherent spleen cell population was depleted of macrophages by carbonyl iron and magnet. Moreover, the immunopotentiating activity was also present in a population of CY-treated tumor-bearer spleen cells highly enriched for T-cells by passage through nylon wool columns. Thus, low-dose CY therapy overcomes the immunosuppressive activity of macrophages and induces the appearance of T-cell-mediated immunopotentiating activity, thereby leading to the development of an augmented level of antitumor cytotoxicity that can cooperate effectively with the tumoricidal activity of CY in the eradication of a late

  15. Appearance of hybridoma growth factor/interleukin-6 in the serum of mice bearing a methylcholanthrene-induced sarcoma.

    PubMed

    Gelin, J; Moldawer, L L; Lonnroth, C; deMan, P; Svanborg-Eden, C; Lowry, S F; Lundholm, K G

    1988-12-15

    Serum concentrations of hybridoma growth factor/interleukin-6 progressively increased in mice bearing a transplantable methylcholanthrene-induced sarcoma with tumor growth. Elevated HGF/interleukin-6 concentrations were also positively correlated with increased serum concentrations of the hepatic acute phase reactant protein, amyloid P. Daily Indomethacin treatment of sarcoma-bearing mice prolonged survival and reduced the magnitude of the serum amyloid P response, but failed to attenuate either tumor growth or serum HGF/interleukin-6 responses. Since previous studies have demonstrated that neither interleukin-1 nor tumor necrosis factor-alpha can be detected in the serum of these sarcoma-bearing mice, and that HGF/interleukin-6 is a principal mediator of the hepatic acute phase response, we conclude that circulating HGF/interleukin-6 may contribute significantly to the host responses which accompany experimentally-introduced cancer. Furthermore, prostanoid inhibition does not appear to regulate the synthesis and release of HGF/interleukin-6 during tumor growth.

  16. Pathogenic significance of serum components in the development of autoimmune polyarthritis in MRL/Mp mice bearing the lymphoproliferation gene.

    PubMed Central

    Itoh, J.; Nose, M.; Kyogoku, M.

    1991-01-01

    MRL/Mp mice bearing the lymphoproliferation gene (lpr) (MRL/Mp-lpr/lpr) spontaneously develop polyarthritis, associated with autoimmune traits, including rheumatoid factor production, which resembles rheumatoid arthritis. To investigate possible arthritogenic activity of serum of these mice, intraarticular injections of the serum components to knee joints of nonarthritic MRL/Mp mice not bearing the lpr gene (MRL/Mp(-)+/+) were performed. Two fractions from the serum were obtained by a gel chromatography. The void fraction (VF), but not the nonvoid fraction (NVF), induced acute inflammatory lesions in the joints by single injection, and destructive arthritis by repeated injections. VF had immune complex activity, and contained a large amount of cryoglobulin, which in itself was found arthritogenic. These findings indicate that the serum components of MRL/Mp-lpr/lpr mice have a potency to cause destructive arthritis. These results are direct evidence in a syngeneic animal model system, which suggests the pathogenic significance of serum components in rheumatoid arthritis. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:1887861

  17. Effect of interleukin-2 treatment combined with magnetic fluid hyperthermia on Lewis lung cancer-bearing mice

    PubMed Central

    HU, RUNLEI; MA, SHENGLIN; KE, XIANFU; JIANG, HONG; WEI, DONGSHAN; WANG, WEI

    2016-01-01

    The present study aimed to investigate the therapeutic effect of interleukin-2 (IL-2) treatment combined with magnetic fluid hyperthermia (MFH) on Lewis lung cancer-bearing mice. Magnetic fluids were prepared in vitro and directly injected into the tumors in the mice, which were subjected to an alternating magnetic field. The temperature in the tumor reached 43°C and was maintained by controlling the strength of magnetic field for 30 min. Twenty-four hours later, IL-2 was injected directly into the tumors. Mice were divided into four groups: Group I (control), II (MFH), III (IL-2) and IV (IL-2+MFH). The tumor grew gradually in groups II and IV (both P<0.05) compared to the control group. Histological analysis showed that the tumor cells underwent apoptosis and necrosis. Immunohistochemistry results demonstrated that heat-shock protein 70 and cluster of differentiation (CD) 8-positive and CD4-positive T cells were strongly expressed following hypothermia. Therefore, the present study provided evidence that IL-2 treatment combined with MFH improves the therapeutic effect on lung cancer-bearing mice. PMID:26870335

  18. Enhancing effects of agelasphin-11 on natural killer cell activities of normal and tumor-bearing mice.

    PubMed

    Kobayashi, E; Motoki, K; Natori, T; Uchida, T; Fukushima, H; Koezuka, Y

    1996-03-01

    Agelasphin-11 (AGL-11), a novel alpha-galactosylceramide isolated from an extract of a marine sponge, Agelas mauritianus, markedly prolonged the life span of mice intraperitoneally inoculated with B16 cells. Since AGL-11 did not show any direct cytotoxic activity against B16 cells, this compound is considered to be a biological response modifier (BRM). We focused on the enhancing effect of this compound on in vivo natural killer (NK) cell activity because several BRMs have already been determined to enhance the in vivo natural killer (NK) cell activity. When we evaluated the enhancing activity of AGL-11 using normal mice, AGL-11 enhanced in vivo NK cell activity more potently than Poly I:C, which is a positive control. In addition, we examined the effect of this compound on the NK cell activity of tumor-bearing mice, and found that AGL-11 recovers the reduced NK cell activity in a tumor-bearing condition to a higher level than that of normal mice. These results suggest that AGL-11 shows antitumor activity by the activation of antitumor effector cells such as NK cells.

  19. 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.

  20. Epididymal protein synthesis and secretion in strains of mice bearing single gene mutations which affect fertility.

    PubMed

    Holland, M K; Orgebin-Crist, M C

    1988-03-01

    Mice bearing gene mutations that, among other effects, render the males infertile were examined. Serum testosterone was within the normal range (0.8-1.8 ng/ml), and sperm numbers in the testis and epididymis were not different between mutant animals and coisogenic wild types. All mutants, except mocha and achondroplasia, displayed normal mating behavior. However, in all genotypes, fewer fertilized eggs were recovered from females mated by mutants. In vitro fertilization tests showed that all mutants--except bouncy--fertilized similar numbers of eggs to wild types. Spermatozoa from bouncy mutants also bound to eggs in lower numbers. These findings indicate that spermatozoa from the bouncy mutant have a severe defect in sperm-zona interaction. When bouncy spermatozoa were tested for sperm-vitelline membrane interaction at a low (10:1) sperm to egg ratio, they penetrated fewer zona-free hamster eggs. Epididymal protein synthesis and secretion were comparable between wild-type animals from all genotypes. However, while the regional pattern of protein synthesis was comparable among all mutants, the absolute rate of protein synthesis (cpm per mg tissue) was lower in some cases. Nevertheless, the proportion of the proteins synthesized that appeared in the medium remained constant. When the regional profile of proteins secreted by mutants was compared to that of their coisogenic wild types, three types of differences were noted: (1) changes in the abundance of a protein, (2) changes in the region of the epididymis from which a protein was secreted, or (3) the absence of a protein.

  1. Alloantigen-activated lymphocytes from mice bearing a spontaneous nonimmunogenic adenocarcinoma inhibit its growth in vivo by recruiting host immunoreactivity

    SciTech Connect

    Giovarelli, M.; Santoni, A.; Forni, G.

    1985-11-01

    Nylon wool columns eluting lymphocytes from the spleen of mice bearing a clinically evident spontaneous, nonimmunogenic adenocarcinoma of recent origin (TS/A) do not display cytotoxic response, release of lymphokines, and proliferation in vitro against TS/A cells, nor do they inhibit TS/A tumor growth in a Winn-type neutralization assay in vivo. After 5-day co-culture with allogeneic spleen cells from mice differing at multiple minor histocompatibility antigens only, these lymphocytes are still noncytolytic against TS/A cells, whereas they release interferon-..gamma.., mediate delayed-type hypersensitivity (DTH) reactions, and inhibit TS/A tumor growth in the Winn assay. In the Winn test, alloactivated lymphocytes from TS/A tumor-bearing mice are more effective than those from normal mice on a per cell basis. The induction of this TS/A tumor inhibition ability depends on the presence in the cultures of Thy-1/sup +/ lymphocytes. The presence of Lyt-2/sup +/ lymphocytes is also important, whereas that of asialo GM1/sup +/ is not. The TS/A inhibition in vivo by alloactivated lymphocytes mostly depends on Thy-1/sup +/, Lyt-2/sup -/ and asialo GM/sup -/ lymphocytes, even though a few Thy/sup -/ cells are also very efficient tumor inhibitors. The alloactivated lymphocytes inhibit TS/A tumor growth by recruiting the radiosensitive effector mechanisms of the recipient mice required for ultimate tumor rejection. TS/A tumor rejection leaves a specific DTH and an immunologic memory resulting in rejection of a second lethal TS/A challenge in a significant number of mice.

  2. Boron neutron capture therapy demonstrated in mice bearing EMT6 tumors following selective delivery of boron by rationally designed liposomes

    PubMed Central

    Kueffer, Peter J.; Maitz, Charles A.; Khan, Aslam A.; Schuster, Seth A.; Shlyakhtina, Natalia I.; Jalisatgi, Satish S.; Brockman, John D.; Nigg, David W.; Hawthorne, M. Frederick

    2013-01-01

    The application of boron neutron capture therapy (BNCT) following liposomal delivery of a 10B-enriched polyhedral borane and a carborane against mouse mammary adenocarcinoma solid tumors was investigated. Unilamellar liposomes with a mean diameter of 134 nm or less, composed of an equimolar mixture of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine and incorporating Na3[1-(2′-B10H9)-2-NH3B10H8] in the aqueous interior and K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer, were injected into the tail veins of female BALB/c mice bearing right flank EMT6 tumors. Biodistribution studies indicated that two identical injections given 24 h apart resulted in tumor boron levels exceeding 67 µg/g tumor at 54 h—with tumor/blood boron ratios being greatest at 96 h (5.68:1; 43 µg boron/g tumor)—following the initial injection. For BNCT experiments, tumor-bearing mice were irradiated 54 h after the initial injection for 30 min with thermal neutrons, resulting in a total fluence of 1.6 × 1012 neutrons per cm2 (±7%). Significant suppression of tumor growth was observed in mice given BNCT vs. control mice (only 424% increase in tumor volume at 14 d post irradiation vs. 1551% in untreated controls). In a separate experiment in which mice were given a second injection/irradiation treatment 7 d after the first, the tumor growth was vastly diminished (186% tumor volume increase at 14 d). A similar response was obtained for mice irradiated for 60 min (169% increase at 14 d), suggesting that neutron fluence was the limiting factor controlling BNCT efficacy in this study. PMID:23536304

  3. Stressful Presentations: Mild Cold Stress in Laboratory Mice Influences Phenotype of Dendritic Cells in Naïve and Tumor-Bearing Mice

    PubMed Central

    Kokolus, Kathleen M.; Spangler, Haley M.; Povinelli, Benjamin J.; Farren, Matthew R.; Lee, Kelvin P.; Repasky, Elizabeth A.

    2013-01-01

    The ability of dendritic cells (DCs) to stimulate and regulate T cells is critical to effective anti-tumor immunity. Therefore, it is important to fully recognize any inherent factors which may influence DC function under experimental conditions, especially in laboratory mice since they are used so heavily to model immune responses. The goals of this report are to 1) briefly summarize previous work revealing how DCs respond to various forms of physiological stress and 2) to present new data highlighting the potential for chronic mild cold stress inherent to mice housed at the required standard ambient temperatures to influence baseline DCs properties in naïve and tumor-bearing mice. As recent data from our group shows that CD8+ T cell function is significantly altered by chronic mild cold stress and since DC function is crucial for CD8+ T cell activation, we wondered whether housing temperature may also be influencing DC function. Here we report that there are several significant phenotypical and functional differences among DC subsets in naïve and tumor-bearing mice housed at either standard housing temperature or at a thermoneutral ambient temperature, which significantly reduces the extent of cold stress. The new data presented here strongly suggests that, by itself, the housing temperature of mice can affect fundamental properties and functions of DCs. Therefore differences in basal levels of stress due to housing should be taken into consideration when interpreting experiments designed to evaluate the impact of additional variables, including other stressors on DC function. PMID:24575090

  4. Boswellic acid disables signal transduction of IL-6-STAT-3 in Ehrlich ascites tumor bearing irradiated mice.

    PubMed

    Moustafa, Enas Mahmoud; Thabet, Noura Magdy; Azab, Khaled Shaaban

    2016-08-01

    Boswellic acid (BA) is known for its ability to trigger apoptosis as well as to inhibit angiogenesis in tumor tissue. In this study, we investigated the effect of BA on the IL-6-STAT-3 signalling pathway in irradiated mice bearing solid tumors of Ehrlich ascites carcinoma (EAC). For this, we administered BA (25 mg·(kg body mass)(-1)·day(-1), by intraperitoneal injection) to mice with EAC, and then exposed them to 4 Gy of gamma radiation. Data analyses of the results revealed a specific impact from BA on IL-6R mRNA and survivin mRNA in EACs and irradiated EAC-bearing mice. Also, significant improvements were observed in the protein expression of JAK-1, P-JAK-1, STAT-3, P-STAT-3, and caspase-3, as well as VEGF and IL-6 levels. We propose that BA interfered with IL-6-STAT-3 signal transduction, thereby preventing the activation of caspase-3 and subsequently triggering the process of apoptosis. However, the alternative angiogenesis pathway, which includes the over-expression of VEGF and which depends on IL-6-STAT-3 signalling, was inhibited by the action of BA. Thus, we recommend that therapeutic strategies for cancer should include treatment with BA.

  5. Simvastatin increases the antineoplastic actions of paclitaxel carried in lipid nanoemulsions in melanoma-bearing mice

    PubMed Central

    Kretzer, Iara F; Maria, Durvanei A; Guido, Maria C; Contente, Thaís C; Maranhão, Raul C

    2016-01-01

    Purpose Lipid nanoemulsions (LDEs) that bind to low-density lipoprotein (LDL) receptors used as carriers of paclitaxel (PTX) can decrease toxicity and increase PTX antitumoral action. The administration of simvastatin (Simva), which lowers LDL-cholesterol, was tested as an adjuvant to commercial PTX and to PTX associated with LDE (LDE-PTX). Materials and methods B16F10 melanoma-bearing mice were treated with saline solution or LDE (controls), Simva, PTX, PTX and Simva, LDE-PTX, and LDE-PTX and Simva: PTX dose 17.5 μmol/kg (three intraperitoneal injections, 3 alternate days): Simva 50 mg/kg/day by gavage, 9 consecutive days. Results Compared with saline controls, 95% tumor-growth inhibition was achieved by LDE-PTX and Simva, 61% by LDE-PTX, 44% by PTX and Simva, and 43% by PTX. Simva alone had no effect. Metastasis developed in only 37% of the LDE-PTX and Simva, 60% in LDE-PTX, and 90% in PTX and Simva groups. Survival rates were higher in LDE-PTX and Simva and in LDE-PTX groups. The LDE-PTX and Simva group presented tumors with reduced cellular density and increased collagen fibers I and III. Tumors from all groups showed reduction in immunohistochemical expression of ICAM, MCP-1, and MMP-9; LDE-PTX and Simva presented the lowest MMP-9 expression. Expression of p21 was increased in the Simva, LDE-PTX, and LDE-PTX and Simva groups. In the Simva and LDE-PTX and Simva groups, expression of cyclin D1, a proliferation and survival promoter of tumor cells, was decreased. Therapy with LDE-PTX and Simva showed negligible toxicity compared with PTX and Simva, which resulted in weight loss and myelosuppression. Conclusion Simva increased the antitumor activity of PTX carried in LDE but not of PTX commercial presentation, possibly because statins increase the expression of LDL receptors that internalize LDE-PTX. PMID:27022257

  6. Bone loss during partial weight bearing (1/6th gravity) is mitigated by resistance and aerobic exercise in mice

    NASA Astrophysics Data System (ADS)

    Boudreaux, R. D.; Metzger, C. E.; Macias, B. R.; Shirazi-Fard, Y.; Hogan, H. A.; Bloomfield, S. A.

    2014-06-01

    Astronauts on long duration missions continue to experience bone loss, as much as 1-2% each month, for up to 4.5 years after a mission. Mechanical loading of bone with exercise has been shown to increase bone formation, mass, and geometry. The aim of this study was to compare the efficacy of two exercise protocols during a period of reduced gravitational loading (1/6th body weight) in mice. Since muscle contractions via resistance exercise impart the largest physiological loads on the skeleton, we hypothesized that resistance training (via vertical tower climbing) would better protect against the deleterious musculoskeletal effects of reduced gravitational weight bearing when compared to endurance exercise (treadmill running). Young adult female BALB/cBYJ mice were randomly assigned to three groups: 1/6 g (G/6; n=6), 1/6 g with treadmill running (G/6+RUN; n=8), or 1/6 g with vertical tower climbing (G/6+CLB; n=9). Exercise was performed five times per week. Reduced weight bearing for 21 days was achieved through a novel harness suspension system. Treadmill velocity (12-20 m/min) and daily run time duration (32-51 min) increased incrementally throughout the study. Bone geometry and volumetric bone mineral density (vBMD) at proximal metaphysis and mid-diaphysis tibia were assessed by in vivo peripheral quantitative computed tomography (pQCT) on days 0 and 21 and standard dynamic histomorphometry was performed on undemineralized sections of the mid-diaphysis after tissue harvest. G/6 caused a significant decrease (P<0.001) in proximal tibia metaphysis total vBMD (-9.6%). These reductions of tibia metaphyseal vBMD in G/6 mice were mitigated in both G/6+RUN and G/6+CLB groups (P<0.05). After 21 days of G/6, we saw an absolute increase in tibia mid-diaphysis vBMD and in distal metaphysis femur vBMD in both G/6+RUN and G/6+CLB mice (P<0.05). Substantial increases in endocortical and periosteal mineralizing surface (MS/BS) at mid-diaphysis tibia in G/6+CLB demonstrate that

  7. The antitumor effects of tetrodotoxin and/or doxorubicin on Ehrlich ascites carcinoma-bearing female mice.

    PubMed

    El-Dayem, Samiha M Abd; Fouda, Fatma M; Ali, Elham H A; Motelp, Bosy A Abd El

    2013-06-01

    The study aimed to investigate the antitumor effect of tetrodotoxin (TTX) and/or doxorubicin (DOX) on Ehrlich ascites carcinoma (EAC)-bearing mice through the investigated biochemical parameters. TTX and/or DOX with or without N-acetylcystiene were administrated after 10 days into EAC-female mice for a period of 2 weeks in six equal doses. Treatment with TTX or DOX caused a significant decrease in the mean tumor weight and an increase in the cumulative mean survival time when compared with EAC group. All the treatments reduced the elevated liver tumor markers and increased liver antioxidant enzymes under investigation in comparison with EAC. Hepatic cells, suffered severely from degeneration and karriolysis in EAC group, revealed some improvement as appearance of healthy hepatocytes by TTX treatment. The present results suggested that TTX had a more powerful inhibitor effect on EAC growth than DOX and TTX plus DOX treatments reflected by antitumor biochemical and histological studies.

  8. Th1 Cytokine Production Induced by Lactobacillus acidophilus in BALB/c Mice Bearing Transplanted Breast Tumor

    PubMed Central

    Imani Fooladi, Abbas Ali; Yazdi, Mohammad Hossein; Pourmand, Mohammad Reza; Mirshafiey, Abbas; Hassan, Zuhair Mohammad; Azizi, Taghi; Mahdavi, Mehdi; Soltan Dallal, Mohammad Mehdi

    2015-01-01

    Background: The immunomodulative effects of Lactic Acid Bacteria as probiotics have been already demonstrated. Objectives: The current study aimed to evaluate the effect of oral administration of Lactobacillus acidophilus on the immune responses and patterns of cytokine production in the BALB/c mice bearing breast cancer. Materials and Methods: The current study used thirty inbred BALB/c mice, six- to eight-week-old; they were divided into two groups of 15 each. One group was used as control in each assay. The L. acidophilus (ATCC4356) used in the study was inoculated in MRS broth and cultivated overnight at 37°C under anaerobic conditions, then collected by centrifugation, and re-suspended in Phosphate-buffered Saline (PBS) media. After preparation of the proper amount of the suspension, it was orally administered to the mice via gavage and the control mice received an equal volume of PBS in the same manner. Results: The results showed that oral administration of L. acidophilus as a potent immunostimulator agent could motivate the proliferation of immune cells. Moreover, it could increase the production of IFN-γ and decrease the production of IL-4, known as Th2 cytokines, in the spleen cell culture. The results showed that the survival time of the L. acidophilus administered mice significantly increased in comparison to that of the control mice. Conclusions: The current study findings suggested that L. acidophilus can promote immune responses with Th1 bias and may increase the antitumor response. Further, the consumption of this probiotic strain may help to manage the immune response in tumor condition, but more studies are needed to investigate the other mechanisms of this effect. PMID:26034546

  9. Dietary rice component, Oryzanol, inhibits tumor growth in tumor-bearing Mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Scope: We investigated the effects of rice bran and components on tumor growth in mice. Methods and results: Mice fed standard diets supplemented with rice bran, '-oryzanol, Ricetrienol®, ferulic acid, or phytic acid for 2 weeks were inoculated with CT-26 colon cancer cells and fed the same diet fo...

  10. An Immune-Modulating Diet in Combination with Chemotherapy Prevents Cancer Cachexia by Attenuating Systemic Inflammation in Colon 26 Tumor-Bearing Mice.

    PubMed

    Nakamura, Kentaro; Sasayama, Akina; Takahashi, Takeshi; Yamaji, Taketo

    2015-01-01

    Cancer cachexia is characterized by muscle wasting caused partly by systemic inflammation. We previously demonstrated an immune-modulating diet (IMD), an enteral diet enriched with immunonutrition and whey-hydrolyzed peptides, to have antiinflammatory effects in some experimental models. Here, we investigated whether the IMD in combination with chemotherapy could prevent cancer cachexia in colon 26 tumor-bearing mice. Forty tumor-bearing mice were randomized into 5 groups: tumor-bearing control (TB), low dose 5-fluorouracil (5-FU) and standard diet (LF/ST), low dose 5-FU and IMD (LF/IMD), high dose 5-FU and standard diet (HF/ST) and high dose 5-FU and IMD (HF/IMD). The ST and IMD mice received a standard diet or the IMD ad libitum for 21 days. Muscle mass in the IMD mice was significantly higher than that in the ST mice. The LF/IMD in addition to the HF/ST and HF/IMD mice preserved their body and carcass weights. Plasma prostaglandin E2 levels were significantly lower in the IMD mice than in the ST mice. A combined effect was also observed in plasma interleukin-6, glucose, and vascular endothelial growth factor levels. Tumor weight was not affected by different diets. In conclusion, the IMD in combination with chemotherapy prevented cancer cachexia without suppressing chemotherapeutic efficacy.

  11. Rebamipide does not interfere with the antitumor effect of radiotherapy or chemotherapy in human oral tumor-bearing nude mice.

    PubMed

    Shibamori, Masafumi; Sato, Masayuki; Uematsu, Naoya; Nakashima, Takako; Sato, Asuka; Yamamura, Yoshiya; Sasabe, Hiroyuki; Umehara, Ken; Sakurai, Kazushi

    2015-09-01

    Recent studies have shown that rebamipide, which suppresses reactive oxygen species, prevents chemoradiotherapy-induced oral mucositis in patients with head and neck cancers. However, anticancer action of radiotherapy and chemotherapy is believed to be partially associated with generation of reactive oxygen species. The aim of this study was to determine whether rebamipide interferes with the antitumor action of radiotherapy and chemotherapy. The effect of rebamipide on tumor cell growth was investigated using a human oral squamous carcinoma cell line, HSC-2, in vitro and in vivo. Rebamipide showed no significant effect on cell or tumor growth in HSC-2 tumor-bearing nude mice. Influences of rebamipide on the antitumor action of radiotherapy and of chemotherapy with cisplatin or docetaxel were investigated using the same animal model. In radiotherapy, the tumor was treated with 2.5 Gy of X-rays for 5 days, and rebamipide (300 mg/kg p.o.) was administered during irradiation periods. In chemotherapy, tumor-bearing mice were treated once with cisplatin (8 mg/kg, i.v.) or docetaxel (15 mg/kg i.v.) and rebamipide (300 mg/kg p.o.) was administered for 5 days following the antitumor drug treatment. Rebamipide did not interfere with the antitumor action of radiotherapy and chemotherapy.

  12. Anti-Tumor Effect of Steamed Codonopsis lanceolata in H22 Tumor-Bearing Mice and Its Possible Mechanism

    PubMed Central

    Li, Wei; Xu, Qi; He, Yu-Fang; Liu, Ying; Yang, Shu-Bao; Wang, Zi; Zhang, Jing; Zhao, Li-Chun

    2015-01-01

    Although previous studies confirmed that steaming and the fermentation process could significantly improve the cognitive-enhancement and neuroprotective effects of Codonopsis lanceolata, the anti-tumor efficacy of steamed C. lanceolata (SCL) and what mechanisms are involved remain largely unknown. The present study was designed to evaluate the anti-tumor effect in vivo of SCL in H22 tumor-bearing mice. The results clearly indicated that SCL could not only inhibit the tumor growth, but also prolong the survival time of H22 tumor-bearing mice. Besides, the serum levels of cytokines, such as interferon gamma (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-2 (IL-2), were enhanced by SCL administration. The observations of Hoechst 33258 staining demonstrated that SCL was able to induce tumor cell apoptosis. Finally, immunohistochemical analysis revealed that SCL treatment significantly increased Bax expression and decreased Bcl-2 and vascular endothelial growth factor (VEGF) expression of H22 tumor tissues in a dose-dependent manner. Moreover, LC/MS analysis of SCL indicated that it mainly contained lobetyolin and six saponins. Taken all together, the findings in the present study clearly demonstrated that SCL inhibited the H22 tumor growth in vivo at least partly via improving the immune functions, inducing apoptosis and inhibiting angiogenesis. PMID:26426041

  13. Extravasation and transcytosis of liposomes in Kaposi's sarcoma-like dermal lesions of transgenic mice bearing the HIV tat gene.

    PubMed

    Huang, S K; Martin, F J; Jay, G; Vogel, J; Papahadjopoulos, D; Friend, D S

    1993-07-01

    Transgenic mice bearing the HIV tat gene develop dermal lesions resembling a common malignant tumor in AIDS, Kaposi's sarcoma (KS). To evaluate the permeability characteristics of these lesions and the therapeutic potential of drug-carrying liposomes, we have studied the localization of sterically stabilized liposomes, which show long circulation time in blood and increased accumulation in tumors. Liposomes encapsulating colloidal gold were injected intravenously into transgenic mice bearing KS lesions, and tissues were processed 24 hours later for both electron microscopy and for light microscopy with silver enhancement. Liposomes and silver marker were detected predominantly in the dermis surrounding the early and mature KS lesions, which were characterized by a proliferation of fibroblast-like spindle cells and abnormal blood vessels close to the epidermis. The silver-enhanced gold marker often surrounded vascular channels and scattered erythrocytes. As determined by electron microscopy, some spindle cells and macrophages had ingested intact liposomes. Transendothelial transport of liposomes was observed both through open channels between endothelial cells and also through endothelial cells lining intact vessels. Both extravasation and transcytosis of liposomes through irregular endothelium were much higher in KS lesions than in the adjacent normal skin. The high accumulation of sterically stabilized liposomes in KS lesions and their intracellular uptake by some spindle cells enhances their potential as carriers of chemotherapeutic agents against this neoplasm. PMID:8317543

  14. Molecular Imaging, Pharmacokinetics, and Dosimetry of 111In-AMBA in Human Prostate Tumor-Bearing Mice

    PubMed Central

    Ho, Chung-Li; Liu, I-Hsiang; Wu, Yu-Hsien; Chen, Liang-Cheng; Chen, Chun-Lin; Lee, Wan-Chi; Chuang, Cheng-Hui; Lee, Te-Wei; Lin, Wuu-Jyh; Shen, Lie-Hang; Chang, Chih-Hsien

    2011-01-01

    Molecular imaging with promise of personalized medicine can provide patient-specific information noninvasively, thus enabling treatment to be tailored to the specific biological attributes of both the disease and the patient. This study was to investigate the characterization of DO3A-CH2CO-G-4-aminobenzoyl-Q-W-A-V-G-H-L-M-NH2 (AMBA) in vitro, MicroSPECT/CT imaging, and biological activities of 111In-AMBA in PC-3 prostate tumor-bearing SCID mice. The uptake of 111In-AMBA reached highest with 3.87 ± 0.65% ID/g at 8 h. MicroSPECT/CT imaging studies suggested that the uptake of 111In-AMBA was clearly visualized between 8 and 48 h postinjection. The distribution half-life (t1/2α) and the elimination half-life (t1/2β) of 111In-AMBA in mice were 1.53 h and 30.7 h, respectively. The Cmax and AUC of 111In-AMBA were 7.57% ID/g and 66.39 h∗% ID/g, respectively. The effective dose appeared to be 0.11 mSv/MBq−1. We demonstrated a good uptake of 111In-AMBA in the GRPR-overexpressed PC-3 tumor-bearing SCID mice. 111In-AMBA is a safe, potential molecular image-guided diagnostic agent for human GRPR-positive tumors, ranging from simple and straightforward biodistribution studies to improve the efficacy of combined modality anticancer therapy. PMID:21660132

  15. Experimental treatment of breast cancer-bearing BALB/c mice by artemisinin and transferrin-loaded magnetic nanoliposomes

    PubMed Central

    Gharib, Amir; Faezizadeh, Zohreh; Mesbah-Namin, Seyed Ali Reza; Saravani, Ramin

    2015-01-01

    Background: The combination of artemisinin and transferrin exhibits versatile anticancer activities. In previous, we successfully prepared artemisinin and transferrin-loaded magnetic nanoliposomes and evaluated their anti-proliferative activity against MCF-7 and MDA-MB-231 cell lines in vitro. In this study, we investigate the in vivo anti-breast cancer activity of artemisinin and transferrin-loaded magnetic nanoliposome against breast transplanted tumors in BALB/c mice model. Materials and Methods: Artemisinin and transferrin-loaded magnetic nanoliposomes were prepared and characterized for some physiochemical properties. Pieces of tumor tissue from the breast cancer-bearing BALB/c mice were transplanted subcutaneously to the syngeneic female BALB/c mice. In the presence of the external magnet that placed at the breast tumor site, the tissue distribution and tumor-suppressing effects of prepared nanoliposomes on tumor growth was evaluated. Results: The prepared nanoliposomes have fine spherical shape, rough surface, nano-sized diameter and magnetic properties. At 2 h after treatment, the intravenous administration of artemisinin and transferrin-loaded magnetic nanoliposomes followed using the magnetic field approximately produced 10- and 5.5-fold higher levels of artemisinin and transferrin in the tumors, respectively, compared with free artemisinin and transferrin. Moreover, in the presence of an external magnetic field, the prepared nanoliposomes could significantly induce apoptosis in the mice breast cancer cells as well as could reduce tumor volume in tumorized mice at 15 days after treatment. Conclusion: The data suggested that the artemisinin and transferrin-loaded magnetic nanoliposomes would be a good choice for the breast tumor-targeted therapy, due to its high targeting efficiency. PMID:26109756

  16. Dynamic weight bearing is an efficient and predictable method for evaluation of arthritic nociception and its pathophysiological mechanisms in mice

    PubMed Central

    Quadros, Andreza U.; Pinto, Larissa G.; Fonseca, Miriam M.; Kusuda, Ricardo; Cunha, Fernando Q.; Cunha, Thiago M.

    2015-01-01

    The assessment of articular nociception in experimental animals is a challenge because available methods are limited and subject to investigator influence. In an attempt to solve this problem, the purpose of this study was to establish the use of dynamic weight bearing (DWB) as a new device for evaluating joint nociception in an experimental model of antigen-induced arthritis (AIA) in mice. AIA was induced in Balb/c and C57BL/6 mice, and joint nociception was evaluated by DWB. Western Blotting and real-time PCR were used to determine protein and mRNA expression, respectively. DWB detected a dose- and time-dependent increase in joint nociception during AIA and was able to detect the dose-response effects of different classes of analgesics. Using DWB, it was possible to evaluate the participation of spinal glial cells (microglia and astrocytes) and cytokines (IL-1β and TNFα) for the genesis of joint nociception during AIA. In conclusion, the present results indicated that DWB is an effective, objective and predictable test to study both the pathophysiological mechanisms involved in arthritic nociception in mice and for evaluating novel analgesic drugs against arthritis. PMID:26511791

  17. Age-associated impairment of antitumor immunity in carcinoma-bearing mice and restoration by oral administration of Lentinula edodes mycelia extract.

    PubMed

    Ishikawa, Satoru; Matsui, Yasunori; Wachi, Satoshi; Yamaguchi, Hiroshi; Harashima, Nanae; Harada, Mamoru

    2016-08-01

    Because cancer is associated with aging, immunological features in the aged should be considered in anticancer immunotherapy. In this study, we investigated antitumor immunity in aged mice using a CT26 colon carcinoma model. The tumor growth of CT26 was accelerated in aged mice compared with that in young mice, but this difference was not observed in nude mice. The serum levels of IL-6 and TNF-α were higher in aged mice than those in young mice, irrespective of the CT26-bearing state. The in vitro induction of CT26-specific CTLs from aged mice that were vaccinated with doxorubicin (DTX)-treated CT26 cells was impaired. In vivo neutralization of IL-6, but not TNF-α, showed a tendency to restore the in vitro induction of CT26-specific CTLs from vaccinated aged mice. Analyses on tumor-infiltrating immune cells as early as day 5 after CT26 inoculation revealed that monocytic and granulocytic MDSCs preferentially infiltrated into tumor sites in aged mice compared with young mice. Alternatively, oral administration of Lentinula edodes mycelia (L.E.M.) extract, which has the potential to suppress inflammation in tumor-bearing hosts, decreased the serum levels of IL-6 in aged mice. When administration of L.E.M. extract was started 1 week earlier, CT26 growth was retarded in aged mice and the in vivo priming of tumor-specific CTLs was improved in CT26-vaccinated aged mice. These results indicate early infiltration of MDSCs is related to impaired immunity of aged hosts and that oral administration of L.E.M. extract can mitigate the impairment.

  18. Age-associated impairment of antitumor immunity in carcinoma-bearing mice and restoration by oral administration of Lentinula edodes mycelia extract.

    PubMed

    Ishikawa, Satoru; Matsui, Yasunori; Wachi, Satoshi; Yamaguchi, Hiroshi; Harashima, Nanae; Harada, Mamoru

    2016-08-01

    Because cancer is associated with aging, immunological features in the aged should be considered in anticancer immunotherapy. In this study, we investigated antitumor immunity in aged mice using a CT26 colon carcinoma model. The tumor growth of CT26 was accelerated in aged mice compared with that in young mice, but this difference was not observed in nude mice. The serum levels of IL-6 and TNF-α were higher in aged mice than those in young mice, irrespective of the CT26-bearing state. The in vitro induction of CT26-specific CTLs from aged mice that were vaccinated with doxorubicin (DTX)-treated CT26 cells was impaired. In vivo neutralization of IL-6, but not TNF-α, showed a tendency to restore the in vitro induction of CT26-specific CTLs from vaccinated aged mice. Analyses on tumor-infiltrating immune cells as early as day 5 after CT26 inoculation revealed that monocytic and granulocytic MDSCs preferentially infiltrated into tumor sites in aged mice compared with young mice. Alternatively, oral administration of Lentinula edodes mycelia (L.E.M.) extract, which has the potential to suppress inflammation in tumor-bearing hosts, decreased the serum levels of IL-6 in aged mice. When administration of L.E.M. extract was started 1 week earlier, CT26 growth was retarded in aged mice and the in vivo priming of tumor-specific CTLs was improved in CT26-vaccinated aged mice. These results indicate early infiltration of MDSCs is related to impaired immunity of aged hosts and that oral administration of L.E.M. extract can mitigate the impairment. PMID:27312060

  19. 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

  20. Whole-Retina Reduced Electrophysiological Activity in Mice Bearing Retina-Specific Deletion of Vesicular Acetylcholine Transporter

    PubMed Central

    Bedore, Jake; Martyn, Amanda C.; Li, Anson K. C.; Dolinar, Eric A.; McDonald, Ian S.; Coupland, Stuart G.; Prado, Vania F.; Prado, Marco A.; Hill, Kathleen A.

    2015-01-01

    Background Despite rigorous characterization of the role of acetylcholine in retinal development, long-term effects of its absence as a neurotransmitter are unknown. One of the unanswered questions is how acetylcholine contributes to the functional capacity of mature retinal circuits. The current study investigates the effects of disrupting cholinergic signalling in mice, through deletion of vesicular acetylcholine transporter (VAChT) in the developing retina, pigmented epithelium, optic nerve and optic stalk, on electrophysiology and structure of the mature retina. Methods & Results A combination of electroretinography, optical coherence tomography imaging and histological evaluation assessed retinal integrity in mice bearing retina- targeted (embryonic day 12.5) deletion of VAChT (VAChTSix3-Cre-flox/flox) and littermate controls at 5 and 12 months of age. VAChTSix3-Cre-flox/flox mice did not show any gross changes in nuclear layer cellularity or synaptic layer thickness. However, VAChTSix3-Cre-flox/flox mice showed reduced electrophysiological response of the retina to light stimulus under scotopic conditions at 5 and 12 months of age, including reduced a-wave, b-wave, and oscillatory potential (OP) amplitudes and decreased OP peak power and total energy. Reduced a-wave amplitude was proportional to the reduction in b-wave amplitude and not associated with altered a-wave 10%-90% rise time or inner and outer segment thicknesses. Significance This study used a novel genetic model in the first examination of function and structure of the mature mouse retina with disruption of cholinergic signalling. Reduced amplitude across the electroretinogram wave form does not suggest dysfunction in specific retinal cell types and could reflect underlying changes in the retinal and/or extraretinal microenvironment. Our findings suggest that release of acetylcholine by VAChT is essential for the normal electrophysiological response of the mature mouse retina. PMID:26226617

  1. Skeletal muscle atrophy is attenuated in tumor-bearing mice under chemotherapy by treatment with fish oil and selenium

    PubMed Central

    Wang, Hang; Li, Tsung-Lin; Hsia, Simon; Su, I-Li; Chan, Yi-Lin; Wu, Chang-Jer

    2015-01-01

    Chemotherapy can cause cachexia, which is manifested by weight loss, inflammation and muscle atrophy. However, the mechanisms of tumor and chemotherapy on skeletal muscle proteolysis, remained unclear. In this report, we demonstrated that tumor-induced myostatin in turn induced TNF-α, thus activating calcium-dependent and proteasomal protein degradation. Chemotherapy activated myostatin-mediated proteolysis and muscle atrophy by elevating IL-6. In tumor-bearing mice under chemotherapy, supplementation with fish oil and selenium prevented a rise in IL-6, TNF-α and myostatin and muscle atrophy. The findings presented here allow us to better understand the molecular basis of cancer cachexia and potentiate nutrition supplementation in future cancer chemotherapy. PMID:25797259

  2. Potent anti-tumor effects of EGFR-targeted hybrid peptide on mice bearing liver metastases.

    PubMed

    Gaowa, Arong; Horibe, Tomohisa; Kohno, Masayuki; Harada, Hiroshi; Hiraoka, Masahiro; Kawakami, Koji

    2016-01-01

    In this study, we investigated the therapeutic efficacy of EGFR2R-lytic hybrid peptide for the treatment of liver metastasis from colon carcinoma. The cytotoxic activity of the hybrid peptide against luciferase-expressing human colon cancer (HCT-116-luc) cells was determined by the WST-8 assay. The experimental mouse model of liver metastases was generated by splenic injection of HCT-116-luc cells. The hybrid peptide was intravenously injected into mice the day after cell implantation at a dose of 5 mg/kg and this was repeated on alternate days for a total of 7 doses. Saline-treated mice were used as controls. Tumor growth and therapeutic responses were monitored by an IVIS imaging system. It was shown that the hybrid peptide exhibited potent cytotoxic activity against HCT-116-luc cells and the liver metastases were significantly reduced after intravenous injections of hybrid peptide compared with controls. Furthermore, Kaplan–Meier analysis showed that hybrid peptide-treated mice had significantly longer survival than controls. In addition, bright-field and ex vivo imaging of liver tissue revealed that mice treated with the hybrid peptide had significantly fewer tumors compared with controls. These results demonstrated that the EGFR2R-lytic hybrid peptide is a potential treatment option for patients with colorectal cancer metastases in the liver.

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

    PubMed Central

    2013-01-01

    Background Albendazole (ABZ) is a microtubule-targeting anthelmintic with a remarkable activity against a variety of human cancer cells. In this study, we examined if the antitumor activity of ABZ could be enhanced by its combination with other microtubule-binding agents. Methods The interactions between ABZ and microtubule-binding agents, paclitaxel, vinblastine, colchicine, and 2-methoxyestradiol were characterized using median effect analysis method in HCT-116 colorectal cancer cells and DU145 prostate cancer cell line. The mechanism underlying the synergistic interaction related to tubulin polymerization and apoptosis was then investigated. Finally, the effect of the combination therapy on the survival of HCT-116 tumor-bearing nude mice was evaluated. Results Among the tested drugs, a synergistic anti-proliferative effect was observed with the combination of low concentrations of ABZ plus colchicine and ABZ plus 2-methoxyestradiol (2ME). Exploring the mechanism of the interaction between ABZ and 2ME revealed that the combination therapy synergistically activated the extrinsic pathway of apoptosis. Consistent with in vitro results, the combination of low concentration of ABZ with 2ME prolonged the survival of mice-bearing HCT-116 tumors. High concentration of ABZ in combination with 2ME, however, proved to be less effective than ABZ alone. Conclusions The combination of low doses of ABZ and 2ME has shown promising results in our pre-clinical model. Additionally, the finding that the combination of two microtubule-binding agents that share the same binding site can act synergistically may lead to the development of new therapeutic strategies in cancer treatment. PMID:23432760

  4. Pharmacology of liposomal vincristine in mice bearing L1210 ascitic and B16/BL6 solid tumours.

    PubMed Central

    Mayer, L. D.; Masin, D.; Nayar, R.; Boman, N. L.; Bally, M. B.

    1995-01-01

    Vincristine pharmacokinetic, tumour uptake and therapeutic characteristics were investigated here in order to elucidate the processes underlying the enhanced efficacy observed for vincristine entrapped in small (120 nm) distearoylphosphatidylcholine/cholesterol liposomes. Plasma vincristine levels after intravenous (i.v.) injection are elevated more than 100-fold in the liposomal formulation compared with free drug in tumour-bearing as well as non-tumour-bearing mice over 24 h. Biodistribution studies demonstrate that the extent and duration of tumour exposure to vincristine is dramatically improved when the drug is administered i.v. in liposomal form. Specifically, 72 h trapezoidal area under the curve values for liposomal vincristine in the murine L1210 ascitic and B16/BL6 solid tumours are 12.9- to 4.1-fold larger, respectively, than observed for free drug. Similar to previous results with the L1210 model, increased drug delivery to the B16 tumour results in significant inhibition of tumour growth, whereas no anti-tumour activity is observed with free vincristine. Comparisons of drug and liposomal lipid accumulation in tumour and muscle tissue indicate that the enhanced efficacy of liposomal vincristine is related predominantly to drug delivered by liposomes to the tumour site rather than drug released from liposomes in the circulation. Consequently, improvements in liposomal vincristine formulations must focus on factors that increase uptake of liposomes into tumour sites as well as enhance liposomal drug retention in the circulation. PMID:7880728

  5. Radiation dosimetry of 131I-chlorotoxin for targeted radiotherapy in glioma-bearing mice.

    PubMed

    Shen, Sui; Khazaeli, M B; Gillespie, G Yancey; Alvarez, Vernon L

    2005-01-01

    Chlorotoxin, or TM-601, is a peptide derived from the venom of the scorpionLeiurus Quinquestriatus that specifically binds to malignant brain tumors, but not to normal tissues. Targeted radiotherapy using 131I-Chlorotoxin is promising for post-surgery treatment of brain tumors. This study reports dosimetry results of 131I-Chlorotoxin in athymic nude mice with intracranially implanted human glioma xenografts and projected radiation doses in patients receiving 370 MBq of 131I-Chlorotoxin. 125I/131I-Chlorotoxin were injected into the right brain where D54 MG xenografts were implanted. Mice were sacrificed 24-96 h later. The blood, normal organs, and tumors were weighed and counted to determine 131I-Chlorotoxin concentration. The radiation dose from 131I was calculated based on non-penetrating radiation in the mouse model. Assuming similar tissue uptake in mice and patients, radiation doses for patients were extrapolated. Distributions of 125I/131I-Chlorotoxin were only significant in tumor, stomach, kidneys, and brain (injection site), reflecting non-specific uptake of Chlorotoxin in normal tissues. Mean radiation dose (cGy/37 kBq) was 58.2 for tumor, 17.9 for brains, 1.8 for marrow, 27.1 for stomach, 16.0 for kidneys in mice. For intracranial injection of 370 MBq 131I-Chlorotoxin in patients, extrapolated patient dose (cGy) was 70 for brains, 6 for marrow, 35 for stomach, 60 to kidneys, 227 to tumor, suggesting that 3.7 GBq of 131I-Chlorotoxin can be safely administrated to patients. These promising results demonstrated potential in improving patient survival using this novel targeting agent.

  6. Eccentric contraction-induced myofiber growth in tumor-bearing mice.

    PubMed

    Hardee, Justin P; Mangum, Joshua E; Gao, Song; Sato, Shuichi; Hetzler, Kimbell L; Puppa, Melissa J; Fix, Dennis K; Carson, James A

    2016-01-01

    Cancer cachexia is characterized by the progressive loss of skeletal muscle mass. While mouse skeletal muscle's response to an acute bout of stimulated low-frequency concentric muscle contractions is disrupted by cachexia, gaps remain in our understanding of cachexia's effects on eccentric contraction-induced muscle growth. The purpose of this study was to determine whether repeated bouts of stimulated high-frequency eccentric muscle contractions [high-frequency electrical muscle stimulation (HFES)] could stimulate myofiber growth during cancer cachexia progression, and whether this training disrupted muscle signaling associated with wasting. Male Apc(Min/+) mice initiating cachexia (N = 9) performed seven bouts of HFES-induced eccentric contractions of the left tibialis anterior muscle over 2 wk. The right tibialis anterior served as the control, and mice were killed 48 h after the last stimulation. Age-matched C57BL/6 mice (N = 9) served as wild-type controls. Apc(Min/+) mice lost body weight, muscle mass, and type IIA, IIX, and IIB myofiber cross-sectional area. HFES increased myofiber cross-sectional area of all fiber types, regardless of cachexia. Cachexia increased muscle noncontractile tissue, which was attenuated by HFES. Cachexia decreased the percentage of high succinate dehydrogenase activity myofibers, which was increased by HFES, regardless of cachexia. While cachexia activated AMP kinase, STAT3, and ERK1/2 signaling, HFES decreased AMP kinase phosphorylation, independent of the suppression of STAT3. These results demonstrate that cachectic skeletal muscle can initiate a growth response to repeated eccentric muscle contractions, despite the presence of a systemic cachectic environment.

  7. Therapeutic effect of adriamycin encapsulated in long-circulating liposomes on Meth-A-sarcoma-bearing mice.

    PubMed

    Oku, N; Doi, K; Namba, Y; Okada, S

    1994-08-01

    Long-circulating liposomes modified with a uronic-acid derivative, palmityl-D-glucuronide (PGIcUA), have been developed previously for the passive targeting of liposomes to tumor tissues. In this study, we examined the therapeutic effect of adriamycin (ADM) encapsulated in PGIcUA liposomes composed of dipalmitoylphosphatidylcholine (DPPC), cholesterol (Chol) and PGIcUA (molar ratio, 40/40/10) since this amount of PGIcUA was enough to endow liposomes with long-circulating activity. Long-circulating activity was also observed with palmityl-D-galacturonide (PGalUA) modified liposomes, suggesting that uronic acid plays an important role in preventing liposomes from being trapped in the reticuloendothelial system (RES). ADM was loaded in liposomes by a remote-loading method. Free or liposomal ADM was injected i.v. into BALB/c mice bearing s.c.-implanted Meth-A sarcoma. The liposomal formulation was efficient for reducing tumors, prolonging survival time and curing the animals, especially in the case of large tumors where free ADM was not. Furthermore, PGlcUA liposomes were more effective than conventional liposomes containing dipalmitoylphosphatidylglycerol (DPPG) instead of PGlcUA for prolonging survival time in mice. It might therefore be appropriate to use PGlcUA liposomes as the carriers of anticancer drugs. PMID:8050822

  8. Cinacalcet attenuates hypercalcemia observed in mice bearing either Rice H-500 Leydig cell or C26-DCT colon tumors.

    PubMed

    Colloton, Matthew; Shatzen, Edward; Wiemann, Bernadette; Starnes, Charlie; Scully, Sheila; Henley, Charles; Martin, David

    2013-07-15

    Excessive secretion of parathyroid hormone-related protein (PTHrP) by tumors stimulates bone resorption and increases renal tubular reabsorption of calcium, resulting in hypercalcemia of malignancy. We investigated the ability of cinacalcet, an allosteric modulator of the calcium-sensing receptor, to attenuate hypercalcemia by assessing its effects on blood ionized calcium, serum PTHrP, and calcium-sensing receptor mRNA in mice bearing either Rice H-500 Leydig cell or C26-DCT colon tumors. Cinacalcet effectively decreased hypercalcemia in a dose- and enantiomer-dependent manner; furthermore, cinacalcet normalized phosphorus levels, but did not affect serum PTHrP. Ribonuclease protection assay results demonstrated presence of PTHrP receptor, but not calcium-sensing receptor mRNA in C26-DCT tumors. The mechanism by which cinacalcet lowered serum calcium was investigated in parathyroidectomized rats (i.e., without PTH) made hypercalcemic by PTHrP. Cinacalcet attenuated PTHrP-mediated elevations in blood ionized calcium, which were accompanied by increased plasma calcitonin. Taken together these results suggest that the cinacalcet-mediated decrease in serum calcium is not the result of a direct effect on tumor cells, but rather is the result of increased calcitonin release. In summary, cinacalcet effectively reduced tumor-mediated hypercalcemia and corrected hypophosphatemia in mice. Further investigation of cinacalcet for treatment of hypercalcemia of malignancy is warranted.

  9. Production of a novel multi-epitope peptide vaccine for cancer immunotherapy in TC-1 tumor-bearing mice.

    PubMed

    Nezafat, Navid; Sadraeian, Mohammad; Rahbar, Mohammad Reza; Khoshnoud, Mohammad Javad; Mohkam, Milad; Gholami, Ahmad; Banihashemi, Mehrzad; Ghasemi, Younes

    2015-01-01

    In our previous research, several bioinformatic strategies were utilized to design an efficient multi-epitope peptide vaccine (MEV) against cancer. The designed vaccine consists of Wilms tumor-1 (WT-1) and human papillomavirus (HPV) E7 cytotoxic T lymphocyte (CTL) epitopes, tetanus toxin fragment C (TTFrC) and HLA-DR epitope (PADRE) helper T lymphocyte (HTL) epitopes and heparin-binding hemagglutinin (HBHA) as an immunostimulatory adjuvant. All segments were fused together by suitable linkers. In the current study, we cloned and expressed the designed MEV in E. coli. We subsequently performed in vivo preventative and therapeutic assays to evaluate antitumor efficacy of the vaccine against the HPV-16 E7-expressing murine tumor cell line TC-1 as a model for cancer immunotherapy. The results showed that in preventive experiments, vaccination with MEV significantly augmented the IgG antibody titer and the percentage of tumor-free mice compared to control groups (PBS and E7). Moreover, in therapeutic experiments, vaccination with MEV led to a reduction in the number of metastatic nodules, lung weights and the ratio of lung weights to body weights compared to other groups. In sum, our epitope vaccine could efficiently induce preventive and therapeutic antitumor immunity in TC-1 tumor bearing mice.

  10. Cisplatin- and dietary ascorbic acid-mediated changes in the mitochondria of Dalton's lymphoma-bearing mice.

    PubMed

    Martha, Kham R M; Rosangkima, Gabriel; Amenla, Longchar; Rongpi, Thengtom; Prasad, Surya B

    2013-06-01

    Cisplatin treatment caused a significant increase in the life span of ascites Dalton's lymphoma (DL) Tumor-bearing (TB) mice. However, as compared to cisplatin (CP) alone, combination treatment with ascorbic acid plus CP resulted in better therapeutic efficacy against murine DL. Cisplatin treatment of TB mice resulted in the appearance of thickened and irregular arrangement of mitochondrial cristae in the liver, kidney and DL tumor cells. Combination treatment of the hosts with ascorbic acid and CP lessened deformities in the mitochondria of liver and kidney, while in tumor cells, this increased the formation of vacuoles and disruption in mitochondrial cristae. Cisplatin treatment decreased the succinate dehydrogenase (SDH) activity in the mitochondria of kidney and DL cells and combination treatment caused further decrease in SDH activity in kidney and DL cells during 24-48 h of treatment. After CP treatment, the protein content in the mitochondria of these tissues decreased, and during combination treatment, it showed significant improvement. Mitochondrial lipid peroxidation (LPO) increased in these tissues after CP treatment. However, combination treatment significantly decreased mitochondrial LPO in liver and kidney but increased in DL cells. This increase in mitochondrial LPO in DL cells and decrease in liver and kidney could play an important role in the antitumor activity of combination treatment and at the same time reduce CP-induced toxicity in the host. However, further study may be desirable to explore some aspects of the mechanism(s) involved in these changes in mitochondria.

  11. Pharmacokinetics and tissue distribution of inositol hexaphosphate in C.B17 SCID mice bearing human breast cancer xenografts.

    PubMed

    Eiseman, Julie; Lan, Jing; Guo, Jianxia; Joseph, Erin; Vucenik, Ivana

    2011-10-01

    Inositol hexaphosphate (IP(6)) is effective in preclinical cancer prevention and chemotherapy. In addition to cancer, IP(6) has many other beneficial effects for human health, such as reduction in risk of developing cardiovascular disease and diabetes and inhibition of kidney stone formation. Studies presented here describe the pharmacokinetics, tissue distribution, and metabolism of IP(6) following intravenous (IV) or per os (PO) administration to mice. SCID mice bearing MDA-MB-231 xenografts were treated with 20 mg/kg IP(6) (3 μCi per mouse [(14)C]-uniformly ring-labeled IP(6)) and euthanized at various times after IP(6) treatment. Plasma and tissues were analyzed for [(14)C]-IP(6) and metabolites by high-performance liquid chromatography with radioactivity detection. Following IV administration of IP(6), plasma IP(6) concentrations peaked at 5 minutes and were detectable until 45 minutes. Liver IP(6) concentrations were more than 10-fold higher than plasma concentrations, whereas other normal tissue concentrations were similar to plasma. Only inositol was detected in xenografts. After PO administration, IP(6) was detected in liver; but only inositol was detectable in other tissues. After both IV and PO administration, exogenous IP(6) was rapidly dephosphorylated to inositol; however, alterations in endogenous IPs were not examined.

  12. Localization of sunitinib, its metabolites and its target receptors in tumour-bearing mice: a MALDI-MS imaging study

    PubMed Central

    Torok, S; Vegvari, A; Rezeli, M; Fehniger, T E; Tovari, J; Paku, S; Laszlo, V; Hegedus, B; Rozsas, A; Dome, B; Marko-Varga, G

    2015-01-01

    Background and Purpose The clinical effects of anti-angiogenic agents remain controversial. Therefore, elucidating the pharmacological properties of these compounds is a pivotal issue. Experimental Approach The effects of treatment with sunitinib on tumour and normal tissues of mice bearing C-26 adenocarcinoma cells were analysed by matrix-assisted laser desorption ionization MS imaging (MALDI-MSI). Expression of the key targets of sunitinib – angiogenic receptors – was studied by immunofluorescent labelling. Key Results MALDI-MS assays showed that sunitinib and its fragment ions were present throughout tumour and normal tissues. Major metabolites were identified in blood and solid tissues, while minor drug metabolites were detectable only in blood. Tumour growth and intratumour VEGF receptor-2 expressions were significantly reduced in sunitinib-treated mice, while the expression of the other targeted receptors, PDGF receptor -α or -β and fibroblast growth factor receptor-1, remained unaffected. Within tumour tissue, the close proximity of sunitinib metabolites to the precursor ion suggested in situ metabolism of the administered drug. There were intratumour areas where the signal intensity of sunitinib correlated with expression of VEGF receptor-2. Conclusions and Implications This is the first study that demonstrates MALDI-MSI is a versatile platform to study the intratumour localization of an unlabelled anti-angiogenic drug. The combination of MALDI-MSI and immunofluorescence analysis can provide further insights into the molecular interaction of drug compounds and their targets within tumour tissue. PMID:25363319

  13. Vaccine Efficacy in Senescent Mice Challenged with Recombinant SARS-CoV Bearing Epidemic and Zoonotic Spike Variants

    PubMed Central

    Deming, Damon; Sheahan, Timothy; Heise, Mark; Yount, Boyd; Davis, Nancy; Sims, Amy; Suthar, Mehul; Harkema, Jack; Whitmore, Alan; Pickles, Raymond; West, Ande; Donaldson, Eric; Curtis, Kristopher; Johnston, Robert; Baric, Ralph

    2006-01-01

    eosinophilic infiltrates within the lungs of SARS-CoV–challenged mice. VRP-N–induced pathology presented at day 4, peaked around day 7, and persisted through day 14, and was likely mediated by cellular immune responses. Conclusions This study identifies gaps and challenges in vaccine design for controlling future SARS-CoV zoonosis, especially in vulnerable elderly populations. The availability of a SARS-CoV virus bearing heterologous S glycoproteins provides a robust challenge inoculum for evaluating vaccine efficacy against zoonotic strains, the most likely source of future outbreaks. PMID:17194199

  14. Image-guided microbeam irradiation to brain tumour bearing mice using a carbon nanotube x-ray source array

    NASA Astrophysics Data System (ADS)

    Zhang, Lei; Yuan, Hong; Burk, Laurel M.; Inscoe, Christy R.; Hadsell, Michael J.; Chtcheprov, Pavel; Lee, Yueh Z.; Lu, Jianping; Chang, Sha; Zhou, Otto

    2014-03-01

    Microbeam radiation therapy (MRT) is a promising experimental and preclinical radiotherapy method for cancer treatment. Synchrotron based MRT experiments have shown that spatially fractionated microbeam radiation has the unique capability of preferentially eradicating tumour cells while sparing normal tissue in brain tumour bearing animal models. We recently demonstrated the feasibility of generating orthovoltage microbeam radiation with an adjustable microbeam width using a carbon nanotube based x-ray source array. Here we report the preliminary results from our efforts in developing an image guidance procedure for the targeted delivery of the narrow microbeams to the small tumour region in the mouse brain. Magnetic resonance imaging was used for tumour identification, and on-board x-ray radiography was used for imaging of landmarks without contrast agents. The two images were aligned using 2D rigid body image registration to determine the relative position of the tumour with respect to a landmark. The targeting accuracy and consistency were evaluated by first irradiating a group of mice inoculated with U87 human glioma brain tumours using the present protocol and then determining the locations of the microbeam radiation tracks using γ-H2AX immunofluorescence staining. The histology results showed that among 14 mice irradiated, 11 received the prescribed number of microbeams on the targeted tumour, with an average localization accuracy of 454 µm measured directly from the histology (537 µm if measured from the registered histological images). Two mice received one of the three prescribed microbeams on the tumour site. One mouse was excluded from the analysis due to tissue staining errors.

  15. Neem tree (Azadirachta indica) extract specifically suppresses the growth of tumors in H22-bearing Kunming mice.

    PubMed

    He, Zhenxiang; Jiang, Cuihua; Zhang, Jian; Yin, Zhiqi; Yin, Zengfang; Zhu, Yunfeng; Fu, Jie

    2016-01-01

    Recently, neem tree (Azadirachta indica) extract (NTE) has been reported to have various antitumor activities against gastric, breast, prostate, and skin cancer, respectively. The current study was designed to evaluate the effect of NTE on hepatic cancer in a mouse model. The possible side effects elicited by NTE were also evaluated. The components in NTE were analyzed by liquid chromatography-mass spectrometry (LC-MS). H22 cells-bearing Kumming mice were generated by injecting H22 cells subcutaneously into the right forelimb armpit of the mice. Then the mice were treated daily for 27 days with NTE (150, 300, and 600 mg/kg body weight) by intragastric administration, using carboxymethyl cellulose (CMC, 1%) as blank control and cyclophosphamide (CTX, 20 mg/kg) as positive control. The antitumor effect of NTE was evaluated by assessment of survival rate, body weight, tumor volume and weight, tumor histology, thymus and spleen indexes, and liver histology. The tumor weight and volume in groups of NTE and CTX were significantly lower than those in the CMC group. The survival rate in the NTE group receiving the high dose (600 mg/kg) was significantly higher than that in the CTX and CMC groups. Compared with CTX, NTE was observed to have a tumor-specific cytotoxicity without impairing the normal liver tissue. Additionally, the higher indexes of thymus and spleen indicated that NTE could facilitate the growth of immune organs. The results indicate that NTE is a promising candidate for the antitumor treatment with high efficacy and safety.

  16. Effects of load-bearing exercise on skeletal structure and mechanics differ between outbred populations of mice.

    PubMed

    Wallace, Ian J; Judex, Stefan; Demes, Brigitte

    2015-03-01

    Effects of load-bearing exercise on skeletal structure and mechanical properties can vary between inbred strains of mice. Here, we examine whether such variation also exists at the population level. An experiment was performed with two outbred mouse stocks that have been reproductively isolated for >120 generations (Hsd:ICR, Crl:CD1). Growing females from each stock were either treated with a treadmill-running regimen for 1 month or served as controls. Limb forces were recorded with a force plate and cage activity monitored to verify that they were similar between stocks. After the experiment, femoral cortical and trabecular bone structure were quantified with micro-CT in the mid-diaphysis and distal metaphysis, respectively, and diaphyseal structural strength was determined with mechanical testing. Among Hsd:ICR mice, running led to significant improvements in diaphyseal bone quantity, structural geometry, and mechanical properties, as well as enhanced trabecular morphology. In contrast, among Crl:CD1 mice, the same running regimen had little effect on cortical and trabecular structure and significantly reduced diaphyseal resistance to fracture. In neither stock was body mass, muscle mass, or cage activity level different between runners and controls. Given that most environmental variables were controlled in this study, the differential effects of exercise on Hsd:ICR and Crl:CD1 bones were likely due to genetic differences between stocks. These results suggest that the benefits of loading for bone may vary between human populations (e.g., ethnic groups), in which case exercise programs and technologies designed to promote bone health with mechanical signals may be more advantageous to certain populations than others. PMID:25460574

  17. Study of DNA synthesis and mitotic activity of hepatocytes and its relation to angiogenesis in hepatectomised tumour bearing mice.

    PubMed

    Andrini, Laura B; García, Marcela N; Inda, Ana María; Errecalde, Ana Lía

    2013-11-01

    Partial hepatectomy (PH) alters serum concentrations of substances involved in cellular proliferation, leading to the compensatory liver hyperplasia. Furthermore, angiogenesis is mainly stimulated by vascular endothelial growth factor (VEGF) and is a fundamental requirement either in liver regeneration or in tumours growth. This study looks at the expression of VEGF, DNA synthesis (DNAs) and mitotic activity (MA) in hepatectomised (H) and hepatectomised-tumour bearing (HTB) mice throughout a 24 h period. Adult male mice were sacrificed every 4 h from 26 to 50 h post-hepatectomy. H mice show a circadian rhythm in VEGF expression with a maximum value of 2.6 ± 0.1 at 08/46 h of day/hours posthepatectomy (HD/HPH); in DNAs, the maximum value was 3.4 ± 0.3 at 16/30 (HD/HPH) and in MA it was 2.3 ± 0.01 at 12/50 (HD/HPH). In HTB animals the peak of VEGF expression appears at 16/30 (HD/HPH) with a maximum value of 3.7 ± 0.1, the peak of DNAs was at 00/38 (HD/HPH) with a value of 4.6 ± 0.3 and the maximum value of MA of 08/46 (HD/HPH) with a value of 3.01 ± 0.3. We can conclude that the presence of the tumour induces modifications in the intensity and the temporal distribution of the circadian curves of VEGF expression, DNAs and MA of hepatectomised animals.

  18. Image-guided microbeam irradiation to brain tumour bearing mice using a carbon nanotube x-ray source array.

    PubMed

    Zhang, Lei; Yuan, Hong; Burk, Laurel M; Inscoe, Christy R; Hadsell, Michael J; Chtcheprov, Pavel; Lee, Yueh Z; Lu, Jianping; Chang, Sha; Zhou, Otto

    2014-03-01

    Microbeam radiation therapy (MRT) is a promising experimental and preclinical radiotherapy method for cancer treatment. Synchrotron based MRT experiments have shown that spatially fractionated microbeam radiation has the unique capability of preferentially eradicating tumour cells while sparing normal tissue in brain tumour bearing animal models. We recently demonstrated the feasibility of generating orthovoltage microbeam radiation with an adjustable microbeam width using a carbon nanotube based x-ray source array. Here we report the preliminary results from our efforts in developing an image guidance procedure for the targeted delivery of the narrow microbeams to the small tumour region in the mouse brain. Magnetic resonance imaging was used for tumour identification, and on-board x-ray radiography was used for imaging of landmarks without contrast agents. The two images were aligned using 2D rigid body image registration to determine the relative position of the tumour with respect to a landmark. The targeting accuracy and consistency were evaluated by first irradiating a group of mice inoculated with U87 human glioma brain tumours using the present protocol and then determining the locations of the microbeam radiation tracks using γ-H2AX immunofluorescence staining. The histology results showed that among 14 mice irradiated, 11 received the prescribed number of microbeams on the targeted tumour, with an average localization accuracy of 454 µm measured directly from the histology (537 µm if measured from the registered histological images). Two mice received one of the three prescribed microbeams on the tumour site. One mouse was excluded from the analysis due to tissue staining errors.

  19. Neem tree (Azadirachta indica) extract specifically suppresses the growth of tumors in H22-bearing Kunming mice.

    PubMed

    He, Zhenxiang; Jiang, Cuihua; Zhang, Jian; Yin, Zhiqi; Yin, Zengfang; Zhu, Yunfeng; Fu, Jie

    2016-01-01

    Recently, neem tree (Azadirachta indica) extract (NTE) has been reported to have various antitumor activities against gastric, breast, prostate, and skin cancer, respectively. The current study was designed to evaluate the effect of NTE on hepatic cancer in a mouse model. The possible side effects elicited by NTE were also evaluated. The components in NTE were analyzed by liquid chromatography-mass spectrometry (LC-MS). H22 cells-bearing Kumming mice were generated by injecting H22 cells subcutaneously into the right forelimb armpit of the mice. Then the mice were treated daily for 27 days with NTE (150, 300, and 600 mg/kg body weight) by intragastric administration, using carboxymethyl cellulose (CMC, 1%) as blank control and cyclophosphamide (CTX, 20 mg/kg) as positive control. The antitumor effect of NTE was evaluated by assessment of survival rate, body weight, tumor volume and weight, tumor histology, thymus and spleen indexes, and liver histology. The tumor weight and volume in groups of NTE and CTX were significantly lower than those in the CMC group. The survival rate in the NTE group receiving the high dose (600 mg/kg) was significantly higher than that in the CTX and CMC groups. Compared with CTX, NTE was observed to have a tumor-specific cytotoxicity without impairing the normal liver tissue. Additionally, the higher indexes of thymus and spleen indicated that NTE could facilitate the growth of immune organs. The results indicate that NTE is a promising candidate for the antitumor treatment with high efficacy and safety. PMID:27248120

  20. Water-soluble extract of Saxifraga stolonifera has anti-tumor effects on Lewis lung carcinoma-bearing mice.

    PubMed

    Liu, Dong; Yang, Ping; Zhang, Yu-Qing

    2016-10-01

    Saxifraga stolonifera is an evergreen and herbaceous plant well known in Korea, Japan and western China, which has great potential applications in gardening and pharmacology. The aim of this study is to evaluate the anti-tumor effects of S. stolonifera extraction on lung tumors of Lewis mice. By the measurement of MS/MS, we found that there were four main bioactive components in methanol extract of S. stolonifera, including gallic acid, norbergenin, protocatechuic acid and bergenin, and the results of quantitative analysis showed that the contents of gallic acid, protocatechuic acid and bergenin in methanol extract of S. stolonifera were 5.150, 1.492, 24.559mg/g, respectively. Animal experiment showed that the mean tumor weight of Lewis lung carcinoma-bearing mice treated with water-soluble extract of S. stolonifera was obviously smaller than model group (cis-DDP), and its inhibition rate was 49.2%. In addition, histopathological evaluation and immunohistochemical assay confirmed the anti-tumor effects of S. stolonifera. Investigation of four haematological parameters revealed that the Lewis mice fed with S. stolonifera showed good resilience in the level of leukocyte, haemoglobin, blood platelets and red blood cell compared with the model group. In addition, RT-PCR suggested that the relative expression of pro-apoptosis gene p53, Sox and Bax was enhanced, while the relative expression of anti-apoptosis gene Bcl2 was diminished in comparison with model group. These results suggested that water-soluble extract of S. stolonifera has anti-tumor effects on Lewis lung tumors. PMID:27575479

  1. PET/CT Based In Vivo Evaluation of 64Cu Labelled Nanodiscs in Tumor Bearing Mice

    PubMed Central

    Huda, Pie; Binderup, Tina; Pedersen, Martin Cramer; Midtgaard, Søren Roi; Elema, Dennis Ringkjøbing; Kjær, Andreas; Jensen, Mikael; Arleth, Lise

    2015-01-01

    64Cu radiolabelled nanodiscs based on the 11 α-helix MSP1E3D1 protein and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine lipids were, for the first time, followed in vivo by positron emission tomography for evaluating the biodistribution of nanodiscs. A cancer tumor bearing mouse model was used for the investigations, and it was found that the approximately 13 nm nanodiscs, due to their size, permeate deeply into cancer tissue. This makes them promising candidates for both drug delivery purposes and as advanced imaging agents. For the radiolabelling, a simple approach for 64Cu radiolabelling of proteins via a chelating agent, DOTA, was developed. The reaction was performed at sufficiently mild conditions to be compatible with labelling of the protein part of a lipid-protein particle while fully conserving the particle structure including the amphipathic protein fold. PMID:26132074

  2. Phenotypic dynamics of microglial and monocyte-derived cells in glioblastoma-bearing mice

    PubMed Central

    Ricard, Clément; Tchoghandjian, Aurélie; Luche, Hervé; Grenot, Pierre; Figarella-Branger, Dominique; Rougon, Geneviève; Malissen, Marie; Debarbieux, Franck

    2016-01-01

    Inflammatory cells, an integral component of tumor evolution, are present in Glioblastomas multiforme (GBM). To address the cellular basis and dynamics of the inflammatory microenvironment in GBM, we established an orthotopic syngenic model by grafting GL261-DsRed cells in immunocompetent transgenic LysM-EGFP//CD11c-EYFP reporter mice. We combined dynamic spectral two-photon imaging with multiparametric cytometry and multicolor immunostaining to characterize spatio-temporal distribution, morphology and activity of microglia and blood-derived infiltrating myeloid cells in live mice. Early stages of tumor development were dominated by microglial EYFP+ cells invading the tumor, followed by massive recruitment of circulating LysM-EGFP+ cells. Fluorescent invading cells were conventional XCR1+ and monocyte-derived dendritic cells distributed in subpopulations of different maturation stages, located in different areas relative to the tumor core. The lethal stage of the disease was characterized by the progressive accumulation of EGFP+/EYFP+ monocyte-derived dendritic cells. This local phenotypic regulation of monocyte subtypes marked a transition in the immune response. PMID:27193333

  3. Disparate impact of butyroyloxymethyl diethylphosphate (AN-7), a histone deacetylase inhibitor, and doxorubicin in mice bearing a mammary tumor.

    PubMed

    Tarasenko, Nataly; Cutts, Suzanne M; Phillips, Don R; Inbal, Aida; Nudelman, Abraham; Kessler-Icekson, Gania; Rephaeli, Ada

    2012-01-01

    The histone deacetylase inhibitor (HDACI) butyroyloxymethyl diethylphosphate (AN-7) synergizes the cytotoxic effect of doxorubicin (Dox) and anti-HER2 on mammary carcinoma cells while protecting normal cells against their insults. This study investigated the concomitant changes occurring in heart tissue and tumors of mice bearing a subcutaneous 4T1 mammary tumor following treatment with AN-7, Dox, or their combination. Dox or AN-7 alone led to inhibition of both tumor growth and lung metastases, whereas their combination significantly increased their anticancer efficacy and attenuated Dox- toxicity. Molecular analysis revealed that treatment with Dox, AN-7, and to a greater degree, AN-7 together with Dox increased tumor levels of γH2AX, the marker for DNA double-strand breaks and decreased the expression of Rad51, a protein needed for DNA repair. These events culminated in increased apoptosis, manifested by the appearance of cytochrome-c in the cytosol. In the myocardium, Dox-induced cardiomyopathy was associated with an increase in γH2AX expression and a reduction in Rad51 and MRE11 expression and increased apoptosis. The addition of AN-7 to the Dox treatment protected the heart from Dox insults as was manifested by a decrease in γH2AX levels, an increase in Rad51 and MRE11 expression, and a diminution of cytochrome-c release. Tumor fibrosis was high in untreated mice but diminished in Dox- and AN-7-treated mice and was almost abrogated in AN-7+Dox-treated mice. By contrast, in the myocardium, Dox alone induced a dramatic increase in fibrosis, and AN7+Dox attenuated it. The high expression levels of c-Kit, Ki-67, c-Myc, lo-FGF, and VEGF in 4T1 tumors were significantly reduced by Dox or AN-7 and further attenuated by AN-7+Dox. In the myocardium, Dox suppressed these markers, whereas AN-7+Dox restored their expression. In conclusion, the combination of AN-7 and Dox results in two beneficial effects, improved anticancer efficacy and cardioprotection.

  4. The effect of lithium chloride on tumour appearance and survival of melanoma-bearing mice.

    PubMed

    Ballin, A; Aladjem, M; Banyash, M; Boichis, H; Barzilay, Z; Gal, R; Witz, I P

    1983-07-01

    The possible effect of lithium chloride, a compound which reduces the incidence of infection in cancer patients, was investigated on murine melanoma. C57 BL syngeneic mice were inoculated i.p. with B16 melanoma cells. The animals were divided into 4 groups, receiving daily i.p. treatment with saline--group 1, controls; lithium chloride--group 2, bleomycin and vinblastine--group 3, and lithium chloride with bleomycin and vinblastine--group 4. Animals in group 4 had a significant delay in tumour appearance, a higher degree of tumour necrosis, and a longer survival rate. In addition a significant reduction of serum lithium concentration was noted in animals of this group in comparison with animals in group 2, treated with lithium chloride alone. There was no lithium-induced leukocytosis.

  5. Combined optical tomographic and magnetic resonance imaging of tumor bearing mice

    NASA Astrophysics Data System (ADS)

    Masciotti, J.; Abdoulaev, G.; Hur, J.; Papa, J.; Bae, J.; Huang, J.; Yamashiro, D.; Kandel, J.; Hielscher, A. H.

    2005-04-01

    With the advent of small animal imaging systems, it has become possible to non-invasively monitor the progression of diseases in living small animals and study the efficacy of drugs and treatment protocols. Magnetic resonance imaging (MRI) is an established imaging modality capable of obtaining high resolution anatomical images as well as studying cerebral blood volume (CBV), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO2). Optical tomography, on the other hand, is an emerging imaging modality, which, while much lower in spatial resolution and insensitive to CBF, can separate the effects of oxyhemoglobin, deoxyhemoglobin, and CBV with high temporal resolution. In this study we present our first results concerning coregistration of MRI and optical data. By applying both modalities to imaging of kidney tumors in mice that undergo VEGF treatment, we illustrate how these imaging modalities can supplement each other and cross validation can be performed.

  6. Antitumor effect of beta2-microglobulin in leukemic cell-bearing mice via apoptosis-inducing activity: activation of caspase-3 and nuclear factor-kappaB.

    PubMed

    Mori, M; Terui, Y; Tanaka, M; Tomizuka, H; Mishima, Y; Ikeda, M; Kasahara, T; Uwai, M; Ueda, M; Inoue, R; Itoh, T; Yamada, M; Hayasawa, H; Furukawa, Y; Ishizaka, Y; Ozawa, K; Hatake, K

    2001-06-01

    We have reported previously that beta2-microglobulin (beta2m) induces apoptosis in leukemic cells in vitro, and that an interaction between beta2m and HLA class I antigen induces apoptosis. Here we examined whether beta2m can induce apoptosis in leukemic cells in vivo and whether it has an antitumor effect in tumor-bearing mice. Daily administration of 50 or 250 microg of beta2m induced apoptosis and an antitumor effect on K562 leukemia cell-bearing mice in the same manner as tumor necrosis factor-alpha. In tumor tissues in beta2m-treated mice, both caspase-3 and nuclear factor-kappaB (NF-kappaB) were stained more strongly than in control mice by anti-caspase-3 and anti-NF-kappaB p65/Rel A polyclonal antibodies. We also observed the in vivo immunological effects of beta2m on lymphoid and hematopoietic organs, such as thymus, bone marrow, Peyer's patches, liver, and spleen in normal mice. Using antibodies against caspase-3 and NF-kappaB, immunohistochemical staining showed that no specific tissues were damaged or stained in normal mice. We conclude that beta2m stimulates caspase-3 and NF-kappaB pathways to induce apoptosis, making it a useful approach to a new therapy for leukemia.

  7. Effect of Alstonia scholaris in enhancing the anticancer activity of berberine in the Ehrlich ascites carcinoma-bearing mice.

    PubMed

    Jagetia, Ganesh Chandra; Baliga, Manjeshwar Shrinath

    2004-01-01

    The chemomodulatory activity of Alstonia scholaris extract (ASE) was studied in combination with berberine hydrochloride (BCL), a topoisomerase inhibitor, in Ehrlich ascites carcinoma-bearing mice. The tumor-bearing animals were injected with various doses of ASE, and 8 mg/kg of BCL (one-fifth of the 50% lethal dose) was combined with different doses of ASE (60-240 mg/kg). The combination of 180 mg/kg of ASE with 8 mg/kg of BCL showed the greatest antitumor effect; the number of tumor-free survivors was more, and the median survival time and the average survival time increased up to 47 and 40.5 days, respectively, when compared with either treatment alone. Similarly, when 180 mg/kg of ASE was combined with different doses of BCL (2-12 mg/kg), a dose-dependent increase in the anticancer activity was observed up to 8 mg/kg of BCL. However, a further increase in the BCL dose to 10 and 12 mg/kg resulted in toxic side effects. The best effect was observed when 180 mg/kg of ASE was combined with 6 or 8 mg/kg of BCL, where an increase in the antineoplastic activity was reported. The efficacy of the combination of 180 mg/kg of ASE was also tested with 6 mg/kg body weight of BCL in various stages of tumorigenesis, and it was effective when given in the early stages, although the efficiency decreased with an increase in the tumor developmental stages.

  8. The appearance of T cells bearing self-reactive T cell receptor in the livers of mice injected with bacteria.

    PubMed

    Abo, T; Ohteki, T; Seki, S; Koyamada, N; Yoshikai, Y; Masuda, T; Rikiishi, H; Kumagai, K

    1991-08-01

    We demonstrated in the present study that with bacterial stimulation, an increased number of alpha/beta T cells proliferated in the liver of mice and that even T cells bearing self-reactive T cell receptor (TCR) (or forbidden T cell clones), as estimated by anti-V beta monoclonal antibodies in conjunction with immunofluorescence tests, appeared in the liver and, to some extent, in the periphery. The majority (greater than 80%) of forbidden clones induced had double-negative CD4-8-phenotype. In a syngeneic mixed lymphocyte reaction, these T cells appear to be self-reactive. Such forbidden clones and normal T cells in the liver showed a two-peak pattern of TCR expression, which consisted of alpha/beta TCR dull and bright positive cells, as seen in the thymus. A systematic analysis of TCR staining patterns in the various organs was then carried out. T cells from not only the thymus but also the liver had the two-peak pattern of alpha/beta TCR, whereas all of the other peripheral lymphoid organs had a single-peak pattern of TCR. However, T cells in the liver were not comprised of double-positive CD4+8+ cells, which predominantly reside in the thymus. The present results therefore suggest that T cell proliferation in the liver might reflect a major extrathymic pathway for T cell differentiation and that this hepatic pathway has the ability to produce T cells bearing self-reactive TCR under bacterial stimulation, probably due to the lack of a double-positive stage for negative selection.

  9. The glycolytic inhibitor 2-deoxy-D-glucose enhances the efficacy of etoposide in ehrlich ascites tumor-bearing mice.

    PubMed

    Gupta, Seema; Mathur, Rohit; Dwarakanath, B S

    2005-01-01

    Earlier studies have shown that 2-deoxy-D-glucose (2-DG), a glucose analogue and inhibitor of glycolytic ATP production significantly enhances the cytotoxic effects of anticancer agents like topoisomerase inhibitors (etoposide and camptothecin) and a radiomimetic drug (bleomycin) in established human tumor cell lines. Therefore, combination of 2-DG and DNA damage causing cytotoxic agents could be very useful in enhancing local tumor control. The purpose of the present studies was to investigate the therapeutic effects of etoposide and 2-DG in Ehrlich ascites tumor (EAT) bearing mice, grown as solid tumor as well as in the ascites form. Cell growth, cell cycle perturbations (flow cytometry), cytogenetic damage (micronuclei assay) and apoptosis (DNA content, morphological changes) were studied as parameters of cellular response, while delay in tumor growth and cure rate (tumor free survival) were evaluated as parameters of systemic response. Body weight and general condition as well as the damage to bone marrow and spleen was monitored to evaluate normal tissue toxicity. Intraperitoneal administration of etoposide (30 mg/Kg b. wt.) resulted in significant tumor growth delay and cure (approximately 11%) only in subcutaneous tumors leading to local tumor control. When etoposide was combined with 2-DG (2 g/Kg b. wt.; i.v./i.p.; 4 h after etoposide injection), these effects were further enhanced resulting in a cure rate of approximately 22% in case of subcutaneous tumors and 20% in ascites bearing mice. Analysis of cells obtained from ascitic fluid as well as solid tumors during follow up clearly showed that etoposide induced cell death was mainly due to apoptosis, which was enhanced further by 2-DG. Although, there was a significant level of toxicity revealed by reduced animal survival, decrease in body weight and damage to sensitive organ status like spleen and bone marrow at 60 mg/Kg b. wt. of etoposide, it was not significant at 30 mg/Kg b.wt. 2-DG, however, did not

  10. Boron-11 NMR of borocaptate: relaxation and in vivo detection in melanoma-bearing mice.

    PubMed

    Bendel, P; Frantz, A; Zilberstein, J; Kabalka, G W; Salomon, Y

    1998-03-01

    Longitudinal and transverse relaxation rates for the 11B resonances in sodium borocaptate (BSH) at varying concentrations were measured in undiluted horse serum in a 4.7 Tesla field. The results could be fit by a model that assumes fast exchange of the BSH molecule between a free and a bound state, using values of 0.77+/-0.7 MHz for the 11B quadrupole coupling constant and (6.3+/-0.9) x 10(-9) s for the rotational correlation time in the bound state. These results were used as a basis for assessing the requirements and limitations of quantitative determination of BSH concentrations in vivo, using 11B NMR. Surface coil 11B NMR spectroscopy was performed on a total of 14 mice injected with BSH. Some of the animals (n=9) had implanted M2R melanoma tumors grown to various sizes in the rear thigh, in which case the surface coil was placed against the tumor, whereas for the other animals (without tumor), the coil was placed against the rear thigh muscle. NMR spectra were acquired under fully relaxed conditions. The spectra were quantitated by peak integration; apparent absolute BSH concentrations were derived by comparison with spectra from a phantom with known BSH concentration, using extrapolation of the time-domain data to zero preacquisition delay. The results indicate significantly higher 11B BSH signal intensities in tumors, compared with muscle tissue, whereas the uptake and clearance kinetics were similar.

  11. A novel TLR7 agonist reverses NK cell anergy and cures RMA-S lymphoma-bearing mice.

    PubMed

    Wiedemann, Gabriela Maria; Jacobi, Severin Johannes; Chaloupka, Michael; Krächan, Angelina; Hamm, Svetlana; Strobl, Stefan; Baumgartner, Roland; Rothenfusser, Simon; Duewell, Peter; Endres, Stefan; Kobold, Sebastian

    2016-07-01

    Toll-like receptor 7 (TLR7) agonists are potent immune stimulants able to overcome cancer-associated immune suppression. Due to dose-limiting systemic toxicities, only the topically applied TLR7 agonist (imiquimod) has been approved for therapy of skin tumors. There is a need for TLR7-activating compounds with equivalent efficacy but less toxicity. SC1, a novel small molecule agonist for TLR7, is a potent type-1 interferon inducer, comparable to the reference TLR7 agonist resiquimod, yet with lower induction of proinflammatory cytokines. In vivo, SC1 activates NK cells in a TLR7-dependent manner. Mice bearing the NK cell-sensitive lymphoma RMA-S are cured by repeated s. c. administrations of SC1 as efficiently as by the administration of resiquimod. No relevant toxicities were observed. Mechanistically, SC1 reverses NK cell anergy and restores NK cell-mediated tumor cell killing in an IFN-α-dependent manner. TLR7 targeting by SC1-based compounds may form an attractive strategy to activate NK cell responses for cancer therapy. PMID:27622045

  12. 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

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

    PubMed

    Li, Jianbo; Bao, Baoliang; Liu, Lei; Wang, Xuemei

    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

  14. 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.

  15. Antitumor activity of crude polysaccharides isolated from Solanum nigrum Linne on U14 cervical carcinoma bearing mice.

    PubMed

    Li, Jian; Li, Qingwang; Feng, Tao; Zhang, Tao; Li, Kun; Zhao, Rui; Han, Zengsheng; Gao, Dawei

    2007-09-01

    Solanum nigrum Linne (SNL) has been used in traditional Chinese medicine for centuries because of its diuretic and antipyretic effects. The present study examined the effect of the crude polysaccharides isolated from Solanum nigrum Linne (SNL-P) on tumor growth. SNL-P had a significant growth inhibition effect on cervical cancer (U14) of tumor-bearing mice. Further analysis of the tumor inhibition mechanism indicated that the number of apoptotic tumor cells increased significantly, the expression of Bax increased and the expression of Bcl-2 and mutant p53 decreased dramatically in cervical cancer sections after oral administration of SNL-P for 12 days. Moreover, SNL-P treatment decreased the level of blood serum TNF-alpha. These results indicated that the tumor growth inhibition of SNL-P administration might correlate with the reduction of TNF-alpha level of blood serum, which resulted in a massive necrosis in tumor tissues and the up-regulation of Bax and down-regulation of Bcl-2 and mutant p53 gene expression, which triggered apoptosis in tumor cells. These findings demonstrated that the SNL-P is a potential antitumor agent. PMID:17486683

  16. New strategy for the identification of squamous carcinoma antigens that induce therapeutic immune responses in tumor-bearing mice.

    PubMed

    O-Sullivan, I; Chopra, A; Kim, T S; Magnuson, S; Falduto, M T; Huang, J; Cohen, E P

    2007-04-01

    This study describes a new strategy for the identification of squamous carcinoma antigens tumor-associated antigens (TAA). The antigens were discovered by comparing microarrays of squamous carcinoma vaccines highly enriched for immunotherapeutic cells with non-enriched vaccines. The vaccines were prepared by transferring sheared genomic DNA fragments (25 kb) from KLN205 cells, a squamous carcinoma cell line (DBA/2 mouse origin (H-2(d)) into LM fibroblasts (C3H/He origin, H-2(k)). The transferred tumor DNA segments integrate spontaneously into the genome of the recipient cells, replicate as the cells divide and are expressed. As only a small proportion of the transfected cell population was expected to have incorporated DNA segments that included genes specifying TAA (the vast majority specify normal cellular constituents), a novel strategy was employed to enrich the vaccine for TAA-positive cells. Microarrays were used to compare genes expressed by enriched and non-enriched vaccines. Seventy-five genes were overexpressed in cells from the enriched vaccine. One, the gene for Cytochrome P450 (family 2, subfamily e, polypeptide 1) (Cyp2e1), was overexpressed in the enriched but not the non-enriched vaccine. A vaccine for squamous carcinoma was prepared by transfer of a 357 bp fragment of the gene for Cyp2e1 into the fibroblast cell line. Robust immunity, sufficient to result in indefinite survival, was induced in tumor-bearing mice immunized with cells transfected with this gene fragment.

  17. Effect of Sipjeondaebo-tang on cancer-induced anorexia and cachexia in CT-26 tumor-bearing mice.

    PubMed

    Choi, Youn Kyung; Jung, Ki Yong; Woo, Sang-Mi; Yun, Yee Jin; Jun, Chan-Yong; Park, Jong Hyeong; Shin, Yong Cheol; Cho, Sung-Gook; Ko, Seong-Gyu

    2014-01-01

    Cancer-associated anorexia and cachexia are a multifactorial condition described by a loss of body weight and muscle with anorexia, asthenia, and anemia. Moreover, they correlate with a high mortality rate, poor response to chemotherapy, poor performance status, and poor quality of life. Cancer cachexia is regulated by proinflammatory cytokines such as interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor- α (TNF- α). In addition, glucagon like peptide-1 (GIP-1), peptide YY (PYY), ghrelin, and leptin plays a crucial role in food intake. In this study, we investigated the therapeutic effects of one of the traditional herbal medicines, Sipjeondaebo-tang (Juzen-taiho-to in Japanese; SJDBT), on cancer anorexia and cachexia in a fundamental mouse cancer anorexia/cachexia model, CT-26 tumor-bearing mice. SJDBT was more significantly effective in a treatment model where it was treated after anorexia and cachexia than in a prevention model where it was treated before anorexia and cachexia on the basis of parameters such as weights of muscles and whole body and food intakes. Moreover, SJDBT inhibited a production of IL-6, MCP-1, PYY, and GLP-1 and ameliorated cancer-induced anemia. Therefore, our in vivo studies provide evidence on the role of SJDBT in cancer-associated anorexia and cachexia, thereby suggesting that SJDBT may be useful for treating cancer-associated anorexia and cachexia.

  18. Modification of radio-thermo-chemotherapy by AK-2123 and hydralazine in tumor bearing mice.

    PubMed

    Kunugita, N; Mei, N; Norimura, T; Kagiya, T V

    1996-09-01

    The effects of chemical modifiers of hypoxic radiosensitizer, a 3-nitrotriazole derivative AK-2123 (200 mg/kg) before treatment, and vasodilator of hydralazine (HDZ; 5.0 mg/kg) after treatment on tumor growth of SCCVII of mice were investigated in the radio-thermotherapy combined with mitomycin C (MMC; 2.0 mg/kg) or adriamycin (ADM; 3 mg/kg). The tumor treated by 10 Gy alone (tumor doubling time = 7.5 days), MMC alone (6.9 days), and hyperthermia (43 degrees C, 30 min; HT) alone (8.0 days) showed a slight growth delay (control: 5.6 days). Prolonged growth delay (23.2 days) was observed by MMC-radio-thermotherapy (MMC-10Gy/HT) than that (12.4 days) by 10 Gy/HT. The modification of MMC-radio-thermotherapy by HDZ administered between 10 Gy and HT (MMC-10 Gy/HDZ/HT) resulted in the significant prolongation of tumor growth delay (31.7 days). AK-2123 administration before this treatment, (MMC-AK-2123)-10 Gy/HDZ/HT), enhanced a further tumor growth delay (37.6 days) which is equal to that by 50 Gy alone and resulted in the highest dose modifying factor (DMF) of 5.2. While modification of ADM-radio-thermotherapy by AK-2123 and HDZ, (ADM-AK-2123)-10 Gy/HDZ/HT, gave the equal tumor growth delay to that by 30 Gy alone (DMF = 3.1). These high efficacies of radio-thermo-chemotherapy modified by AK-2123 and HDZ may be caused by tumor blood flow reduction.

  19. Dietary supplementation with a specific combination of high protein, leucine, and fish oil improves muscle function and daily activity in tumour-bearing cachectic mice

    PubMed Central

    van Norren, K; Kegler, D; Argilés, J M; Luiking, Y; Gorselink, M; Laviano, A; Arts, K; Faber, J; Jansen, H; van der Beek, E M; van Helvoort, A

    2009-01-01

    Cancer cachexia is characterised by metabolic alterations leading to loss of adipose tissue and lean body mass and directly compromises physical performance and the quality of life of cancer patients. In a murine cancer cachectic model, the effects of dietary supplementation with a specific combination of high protein, leucine and fish oil on weight loss, muscle function and physical activity were investigated. Male CD2F1 mice, 6–7 weeks old, were divided into body weight-matched groups: (1) control, (2) tumour-bearing, and (3) tumour-bearing receiving experimental diets. Tumours were induced by s.c. inoculation with murine colon adenocarcinoma (C26) cells. Food intake, body mass, tumour size and 24 h-activity were monitored. Then, 20 days after tumour/vehicle inoculation, the animals were killed and muscle function was tested ex vivo. Tumour-bearing mice showed reduced carcass, muscle and fat mass compared with controls. EDL muscle performance and total daily activity were impaired in the tumour-bearing mice. Addition of single nutrients resulted in no or modest effects. However, supplementation of the diet with the all-in combination of high protein, leucine and fish oil significantly reduced loss of carcass, muscle and fat mass (loss in mass 45, 52 and 65% of TB-con, respectively (P<0.02)) and improved muscle performance (loss of max force reduced to 55–64% of TB-con (P<0.05)). Moreover, total daily activity normalised after intervention with the specific nutritional combination (50% of the reduction in activity of TB-con (P<0.05)). In conclusion, a nutritional combination of high protein, leucine and fish oil reduced cachectic symptoms and improved functional performance in cancer cachectic mice. Comparison of the nutritional combination with its individual modules revealed additive effects of the single components provided. PMID:19259092

  20. Subcutaneous injection of water-soluble multi-walled carbon nanotubes in tumor-bearing mice boosts the host immune activity

    NASA Astrophysics Data System (ADS)

    Meng, Jie; Yang, Man; Jia, Fumin; Kong, Hua; Zhang, Weiqi; Wang, Chaoying; Xing, Jianmin; Xie, Sishen; Xu, Haiyan

    2010-04-01

    The immunological responses induced by oxidized water-soluble multi-walled carbon nanotubes on a hepatocarcinoma tumor-bearing mice model via a local administration of subcutaneous injection were investigated. Experimental results show that the subcutaneously injected carbon nanotubes induced significant activation of the complement system, promoted inflammatory cytokines' production and stimulated macrophages' phagocytosis and activation. All of these responses increased the general activity of the host immune system and inhibited the progression of tumor growth.

  1. Inhibition of Tumor Growth and Immunomodulatory Effects of Flavonoids and Scutebarbatines of Scutellaria barbata D. Don in Lewis-Bearing C57BL/6 Mice

    PubMed Central

    Gong, Tao; Wang, Chun-Fei; Yuan, Jia-Rui; Li, Yu; Gu, Jun-Fei; Zhao, Bing-Jie; Zhang, Li; Jia, Xiao-Bin; Feng, Liang; Liu, Shen-Lin

    2015-01-01

    Immunomodulatory effect has been found to be an important therapeutic measure for immune responses against cancer. In this study, we evaluated the inhibition of Scutellaria barbata D. Don (SB), an anti-inflammatory and an antitumor Chinese herb, including flavonoids and scutebarbatines on tumor growth and its immunomodulatory effects in vivo. HPLC and LC/MS/MS methods were conducted for the analysis of flavonoids and scutebarbatines in SB. Lewis-bearing C57BL/6 mice model was established and tumor volume was evaluated by high frequency color ultrasound experiment. ELISA and western blot analysis were performed for the determination of immunomodulatory factors. SB treatment at the dose of 10, 6.67, and 3.33 g crude drug/kg/d significantly inhibited tumor growth of Lewis-bearing C57BL/6 mice with the inhibition rates of 44.41 ± 5.44%, 33.56 ± 4.85%, and 27.57 ± 4.96%, respectively. More importantly, the spleen and thymus indexes were increased remarkably by SB treatment. SB could decrease IL-17, IL-10, FOXP3, TGF-β1, RORγt, and IL-6 levels whereas it could increase remarkably IL-2 and IFN-γ levels. Our results demonstrated that SB could inhibit tumor growth in vivo through regulating immune function in tumor-bearing mice and suggested that the immunomodulatory function of SB had a potential therapeutic effect in lung cancer. PMID:26064167

  2. Structure of the TCR expressed on a gastritogenic T cell clone, II-6, and frequent appearance of similar clonotypes in mice bearing autoimmune gastritis.

    PubMed

    Katakai, T; Agata, Y; Shimizu, A; Ohshima, C; Nishio, A; Inaba, M; Kasakura, S; Mori, K J; Masuda, T

    1997-12-01

    A parietal cell-specific Th1 clone, II-6, which was established from a BALB/c mouse bearing post-thymectomy autoimmune gastritis (AIG), recognizes a peptide of the alpha subunit (alpha891-905) of H+/K+-ATPase and induces gastritis in nu/nu BALB/c mice by adoptive cell transfer. In the present study, the primary structure of the TCR of II-6 was determined as Valpha10-Jalpha c5a-Calpha and Vbeta14-Jbeta2.3-Cbeta2 by cDNA cloning. Using PCR with specific primers, we defined the use of this II-6 TCR in nu/nu mice with transferred II-6 cells and in mice that spontaneously developed AIG by thymectomy on day 3 after birth (d3-Tx). II-6 TCR mRNAs were detected in the gastric mucosa of all of the nu/nu mice, suggesting that II-6 cells indeed home to the gastric mucosa and thereby were directly involved in the destruction of target parietal cells. TCR beta chain mRNAs encoding CDR3 region sequences almost identical with that of II-6 were also found in the gastric mucosa in 43% (six of 14 mice tested) of the d3-Tx AIG mice at 4-12 weeks old by nested RT-PCR. Such a frequent appearance of similar clonotypes in independent individuals suggests that T cells bearing II-6-like TCR including the II-6 itself might be directly involved in, although not essential for, the pathogenesis of AIG in 3d-Tx mice.

  3. Combination treatment with oncolytic Vaccinia virus and cyclophosphamide results in synergistic antitumor effects in human lung adenocarcinoma bearing mice

    PubMed Central

    2014-01-01

    Background The capacity of the recombinant Vaccinia virus GLV-1h68 as a single agent to efficiently treat different human or canine cancers has been shown in several preclinical studies. Currently, its human safety and efficacy are investigated in phase I/II clinical trials. In this study we set out to evaluate the oncolytic activity of GLV-1h68 in the human lung adenocarcinoma cell line PC14PE6-RFP in cell cultures and analyzed the antitumor potency of a combined treatment strategy consisting of GLV-1h68 and cyclophosphamide (CPA) in a mouse model of PC14PE6-RFP lung adenocarcinoma. Methods PC14PE6-RFP cells were treated in cell culture with GLV-1h68. Viral replication and cell survival were determined by plaque assays and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, respectively. Subcutaneously implanted PC14PE6-RFP xenografts were treated by systemic injection of GLV-1h68, CPA or a combination of both. Tumor growth and viral biodistribution were monitored and immune-related antigen profiling of tumor lysates was performed. Results GLV-1h68 efficiently infected, replicated in and lysed human PC14PE6-RFP cells in cell cultures. PC14PE6-RFP tumors were efficiently colonized by GLV-1h68 leading to much delayed tumor growth in PC14PE6-RFP tumor-bearing nude mice. Combination treatment with GLV-1h68 and CPA significantly improved the antitumor efficacy of GLV-1h68 and led to an increased viral distribution within the tumors. Pro-inflammatory cytokines and chemokines were distinctly elevated in tumors of GLV-1h68-treated mice. Factors expressed by endothelial cells or present in the blood were decreased after combination treatment. A complete loss in the hemorrhagic phenotype of the PC14PE6-RFP tumors and a decrease in the number of blood vessels after combination treatment could be observed. Conclusions CPA and GLV-1h68 have synergistic antitumor effects on PC14PE6-RFP xenografts. We strongly suppose that in the PC14PE6-RFP model the

  4. Antitumor activity and systemic effects of PVM/MA-shelled selol nanocapsules in lung adenocarcinoma-bearing mice.

    PubMed

    de Souza, Ludmilla Regina; Muehlmann, Luis Alexandre; Matos, Lívia Carneiro; Simón-Vázquez, Rosana; Lacava, Zulmira Guerreiro Marques; De-Paula, Alfredo Maurício Batista; Mosiniewicz-Szablewska, Ewa; Suchocki, Piotr; Morais, Paulo César; González-Fernández, África; Báo, Sônia Nair; Azevedo, Ricardo Bentes

    2015-12-18

    Selol is a semi-synthetic compound containing selenite that is effective against cancerous cells and safer for clinical applications in comparison with other inorganic forms of selenite. Recently, we have developed a formulation of poly(methyl vinyl ether-co-maleic anhydride)-shelled selol nanocapsules (SPN), which reduced the proliferative activity of lung adenocarcinoma cells and presented little deleterious effects on normal cells in in vitro studies. In this study, we report on the antitumor activity and systemic effects induced by this formulation in chemically induced lung adenocarcinoma-bearing mice. The in vivo antitumor activity of the SPN was verified by macroscopic quantification, immunohistochemistry and morphological analyses. Toxicity analyses were performed by evaluations of the kidney, liver, and spleen; analyses of hemogram and plasma levels of alanine aminotransferase, aspartate transaminase, urea, and creatinine; and DNA fragmentation and cell cycle activity of the bone marrow cells. Furthermore, we investigated the potential of the SPN formulation to cause hemolysis, activate the complement system, provoke an inflammatory response and change the conformation of the plasma proteins. Our results showed that the SPN reduced the area of the surface tumor nodules but not the total number of tumor nodules. The biochemical and hematological findings were suggestive of the low systemic toxicity of the SPN formulation. The surface properties of the selol nanocapsules point to characteristics that are consistent with the treatment of the tumors in vivo: low hemolytic activity, weak inflammatory reaction with no activation of the complement system, and mild or absent conformational changes of the plasma proteins. In conclusion, this report suggests that the SPN formulation investigated herein exhibits anti-tumoral effects against lung adenocarcinoma in vivo and is associated with low systemic toxicity and high biocompatibility. PMID:26580675

  5. Intracerebral Distribution of the Oncometabolite d-2-Hydroxyglutarate in Mice Bearing Mutant Isocitrate Dehydrogenase Brain Tumors: Implications for Tumorigenesis

    PubMed Central

    Pickard, Amanda J.; Sohn, Albert S. W.; Bartenstein, Thomas F.; He, Shan; Zhang, Yi; Gallo, James M.

    2016-01-01

    The prevalence of mutant isocitrate dehydrogenase 1 (IDH1) brain tumors has generated significant efforts to understand the role of the mutated enzyme product d-2-hydroxyglutarate (D2HG), an oncometabolite, in tumorigenesis, as well as means to eliminate it. Glymphatic clearance was proposed as a pathway that could be manipulated to accelerate D2HG clearance and dictated the study design that consisted of two cohorts of mice bearing U87/mutant IDH1 intracerebral tumors that underwent two microdialysis – providing D2HG interstitial fluid concentrations – sampling periods of awake and asleep (activate glymphatic clearance) in a crossover manner. Glymphatic clearance was found not to have a significant effect on D2HG brain tumor interstitial fluid concentrations that were 126.9 ± 74.8 μM awake and 117.6 ± 98.6 μM asleep. These concentrations, although low relative to total brain tumor concentrations of 6.8 ± 3.6 mM, were considered sufficient to be transported by interstitial fluid and taken up into normal cells to cause deleterious effects. A model of D2HG CNS distribution supported this contention and was further supported by in vitro studies that showed D2HG could interfere with immune cell function. The study provides insight into the compartmental distribution of D2HG in the brain, wherein the interstitial fluid serves as a dynamic pathway for D2HG to enter normal cells and contribute to tumorigenesis. PMID:27781195

  6. Antitumor activity and systemic effects of PVM/MA-shelled selol nanocapsules in lung adenocarcinoma-bearing mice

    NASA Astrophysics Data System (ADS)

    de Souza, Ludmilla Regina; Alexandre Muehlmann, Luis; Carneiro Matos, Lívia; Simón-Vázquez, Rosana; Guerreiro Marques Lacava, Zulmira; Maurício Batista De-Paula, Alfredo; Mosiniewicz-Szablewska, Ewa; Suchocki, Piotr; César Morais, Paulo; González-Fernández, África; Nair Báo, Sônia; Bentes Azevedo, Ricardo

    2015-12-01

    Selol is a semi-synthetic compound containing selenite that is effective against cancerous cells and safer for clinical applications in comparison with other inorganic forms of selenite. Recently, we have developed a formulation of poly(methyl vinyl ether-co-maleic anhydride)-shelled selol nanocapsules (SPN), which reduced the proliferative activity of lung adenocarcinoma cells and presented little deleterious effects on normal cells in in vitro studies. In this study, we report on the antitumor activity and systemic effects induced by this formulation in chemically induced lung adenocarcinoma-bearing mice. The in vivo antitumor activity of the SPN was verified by macroscopic quantification, immunohistochemistry and morphological analyses. Toxicity analyses were performed by evaluations of the kidney, liver, and spleen; analyses of hemogram and plasma levels of alanine aminotransferase, aspartate transaminase, urea, and creatinine; and DNA fragmentation and cell cycle activity of the bone marrow cells. Furthermore, we investigated the potential of the SPN formulation to cause hemolysis, activate the complement system, provoke an inflammatory response and change the conformation of the plasma proteins. Our results showed that the SPN reduced the area of the surface tumor nodules but not the total number of tumor nodules. The biochemical and hematological findings were suggestive of the low systemic toxicity of the SPN formulation. The surface properties of the selol nanocapsules point to characteristics that are consistent with the treatment of the tumors in vivo: low hemolytic activity, weak inflammatory reaction with no activation of the complement system, and mild or absent conformational changes of the plasma proteins. In conclusion, this report suggests that the SPN formulation investigated herein exhibits anti-tumoral effects against lung adenocarcinoma in vivo and is associated with low systemic toxicity and high biocompatibility.

  7. Internal radiotherapy and dosimetric study for 111In/ 177Lu-pegylated liposomes conjugates in tumor-bearing mice

    NASA Astrophysics Data System (ADS)

    Wang, Hsin-Ell; Yu, Hung-Man; Lu, Yi-Ching; Heish, Ning-Ning; Tseng, Yun-Long; Huang, Kuang-Liang; Chuang, Kuo-Tang; Chen, Chin-Hsiung; Hwang, Jeng-Jong; Lin, Wuu-Jyh; Wang, Shyh-Jen; Ting, Gann; Whang-Peng, Jacqueline; Deng, Win-Ping

    2006-12-01

    In vivo characterization and dosimetric analysis has been performed to evaluate the potential of pegylated liposomes as carriers of radionuclides in tumor internal radiotherapy. MethodsThe DTPA/PEG-liposomes were synthesized with a medium size of 110 nm, conjugated with 111In/ 177Lu-(oxine) 3 to afford 111In/ 177Lu-liposome. The stability of 111In/ 177Lu-liposome in serum was investigated. The biodistribution, scintigraphic imaging and pharmacokinetics of 111In/ 177Lu-liposomes after intravenous(i.v.) injection into C-26 tumor-bearing BALB/cByJ mice were studied. Radiation dose was estimated by MIRD-III program. ResultsThe incorporation efficiency of 111In/ 177Lu into liposomes was 95%. After incubation at 37 °C for 72 h in serum, more than 83% of radioactivity was still retained in the intact 111In/ 177Lu-liposomes. The biodistribution of 111In-liposomes showed that the radioactivity in the blood decreased from 23.14±8.16%ID/g at 1 h to 0.02±0.00%ID/g at 72 h post-injection (p.i.), while reaching its maximum accumulation in tumors at 48 h p.i., with half-life in blood of 10.2 h. The results were supported by that of 177Lu-liposomes. Scintigraphic imaging with 111In-liposomes showed unambiguous tumor images at 48 h p.i. Dose estimation showed that the absorbed dose in tumor from 177Lu-liposomes was 5.74×10 -5 Gy/MBq. ConclusionsThis study provides an in vivo characterization and dosimetric evaluation for the use of liposome systems as carriers in targeted radionuclide therapy. The results suggest that adequate tumor targeting as well as dose delivered to tumors could be achieved by the use of radionuclide targeted liposomes.

  8. Immunotherapy of BALB/c mice bearing Ehrlich ascites tumor with vitamin D-binding protein-derived macrophage activating factor.

    PubMed

    Yamamoto, N; Naraparaju, V R

    1997-06-01

    Vitamin D3-binding protein (DBP; human DBP is known as Gc protein) is the precursor of macrophage activating factor (MAF). Treatment of mouse DBP with immobilized beta-galactosidase or treatment of human Gc protein with immobilized beta-galactosidase and sialidase generated a remarkably potent MAF, termed DBPMAF or GcMAF, respectively. The domain of Gc protein responsible for macrophage activation was cloned and enzymatically converted to the cloned MAF, designated CdMAF. In Ehrlich ascites tumor-bearing mice, tumor-specific serum alpha-N-acetylgalactosaminidase (NaGalase) activity increased linearly with time as the transplanted tumor cells grew in the peritoneal cavity. Therapeutic effects of DBPMAF, GcMAF, and CdMAF on mice bearing Ehrlich ascites tumor were assessed by survival time, the total tumor cell count in the peritoneal cavity, and serum NaGalase activity. Mice that received a single administration of DBPMAF or GcMAF (100 pg/mouse) on the same day after transplantation of tumor (1 x 10(5) cells) showed a mean survival time of 35 +/- 4 days, whereas tumor-bearing controls had a mean survival time of 16 +/- 2 days. When mice received the second DBPMAF or GcMAF administration at day 4, they survived more than 50 days. Mice that received two DBPMAF administrations, at days 4 and 8 after transplantation of 1 x 10(5) tumor cells, survived up to 32 +/- 4 days. At day 4 posttransplantation, the total tumor cell count in the peritoneal cavity was approximately 5 x 10(5) cells. Mice that received two DBPMAF administrations, at days 0 and 4 after transplantation of 5 x 10(5) tumor cells, also survived up to 32 +/- 4 days, while control mice that received the 5 x 10(5) ascites tumor cells only survived for 14 +/- 2 days. Four DBPMAF, GcMAF, or CdMAF administrations to mice transplanted with 5 x 10(5) Ehrlich ascites tumor cells with 4-day intervals showed an extended survival of at least 90 days and an insignificantly low serum NaGalase level between days 30 and 90

  9. Hindlimb Skeletal Muscle Function and Skeletal Quality and Strength in +/G610C Mice With and Without Weight-Bearing Exercise.

    PubMed

    Jeong, Youngjae; Carleton, Stephanie M; Gentry, Bettina A; Yao, Xiaomei; Ferreira, J Andries; Salamango, Daniel J; Weis, MaryAnn; Oestreich, Arin K; Williams, Ashlee M; McCray, Marcus G; Eyre, David R; Brown, Marybeth; Wang, Yong; Phillips, Charlotte L

    2015-10-01

    Osteogenesis imperfecta (OI) is a heterogeneous heritable connective tissue disorder associated with reduced bone mineral density and skeletal fragility. Bone is inherently mechanosensitive, with bone strength being proportional to muscle mass and strength. Physically active healthy children accrue more bone than inactive children. Children with type I OI exhibit decreased exercise capacity and muscle strength compared with healthy peers. It is unknown whether this muscle weakness reflects decreased physical activity or a muscle pathology. In this study, we used heterozygous G610C OI model mice (+/G610C), which model both the genotype and phenotype of a large Amish OI kindred, to evaluate hindlimb muscle function and physical activity levels before evaluating the ability of +/G610C mice to undergo a treadmill exercise regimen. We found +/G610C mice hindlimb muscles do not exhibit compromised muscle function, and their activity levels were not reduced relative to wild-type mice. The +/G610C mice were also able to complete an 8-week treadmill regimen. Biomechanical integrity of control and exercised wild-type and +/G610C femora were analyzed by torsional loading to failure. The greatest skeletal gains in response to exercise were observed in stiffness and the shear modulus of elasticity with alterations in collagen content. Analysis of tibial cortical bone by Raman spectroscopy demonstrated similar crystallinity and mineral/matrix ratios regardless of sex, exercise, and genotype. Together, these findings demonstrate +/G610C OI mice have equivalent muscle function, activity levels, and ability to complete a weight-bearing exercise regimen as wild-type mice. The +/G610C mice exhibited increased femoral stiffness and decreased hydroxyproline with exercise, whereas other biomechanical parameters remain unaffected, suggesting a more rigorous exercise regimen or another exercise modality may be required to improve bone quality of OI mice.

  10. Localisation of [131I]MIBG in nude mice bearing SK-N-SH human neuroblastoma xenografts: effect of specific activity.

    PubMed Central

    Vaidyanathan, G.; Friedman, H. S.; Keir, S. T.; Zalutsky, M. R.

    1996-01-01

    The biodistribution of no-carrier-added (n.c.a.) meta-[131I]iodobenzylguanidine ([131I]MIBG) and that prepared by the standard isotopic exchange method were compared in athymic mice bearing SK-N-SH human neuroblastoma xenografts. No advantage in tumour uptake was observed for the n.c.a. preparation. BALB/c nu/nu mice exhibited lower uptake in highly innervated normal tissues (heart and adrenals) than normal BALB/c mice. In another experiment, the distribution of n.c.a. [131I]MIBG in the absence or presence (3-9 micrograms) of MIBG carrier was determined. At both 4 h and 24 h, the heart uptake was reduced by a factor of 1.5 even at a dose of 3 micrograms MIBG. Tumour uptake was not significantly altered by various amounts of unlabelled MIBG at either time point. PMID:8630274

  11. Targeting a mimotope vaccine to activating Fcgamma receptors empowers dendritic cells to prime specific CD8+ T cell responses in tumor-bearing mice.

    PubMed

    Gil, Margaret; Bieniasz, Magdalena; Wierzbicki, Andrzej; Bambach, Barbara J; Rokita, Hanna; Kozbor, Danuta

    2009-11-15

    A major challenge for inducing antitumor immune responses with native or modified tumor/self-Ags in tumor-bearing hosts relates to achieving efficient uptake and processing by dendritic cells (DCs) to activate immune effector cells and limit the generation of regulatory T cell activity. We analyzed the ability of therapeutic DC vaccines expressing a CD166 cross-reactive mimotope of the GD2 ganglioside, 47-LDA, to selectively expand adoptively transferred, tumor-specific T cells in NXS2 neuroblastoma tumor-bearing syngeneic mice. Before the adoptive cell transfer and DC vaccination, the tumor-bearing mice were lymphodepleted by nonmyeloablative total body irradiation or a myeloablative regimen that required bone marrow transplantation. The 47-LDA mimotope was presented to DCs either as a linear polypeptide in conjunction with universal Th epitopes or as a fusion protein with the murine IgG2a Fc fragment (47-LDA-Fcgamma2a) to deliver the antigenic cassette to the activating Fcgamma receptors. We demonstrate that immunization of adoptively transferred T cells in tumor-bearing mice with the 47-LDA mimotope expressed in the context of the activating Fc fusion protein induced higher levels of antitumor immune responses and protection than the 47-LDA polypeptide-DC vaccine. The antitumor efficacy of the therapeutic 47-LDA-Fcgamma2a-DC vaccine was comparable to that achieved by a virotherapy-associated cancer vaccine using a recombinant oncolytic vaccinia virus expressing the 47-LDA-Fcgamma2a fusion protein. The latter treatment, however, did not require total body irradiation or adoptive cell transfer and resulted in induction of antitumor immune responses in the setting of established tolerance, paving the way for testing novel anticancer treatment strategies.

  12. Targeting a Mimotope Vaccine to Activating Fcγ Receptors Empowers Dendritic Cells to Prime Specific CD8+ T Cell Responses in Tumor-Bearing Mice1

    PubMed Central

    Gil, Margaret; Bieniasz, Magdalena; Wierzbicki, Andrzej; Bambach, Barbara J.; Rokita, Hanna; Kozbor, Danuta

    2009-01-01

    A major challenge for inducing antitumor immune responses with native or modified tumor/self-Ags in tumor-bearing hosts relates to achieving efficient uptake and processing by dendritic cells (DCs) to activate immune effector cells and limit the generation of regulatory T cell activity. We analyzed the ability of therapeutic DC vaccines expressing a CD166 cross-reactive mimotope of the GD2 ganglioside, 47-LDA, to selectively expand adoptively transferred, tumor-specific T cells in NXS2 neuroblastoma tumor-bearing syngeneic mice. Before the adoptive cell transfer and DC vaccination, the tumor-bearing mice were lymphodepleted by nonmyeloablative total body irradiation or a myeloablative regimen that required bone marrow transplantation. The 47-LDA mimotope was presented to DCs either as a linear polypeptide in conjunction with universal Th epitopes or as a fusion protein with the murine IgG2a Fc fragment (47-LDA-Fcγ2a) to deliver the antigenic cassette to the activating Fcγ receptors. We demonstrate that immunization of adoptively transferred T cells in tumor-bearing mice with the 47-LDA mimotope expressed in the context of the activating Fc fusion protein induced higher levels of antitumor immune responses and protection than the 47-LDA polypeptide-DC vaccine. The antitumor efficacy of the therapeutic 47-LDA-Fcγ2a-DC vaccine was comparable to that achieved by a virotherapy-associated cancer vaccine using a recombinant oncolytic vaccinia virus expressing the 47-LDA-Fcγ2a fusion protein. The latter treatment, however, did not require total body irradiation or adoptive cell transfer and resulted in induction of antitumor immune responses in the setting of established tolerance, paving the way for testing novel anticancer treatment strategies. PMID:19846865

  13. Expansion of CD11b(+)Ly6G (+)Ly6C (int) cells driven by medroxyprogesterone acetate in mice bearing breast tumors restrains NK cell effector functions.

    PubMed

    Spallanzani, Raúl Germán; Dalotto-Moreno, Tomás; Raffo Iraolagoitia, Ximena Lucía; Ziblat, Andrea; Domaica, Carolina Inés; Avila, Damián Ezequiel; Rossi, Lucas Ezequiel; Fuertes, Mercedes Beatriz; Battistone, María Agustina; Rabinovich, Gabriel Adrián; Salatino, Mariana; Zwirner, Norberto Walter

    2013-12-01

    The progesterone analog medroxyprogesterone acetate (MPA) is widely used as a hormone replacement therapy in postmenopausal women and as contraceptive. However, prolonged administration of MPA is associated with increased incidence of breast cancer through ill-defined mechanisms. Here, we explored whether exposure to MPA during mammary tumor growth affects myeloid-derived suppressor cells (MDSCs; CD11b(+)Gr-1(+), mostly CD11b(+)Ly6G(+)Ly6C(int) and CD11b(+)Ly6G(-)Ly6C(high) cells) and natural killer (NK) cells, potentially restraining tumor immunosurveillance. We used the highly metastatic 4T1 breast tumor (which does not express the classical progesterone receptor and expands MDSCs) to challenge BALB/c mice in the absence or in the presence of MPA. We observed that MPA promoted the accumulation of NK cells in spleens of tumor-bearing mice, but with reduced degranulation ability and in vivo cytotoxic activity. Simultaneously, MPA induced a preferential expansion of CD11b(+)Ly6G(+)Ly6C(int) cells in spleen and bone marrow of 4T1 tumor-bearing mice. In vitro, MPA promoted nuclear mobilization of the glucocorticoid receptor (GR) in 4T1 cells and endowed these cells with the ability to promote a preferential differentiation of bone marrow cells into CD11b(+)Ly6G(+)Ly6C(int) cells that displayed suppressive activity on NK cell degranulation. Sorted CD11b(+)Gr-1(+) cells from MPA-treated tumor-bearing mice exhibited higher suppressive activity on NK cell degranulation than CD11b(+)Gr-1(+) cells from vehicle-treated tumor-bearing mice. Thus, MPA, acting through the GR, endows tumor cells with an enhanced capacity to expand CD11b(+)Ly6G(+)Ly6C(int) cells that subsequently display a stronger suppression of NK cell-mediated anti-tumor immunity. Our results describe an alternative mechanism by which MPA may affect immunosurveillance and have potential implication in breast cancer incidence. PMID:24114144

  14. Systemic Agonistic Anti-CD40 Treatment of Tumor-Bearing Mice Modulates Hepatic Myeloid-Suppressive Cells and Causes Immune-Mediated Liver Damage.

    PubMed

    Medina-Echeverz, José; Ma, Chi; Duffy, Austin G; Eggert, Tobias; Hawk, Nga; Kleiner, David E; Korangy, Firouzeh; Greten, Tim F

    2015-05-01

    Immune-stimulatory mAbs are currently being evaluated as antitumor agents. Although overall toxicity from these agents appears to be moderate, liver toxicities have been reported and are not completely understood. We studied the effect of systemic CD40 antibody treatment on myeloid cells in the spleen and liver. Naïve and tumor-bearing mice were treated systemically with agonistic anti-CD40 antibody. Immune cell subsets in the liver and spleen, serum transaminases, and liver histologies were analyzed after antibody administration. Nox2(-/-), Cd40(-/-), and bone marrow chimeric mice were used to study the mechanism by which agonistic anti-CD40 mediates its effects in vivo. Suppressor function of murine and human tumor-induced myeloid-derived suppressor cells (MDSC) was studied upon CD40 ligation. Agonistic CD40 antibody caused liver damage within 24 hours after injection in two unrelated tumor models and mice strains. Using bone marrow chimeras, we demonstrate that CD40 antibody-induced hepatitis in tumor-bearing mice was dependent on the presence of CD40-expressing hematopoietic cells. Agonistic CD40 ligation-dependent liver damage was induced by the generation of reactive oxygen species. Furthermore, agonistic CD40 antibody resulted in increased CD80-positive and CD40-positive liver CD11b(+)Gr-1(+) immature myeloid cells. CD40 ligation on tumor-induced murine and human CD14(+)HLA-DR(low) peripheral blood mononuclear cells from patients with cancer reduced their immune suppressor function. Collectively, agonistic CD40 antibody treatment activated tumor-induced myeloid cells, caused myeloid-dependent hepatotoxicity, and ameliorated the suppressor function of murine and human MDSC. Collectively, our data suggest that CD40 may mature immunosuppressive myeloid cells and thereby cause liver damage in mice with an accumulation of tumor-induced hepatic MDSC. PMID:25637366

  15. Systemic Agonistic Anti-CD40 Treatment of Tumor-Bearing Mice Modulates Hepatic Myeloid-Suppressive Cells and Causes Immune-Mediated Liver Damage.

    PubMed

    Medina-Echeverz, José; Ma, Chi; Duffy, Austin G; Eggert, Tobias; Hawk, Nga; Kleiner, David E; Korangy, Firouzeh; Greten, Tim F

    2015-05-01

    Immune-stimulatory mAbs are currently being evaluated as antitumor agents. Although overall toxicity from these agents appears to be moderate, liver toxicities have been reported and are not completely understood. We studied the effect of systemic CD40 antibody treatment on myeloid cells in the spleen and liver. Naïve and tumor-bearing mice were treated systemically with agonistic anti-CD40 antibody. Immune cell subsets in the liver and spleen, serum transaminases, and liver histologies were analyzed after antibody administration. Nox2(-/-), Cd40(-/-), and bone marrow chimeric mice were used to study the mechanism by which agonistic anti-CD40 mediates its effects in vivo. Suppressor function of murine and human tumor-induced myeloid-derived suppressor cells (MDSC) was studied upon CD40 ligation. Agonistic CD40 antibody caused liver damage within 24 hours after injection in two unrelated tumor models and mice strains. Using bone marrow chimeras, we demonstrate that CD40 antibody-induced hepatitis in tumor-bearing mice was dependent on the presence of CD40-expressing hematopoietic cells. Agonistic CD40 ligation-dependent liver damage was induced by the generation of reactive oxygen species. Furthermore, agonistic CD40 antibody resulted in increased CD80-positive and CD40-positive liver CD11b(+)Gr-1(+) immature myeloid cells. CD40 ligation on tumor-induced murine and human CD14(+)HLA-DR(low) peripheral blood mononuclear cells from patients with cancer reduced their immune suppressor function. Collectively, agonistic CD40 antibody treatment activated tumor-induced myeloid cells, caused myeloid-dependent hepatotoxicity, and ameliorated the suppressor function of murine and human MDSC. Collectively, our data suggest that CD40 may mature immunosuppressive myeloid cells and thereby cause liver damage in mice with an accumulation of tumor-induced hepatic MDSC.

  16. Sunitinib prevents cachexia and prolongs survival of mice bearing renal cancer by restraining STAT3 and MuRF-1 activation in muscle

    PubMed Central

    Moschetta, Michele; Bassi, Andrea; Rovida, Alessandra; Scarlato, Valentina; Talamini, Laura; Fiordaliso, Fabio; Bisighini, Cinzia; Damia, Giovanna; Bani, Maria Rosa; Piccirillo, Rosanna; Giavazzi, Raffaella

    2015-01-01

    Tyrosine kinase inhibitors, affecting angiogenesis, have shown therapeutic efficacy in renal cell carcinoma (RCC). The increased overall survival is not fully explained by their anti-tumor activity, since these drugs frequently induce disease stabilization rather than regression. RCC patients frequently develop cachectic syndrome. We used the RXF393 human renal carcinoma xenograft that recapitulates the characteristics of the disease, including the growth in the mouse kidney (orthotopic implantation), and the induction of cachexia with subsequent premature death. Sunitinib prevents body weight loss and muscle wasting and significantly improves the survival of RXF393-bearing nude mice. The anti-cachectic effect was not associated to direct anti-tumor activity of the drug. Most relevant is the ability of sunitinib to reverse the cachectic phenotype and rescue the animals from the loss of fat tissue. Body weight loss is prevented also in mice bearing the C26 colon carcinoma, classically reported to induce cachexia in immunocompetent mice. Among the mechanisms, we herein show that sunitinib is able to restrain the overactivation of STAT3 and MuRF-1 pathways, involved in enhanced muscle protein catabolism during cancer cachexia. We suggest that off-target effects of angiogenesis inhibitors targeting STAT3 are worth considering as a therapeutic option for patients who develop cachexia, independently of their anti-tumor activity. PMID:25460504

  17. Oral beta-glucan adjuvant therapy converts nonprotective Th2 response to protective Th1 cell-mediated immune response in mammary tumor-bearing mice.

    PubMed

    Baran, Jarek; Allendorf, Daniel J; Hong, Feng; Ross, Gordon D

    2007-01-01

    Beta (1-3)-D-glucans were identified almost 40 years ago as biological response modifiers that stimulated tumor rejection. In vitro studies have shown that beta-glucans bind to a lectin domain within complement receptor type 3 (CR3), or to, more recently described dectin-1 a beta-glucan specific receptor, acting mainly on phagocytic cells. In this study, we assessed the intracellular cytokine profiles of peripheral blood lymphocytes from mice bearing mammary tumors receiving i.v. anti-tumor mAbs combined or not with whole glucan particle suspension given orally (WGP, 400 microg every 24 hours). The proportions of T cells producing IL-4 and IFNgamma were determined by flow cytometry. The proportion of T cells producing IL-4 was significantly higher in tumor-bearing mice not receiving beta-glucan-enhanced therapy. Conversely, T cells from mice undergoing beta-glucan-enhanced therapy showed increased production of the Th1 cytokine IFNgamma. The switch from a Th2 to a Th1 response after WGP therapy was possibly mediated by intestinal mucosal macrophages releasing IL-12.

  18. Effect of farmorubicin both free and associated with poly(butylcyanoacrylate) nanoparticles on phagocytic and NK activity of peritoneal exudate cells from tumor-bearing mice.

    PubMed

    Simeonova, Margarita Y; Antcheva, Margarita N

    2007-05-01

    The effect of Epirubicin (farmorubicin, FR), either free or associated with poly(butylcyanoacrylate) nanoparticles (PBCN) upon the phagocytic and natural killer (NK) activity of peritoneal exudate cells (PECs) harvested from Lewis lung carcinoma (LLC)-bearing-mice was investigated. Phagocytic and NK activity were tested 72 and 96 h, respectively after the last four intraperitoneal (i.p.) injections of the tested compounds have been administered to the mice. Phagocytic activity was evaluated in vitro by phagocytic index and ingestion capacity using a phagocytic assay. NK activity was evaluated in a direct cytotoxic test, in which PECs were used as effector cells while human erythroleukemic K-562 cells were used as target cells. The phagocytic activity of PECs, harvested from tumor-bearing mice, was stimulated after treatment with FR free, FR associated with polymer nanoparticles and with unloaded PBCN. The NK activity of PECs was strongly stimulated by unloaded PBCN. FR both free and encapsulated into the polymer matrix during the polymerization of n-butylcyanoacrylate (n-BCA) stimulated the NK activity of PECs, while FR adsorbed onto nanoparticles restrained it. These results suggest that the association of FR with nanoparticles modifies selectively its immunomodulating ability without producing any significant immunological disturbances. The toxicity of some of FR polymer forms towards PECs, displaying NK activity, probably comes from the enhanced local drug concentration on the membrane surface of the immune cells. However, it is insufficient to preclude the use of nanoparticles as drug delivery system.

  19. A 5-fluorouracil-loaded floating gastroretentive hollow microsphere: development, pharmacokinetic in rabbits, and biodistribution in tumor-bearing mice.

    PubMed

    Huang, Yu; Wei, Yumeng; Yang, Hongru; Pi, Chao; Liu, Hao; Ye, Yun; Zhao, Ling

    2016-01-01

    5-Fluorouracil (5-FU) was loaded in hollow microspheres to improve its oral bioavailability. 5-FU hollow microspheres were developed by a solvent diffusion-evaporation method. The effect of Span 80 concentration, ether/ethanol volume ratio, and polyvinyl pyrrolidone/ethyl cellulose weight ratio on physicochemical characteristics, floating, and in vitro release behaviors of 5-FU hollow microspheres was investigated and optimized. The formulation and technology composed of Span 80 (1.5%, w/v), ether/ethanol (1.0:10.0, v/v), and polyvinyl pyrrolidone/ethyl cellulose (1.0:10.0, w/w) were employed to develop three batch samples, which showed an excellent reproducibility. The microspheres were spherical with a hollow structure with high drug loading amount (28.4%±0.5%) and production yield (74.2%±0.6%); they exhibited excellent floating and sustained release characteristics in simulated gastric and intestinal fluid. Pharmacokinetic studies demonstrated that 5-FU hollow microspheres significantly enhanced oral bioavailability (area under curve, [AUC](0-t): 12.53±1.65 mg/L(*)h vs 7.80±0.83 and 5.82±0.83 mg/L(*)h) with longer elimination half-life (t1/2) (15.43±2.12 hours vs 2.25±0.22 and 1.43±0.18 hours) and mean residence time (7.65±0.97 hours vs 3.61±0.41 and 2.34±0.35 hours), in comparison with its solid microspheres and powder. In vivo distribution results from tumor-bearing nude mice demonstrated that the animals administered with 5-FU hollow microspheres had much higher drug content in tumor, plasma, and stomach at 1 and 8 hours except for 0.5 hours sample collection time point in comparison with those administered with 5-FU solid microspheres and its powder. These results suggested that the hollow microspheres would be a promising controlled drug delivery system for an oral chemotherapy agent like 5-FU.

  20. A 5-fluorouracil-loaded floating gastroretentive hollow microsphere: development, pharmacokinetic in rabbits, and biodistribution in tumor-bearing mice

    PubMed Central

    Huang, Yu; Wei, Yumeng; Yang, Hongru; Pi, Chao; Liu, Hao; Ye, Yun; Zhao, Ling

    2016-01-01

    5-Fluorouracil (5-FU) was loaded in hollow microspheres to improve its oral bioavailability. 5-FU hollow microspheres were developed by a solvent diffusion–evaporation method. The effect of Span 80 concentration, ether/ethanol volume ratio, and polyvinyl pyrrolidone/ethyl cellulose weight ratio on physicochemical characteristics, floating, and in vitro release behaviors of 5-FU hollow microspheres was investigated and optimized. The formulation and technology composed of Span 80 (1.5%, w/v), ether/ethanol (1.0:10.0, v/v), and polyvinyl pyrrolidone/ethyl cellulose (1.0:10.0, w/w) were employed to develop three batch samples, which showed an excellent reproducibility. The microspheres were spherical with a hollow structure with high drug loading amount (28.4%±0.5%) and production yield (74.2%±0.6%); they exhibited excellent floating and sustained release characteristics in simulated gastric and intestinal fluid. Pharmacokinetic studies demonstrated that 5-FU hollow microspheres significantly enhanced oral bioavailability (area under curve, [AUC](0−t): 12.53±1.65 mg/L*h vs 7.80±0.83 and 5.82±0.83 mg/L*h) with longer elimination half-life (t1/2) (15.43±2.12 hours vs 2.25±0.22 and 1.43±0.18 hours) and mean residence time (7.65±0.97 hours vs 3.61±0.41 and 2.34±0.35 hours), in comparison with its solid microspheres and powder. In vivo distribution results from tumor-bearing nude mice demonstrated that the animals administered with 5-FU hollow microspheres had much higher drug content in tumor, plasma, and stomach at 1 and 8 hours except for 0.5 hours sample collection time point in comparison with those administered with 5-FU solid microspheres and its powder. These results suggested that the hollow microspheres would be a promising controlled drug delivery system for an oral chemotherapy agent like 5-FU. PMID:27042001

  1. Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice

    PubMed Central

    Basile, Lena A; Gallaher, Timothy K; Shibata, Darryl; Miller, Joseph D; Douer, Dan

    2008-01-01

    Background Interleukin-12 (IL-12) is a cytokine well known for its role in immunity. A lesser known function of IL-12 is its role in hematopoiesis. The promising data obtained in the preclinical models of antitumor immunotherapy raised hope that IL-12 could be a powerful therapeutic agent against cancer. However, excessive clinical toxicity, largely due to repeat dose regimens, and modest clinical response observed in the clinical trials have pointed to the necessity to design protocols that minimize toxicity without affecting the anti-tumor effect of IL-12. We have focused on the lesser known role of IL-12 in hematopoiesis and hypothesized that an important clinical role for IL-12 in cancer may be as an adjuvant hematological cancer therapy. In this putative clinical function, IL-12 is utilized for the prevention of cancer therapy-related cytopenias, while providing concomitant anti-tumor responses over and above responses observed with the primary therapy alone. This putative clinical function of IL-12 focuses on the dual role of IL-12 in hematopoiesis and immunity. Methods We assessed the ability of IL-12 to facilitate hematopoietic recovery from radiation (625 rad) and chemotherapy (cyclophosphamide) in two tumor-bearing murine models, namely the EL4 lymphoma and the Lewis lung cancer models. Antitumor effects and changes in bone marrow cellularity were also assessed. Results We show herein that carefully designed protocols, in mice, utilizing IL-12 as an adjuvant to radiation or chemotherapy yield facile and consistent, multilineage hematopoietic recovery from cancer therapy-induced cytopenias, as compared to vehicle and the clinically-utilized cytokine granulocyte colony-stimulating factor (G-CSF) (positive control), while still providing concomitant antitumor responses over and above the effects of the primary therapy alone. Moreover, our protocol design utilizes single, low doses of IL-12 that did not yield any apparent toxicity. Conclusion Our results

  2. Antioxidants selenomethionine and D-pantethine decrease the negative side effects of doxorubicin in NL/Ly lymphoma-bearing mice

    PubMed Central

    Panchuk, Rostyslav R.; Skorokhyd, Nadia R.; Kozak, Yuliya S.; Lehka, Liliya V.; Chumak, Vira V.; Omelyanchik, Sofya N.; Gurinovich, Valery A.; Moiseenok, Andrey G.; Stoika, Rostyslav S.

    2016-01-01

    Aim To investigate the potential tissue-protective effects of antioxidants selenomethionine and D-pantethine applied together with doxorubicin (Dx) on NK/Ly lymphoma-bearing mice. The impact of this chemotherapy scheme on animal survival, blood cell profile, hepatotoxicity, glutathione level, and activity of glutathione-converting enzymes in the liver was compared with the action of Dx applied alone. Methods The hematological profile of animals was studied by the analysis of blood smears under light microscopy. Hepatotoxicity of studied drugs was evaluated measuring the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes, De Ritis ratio, and coenzyme A fractions by McDougal assay. Glutathione level in animal tissues was measured with Ellman reagent, and the activity of glutathione reductase, transferase, and peroxidase was measured using standard biochemical assays. Results D-pantethine (500 mg/kg) and, to a lower extent, selenomethionine (600 µg/kg) partially reduced the negative side effects (leukocytopenia and erythropenia) of Dx (5 mg/kg) in NK/Ly lymphoma bearing animals on the 14th day of their treatment. This increased animal survival time from 47-48 to 60+ days and improved the quality of their life. This ability of D-pantethine and selenomethionine was realized via hepatoprotective and immunomodulating activities. D-pantethine also restored the levels of acid-soluble and free CoA in the liver of tumor-bearing animals, while selenomethionine caused the recovery of glutathione peroxidase levels in the liver, which was significantly diminished under Dx treatment. Both compounds decreased glutathione level in the liver, which was considerably induced by Dx. Conclusions Antioxidants selenomethionine and D-pantethine partially reversed the negative side effects of Dx in NK/Ly lymphoma-bearing mice and significantly increased the therapeutic efficiency of this drug in tumor treatment. PMID:27106359

  3. Treatment of mice bearing a Krebs ascitic tumor by means of a protocol based on radioactive copper (64Cu). IV. Consequences of the nature of cancer: tumor-resistant mice.

    PubMed

    Guillé, E; Apelgot, S

    1990-01-01

    In the efficient treatment described (Anticancer Research 9: 941-946, 1989) some compounds (64Cu and thioproline) act against the malignant genomes, and other components (metal ions, amino acids, vitamin D2, thyroxine and chelating substances) act against the functioning of the host cells having the cancer functioning (cancer cells). The experiments described show that this treatment developed with mice injected on day zero with 5 x 10(5) Krebs ascitic cells, is also efficient for mice bearing a spontaneous malignant tumor even if it is not an ascitic tumor. After the decrease in weight due to the loss of the tumor, a typical weight evolution was observed characterized by a second weight increase followed by a decrease leading to normal weight. This last weight remained stable. This typical weight evolution in tumor-free mice (after spontaneous tumor or experimental Krebs ascitic tumor) was related to the age of the tumor at the beginning of the treatment, that is, according to our hypothesis (Anticancer Res 9:955-960, 1989) to the cancer evolution emphasizing the great importance of all physiological phenomena related to this cancer course. To test the consequence of this treatment, some of these tumor-free mice were injected with 5 x 10(5) ascitic cells. No tumor developed in these tumor-free mice meaning that they also were tumor-resistant. This last result is in agreement with the forecast of the systemic analysis on which the efficient treatment was based.

  4. Anti-angiogenic therapy for normalization of tumor vasculature: A potential effect of Buyang Huanwu decoction on nude mice bearing human hepatocellular carcinoma xenografts with high metastatic potential

    PubMed Central

    MIN, LIANG; LING, WEI; HUA, RONG; QI, HONG; CHEN, SHENXU; WANG, HAIQIAO; TANG, LUMEN; SHANGGUAN, WENJI

    2016-01-01

    The present study aimed to investigate the effect of Buyang Huanwu decoction (BYHWD) on tumor growth, metastasis and angiogenesis in nude mice bearing human hepatocellular carcinoma (HCC) HCCLM3 xenografts. A total of 96 nude mice bearing HCCLM3 xenografts were randomly divided into four groups: BYHWD group (LB), Yi-qi decoction group (LY), Huo-xue decoction group (LH) and model group (LM). Each of these groups was divided into three subgroups (n=8), which were observed on days 21, 25, 38 following treatment, respectively. The tumor weights, volumes and pulmonary metastases were recorded. The expression of CD105 and the microvessel density (MVD) were assessed, and the expression levels of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF-1α), and regulator of G protein signaling 5 (RGS-5) were analyzed using immunohistochemical staining. Compared with the LM group, no significant decrease in tumor weight or volume were observed in the herbal medicine treatment groups, the number of the metastases in the lungs decreased, whereas the expression levels of RGS-5 and HIF-1α decreased in the LB group on day 35. However, the expression levels of VEGF increased in the LB group on days 28 and 35 post-treatment. The results of the present study suggested that BYHWD may inhibit angiogenesis and metastasis by affecting the expression levels of VEGF, RGS-5 and HIF-1α, and suggested that BYHWD may contribute to the tumor microenvironment and vasculature normalization in HCC. PMID:26846752

  5. RA-XII inhibits tumour growth and metastasis in breast tumour-bearing mice via reducing cell adhesion and invasion and promoting matrix degradation

    PubMed Central

    Leung, Hoi-Wing; Zhao, Si-Meng; Yue, Grace Gar-Lee; Lee, Julia Kin-Ming; Fung, Kwok-Pui; Leung, Ping-Chung; Tan, Ning-Hua; Lau, Clara Bik-San

    2015-01-01

    Cancer cells acquire invasive ability to degrade and adhere to extracellular matrix (ECM) and migrate to adjacent tissues. This ultimately results metastasis. Hence, the present study investigated the in vitro effects of cyclopeptide glycoside, RA-XII on cell adhesion, invasion, proliferation and matrix degradation, and its underlying mechanism in murine breast tumour cells, 4T1. The effect of RA-XII on tumour growth and metastasis in 4T1-bearing mice was also investigated. Our results showed that RA-XII inhibited tumour cell adhesion to collagen, fibronectin and laminin, RA-XII also reduced the expressions of vascular cell adhesion molecule, intracellular adhesion molecule and integrins, and integrin binding. In addition, RA-XII significantly inhibited breast tumour cell migration via interfering cofilin signaling and chemokine receptors. The activities of matrix metalloproteinase-9 and urokinase-type of plasminogen activator, and the expressions of ECM-associated proteinases were attenuated significantly by RA-XII. Furthermore, RA-XII induced G1 phase arrest and inhibited the expressions of cyclins and cyclin-dependent kinases. RA-XII inhibited the expressions of molecules in PI3K/AKT, NF-kappaB, FAK/pSRC, MAPK and EGFR signaling. RA-XII was also shown to have anti-tumour, anti-angiogenic and anti-metastatic activities in metastatic breast tumour-bearing mice. These findings strongly suggested that RA-XII is a potential anti-metastatic agent for breast cancer. PMID:26592552

  6. Sequential appearance of T-cell receptor gamma delta- and alpha beta-bearing intestinal intra-epithelial lymphocytes in mice after irradiation.

    PubMed

    Yoshikai, Y; Ishida, A; Murosaki, S; Ando, T; Nomoto, K

    1991-12-01

    We have previously reported that T-cell receptor (TcR) gamma delta-bearing T cells precede TcR alpha beta-bearing T cells in appearance in the thymus after whole-body irradiation. In the present study, the kinetics of appearance of intestinal intra-epithelial lymphocytes (IEL) was examined in mice after whole-body irradiation with a lethal dose of 9.5 Gy or with a sublethal dose of 6 Gy. The number of CD3+ IEL decreased to the lowest value 4 days after irradiation with 9.5 Gy, and thereafter increased to half as many as the normal level by day 7. Thy-1+TcR alpha beta- IEL and Thy-TcR alpha beta- IEL recovered considerably by day 7 after the irradiation, whereas Thy-1+TcR alpha beta+ IEL and Thy-1+TcR alpha beta+ IEL hardly recovered at this stage. All mice died within 12 days after irradiation with a lethal dose of 9.5 Gy. On the other hand, when irradiation dose was decreased to 6 Gy, all mice survived beyond 40 days after irradiation. The number of CD3+ IEL recovered to the normal level by 10 days after irradiation with 6 Gy. Consistently with the results in mice irradiated with a lethal dose, the first cells to increase in IEL of mice irradiated with a sublethal dose were TcR gamma delta+ IEL expressing Thy-1 antigen. The number of Thy-1+TcR gamma delta+ IEL increased to approximately two-fold as many as that in normal mice by day 10, while TcR alpha beta+ IEL began to increase in number from day 20 after irradiation and recovered to the normal level by day 40 after irradiation. Thus, sequential appearance of TcR gamma delta+ and TcR alpha beta+ IEL was evident after irradiation, similar to that seen in the thymus after irradiation. The IEL on day 10 after a sublethal irradiation, which is composed mainly of Thy-1+TcR gamma delta+ IEL, exhibited a strong cytolytic activity against P815 in the presence of anti-CD3 mAb, suggesting that the early appearing Thy-1+TcR gamma delta+ IEL may play important roles in epithelial immunity at an early stage after irradiation.

  7. Elevated mRNA-levels of gonadotropin-releasing hormone and its receptor in plaque-bearing Alzheimer's disease transgenic mice.

    PubMed

    Nuruddin, Syed; Syverstad, Gry Helen Enger; Lillehaug, Sveinung; Leergaard, Trygve B; Nilsson, Lars N G; Ropstad, Erik; Krogenæs, Anette; Haraldsen, Ira Ronit Hebold; Torp, Reidun

    2014-01-01

    Research on Alzheimer's disease (AD) has indicated an association between hormones of the hypothalamic-pituitary-gonadal (HPG) axis and cognitive senescence, indicating that post meno-/andropausal changes in HPG axis hormones are implicated in the neuropathology of AD. Studies of transgenic mice with AD pathologies have led to improved understanding of the pathophysiological processes underlying AD. The aims of this study were to explore whether mRNA-levels of gonadotropin-releasing hormone (Gnrh) and its receptor (Gnrhr) were changed in plaque-bearing Alzheimer's disease transgenic mice and to investigate whether these levels and amyloid plaque deposition were downregulated by treatment with a gonadotropin-releasing hormone analog (Gnrh-a; Leuprorelin acetate). The study was performed on mice carrying the Arctic and Swedish amyloid-β precursor protein (AβPP) mutations (tgArcSwe). At 12 months of age, female tgArcSwe mice showed a twofold higher level of Gnrh mRNA and more than 1.5 higher level of Gnrhr mRNA than age matched controls. Male tgArcSwe mice showed the same pattern of changes, albeit more pronounced. In both sexes, Gnrh-a treatment caused significant down-regulation of Gnrh and Gnrhr mRNA expression. Immunohistochemistry combined with quantitative image analysis revealed no significant changes in the plaque load after Gnrh-a treatment in hippocampus and thalamus. However, plaque load in the cerebral cortex of treated females tended to be lower than in female vehicle-treated mice. The present study points to the involvement of hormonal changes in AD mice models and demonstrates that these changes can be effectively counteracted by pharmacological treatment. Although known to increase in normal aging, our study shows that Gnrh/Gnrhr mRNA expression increases much more dramatically in tgArcSwe mice. Treatment with Leuprorelin acetate successfully abolished the transgene specific effects on Gnrh/Gnrhr mRNA expression. The present experimental approach

  8. Elevated mRNA-Levels of Gonadotropin-Releasing Hormone and Its Receptor in Plaque-Bearing Alzheimer's Disease Transgenic Mice

    PubMed Central

    Lillehaug, Sveinung; Leergaard, Trygve B.; Nilsson, Lars N. G.; Ropstad, Erik; Krogenæs, Anette; Haraldsen, Ira Ronit Hebold; Torp, Reidun

    2014-01-01

    Research on Alzheimer's disease (AD) has indicated an association between hormones of the hypothalamic–pituitary–gonadal (HPG) axis and cognitive senescence, indicating that post meno-/andropausal changes in HPG axis hormones are implicated in the neuropathology of AD. Studies of transgenic mice with AD pathologies have led to improved understanding of the pathophysiological processes underlying AD. The aims of this study were to explore whether mRNA-levels of gonadotropin-releasing hormone (Gnrh) and its receptor (Gnrhr) were changed in plaque-bearing Alzheimer's disease transgenic mice and to investigate whether these levels and amyloid plaque deposition were downregulated by treatment with a gonadotropin-releasing hormone analog (Gnrh-a; Leuprorelin acetate). The study was performed on mice carrying the Arctic and Swedish amyloid-β precursor protein (AβPP) mutations (tgArcSwe). At 12 months of age, female tgArcSwe mice showed a twofold higher level of Gnrh mRNA and more than 1.5 higher level of Gnrhr mRNA than age matched controls. Male tgArcSwe mice showed the same pattern of changes, albeit more pronounced. In both sexes, Gnrh-a treatment caused significant down-regulation of Gnrh and Gnrhr mRNA expression. Immunohistochemistry combined with quantitative image analysis revealed no significant changes in the plaque load after Gnrh-a treatment in hippocampus and thalamus. However, plaque load in the cerebral cortex of treated females tended to be lower than in female vehicle-treated mice. The present study points to the involvement of hormonal changes in AD mice models and demonstrates that these changes can be effectively counteracted by pharmacological treatment. Although known to increase in normal aging, our study shows that Gnrh/Gnrhr mRNA expression increases much more dramatically in tgArcSwe mice. Treatment with Leuprorelin acetate successfully abolished the transgene specific effects on Gnrh/Gnrhr mRNA expression. The present experimental approach

  9. Interleukin-15-transferred cytokine-induced killer cells elevated anti-tumor activity in a gastric tumor-bearing nude mice model.

    PubMed

    Peng, Zheng; Liang, Wentao; Li, Zexue; Xu, Yingxin; Chen, Lin

    2016-02-01

    Gastric cancer is the second leading cause of cancer-related mortality worldwide. Adoptive cell therapy (ACT) for gastric cancer is a novel therapy modality. However, the therapeutic effectiveness in vivo is still limited. The objective of this study was to assess the value of interleukin-15 (IL-15)-transferred cytokine-induced killer (CIK) cells in ACT for gastric cancer. IL-15-IRES-TK retroviral vector was constructed and transferred into the CIK cells. A gastric tumor-bearing nude mice model was constructed by subcutaneously injecting gastric cancer cells, BGC-823. Gastric tumor-bearing nude mice were randomly divided into three groups (five mice each group) and injected with physiological saline, CIK cells, and IL-15-IRES-TK-transfected CIK cells for 2 weeks, respectively. IL-15-IRES-TK-transferred CIK cells were prepared successfully and flow cytometry (FCM) analysis indicated that the transfection rate reached 85.7% after 5 days culture. In vivo experiment, we found that CIK cells retarded tumor growth by reducing tumor volume and tumor weight, as well as increasing tumor inhibition rate. Furthermore, IL-15-IRES-TK-transferred CIK cells showed a much stronger inhibition on tumor growth than CIK cells alone. Tumor morphology observation and growth indexes also showed that IL-15-transfected CIK cells had stronger cytotoxicity to tumor tissue than CIK cells. IL-15-IRES-TK transfection could elevate the effects of CIK cells to gastric carcinoma. The engineered CIK cells carrying IL-15-IRES-TK may be used in the ACT for gastric carcinoma, but prudent clinical trial is still indispensable.

  10. Hypolocomotion, asymmetrically directed behaviors (licking, lifting, flinching, and shaking) and dynamic weight bearing (gait) changes are not measures of neuropathic pain in mice

    PubMed Central

    2010-01-01

    Background Spontaneous (non-evoked) pain is a major clinical symptom of neuropathic syndromes, one that is understudied in basic pain research for practical reasons and because of a lack of consensus over precisely which behaviors reflect spontaneous pain in laboratory animals. It is commonly asserted that rodents experiencing pain in a hind limb exhibit hypolocomotion and decreased rearing, engage in both reflexive and organized limb directed behaviors, and avoid supporting their body weight on the affected side. Furthermore, it is assumed that the extent of these positive or negative behaviors can be used as a dependent measure of spontaneous chronic pain severity in such animals. In the present study, we tested these assumptions via blinded, systematic observation of digital video of mice with nerve injuries (chronic constriction or spared nerve injury), and automated assessment of locomotor behavior using photocell detection and dynamic weight bearing (i.e., gait) using the CatWalk® system. Results We found no deficits in locomotor activity or rearing associated with neuropathic injury. The frequency of asymmetric (ipsilaterally directed) behaviors were too rare to be seriously considered as representing spontaneous pain, and in any case did not statistically exceed what was blindly observed on the contralateral hind paw and in control (sham operated and unoperated) mice. Changes in dynamic weight bearing, on the other hand, were robust and ipsilateral after spared nerve injury (but not chronic constriction injury). However, we observed timing, pharmacological, and genetic dissociation of mechanical allodynia and gait alterations. Conclusions We conclude that spontaneous neuropathic pain in mice cannot be assessed using any of these measures, and thus caution is warranted in making such assertions. PMID:20529328

  11. T-cell receptor gene therapy in human melanoma-bearing immune-deficient mice: human but not mouse T cells recapitulate outcome of clinical studies.

    PubMed

    Straetemans, Trudy; Coccoris, Miriam; Berrevoets, Cor; Treffers-Westerlaken, Elike; Scholten, Csilla E V; Schipper, Debby; Ten Hagen, Timo L M; Debets, Reno

    2012-02-01

    Adoptive cell therapy using T-cell receptor (TCR)-engineered T cells is a clinically feasible and promising approach to target tumors, but is currently faced with compromised antitumor efficacies in patients. Here, we extensively validated immune-deficient mice to facilitate further development of the therapeutic potential of TCR-engineered T cells. Treatment of human melanoma-bearing SCID or NSG mice with high doses of human T cells transduced with an hgp100/HLA-A2-specific TCR did not result in antitumor responses irrespective of chemotherapeutic preconditioning. Imaging of human green fluorescent protein-labeled T cells demonstrated significant T-cell accumulation in intratumoral vasculature directly upon T-cell transfer, which was followed by loss of T cells within 72 hr. Peripheral persistence of human T cells was highly compromised and appeared related to T-cell differentiation. On the contrary, adoptive transfer (AT) of relatively low numbers of hgp100/HLA-A2 TCR-transduced mouse T cells resulted in rapid clearance of large established human melanomas. Unexpectedly and in contrast to reported studies with chimeric antibody receptor-engineered T cells, antitumor activity and homeostatic expansion of T cells were independent of TCR transgene as evidenced in two SCID strains and using two different human melanoma cell lines. Interestingly, the xeno-reactive melanoma response of mouse T cells appeared to be dictated by CD4(+) tumor-infiltrating lymphocytes and did not require in vitro T-cell activation, retroviral gene transfer, or subcutaneous interleukin-2 support. Taken together, AT of human but not mouse T cells in human melanoma-bearing immune-deficient mice is in close accordance with clinical studies. PMID:21958294

  12. Pharmacokinetic studies of mouse monoclonal antibodies to a rat colon carcinoma: I. Comparison of biodistribution in normal rats, syngeneic tumor-bearing rats, or tumor-bearing nude mice

    SciTech Connect

    Laborda, J.; Douillard, J.Y.; Burg, C.; Lizzio, E.F.; Ridge, J.; Levenbook, I.; Hoffman, T. )

    1990-06-01

    The pharmacokinetics of two iodine-131-({sup 131}I) labeled murine anti-rat colon carcinoma monoclonal antibodies (D3 and E4) were compared in normal Sprague Dawley rats, syngeneic BDIX rats, or nude mice bearing that tumor. Results of antibody uptake after i.v. administration were analyzed in terms of accumulation and localization indices for normal tissues and tumor. Statistically significant differences between rat and mouse tissue biodistribution were found. D3, which reacts in vitro with the tumor and several normal rat tissues, cleared quickly from the blood of rats and was specifically targeted to several normal tissues, notably the lung. Virtually no targeting to the tumor was observed. Nude mice, however, showed a slower blood clearance and specific antibody targeting only in the tumor. Similar results were seen after injection of another antibody, E4, which is tumor-specific in vitro. Data suggest that studies on the xenogeneic nude mouse model may not necessarily be relevant to the choice of monoclonal antibodies for clinical diagnostic imaging or therapy.

  13. Prophylactic Administration of Fucoidan Represses Cancer Metastasis by Inhibiting Vascular Endothelial Growth Factor (VEGF) and Matrix Metalloproteinases (MMPs) in Lewis Tumor-Bearing Mice

    PubMed Central

    Huang, Tse-Hung; Chiu, Yi-Han; Chan, Yi-Lin; Chiu, Ya-Huang; Wang, Hang; Huang, Kuo-Chin; Li, Tsung-Lin; Hsu, Kuang-Hung; Wu, Chang-Jer

    2015-01-01

    Fucoidan, a heparin-like sulfated polysaccharide, is rich in brown algae. It has a wide assortment of protective activities against cancer, for example, induction of hepatocellular carcinoma senescence, induction of human breast and colon carcinoma apoptosis, and impediment of lung cancer cells migration and invasion. However, the anti-metastatic mechanism that fucoidan exploits remains elusive. In this report, we explored the effects of fucoidan on cachectic symptoms, tumor development, lung carcinoma cell spreading and proliferation, as well as expression of metastasis-associated proteins in the Lewis lung carcinoma (LLC) cells-inoculated mice model. We discovered that administration of fucoidan has prophylactic effects on mitigation of cachectic body weight loss and improvement of lung masses in tumor-inoculated mice. These desired effects are attributed to inhibition of LLC spreading and proliferation in lung tissues. Fucoidan also down-regulates expression of matrix metalloproteinases (MMPs), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and vascular endothelial growth factor (VEGF). Moreover, the tumor-bearing mice supplemented with fucoidan indeed benefit from an ensemble of the chemo-phylacticity. The fact is that fucoidan significantly decreases viability, migration, invasion, and MMPs activities of LLC cells. In summary, fucoidan is suitable to act as a chemo-preventative agent for minimizing cachectic symptoms as well as inhibiting lung carcinoma metastasis through down-regulating metastatic factors VEGF and MMPs. PMID:25854641

  14. Prophylactic administration of fucoidan represses cancer metastasis by inhibiting vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in Lewis tumor-bearing mice.

    PubMed

    Huang, Tse-Hung; Chiu, Yi-Han; Chan, Yi-Lin; Chiu, Ya-Huang; Wang, Hang; Huang, Kuo-Chin; Li, Tsung-Lin; Hsu, Kuang-Hung; Wu, Chang-Jer

    2015-04-01

    Fucoidan, a heparin-like sulfated polysaccharide, is rich in brown algae. It has a wide assortment of protective activities against cancer, for example, induction of hepatocellular carcinoma senescence, induction of human breast and colon carcinoma apoptosis, and impediment of lung cancer cells migration and invasion. However, the anti-metastatic mechanism that fucoidan exploits remains elusive. In this report, we explored the effects of fucoidan on cachectic symptoms, tumor development, lung carcinoma cell spreading and proliferation, as well as expression of metastasis-associated proteins in the Lewis lung carcinoma (LLC) cells-inoculated mice model. We discovered that administration of fucoidan has prophylactic effects on mitigation of cachectic body weight loss and improvement of lung masses in tumor-inoculated mice. These desired effects are attributed to inhibition of LLC spreading and proliferation in lung tissues. Fucoidan also down-regulates expression of matrix metalloproteinases (MMPs), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and vascular endothelial growth factor (VEGF). Moreover, the tumor-bearing mice supplemented with fucoidan indeed benefit from an ensemble of the chemo-phylacticity. The fact is that fucoidan significantly decreases viability, migration, invasion, and MMPs activities of LLC cells. In summary, fucoidan is suitable to act as a chemo-preventative agent for minimizing cachectic symptoms as well as inhibiting lung carcinoma metastasis through down-regulating metastatic factors VEGF and MMPs.

  15. A polysaccharide from Ganoderma atrum inhibits tumor growth by induction of apoptosis and activation of immune response in CT26-bearing mice.

    PubMed

    Zhang, Shenshen; Nie, Shaoping; Huang, Danfei; Huang, Jianqin; Feng, Yanling; Xie, Mingyong

    2014-09-24

    Ganoderma atrum is one species of edible and pharmaceutical mushroom with various biological activities. Recently, a novel polysaccharide, PSG-1, was purified from G. atrum. The antitumor activity and its mechanism of action were studied. In vitro, PSG-1 has little effect on inhibiting proliferation of CT26 tumor cells. However, the tumor size was significantly decreased in PSG-1-treated mice. The results showed that PSG-1 induced apoptosis in CT26 cells. Moreover, the intracellular cyclic AMP (cAMP) level and protein kinase A (PKA) activity were markedly increased in PSG-1-treated mice. In contrast, the contents of cyclic GMP and DAG and the PKC activity were decreased. Similarly, the expression of PKA protein was upregulated, while PKC protein expression in PSG-1-treated group was lowered. Additionally, PSG-1 increased the immune organ index and serum biochemistry parameter. In general, PSG-1 enhances the antitumor immune response, induces apoptosis in CT26-bearing mice, and could be a safe and effective adjuvant for tumor therapy or functional food.

  16. Cattle bile but not bear bile or pig bile induces lipid profile changes and fatty liver injury in mice: mediation by cholic acid.

    PubMed

    Watanabe, Shiro; Tsuneyama, Koichi

    2012-02-01

    Three types of animal bile preparation, bear bile (BB), cattle bile (CB) and pig bile (PB) differ in bile acid composition and are supposed to exert different pharmacotoxicological actions. Dietary supplementation with CB at 1% (w/w) for 4 weeks decreased triacylglycerol (TAG) level but increased total cholesterol (CHO) level in serum, which were associated with fatty liver injury in mice. The increased levels of cholesterol esters (CE) and monounsaturated fatty acids (MUFA) in the serum and liver were observed in the mice fed the CB-supplemented diet. Lipid abnormalities and fatty liver injury observed in the mice fed the CB diet were not induced by the supplementation with BB and PB. The supplementation with cholic acid (CA), the most abundant bile acid in CB, could induce lipid abnormalities and fatty liver injury, which were indistinguishable from those induced by CB supplementation. CB and CA supplementation induced similar changes in the expression levels of mRNAs in the liver. Thus, CB induced lipid abnormalities and fatty liver injury, which can be attributed to the actions of CA contained in CB. The inabilities of BB and PB to induce lipid abnormalities and fatty liver injury are supposed to be due to their limited contents of CA.

  17. Safety Studies in Tumor and Non-Tumor-Bearing Mice in Support of Clinical Trials Using Oncolytic VSV-IFNβ-NIS.

    PubMed

    Zhang, Lianwen; Steele, Michael B; Jenks, Nathan; Grell, Jacquelyn; Suksanpaisan, Lukkana; Naik, Shruthi; Federspiel, Mark J; Lacy, Martha Q; Russell, Stephen J; Peng, Kah-Whye

    2016-09-01

    Oncolytic VSV-IFNβ-NIS is selectively destructive to tumors. Here, we present the IND enabling preclinical rodent studies in support of clinical testing of vesicular stomatitis virus (VSV) as a systemic therapy. Efficacy studies showed dose-dependent tumor regression in C57BL/KaLwRij mice bearing syngeneic 5TGM1 plasmacytomas after systemic VSV administration. In contrast, the virus was effective at all doses tested against human KAS6/1 xenografts in SCID mice. Intravenous administration of VSV-mIFNβ-NIS is well tolerated in C57BL/6 mice up to 5 × 10(10) TCID50 (50% tissue culture infective dose)/kg with no neurovirulence, no cytokine storm, and no abnormalities in tissues. Dose-limiting toxicities included elevated transaminases, thrombocytopenia, and lymphopenia. Inactivated viral particles did not cause hepatic toxicity. Intravenously administered VSV was preferentially sequestered by macrophages in the spleen and liver. Quantitative RT-PCR analysis for total viral RNA on days 2, 7, 21, and 58 showed highest VSV RNA in day 2 samples; highest in spleen, liver, lung, lymph node, kidney, gonad, and bone marrow. No infectious virus was recovered from tissues at any time point. The no observable adverse event level and maximum tolerated dose of VSV-mIFNβ-NIS in C57BL/6 mice are 10(10) TCID50/kg and 5 × 10(10) TCID50/kg, respectively. Clinical translation of VSV-IFNβ-NIS is underway in companion dogs with cancer and in human patients with relapsed hematological malignancies and endometrial cancer. PMID:27532609

  18. The influence of EDTMP-concentration on the biodistribution of radio-lanthanides and 225-Ac in tumor-bearing mice. The ISOLDE Collaboration.

    PubMed

    Beyer, G J; Offord, R; Künzi, G; Aleksandrova, Y; Ravn, U; Jahn, S; Barker, J; Tengblad, O; Lindroos, M

    1997-07-01

    High-resolution gamma spectroscopy was applied to measure simultaneously the biodistribution of carrier-free radionuclides of several lanthanides (141Ce, 145Sm, 149Gd, 167Tm) and 225Ac in tumor-bearing nude mice. Mixtures of the radiotracers were injected in solutions containing different concentrations of EDTMP (ethylenediaminetetramethylenephosphonic acid). The strong dependence of liver uptake on the ionic radius of the radio-lanthanides was confirmed for all tracers used. The ratios of radioactivity concentrated in tumour that concentrated in liver are strongly influenced by the EDTMP concentration, reaching values close to 10 for Tm, 3 for Sm, and 1 for Ac. The optimal EDTMP concentrations, giving highest tumor-to-liver ratios of enrichment, were between 1 and 10 mM for 100 microL injected volume for the animal model used in this experiment. In radionuclide therapy using EDTMP as ligands, close control of ligand concentration will be necessary.

  19. The Effect of Docetaxel-Loaded Micro-Bubbles Combined with Low-Frequency Ultrasound in H22 Hepatocellular Carcinoma-Bearing Mice.

    PubMed

    Ren, Shu-Ting; Shen, Shu; He, Xin-Ying; Liao, Yi-Ran; Sun, Peng-Fei; Wang, Bing; Zhao, Wen-Bao; Han, Shui-Ping; Wang, Yi-Li; Tian, Tian

    2016-02-01

    A novel lipid micro-bubble (MB) loaded with docetaxel (DOC-MB) was investigated in a previous study. However, its anti-tumor effects and mechanism of action in combination with low-frequency ultrasound (LFUS) in vivo are still unclear. DOC-MBs containing 5.0 mg of DOC were prepared by lyophilization with modification via ultrasonic emulsification. Then, the effects of DOC-MBs combined with LFUS on tumor growth, proliferating cell nuclear antigen (PCNA) expression and cell apoptosis, as well as local DOC delivery, were investigated in H22 hepatocellular carcinoma (HCC)-bearing mice. Compared with the previously prepared DOC-MBs (1.6 mg of DOC loaded), the encapsulation efficiency (81.2% ± 3.89%) and concentration ([7.94 ± 0.04] × 10(9) bubbles/mL) of the DOC-MBs containing 5.0 mg of DOC were higher, but the bubble size (1.368 ± 0.004 μm) was smaller. After treatment with the DOC-MBs and LFUS, the H22 HCC growth inhibition rate was significantly increased, PCNA expression in tumor tissue was significantly inhibited and local release of DOC was induced. In conclusion, new DOC-MBs containing 5.0 mg of DOC were successfully prepared with a high encapsulation efficiency and superior bubble size and concentration, and their combination with LFUS significantly enhanced the anti-tumor effect of DOC in H22 HCC-bearing mice by inhibiting tumor cell proliferation and increasing local drug delivery.

  20. 6-Thioguanine-loaded polymeric micelles deplete myeloid-derived suppressor cells and enhance the efficacy of T cell immunotherapy in tumor-bearing mice.

    PubMed

    Jeanbart, Laura; Kourtis, Iraklis C; van der Vlies, André J; Swartz, Melody A; Hubbell, Jeffrey A

    2015-08-01

    Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that suppress effector T cell responses and can reduce the efficacy of cancer immunotherapies. We previously showed that ultra-small polymer nanoparticles efficiently drain to the lymphatics after intradermal injection and target antigen-presenting cells, including Ly6c(hi) Ly6g(-) monocytic MDSCs (Mo-MDSCs), in skin-draining lymph nodes (LNs) and spleen. Here, we developed ultra-small polymer micelles loaded with 6-thioguanine (MC-TG), a cytotoxic drug used in the treatment of myelogenous leukemia, with the aim of killing Mo-MDSCs in tumor-bearing mice and thus enhancing T cell-mediated anti-tumor responses. We found that 2 days post-injection in tumor-bearing mice (B16-F10 melanoma or E.G7-OVA thymoma), MC-TG depleted Mo-MDSCs in the spleen, Ly6c(lo) Ly6g(+) granulocytic MDSCs (G-MDSCs) in the draining LNs, and Gr1(int) Mo-MDSCs in the tumor. In both tumor models, MC-TG decreased the numbers of circulating Mo- and G-MDSCs, as well as of Ly6c(hi) macrophages, for up to 7 days following a single administration. MDSC depletion was dose dependent and more effective with MC-TG than with equal doses of free TG. Finally, we tested whether this MDSC-depleting strategy might enhance cancer immunotherapies in the B16-F10 melanoma model. We found that MC-TG significantly improved the efficacy of adoptively transferred, OVA-specific CD8(+) T cells in melanoma cells expressing OVA. These findings highlight the capacity of MC-TG in depleting MDSCs in the tumor microenvironment and show promise in promoting anti-tumor immunity when used in combination with T cell immunotherapies. PMID:25982370

  1. Survival of residual neutrophils and accelerated myelopoiesis limit the efficacy of antibody-mediated depletion of Ly-6G+ cells in tumor-bearing mice.

    PubMed

    Moses, Katrin; Klein, Johanna C; Männ, Linda; Klingberg, Anika; Gunzer, Matthias; Brandau, Sven

    2016-06-01

    Expansion of Ly-6G(+) myeloid cells has been reported in most murine cancer models. However, divergent findings exist regarding the role and effect of these cells on host immunity and tumor progression. Antibody-mediated depletion of Ly-6G(+) cells is a common technique to assess the in vivo relevance of these cells. Interpretation of results crucially depends on the efficacy and course of depletion. We established murine head and neck cancer models and analyzed the efficacy of antibody-mediated depletion by flow cytometry, conventional histology, and intravital imaging with a novel Ly-6G-transgenic mouse model. The first phase of depletion was characterized by effective elimination of Ly-6G(+) cells from the peripheral blood. Nevertheless, viable, resistant cells were found to reside in the tumor tissue and spleen. This peripheral depletion phase was associated with high systemic levels of granulocyte colony-stimulating factor and KC and enhanced splenic production of Ly-6G(+) cells. Even under sustained treatment with either αGr-1 or αLy-6G antibodies, peripheral blood depletion ended after approximately 1 wk and was followed by reappearance of immature Ly-6G(+) cells with an immunoregulatory phenotype. Reappearance of these depletion-resistant immature cells was enhanced in tumor-bearing, compared with naïve, control mice. Collectively, our data suggest that depletion of Ly-6G(+) myeloid cells in tumor-bearing mice is counteracted by the persistence of intratumoral cells, enhanced extramedullary granulopoiesis, and accelerated reappearance of immature cells. Hence, extensive monitoring of in vivo kinetics and tissue distribution of Ly-6G(+) cells is required in depletion studies.

  2. Role of isothiocyanate conjugate of pterostilbene on the inhibition of MCF-7 cell proliferation and tumor growth in Ehrlich ascitic cell induced tumor bearing mice

    SciTech Connect

    Nikhil, Kumar; Sharan, Shruti; Chakraborty, Ajanta; Bodipati, Naganjaneyulu; Krishna Peddinti, Rama; Roy, Partha

    2014-01-15

    Naturally occurring pterostilbene (PTER) and isothiocyanate (ITC) attract great attention due to their wide range of biological properties, including anti-cancer, anti-leukemic, anti-bacterial and anti-inflammatory activities. A novel class of hybrid compound synthesized by introducing an ITC moiety on PTER backbone was evaluated for its anti-cancer efficacy in hormone-dependent breast cancer cell line (MCF-7) in vitro and Ehrlich ascitic tumor bearing mice model in vivo. The novel hybrid molecule showed significant in vitro anti-cancer activity (IC{sub 50}=25±0.38) when compared to reference compound PTER (IC{sub 50}=65±0.42). The conjugate molecule induced both S and G2/M phase cell cycle arrest as indicated by flow cytometry analysis. In addition, the conjugate induced cell death was characterized by changes in cell morphology, DNA fragmentation, activation of caspase-9, release of cytochrome-c into cytosol and increased Bax: Bcl-2 ratio. The conjugate also suppressed the phosphorylation of Akt and ERK. The conjugate induced cell death was significantly increased in presence of A6730 (a potent Akt1/2 kinase inhibitor) and PD98059 (a specific ERK inhibitor). Moreover, the conjugated PTER inhibited tumor growth in Ehrlich ascitic cell induced tumor bearing mice as observed by reduction in tumor volume compared to untreated animals. Collectively, the pro-apoptotic effect of conjugate is mediated through the activation of caspases, and is correlated with the blockade of the Akt and ERK signaling pathways in MCF-7 cells. - Highlights: • Conjugate was prepared by appending isothiocyanate moiety on pterostilbene backbone. • Conjugate showed anticancer effects at comparatively lower dose than pterostilbene. • Conjugate caused blockage of the Akt and ERK signaling pathways in MCF-7 cells. • Conjugate significantly reduced solid tumor volume as compared to pterostilbene.

  3. 6-Thioguanine-loaded polymeric micelles deplete myeloid-derived suppressor cells and enhance the efficacy of T cell immunotherapy in tumor-bearing mice

    DOE PAGES

    Jeanbart, Laura; Kourtis, Iraklis C.; van der Vlies, André J.; Swartz, Melody A.; Hubbell, Jeffrey A.

    2015-05-16

    Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that suppress effector T cell responses and can reduce the efficacy of cancer immunotherapies. We previously showed that ultra-small polymer nanoparticles efficiently drain to the lymphatics after intradermal injection and target antigen-presenting cells, including Ly6chi Ly6g₋monocytic MDSCs (Mo-MDSCs), in skin-draining lymph nodes (LNs) and spleen. Here, we developed ultra-small polymer micelles loaded with 6-thioguanine (MC-TG), a cytotoxic drug used in the treatment of myelogenous leukemia, with the aim of killing Mo-MDSCs in tumor-bearing mice and thus enhancing T cell-mediated anti-tumor responses. We found that 2 days post-injection inmore » tumor-bearing mice (B16-F10 melanoma or E.G7-OVA thymoma), MC-TG depleted Mo-MDSCs in the spleen, Ly6clo Ly6g+ granulocytic MDSCs (G-MDSCs) in the draining LNs, and Gr1int Mo-MDSCs in the tumor. In both tumor models, MC-TG decreased the numbers of circulating Mo- and G-MDSCs, as well as of Ly6chi macrophages, for up to 7 days following a single administration. MDSC depletion was dose dependent and more effective with MC-TG than with equal doses of free TG. Finally, we tested whether this MDSC-depleting strategy might enhance cancer immunotherapies in the B16-F10 melanoma model. We found that MC-TG significantly improved the efficacy of adoptively transferred, OVA-specific CD8+ T cells in melanoma cells expressing OVA. Ultimately, these findings highlight the capacity of MC-TG in depleting MDSCs in the tumor microenvironment and show promise in promoting anti-tumor immunity when used in combination with T cell immunotherapies.« less

  4. [Decreasing toxicity and synergistic effects of intracellular and extracellular polysaccharides from Phellinus igniarius to tumor-bearing mice].

    PubMed

    Meng, Qinglong; Pan, Jingzhi; Chen, Li; Liu, Fusheng; Wang, Qi

    2012-03-01

    To study the toxicity-decreasing and synergistic effect of intracellular and extracellular polysaccharides from Phellinus igniarius on S180 mice. The PIP and PIE were extracted from the products of liquid submerged fermentation of P. igniarius. Transplanting S180 mice tumor models were established so as to observe the changes in tumor inhibiting rate, indexes of the spleen and thymus, body weight, peripheral blood cells and IFN-gamma levels when CTX was used alone and when used in combination with the PIP and PIE from P. igniarius. The results indicate that the PIP and PIE from P. igniarius can increase the activity of body immunity, attenuate the toxicity of CTX as well, and improve the anti-tumor effects. PMID:22715736

  5. Microwaves induce an increase in the frequency of complement receptor-bearing lymphoid spleen cells in mice.

    PubMed

    Wiktor-Jedrzejczak, W; Ahmed, A; Sell, K W; Czerski, P; Leach, W M

    1977-04-01

    A single 30-min exposure of mice to 2450 MHz microwaves (12 to 15 mW/g body weight) in an environmentally controlled waveguide facility induced a significant increase in the proportion of complement-receptor positive lymphoid cells in the spleen. This effect was further enhanced by repeated (three times) exposures, which in addition produced a significant increase in the proportion of Ig+ cells. The proportion of theta-positive cells and the total number of spleen cells remained unchanged.

  6. Analysis of volatile organic compounds released from human lung cancer cells and from the urine of tumor-bearing mice

    PubMed Central

    2012-01-01

    Backgrounds A potential strategy for the diagnosis of lung cancer is to exploit the distinct metabolic signature of this disease by way of biomarkers found in different sample types. In this study, we investigated whether specific volatile organic compounds (VOCs) could be detected in the culture medium of the lung cancer cell line A549 in addition to the urine of mice implanted with A549 cells. Results Several VOCs were found at significantly increased or decreased concentrations in the headspace of the A549 cell culture medium as compared with the culture medium of two normal lung cell lines. We also analyzed the urine of mice implanted with A549 cells and several VOCs were also found to be significantly increased or decreased relative to urine obtained from control mice. It was also revealed that seven VOCs were found at increased concentrations in both sample types. These compounds were found to be dimethyl succinate, 2-pentanone, phenol, 2-methylpyrazine, 2-hexanone, 2-butanone and acetophenone. Conclusions Both sample types produce distinct biomarker profiles, and VOCs have potential to distinguish between true- and false-positive screens for lung cancer. PMID:22364569

  7. The potential effect of patulin on mice bearing melanoma cells: an anti-tumour or carcinogenic effect?

    PubMed

    Boussabbeh, Manel; Ben Salem, Intidhar; Rjiba-Touati, Karima; Bouyahya, Chedy; Neffati, Fadwa; Najjar, Mohamed Fadhel; Bacha, Hassen; Abid-Essefi, Salwa

    2016-05-01

    Mycotoxins are bioactive compounds that are noxious to human. Their effects on oncogenesis have been satisfactorily elucidated, and some of mycotoxins have been classified as carcinogenic to humans. Nevertheless, patulin (PAT) is considered by the International Agency of Research on Cancer as 'not carcinogenic to humans'. The present study was designed to understand the effect of this mycotoxin on melanoma cells (B16F10) by measuring cell proliferation and assessing the anti-tumour effect in vivo in Balb/c mice. Our results revealed that intraperitoneally administration of PAT for 20 days significantly induces tumour regression in B16F10 cell-implanted mice. This effect was evidenced by the activation of apoptosis which is supported by the increase in p53 and Bax expressions, the downregulation of the protein levels of Bcl2, and the increase in caspase-3 activity. Moreover, systemic toxicity analysis demonstrated that there is no potential toxicity following PAT treatment unlike untreated melanoma mice which suffer from anaemia, inflammation and liver dysfunction. Remarkably, this is the first published report demonstrating the therapeutic efficacy of PAT in vivo models. PMID:26619846

  8. Isolation from individual A/J mice of anti-rho-azophenylarsonate antibodies bearing a cross-reactive idiotype

    PubMed Central

    1975-01-01

    Immuization of A/J mice with a KLH-p-azophenylarsonate conjugate induces the formation of antihapten antibodies, some of which share idiotypic specificity common to all recipients. The subpopulation carrying the idiotype generally comprises 20-70% of the total antibody content. Large quantities of antihapten antibody (occasionally over 100 mg) were obtained from individual mice through the induction of an ascites fluid. This facilitated isolation of antibodies with the cross- reactive idiotype by isoelectric focusing. Most of this subpopulation has pI values between 6.65 and 6.95 and essentially all is of the IgG1 subclass. Two peaks, near pI 6.7 and 6.9, were frequently observed. Upon refocusing, the protein artifact of the procedure, but indicates microheterogeneity. The antibodies in the two peaks were found to be idiotypically identical by measurements of cross-inhibition. Preliminary studies have indicated that it is feasible to initiate investigations of primary structure with antibodies from individual inbred mice. PMID:46907

  9. A proteoliposome containing apolipoprotein A-I mutant (V156K) enhances rapid tumor regression activity of human origin oncolytic adenovirus in tumor-bearing zebrafish and mice.

    PubMed

    Seo, Juyi; Yun, Chae-Ok; Kwon, Oh-Joon; Choi, Eun-Jin; Song, Jae-Young; Choi, Inho; Cho, Kyung-Hyun

    2012-08-01

    We recently reported that the efficiency of adenoviral gene delivery and virus stability are significantly enhanced when a proteoliposome (PL) containing apolipoprotein (apo) A-I is used in an animal model. In the current study, we tested tumor removal activity of oncolytic adenovirus (Ad) using PL-containing wildtype (WT) or V156K. Oncolytic Ad with or without PL was injected into tumors of zebrafish and nude mice as a Hep3B tumor xenograft model. The V156K-PL-Ad-injected zebrafish, group showed the lowest tumor tissue volume and nucleic acids in the tumor area, whereas injection of Ad alone did not result in adequate removal of tumor activity. Reactive oxygen species (ROS) contents increased two-fold in tumor-bearing zebrafish; however, the V156K-PL-Ad injected group showed a 40% decrease in ROS levels compared to that in normal zebrafish. After reducing the tumor volume with the V156K-PL-Ad injection, the swimming pattern of the zebrafish changed to be more active and energetic. The oncolytic effect of PL-Ad containing either V156K or WT was about two-fold more enhanced in mice than that of Ad alone 34 days after the injection. Immunohistochemical analysis revealed that the PL-Ad-injected groups showed enhanced efficiency of viral delivery with elevated Ad-E1A staining and a diminished number of proliferating tumor cells. Thus, the antitumor effect of oncolytic Ad was strongly enhanced by a PL-containing apoA-I and its mutant (V156K) without causing side effects in mice and zebrafish models. PMID:22851220

  10. Human amniotic membrane-derived epithelial stem cells display anticancer activity in BALB/c female nude mice bearing disseminated breast cancer xenografts.

    PubMed

    Kang, Nam-Hee; Yi, Bo-Rim; Lim, So Yoon; Hwang, Kyung-A; Baek, Young Seok; Kang, Kyung-Sun; Choi, Kyung-Chul

    2012-06-01

    Breast cancer is one of the most common malignant tumors and the leading cause of mortality among women. In this study, we propose a human stem cell transplantation strategy, an important method for treating various cancers, as a potential breast cancer therapy. To this end, we used human amniotic membrane-derived epithelial stem cells (hAECs) as a cell source for performing human stem cell transplantation. hAECs have multipotent differentiation abilities and possess high proliferative potential. We transplanted hAECs into female BALB/c nude mice bearing tumors originating from MDA-MB-231 breast cancer cells. Co-culturred hAECs and MDA-MB-231 cells at a ratio of 1:4 or 1:8 (tumor cells to stem cells) inhibited breast cancer cell growth by 67.29 and 67.33%, respectively. In the xenograft mouse model, tumor volumes were significantly decreased by 5-flurouracil (5-FU) treatment and two different ratios of hAECs (1:4 and 1:8) by 84.33, 73.88 and 56.89%, respectively. Treatment of nude mice with hAECs (1:4) produced remarkable antitumor effects without any side-effects (e.g., weight loss, death and bruising) compared to the mice that received only 5-FU treatment. Tumor progression was significantly reduced by hAEC treatment compared to the xenograft model. On the other hand, breast tissues (e.g., the epidermis, dermis and reticular layer) appeared to be well-maintained following treatment with hAECs. Taken together, these results provide strong evidence that hAECs can be used as a safe and effective cancer-targeting cytotherapy for treating breast cancer.

  11. Antitumor effect of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles on mice bearing breast cancer: a systemic toxicity assay.

    PubMed

    Peixoto, Raphael Cândido Apolinário; Miranda-Vilela, Ana Luisa; de Souza Filho, José; Carneiro, Marcella Lemos' Brettas; Oliveira, Ricardo G S; da Silva, Matheus Oliveira; de Souza, Aparecido R; Báo, Sônia Nair

    2015-05-01

    Breast cancer is one of the most prevalent cancer types among women. The use of magnetic fluids for specific delivery of drugs represents an attractive platform for chemotherapy. In our previous studies, it was demonstrated that maghemite nanoparticles coated with rhodium (II) citrate (Magh-Rh2Cit) induced in vitro cytotoxicity and in vivo antitumor activity, followed by intratumoral administration in breast carcinoma cells. In this study, our aim was to follow intravenous treatment to evaluate the systemic antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Female Balb/c mice were evaluated with regard to toxicity of intravenous treatments through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine and liver, kidney, and lung histology. The antitumor activity of rhodium (II) citrate (Rh2Cit), Magh-Rh2Cit, and maghemite nanoparticles coated with citrate (Magh-Cit), used as control, was evaluated by tumor volume reduction, histology, and morphometric analysis. Magh-Rh2Cit and Magh-Cit promoted a significant decrease in tumor area, and no experimental groups presented hematotoxic effects or increased levels of serum ALT and creatinine. This observation was corroborated by the histopathological examination of the liver and kidney of mice. Furthermore, the presence of nanoparticles was verified in lung tissue with no morphological changes, supporting the idea that our nanoformulations did not induce toxicity effects. No studies about the systemic action of rhodium (II) citrate-loaded maghemite nanoparticles have been carried out, making this report a suitable starting point for exploring the therapeutic potential of these compounds in treating breast cancer.

  12. The influence of active hexose correlated compound (AHCC) on cisplatin-evoked chemotherapeutic and side effects in tumor-bearing mice

    SciTech Connect

    Hirose, Aya; Sato, Eri; Fujii, Hajime; Sun Buxiang; Nishioka, Hiroshi . E-mail: nishioka@aminoup.co.jp; Aruoma, Okezie I. . E-mail: okezie.aruoma@touro.edu

    2007-07-15

    Cisplatin (cis-diaminedichloroplatinum (II) or CDDP) (a widely used platinum-containing anticancer drug) is nephrotoxic and has a low percentage of tolerance in patients during chemotherapy. The active hexose correlated compound (AHCC) is an extract of Basidiomycotina marketed as a supplement for cancer patients due to its nutrients and fibre content and its ability to strengthen and optimize the capacity of the immune system. The possibility that AHCC could reduce the side effects of cisplatin was assessed in the tumor-bearing BALB/cA mice on the basis of the ability to ameliorate the cisplatin-induced body weight loss, anorexia, nephrotoxicity and hematopoietic toxicity. Although cisplatin (8 mg/kg body weight) reduced the size and weight of the solid tumors, supplementation with AHCC significantly enhanced cisplatin-induced antitumor effect in both the size (p < 0.05) and weight (p < 0.05). Food intake in the cisplatin-treated mice were decreased following commencement of treatment and this remained low compared with the cisplatin-untreated group (control) throughout the experiment period. Supplementation with AHCC increased the food intake in the cisplatin-treated mice. The blood urea nitrogen and serum creatinine concentrations, and the ratio of blood urea nitrogen to serum creatinine were significantly increased in the cisplatin alone treated group compared to the control group. Their increased levels were mitigated by supplementation with AHCC (100 mg/kg body weight) in the cisplatin-treated group. AHCC was also able to modulate the suppression of bone marrow due to cisplatin and the improvement was statistically significant. The histopathological examination of the kidney revealed the presence of cisplatin-induced damage and this was modulated by AHCC treatment. The potential for AHCC to ameliorate the cisplatin-evoked toxicity as well as the chemotherapeutic effect could have beneficial economic implications for patients undergoing chemotherapy with

  13. Bearing system

    DOEpatents

    Kapich, Davorin D.

    1987-01-01

    A bearing system includes backup bearings for supporting a rotating shaft upon failure of primary bearings. In the preferred embodiment, the backup bearings are rolling element bearings having their rolling elements disposed out of contact with their associated respective inner races during normal functioning of the primary bearings. Displacement detection sensors are provided for detecting displacement of the shaft upon failure of the primary bearings. Upon detection of the failure of the primary bearings, the rolling elements and inner races of the backup bearings are brought into mutual contact by axial displacement of the shaft.

  14. Results from screening over 9000 mutation-bearing mice for defects in the electroretinogram and appearance of the fundus.

    PubMed

    Pinto, Lawrence H; Vitaterna, Martha Hotz; Siepka, Sanda M; Shimomura, Kazuhiro; Lumayag, Stephen; Baker, Matthew; Fenner, Deborah; Mullins, Robert F; Sheffield, Val C; Stone, Edwin M; Heffron, Edward; Takahashi, Joseph S

    2004-12-01

    Random mutagenesis combined with phenotypic screening using carefully crafted functional tests has successfully led to the discovery of genes that are essential for a number of functions. This approach does not require prior knowledge of the identity of the genes that are involved and is a way to ascribe function to the nearly 6000 genes for which knowledge of the DNA sequence has been inadequate to determine the function of the gene product. In an effort to identify genes involved in the visual system via this approach, we have tested over 9000 first and third generation offspring of mice treated with the mutagen N-ethyl-N-nitrosourea (ENU) for visual defects, as evidenced by abnormalities in the electroretinogram and appearance of the fundus. We identified 61 putative mutations with this procedure and outline the steps needed to identify the affected genes.

  15. Efficacy of acetylsalicylic acid (aspirin) in skin B16-F0 melanoma tumor-bearing C57BL/6 mice.

    PubMed

    Vad, Nikhil M; Kudugunti, Shashi K; Wang, Hezhen; Bhat, G Jayarama; Moridani, Majid Y

    2014-05-01

    Several epidemiological studies show that aspirin can act as a chemopreventive agent and decrease the incidences of various cancers including melanoma. In this work, we investigated the in vitro and in vivo efficacy of acetylsalicylic acid (ASA) as an antimelanoma agent in B16-F0 cells and skin B16-F0 melanoma tumor mouse model. Our findings indicate that the IC50 (48 h) for ASA in B16-F0 melanoma cells was 100 μM and that ASA caused a dose- and time-dependent GSH depletion and increase in reactive oxygen species (ROS) formation in B16-F0 melanoma cells. Male C57BL/6 mice were inoculated s.c. with 1 × 10(6) B16-F0 melanoma cells. ASA (80, 100, and 150 mg/kg) was initiated on day 1 or day 7, or day 9 after cell inoculation and continued daily for 13, 7, and 5 days, respectively. Animals were weighed daily and sacrificed on day 13. The tumors were excised and weighed. The animals receiving 13 days of ASA therapy at 80, 100, and 150 mg/kg demonstrated tumor growth inhibition by 1 ± 12%, 19 ± 22%, and 50 ± 29%, respectively. Animals receiving 7 days of therapy at 80, 100, and 150 mg/kg demonstrated tumor growth inhibition by 12 ± 14%, 27 ± 14%, and 40 ± 14%, respectively. No significant tumor growth inhibition was observed with 5 days of therapy. ASA at 100 and 150 mg/kg caused significant tumor growth inhibition in C57BL/6 mice when administered for 13 and 7 days, respectively. The results obtained in this study are consistent with the recent epidemiologically based report that aspirin is associated with lower melanoma risk in humans.

  16. Immune competence of cancer-reactive T cells generated de novo in adult tumor-bearing mice.

    PubMed

    May, Kenneth F; Lute, Kenneth; Kocak, Ergun; Abdessalam, Shahab; Yin, Lijie; Li, Ou; Guan, Zhen; Philips, Gary; Zheng, Pan; Liu, Yang

    2007-01-01

    The impact of timing of antigen introduction into fetus and neonates leads to the suggestion that pre-existing antigens are tolerogenic to immunocompetent cells generated thereafter. This hypothesis predicts that in patients with cancer who are undergoing bone marrow transplantation, newly produced T cells with specificity for pre-existing tumor cells will be inactivated by the tumor antigens in the host. Because the effect of tumor cells on developing cancer-reactive T cells has not been investigated, we set out to systematically analyze the impact of tumor cells in the periphery on the development of tumor-reactive T cells in the thymus and their immunocompetence in the periphery. Our data demonstrate that in the host in which a tumor is established in the periphery, the cancer-reactive T cells develop normally, remain fully immunocompetent, become activated in the periphery, and cause regression of large established tumors. The immunocompetence of T cells generated in an antigen-bearing host is also confirmed in a skin graft transplantation model.

  17. 6-Thioguanine-loaded polymeric micelles deplete myeloid-derived suppressor cells and enhance the efficacy of T cell immunotherapy in tumor-bearing mice

    SciTech Connect

    Jeanbart, Laura; Kourtis, Iraklis C.; van der Vlies, André J.; Swartz, Melody A.; Hubbell, Jeffrey A.

    2015-05-16

    Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that suppress effector T cell responses and can reduce the efficacy of cancer immunotherapies. We previously showed that ultra-small polymer nanoparticles efficiently drain to the lymphatics after intradermal injection and target antigen-presenting cells, including Ly6chi Ly6gmonocytic MDSCs (Mo-MDSCs), in skin-draining lymph nodes (LNs) and spleen. Here, we developed ultra-small polymer micelles loaded with 6-thioguanine (MC-TG), a cytotoxic drug used in the treatment of myelogenous leukemia, with the aim of killing Mo-MDSCs in tumor-bearing mice and thus enhancing T cell-mediated anti-tumor responses. We found that 2 days post-injection in tumor-bearing mice (B16-F10 melanoma or E.G7-OVA thymoma), MC-TG depleted Mo-MDSCs in the spleen, Ly6clo Ly6g+ granulocytic MDSCs (G-MDSCs) in the draining LNs, and Gr1int Mo-MDSCs in the tumor. In both tumor models, MC-TG decreased the numbers of circulating Mo- and G-MDSCs, as well as of Ly6chi macrophages, for up to 7 days following a single administration. MDSC depletion was dose dependent and more effective with MC-TG than with equal doses of free TG. Finally, we tested whether this MDSC-depleting strategy might enhance cancer immunotherapies in the B16-F10 melanoma model. We found that MC-TG significantly improved the efficacy of adoptively transferred, OVA-specific CD8+ T cells in melanoma cells expressing OVA. Ultimately, these findings highlight the capacity of MC-TG in depleting MDSCs in the tumor microenvironment and show promise in promoting anti-tumor immunity when used in combination with T cell immunotherapies.

  18. Mesenchymal stromal cells primed with Paclitaxel attract and kill leukaemia cells, inhibit angiogenesis and improve survival of leukaemia-bearing mice.

    PubMed

    Pessina, Augusto; Coccè, Valentina; Pascucci, Luisa; Bonomi, Arianna; Cavicchini, Loredana; Sisto, Francesca; Ferrari, Maura; Ciusani, Emilio; Crovace, Antonio; Falchetti, Maria Laura; Zicari, Sonia; Caruso, Arnaldo; Navone, Stefania; Marfia, Giovanni; Benetti, Anna; Ceccarelli, Piero; Parati, Eugenio; Alessandri, Giulio

    2013-03-01

    Current leukaemia therapy focuses on increasing chemotherapy efficacy. Mesenchymal stromal cells (MSCs) have been proposed for carrying and delivery drugs to improve killing of cancer cells. We have shown that MSCs loaded with Paclitaxel (PTX) acquire a potent anti-tumour activity. We investigated the effect of human MSCs (hMSCs) and mouse SR4987 loaded with PTX (hMSCsPTX and SR4987PTX) on MOLT-4 and L1210, two leukaemia cell (LCs) lines of human and mouse origin, respectively. SR4987PTX and hMSCsPTX showed strong anti-LC activity. hMSCsPTX, co-injected with MOLT-4 cells or intra-tumour injected into established subcutaneous MOLT-4 nodules, strongly inhibited growth and angiogenesis. In BDF1-mice-bearing L1210, the intraperitoneal administration of SR4987PTX doubled mouse survival time. In vitro, both hMSCs and hMSCsPTX released chemotactic factors, bound and formed rosettes with LCs. In ultrastructural analysis of rosettes, hMSCsPTX showed no morphological alterations while the attached LCs were apoptotic and necrotic. hMSCs and hMSCsPTX released molecules that reduced LC adhesion to microvascular endothelium (hMECs) and down-modulated ICAM1 and VCAM1 on hMECs. Priming hMSCs with PTX is a simple procedure that does not require any genetic cell manipulation. Once the effectiveness of hMSCsPTX on established cancers in mice is proven, this procedure could be proposed for leukaemia therapy in humans.

  19. PLGA-encapsulated tea polyphenols enhance the chemotherapeutic efficacy of cisplatin against human cancer cells and mice bearing Ehrlich ascites carcinoma.

    PubMed

    Singh, Madhulika; Bhatnagar, Priyanka; Mishra, Sanjay; Kumar, Pradeep; Shukla, Yogeshwer; Gupta, Kailash Chand

    2015-01-01

    The clinical success of the applicability of tea polyphenols awaits efficient systemic delivery and bioavailability. Herein, following the concept of nanochemoprevention, which uses nanotechnology for enhancing the efficacy of chemotherapeutic drugs, we employed tea polyphenols, namely theaflavin (TF) and epigallocatechin-3-gallate (EGCG) encapsulated in a biodegradable nanoparticulate formulation based on poly(lactide-co-glycolide) (PLGA) with approximately 26% and 18% encapsulation efficiency, respectively. It was observed that TF/EGCG encapsulated PLGA nanoparticles (NPs) offered an up to ~7-fold dose advantage when compared with bulk TF/EGCG in terms of exerting its antiproliferative effects and also enhanced the anticancer potential of cisplatin (CDDP) in A549 (lung carcinoma), HeLa (cervical carcinoma), and THP-1 (acute monocytic leukemia) cells. Cell cycle analysis revealed that TF/EGCG-NPs were more efficient than bulk TF/EGCG in sensitizing A549 cells to CDDP-induced apoptosis, with a dose advantage of up to 20-fold. Further, TF/EGCG-NPs, alone or in combination with CDDP, were more effective in inhibiting NF-κB activation and in suppressing the expression of cyclin D1, matrix metalloproteinase-9, and vascular endothelial growth factor, involved in cell proliferation, metastasis, and angiogenesis, respectively. EGCG and TF-NPs were also found to be more effective than bulk TF/EGCG in inducing the cleavage of caspase-3 and caspase-9 and Bax/Bcl2 ratio in favor of apoptosis. Further, in vivo evaluation of these NPs in combination with CDDP showed an increase in life span (P<0.05) in mice bearing Ehrlich's ascites carcinoma cells, with apparent regression of tumor volume in comparison with mice treated with bulk doses with CDDP. These results indicate that EGCG and TF-NPs have superior cancer chemosensitization activity when compared with bulk TF/EGCG.

  20. Cediranib combined with chemotherapy reduces tumor dissemination and prolongs the survival of mice bearing patient-derived ovarian cancer xenografts with different responsiveness to cisplatin.

    PubMed

    Decio, Alessandra; Cesca, Marta; Bizzaro, Francesca; Porcu, Luca; Bettolini, Rossana; Ubezio, Paolo; Taraboletti, Giulia; Belotti, Dorina; Giavazzi, Raffaella

    2015-10-01

    Cediranib is a pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor that affects tumor angiogenesis and is under investigation in clinical studies on ovarian cancer. Using a panel of eleven patient-derived ovarian cancer xenografts (EOC-PDX) growing orthotopically in the peritoneal cavity of nude mice we investigated the effect of cediranib as monotherapy or in combination with chemotherapy on overall survival (primary endpoint, at euthanasia), and tumor dissemination and metastasis in the peritoneal cavity (secondary endpoint, interim analysis). The response of EOC-PDX to cediranib varied (increment of lifespan, ILS between 12 and 85 %) in the different EOC-PDX, independently from tumor responsiveness to cisplatin (DDP). Cediranib combined with DDP and in maintenance regimen prolonged the survival of mice bearing EOC-PDX with different responsiveness to DDP (ILS between 34 and 224 % with only DDP and between 135 and 337 % with DDP plus Cediranib); survival was extended with the addition of paclitaxel to chemotherapy (50-77 % complete remissions). Cediranib reduced ascites of advanced EOC-PDX, but had limited effect on tumor dissemination; only combined with chemotherapy, ascites and metastases were both reduced. The reduction of tumor dissemination was associated to the increase of overall survival. In conclusion, the response to cediranib differs in the various EOC-PDX, reproducing the heterogeneous response of cancer patients to angiogenesis inhibitors. Cediranib potentiated chemotherapy, significantly inhibiting tumor progression and dissemination to metastatic organs, even in tumors poorly responsive to DDP. EOC-PDX preclinical models with different responsiveness to Cediranib may help in identifying determinants of response to cediranib and mechanisms of adaptation to antiangiogenic treatments.

  1. PLGA-encapsulated tea polyphenols enhance the chemotherapeutic efficacy of cisplatin against human cancer cells and mice bearing Ehrlich ascites carcinoma

    PubMed Central

    Singh, Madhulika; Bhatnagar, Priyanka; Mishra, Sanjay; Kumar, Pradeep; Shukla, Yogeshwer; Gupta, Kailash Chand

    2015-01-01

    The clinical success of the applicability of tea polyphenols awaits efficient systemic delivery and bioavailability. Herein, following the concept of nanochemoprevention, which uses nanotechnology for enhancing the efficacy of chemotherapeutic drugs, we employed tea polyphenols, namely theaflavin (TF) and epigallocatechin-3-gallate (EGCG) encapsulated in a biodegradable nanoparticulate formulation based on poly(lactide-co-glycolide) (PLGA) with approximately 26% and 18% encapsulation efficiency, respectively. It was observed that TF/EGCG encapsulated PLGA nanoparticles (NPs) offered an up to ~7-fold dose advantage when compared with bulk TF/EGCG in terms of exerting its antiproliferative effects and also enhanced the anticancer potential of cisplatin (CDDP) in A549 (lung carcinoma), HeLa (cervical carcinoma), and THP-1 (acute monocytic leukemia) cells. Cell cycle analysis revealed that TF/EGCG-NPs were more efficient than bulk TF/EGCG in sensitizing A549 cells to CDDP-induced apoptosis, with a dose advantage of up to 20-fold. Further, TF/EGCG-NPs, alone or in combination with CDDP, were more effective in inhibiting NF-κB activation and in suppressing the expression of cyclin D1, matrix metalloproteinase-9, and vascular endothelial growth factor, involved in cell proliferation, metastasis, and angiogenesis, respectively. EGCG and TF-NPs were also found to be more effective than bulk TF/EGCG in inducing the cleavage of caspase-3 and caspase-9 and Bax/Bcl2 ratio in favor of apoptosis. Further, in vivo evaluation of these NPs in combination with CDDP showed an increase in life span (P<0.05) in mice bearing Ehrlich’s ascites carcinoma cells, with apparent regression of tumor volume in comparison with mice treated with bulk doses with CDDP. These results indicate that EGCG and TF-NPs have superior cancer chemosensitization activity when compared with bulk TF/EGCG. PMID:26586942

  2. Olmesartan Potentiates the Anti-Angiogenic Effect of Sorafenib in Mice Bearing Ehrlich's Ascites Carcinoma: Role of Angiotensin (1–7)

    PubMed Central

    Abd-Alhaseeb, Mohammad M.; Zaitone, Sawsan A.; Abou-El-Ela, Soad H.; Moustafa, Yasser M.

    2014-01-01

    Local renin-angiotensin systems exist in various malignant tumor tissues; this suggests that the main effector peptide, angiotensin II, could act as a key factor in tumor growth. The underlying mechanisms for the anti-angiogenic effect of angiotensin II type 1 receptor blockers need to be further evaluated. The present study was carried out to investigate the anti-angiogenic effect of olmesartan alone or in combination with sorafenib, an angiotensin (1–7) agonist or an angiotensin (1–7) antagonist in Ehrlich's ascites carcinoma-bearing mice. The tumor was induced by intradermal injection of Ehrlich's ascites carcinoma cells into mice. Tumor discs were used to evaluate the microvessel density; the serum levels of vascular endothelial growth factor (VEGF) and serum insulin-like growth factor I (IGF-I); and their intratumoral receptors, VEGF receptor-2 and IGF-I receptor, respectively. All parameters were determined following the treatment course, which lasted for 21 days post-inoculation. Monotherapy with olmesartan and its combination with sorafenib resulted in a significant reduction in microvessel density and serum levels of VEGF and IGF-I, as well as their intratumoral receptors. In addition, the combination of olmesartan (30 mg/kg) with an angiotensin (1–7) agonist reduced the microvessel density, IGF-I serum levels and the levels of its intratumoral receptor. In conclusion, olmesartan reduced the levels of the angiogenesis markers IGF-I and VEGF and down-regulated the intratumoral expression of their receptors in a dose-dependent manner, and these effects were dependent on the angiotensin (1–7) receptor. These results suggest that olmesartan is a promising adjuvant to sorafenib in the treatment of cancer. PMID:24465768

  3. PLGA-encapsulated tea polyphenols enhance the chemotherapeutic efficacy of cisplatin against human cancer cells and mice bearing Ehrlich ascites carcinoma.

    PubMed

    Singh, Madhulika; Bhatnagar, Priyanka; Mishra, Sanjay; Kumar, Pradeep; Shukla, Yogeshwer; Gupta, Kailash Chand

    2015-01-01

    The clinical success of the applicability of tea polyphenols awaits efficient systemic delivery and bioavailability. Herein, following the concept of nanochemoprevention, which uses nanotechnology for enhancing the efficacy of chemotherapeutic drugs, we employed tea polyphenols, namely theaflavin (TF) and epigallocatechin-3-gallate (EGCG) encapsulated in a biodegradable nanoparticulate formulation based on poly(lactide-co-glycolide) (PLGA) with approximately 26% and 18% encapsulation efficiency, respectively. It was observed that TF/EGCG encapsulated PLGA nanoparticles (NPs) offered an up to ~7-fold dose advantage when compared with bulk TF/EGCG in terms of exerting its antiproliferative effects and also enhanced the anticancer potential of cisplatin (CDDP) in A549 (lung carcinoma), HeLa (cervical carcinoma), and THP-1 (acute monocytic leukemia) cells. Cell cycle analysis revealed that TF/EGCG-NPs were more efficient than bulk TF/EGCG in sensitizing A549 cells to CDDP-induced apoptosis, with a dose advantage of up to 20-fold. Further, TF/EGCG-NPs, alone or in combination with CDDP, were more effective in inhibiting NF-κB activation and in suppressing the expression of cyclin D1, matrix metalloproteinase-9, and vascular endothelial growth factor, involved in cell proliferation, metastasis, and angiogenesis, respectively. EGCG and TF-NPs were also found to be more effective than bulk TF/EGCG in inducing the cleavage of caspase-3 and caspase-9 and Bax/Bcl2 ratio in favor of apoptosis. Further, in vivo evaluation of these NPs in combination with CDDP showed an increase in life span (P<0.05) in mice bearing Ehrlich's ascites carcinoma cells, with apparent regression of tumor volume in comparison with mice treated with bulk doses with CDDP. These results indicate that EGCG and TF-NPs have superior cancer chemosensitization activity when compared with bulk TF/EGCG. PMID:26586942

  4. Absence of CD4(+) T cell help generates corrupt CD8(+) effector T cells in sarcoma-bearing Swiss mice treated with NLGP vaccine.

    PubMed

    Ghosh, Sarbari; Sarkar, Madhurima; Ghosh, Tithi; Guha, Ipsita; Bhuniya, Avishek; Biswas, Jaydip; Mallick, Atanu; Bose, Anamika; Baral, Rathindranath

    2016-07-01

    One of the prime objectives of cancer immunology and immunotherapy is to study the issues related to rescue and/or maintenance of the optimum effector CD8(+) T cell functions by minimizing tumor-induced negative factors. In this regard the influence of host intrinsic CD4(+) helper T cells towards generation and maintenance of CD8(+) effector T cells appears controversial in different experimental settings. Therefore, the present study was aimed to re-analyze the influence of CD4(+) helper T cells towards effector T cells during neem leaf glycoprotein (NLGP)-vaccine-mediated tumor growth restriction. CD4 depletion (mAb; Clone GK1.5) surprisingly resulted in significant increase in CD8(+) T cells in different immune organs from NLGP-treated sarcoma-bearing mice. However, such CD8 surge could not restrict the sarcoma growth in NLGP-treated CD4-depleted mice. Furthermore, CD4 depletion in early phase hinders CD8(+) T cell activation and terminal differentiation by targeting crucial transcription factor Runx3. CD4 depletion decreases accumulation of CD8α(+) dendritic cells within tumor draining lymph node, hampers antigen cross priming and CD86-CD28 interactions for optimum CD8(+) T cell functions. In order to search the mechanism of CD4(+) T cell help on NLGP-mediated CD8 effector functions, the role of CD4(+) helper T cell-derived IL-2 on optimization of CD8 functions was found using STAT5 signaling, but complete response requires physical contact of CD4(+) helper T cells with its CD8 counterpart. In conclusion, it was found that CD4(+) T cell help is not required to generate CD8(+) T cells but was found to be an integral phenomenon in maintenance of its anti-tumor functions even in NLGP-vaccine-mediated sarcoma growth restriction.

  5. Absence of CD4(+) T cell help generates corrupt CD8(+) effector T cells in sarcoma-bearing Swiss mice treated with NLGP vaccine.

    PubMed

    Ghosh, Sarbari; Sarkar, Madhurima; Ghosh, Tithi; Guha, Ipsita; Bhuniya, Avishek; Biswas, Jaydip; Mallick, Atanu; Bose, Anamika; Baral, Rathindranath

    2016-07-01

    One of the prime objectives of cancer immunology and immunotherapy is to study the issues related to rescue and/or maintenance of the optimum effector CD8(+) T cell functions by minimizing tumor-induced negative factors. In this regard the influence of host intrinsic CD4(+) helper T cells towards generation and maintenance of CD8(+) effector T cells appears controversial in different experimental settings. Therefore, the present study was aimed to re-analyze the influence of CD4(+) helper T cells towards effector T cells during neem leaf glycoprotein (NLGP)-vaccine-mediated tumor growth restriction. CD4 depletion (mAb; Clone GK1.5) surprisingly resulted in significant increase in CD8(+) T cells in different immune organs from NLGP-treated sarcoma-bearing mice. However, such CD8 surge could not restrict the sarcoma growth in NLGP-treated CD4-depleted mice. Furthermore, CD4 depletion in early phase hinders CD8(+) T cell activation and terminal differentiation by targeting crucial transcription factor Runx3. CD4 depletion decreases accumulation of CD8α(+) dendritic cells within tumor draining lymph node, hampers antigen cross priming and CD86-CD28 interactions for optimum CD8(+) T cell functions. In order to search the mechanism of CD4(+) T cell help on NLGP-mediated CD8 effector functions, the role of CD4(+) helper T cell-derived IL-2 on optimization of CD8 functions was found using STAT5 signaling, but complete response requires physical contact of CD4(+) helper T cells with its CD8 counterpart. In conclusion, it was found that CD4(+) T cell help is not required to generate CD8(+) T cells but was found to be an integral phenomenon in maintenance of its anti-tumor functions even in NLGP-vaccine-mediated sarcoma growth restriction. PMID:27178306

  6. Germ line transcription in mice bearing neor gene downstream of Igamma3 exon in the Ig heavy chain locus.

    PubMed

    Samara, Maha; Oruc, Zeliha; Dougier, Hei-Lanne; Essawi, Tamer; Cogné, Michel; Khamlichi, Ahmed Amine

    2006-04-01

    Class switch recombination (CSR) is preceded by germ line transcription that initiates from promoters upstream of switch (S) sequences and terminates downstream of associated constant genes. Previous work showed that germ line transcripts and their processing are required for CSR and that germ line transcription is regulated in a major part by a regulatory region located downstream of the Ig heavy chain locus. This long-range, polarized effect can be disturbed by inserting an expressed neomycine resistance (neo(r)) gene. To contribute to a better understanding of the mechanism of such a long-distance regulation, we generated knock-in mice in which a neo(r) gene was inserted downstream of Igamma3 exon leaving intact all the necessary elements for germ line transcription and splicing. We show that the expressed neo(r) gene interferes with transcription initiation from Igamma3, and that it impairs but does not block S recombination to Cgamma3. Moreover, we show for the first time that the neo(r) gene provides through chimeric neo(r)-Cgamma3 transcripts the necessary elements for splicing of germ line transcripts by activating two novel cryptic splice sites, one in the coding region of the intronless neo(r) gene and the other in the Igamma3-Cgamma3 intron.

  7. Lipid-associated methylpheophorbide-a (hexyl-ether) as a photodynamic agent in tumor-bearing mice.

    PubMed

    Mayhew, E; Vaughan, L; Panus, A; Murray, M; Henderson, B W

    1993-12-01

    Liposomes are a potential system for more selective delivery of photosensitizers (PS) to tumors. Pheophorbides are one series of new PS under investigation for use in photodynamic therapy. The pharmacokinetics, anti-tumor response and normal tissue effects of methylpheophorbide-a-(hexyl-ether) (MPH) associated with negatively charged phospholipid vesicles composed of high and low transition temperature lipids were determined in mice. In some preparations monosialoganglioside, which is known to impart long circulation time to liposomes was also included. Normally water-insoluble MPH could be quantitatively incorporated in multilamellar liposomes up to at least 20 mol MPH/mol lipid% for most liposome compositions and sonicated to form clear suspensions. Evidence from electron microscopy and entrapment of aqueous space markers indicated that the particles formed by sonication were not standard liposomes. Anti-tumor responses to light treatment (135 J/cm2, 665 nm argon-dye laser) 24 h after MPH (0.4 mumol/kg) administration were slightly but significantly greater (P < 0.05) for lipid associated MPH compared to MPH solubilized in Tween 80. There were no major differences in tumor uptake and tumor cell photosensitization between lipid or Tween 80 formulations of MPH, whereas, dependent on lipid composition and time after MPH administration, the doses of light required to cause occlusive vascular damage were increased for the lipid formulations. Pharmacokinetic studies showed rapid dissociation between lipids and MPH in vivo. Lipid formulations are useful for solubilizing MPH and may improve the therapeutic effects of this PS.

  8. Anti-hepatocarcinoma effects of berberine nanosuspension against human HepG2 and Huh7 cells as well as H22 tumor bearing mice

    NASA Astrophysics Data System (ADS)

    Wang, Zhi-ping; Wu, Jun-biao; Zhou, Qun; Wang, Yi-fei; Chen, Tongsheng

    2014-09-01

    Hepatocarcinoma, a malignant cancer, threaten human life badly. It is a current issue to seek the effective natural remedy from plant to treat cancer due to the resistance of the advanced hepatocarcinoma to chemotherapy. Berberine (Ber), an isoquinoline derivative alkaloid, has a wide range of pharmacological properties and is considered to have anti-hepatocarcinoma effects. However its low oral bioavailability restricts its wide application. In this report, Ber nanosuspension (Ber-NS) composed of Ber and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was prepared by high pressure homogenization technique. Both in vitro and in vivo anti-hepatocarcinoma effects of Ber-NS relative to effcacy of bulk Ber were evaluated. The particle size and zeta potential of Ber-NS were 73.1 +/- 3.7 nm and 6.99 +/- 0.17 mV, respectively. Ber-NS exhibited significant inhibitory effects against human HepG2 and Huh7 cells, and the corresponding IC50 values were 8.1 and 4.7 μg/ml (18.3 and 6.5 μg/ml of Ber solution). In vivo studies also showed higher antitumor efficacy, and inhibition rates was 63.7% (41.4 % of Ber solution) at 100 mg/kg intragastric administration in the H22 solid tumor bearing mice. These results suggest that the delivery of Ber as a nanosuspension is a promising approach for treating hepatocarcinoma.

  9. A biodistribution study of PEGylated PCL-based nanoparticles in C57BL/6 mice bearing B16/F10 melanoma

    NASA Astrophysics Data System (ADS)

    Lupi, M.; Colombo, C.; Frapolli, R.; Ferrari, R.; Sitia, L.; Dragoni, L.; Bello, E.; Licandro, S. A.; Falcetta, F.; Ubezio, P.; Bigini, P.; Salmona, M.; D'Incalci, M.; Morbidelli, M.; Moscatelli, D.

    2014-08-01

    One of the major drawbacks that limits the clinical application of nanoparticles is the lack of preliminary investigations related to their biocompatibility, biodegradability and biodistribution. In this work, biodegradable PEGylated polymer nanoparticles (NPs) have been synthesized by using macromonomers based on poly(ɛ-caprolaconte) oligomers. More in detail, NPs have been produced by adopting a surfactant-free semibatch emulsion polymerization process using PEG chains as a stabilizing agent. The NPs were also labeled with rhodamine B covalently bound to the NPs to quantitatively study their biodistribution in vivo. NPs were investigated in both in vitro and in vivo preclinical systems to study their biodistribution in mice bearing B16/F10 melanoma, as well as their biocompatibility and biodegradability. The NP concentration was evaluated in different tissues at several times after intravenous injection. The disappearance of the NPs from the plasma was biphasic, with distribution and elimination half-lives of 30 min and 15 h, respectively. NPs were retained in tumors and in filter organs for a long time, were still detectable after 7 d and maintained a steady concentration in the tumor for 120 h. 48 h after injection, 70 ± 15% of the inoculated NPs were excreted in the feces. The favorable tumor uptake, fast excretion and absence of cytotoxicity foster the further development of produced NPs as drug delivery carriers.

  10. In vivo pharmacokinetics, biodistribution and the anti-tumor effect of cyclic RGD-modified doxorubicin-loaded polymers in tumor-bearing mice.

    PubMed

    Wang, Chen; Li, Yuan; Chen, Binbin; Zou, Meijuan

    2016-10-01

    In our previous study, we successfully produced and characterized a multifunctional drug delivery system with doxorubicin (RC/GO/DOX), which was based on graphene oxide (GO) and cyclic RGD-modified chitosan (RC). Its characteristics include: pH-responsiveness, active targeting of hepatocarcinoma cells, and efficient loading with controlled drug release. Here, we report the pharmacokinetics, biodistribution, and anti-tumor efficacy of RC/GO/DOX polymers in tumor-bearing nude mice. The objective of this study is to assess its targeting potential for tumors. Pharmacokinetic and biodistribution profiles demonstrated that tumor accumulation of RC/GO/DOX polymers was almost three times higher than the others, highlighting the efficacy of the active targeting strategy. Furthermore, the tumor inhibition rate of RC/GO/DOX polymers was 56.64%, 2.09 and 2.93 times higher than that of CS/GO/DOX polymers (without modification) and the DOX solution, respectively. Anti-tumor efficacy results indicated that the tumor growth was better controlled by RC/GO/DOX polymers than the others. Hematoxylin and eosin (H&E) staining showed remarkable changes in tumor histology. Compared with the saline group, the tumor section from the RC/GO/DOX group revealed a marked increase in the quantity of apoptotic and necrotic cells, and a reduction in the quantity of the blood vessels. Together, these studies show that this new system could be regarded as a suitable form of DOX-based treatment of the hepatocellular carcinoma.

  11. Radioiodination of 2,3-dimethyl-4H-furo[3,2-c]coumarin and biological evaluation in solid tumor bearing mice.

    PubMed

    Abd Elhalim, S M; Ibrahim, I T

    2014-10-22

    Compound 2,3-dimethyl-4H-furo[3,2-c]coumarin is a coumarin derivative that could be labeled with (125)I. The process of labeling was started using 1mg of the compound, 50µg CAT oxidizing agent, 30min as reaction time at pH with a yield about 95%. The (125)I-coumarin derivative was stable for about 48h. Radiochemical purity of the labeled compound was performed by electrophoresis and HPLC. The labeled compound was separated with purity about 95%. Tumor transplantation to produce a solid tumor in the right leg of albino mice was made by intramuscular injection of 2×10(6) EAC (Ehrlish acittes carcinoma cells). Biodistribution study of (125)I-coumarin derivative revealed that the uptake in tumor bearing leg was over 5% at 1h and 4h post-injection. This uptake encourages the use of (123)I-coumarin derivative in imaging of tumor sites.

  12. Radioiodination of 2,3-dimethyl-4H-furo[3,2-c]coumarin and biological evaluation in solid tumor bearing mice

    PubMed Central

    Abd Elhalim, S.M.; Ibrahim, I.T.

    2015-01-01

    Compound 2,3-dimethyl-4H-furo[3,2-c]coumarin is a coumarin derivative that could be labeled with 125I. The process of labeling was started using 1 mg of the compound, 50 µg CAT oxidizing agent, 30 min as reaction time at pH with a yield about 95%. The 125I-coumarin derivative was stable for about 48 h. Radiochemical purity of the labeled compound was performed by electrophoresis and HPLC. The labeled compound was separated with purity about 95%. Tumor transplantation to produce a solid tumor in the right leg of albino mice was made by intramuscular injection of 2×106 EAC (Ehrlish acittes carcinoma cells). Biodistribution study of 125I-coumarin derivative revealed that the uptake in tumor bearing leg was over 5% at 1 h and 4 h post-injection. This uptake encourages the use of 123I-coumarin derivative in imaging of tumor sites. PMID:25464192

  13. The protective effects of nutritional antioxidant therapy on Ehrlich solid tumor-bearing mice depend on the type of antioxidant therapy chosen: histology, genotoxicity and hematology evaluations.

    PubMed

    Miranda-Vilela, Ana Luisa; Portilho, Flávia A; de Araujo, Vitor G B; Estevanato, Luciana L C; Mezzomo, Bélin P; Santos, Maria de Fátima M de Almeida; Lacava, Zulmira G M

    2011-11-01

    Strong evidence indicates that reactive oxygen species (ROS) play an important role in the initiation as well as the promotion phase of carcinogenesis. Studies support the role of ROS in cancer, in part, by showing that dietary antioxidants act as cancer-preventive agents. Although results are promising, the research on this topic is still controversial. Thus, the aim of this study was to investigate whether vitamins C, E and pequi oil can, individually, provide prevention and/or be used afterward as an adjuvant in cancer therapy. Ehrlich solid tumor-bearing mice received antioxidant as follows: before tumor inoculation, before and after tumor inoculation (continuous administration), and after tumor inoculation; morphometric analyses of tumor, genotoxicity and hematology were then carried out. Antioxidant administrations before tumor inoculation effectively inhibited its growth in the three experimental protocols, but administrations after the tumor's appearance accelerated tumor growth and favored metastases. Continuous administration of pequi oil inhibited the tumor's growth, while the same protocol with vitamins E and C accelerated it, favoring metastasis and increasing oxidative stress on erythrocytes. Except for continuous administration with vitamin E, the development of ascites tumor metastases was linked with increased inflammation. Results suggest that the efficiency and applicability of antioxidants in the medical clinic can depend not only on the nature of the antioxidant, the type and stage of cancer being treated and the prevailing oxygen partial pressure in the tissues, but also on the type of antioxidant therapy chosen.

  14. Antitumor efficacy in H22 tumor bearing mice and immunoregulatory activity on RAW 264.7 macrophages of polysaccharides from Talinum triangulare.

    PubMed

    Wang, Lin; Nie, Zhi-Kui; Zhou, Qing; Zhang, Jiu-Liang; Yin, Jiao-Jiao; Xu, Wei; Qiu, Yu; Ming, Yan-Lin; Liang, Shi

    2014-09-01

    The aim of this paper was to study the antitumor and immunoregulatory activities of a polysaccharide (TTP) from Talinum triangulare. The molecular weight of TTP-IV was 49.9 kDa. The monosaccharide composition analysis of TTP-IV revealed that it was a heteropolysaccharide consisting of rhamnose, arabinose, mannose and galactose with a molar ratio of 1.22 : 1.00 : 1.05 : 1.51. The results of the in vivo study showed that TTP (200 mg per kg bw) significantly inhibited the growth of tumor by 49.07% in H22-bearing Kunming mice. In vitro, the growth of primary murine macrophages was promoted by TTP in a dose- and time-dependent manner significantly. Besides, RAW 264.7 cells were activated by TTP to produce NO and the toxicity of RAW 264.7 supernatant was markedly enhanced in vitro. The levels of iNOS, TLR2, TLR4 and IL-1β were obviously increased by TTP. Therefore, it is suggested that TTP can be utilized as a potent antitumor and immunoenhancing material in functional food.

  15. Plasma, tumor and tissue pharmacokinetics of Docetaxel delivered via nanoparticles of different sizes and shapes in mice bearing SKOV-3 human ovarian carcinoma xenograft

    PubMed Central

    Chu, Kevin S.; Hasan, Warefta; Rawal, Sumit; Walsh, Mark D.; Enlow, Elizabeth M.; Luft, J. Christopher; Bridges, Arlene S.; Kuijer, Jennifer L.; Napier, Mary E.; Zamboni, William C.; DeSimone, Joseph M.

    2013-01-01

    The particle fabrication technique PRINT® was used to fabricate monodisperse size and shape specific poly(lactide-co-glycolide) particles loaded with the chemotherapeutic Docetaxel. The pharmacokinetics of two cylindrical shaped particles with diameter=80nm; height=320nm (PRINT-Doc-80×320) and d=200nm; h=200nm (PRINT-Doc-200×200) were compared to Docetaxel in mice bearing human ovarian carcinoma SKOV-3 flank xenografts. The Docetaxel plasma exposure was ~20-fold higher for both particles compared to docetaxel. Additionally, the volume of distribution (Vd) of Docetaxel in PRINT formulations was ~18-fold (PRINT-Doc-80×320) and ~33-fold (PRINT-Doc-200×200) lower than Docetaxel. The prolonged duration of Docetaxel in plasma when dosed with PRINT formulations subsequently lead to increased tumor exposure of Docetaxel from 0-168 hours (~53% higher for PRINT-Doc-80×320 and ~76% higher for PRINT-Doc-200×200 particles). PRINT-Doc-80×320 had lower exposures in the liver, spleen and lung compared with PRINT-Doc-200×200. Thus, the use of particles with smaller feature size may be preferred to decrease clearance by organs of the mononuclear phagocyte system. PMID:23219874

  16. Synthesis of copper octabromotetracarboranylphenylporphyrin for boron neutron capture therapy and its toxicity and biodistribution in tumour-bearing mice.

    PubMed

    Miura, M; Morris, G M; Micca, P L; Nawrocky, M M; Makar, M S; Cook, S P; Slatkin, D N

    2004-07-01

    Copper tetracarboranyltetraphenylporphyrin (CuTCPH) is a minimally toxic carborane-containing porphyrin that has safely delivered high concentrations of boron for experimental boron neutron capture therapy (BNCT). Copper octabromotetracarboranylphenylporphyrin (CuTCPBr), synthesized by bromination of CuTCPH, is one of several new minimally toxic analogues of CuTCPH being studied in our laboratory, which could possess comparable or better tumour-targeting properties with enhanced tumour cytotoxicity. Its biodistribution, biokinetics and toxicity in mice with subcutaneous EMT-6 (mammary) or SCCVII (squamous cell) carcinomas were compared with those of CuTCPH. The administration of approximately 200 mg kg(-1) of either porphyrin in six intraperitoneal injections over 2 days had no apparent effect, but administration of approximately 400 mg kg(-1) slightly lowered body weights, elevated alanine and aspartate transaminase activities in blood plasma, and depressed blood platelet counts for several days. Enzymes and platelets returned to normal within 5 days after those injections and body weights returned to normal within 2 weeks. High average concentrations of boron from either porphyrin were achieved in the two tumour models from a total dose of approximately 200 mg kg(-1). The high tumour boron concentration decreased slowly while concentrations in blood decreased rapidly. Boron concentrations in brain and skin were consistently lower than in tumour by a factor of 10 or more. Although either CuTCPH or CuTCPBr can be labelled with (64)Cu for imaging by positron emission tomography (PET), CuTCPBr can also be labelled by (76)Br, another PET-imageable nuclide.

  17. Circulation kinetics and biodistribution of dual-labeled polymersomes with modulated surface charge in tumor-bearing mice: comparison with stealth liposomes.

    PubMed

    Lee, Jung Seok; Ankone, Marc; Pieters, Ebel; Schiffelers, Raymond M; Hennink, Wim E; Feijen, Jan

    2011-10-30

    Polymersomes (Ps) based on poly(ethylene glycol)-b-poly(D,L-lactide) (PEG-PDLLA), with similar sizes (90-100 nm), but different zeta potentials (-7.6 to -38.7 mV) were prepared to investigate the effect of surface charge on blood circulation time and tissue distribution in tumor-bearing mice. For the in vivo studies dual labeled Ps were applied, which were obtained by encapsulating (3)H-dextran 70k in the aqueous core of Ps and by post-coupling of (14)C-thioglycolic acid onto acrylated PEG chains of the Ps. Stealth liposomes (103 nm, -6 mV) were used as a control. A substantial longer half lifetime (τ(1/2)) (47.3h) and a reduced liver uptake (27.9% of injected dose (% ID)) of Ps with a zeta potential of -7.6 mV were observed as compared to those of stealth liposomes (10.6h, 39.8% ID) most probably due to the presence of a relatively thicker and denser PEG brush of the Ps as compared to the liposomes. As a result of their longer circulation times a high tumor accumulation of 18.6% ID was obtained for these Ps after 3d circulation in mice while only 11.2% ID of stealth liposomes accumulated in the tumors as a result of their relatively short τ(1/2) in blood. By increasing the zeta potential on Ps, more rapid clearance of Ps from the blood circulation was found due to an enhanced uptake by the liver. Importantly, co-localization of the two labels of Ps was observed during circulation indicating that dual labeled Ps were colloidally stable in blood without leakage of (3)H-dextran. In conclusion, the results show that Ps with a slightly negative surface charge (zeta potential -7.6 mV) are stable in the circulation and have longer circulation times and a higher tumor accumulation in mice than Ps with more negative zeta potentials or the stealth liposomes used as a control. PMID:21820023

  18. Circulation kinetics and biodistribution of dual-labeled polymersomes with modulated surface charge in tumor-bearing mice: comparison with stealth liposomes.

    PubMed

    Lee, Jung Seok; Ankone, Marc; Pieters, Ebel; Schiffelers, Raymond M; Hennink, Wim E; Feijen, Jan

    2011-10-30

    Polymersomes (Ps) based on poly(ethylene glycol)-b-poly(D,L-lactide) (PEG-PDLLA), with similar sizes (90-100 nm), but different zeta potentials (-7.6 to -38.7 mV) were prepared to investigate the effect of surface charge on blood circulation time and tissue distribution in tumor-bearing mice. For the in vivo studies dual labeled Ps were applied, which were obtained by encapsulating (3)H-dextran 70k in the aqueous core of Ps and by post-coupling of (14)C-thioglycolic acid onto acrylated PEG chains of the Ps. Stealth liposomes (103 nm, -6 mV) were used as a control. A substantial longer half lifetime (τ(1/2)) (47.3h) and a reduced liver uptake (27.9% of injected dose (% ID)) of Ps with a zeta potential of -7.6 mV were observed as compared to those of stealth liposomes (10.6h, 39.8% ID) most probably due to the presence of a relatively thicker and denser PEG brush of the Ps as compared to the liposomes. As a result of their longer circulation times a high tumor accumulation of 18.6% ID was obtained for these Ps after 3d circulation in mice while only 11.2% ID of stealth liposomes accumulated in the tumors as a result of their relatively short τ(1/2) in blood. By increasing the zeta potential on Ps, more rapid clearance of Ps from the blood circulation was found due to an enhanced uptake by the liver. Importantly, co-localization of the two labels of Ps was observed during circulation indicating that dual labeled Ps were colloidally stable in blood without leakage of (3)H-dextran. In conclusion, the results show that Ps with a slightly negative surface charge (zeta potential -7.6 mV) are stable in the circulation and have longer circulation times and a higher tumor accumulation in mice than Ps with more negative zeta potentials or the stealth liposomes used as a control.

  19. Evaluation of the angiogenesis inhibitor KR-31831 in SKOV-3 tumor-bearing mice using (64)Cu-DOTA-VEGF(121) and microPET.

    PubMed

    Lee, Iljung; Yoon, Kwang Yup; Kang, Choong Mo; Lin, Xin; Chen, Xiaoyuan; Kim, Jung Young; Kim, Sung-Min; Ryu, Eun Kyoung; Choe, Yearn Seong

    2012-08-01

    KR-31831 ((2R,3R,4S)-6-amino-4-[N-(4-chloropheyl)-N-(1H-imidazol-2ylmethyl)amino]-3-hydroxyl-2-methyl-2-dimethoxymethyl-3,4-dihydro-2H-1-benzopyran), an angiogenesis inhibitor, was evaluated in tumor-bearing mice using molecular imaging technology. Pre-treatment microPET images were acquired on SKOV-3 cell-implanted nude mice after injection with (64)Cu-DOTA-VEGF(121). KR-31831 (50 mg/kg) was then injected intraperitoneally into the treatment group (n=3), while injection vehicle was injected into the control (n=4) and blocking (n=3) groups. After injections occurred daily for 28 days, all groups of mice underwent post-treatment microPET imaging after injection with (64)Cu-DOTA-VEGF(121). The post-treatment images showed high tumor uptake in the control group and reduced tumor uptake in both the blocking and treatment groups. ROI analysis of the tumor images revealed 6.25%±1.18% ID/g at 1 h, 6.55%±0.69% ID/g at 2 h, and 4.68%±0.63% ID/g at 16 h in the control group; 3.87%±0.45% ID/g at 1 h, 4.50%±0.44% ID/g at 2 h, and 3.63%±0.25% ID/g at 16 h in the blocking group; and 4.03%±0.74% ID/g at 1 h, 4.37%±0.67% ID/g at 2 h, and 3.83%±0.90% ID/g at 16 h in the treatment group. Biodistribution obtained after the post-treatment microPET imaging also demonstrated high tumor uptake (3.74%±0.27% ID/g) in the control group and reduced uptakes in both the blocking group (2.69%±0.73% ID/g, P<.05) and the treatment group (3.11%±0.25% ID/g, P<.05), which correlated well with microPET imaging data. Immunofluorescence analysis showed higher levels of VEGFR2 and CD31 expressions in tumor tissues of the control and blocking groups than in tumor tissues of the treatment group. These results suggest that the antiangiogenic activity of KR-31831 is mediated through VEGFR2 and microPET serves as a useful molecular imaging tool for evaluation of a newly developed angiogenesis inhibitor, KR-31831.

  20. Biodistribution and antitumoral effect of long-circulating and pH-sensitive liposomal cisplatin administered in Ehrlich tumor-bearing mice.

    PubMed

    Araújo, José Geraldo Coimbra; Mota, Luciene das Graças; Leite, Elaine Amaral; Maroni, Laís de Carvalho; Wainstein, Alberto Julius Alves; Coelho, Luiz Gonzaga Vaz; Savassi-Rocha, Paulo Roberto; Pereira, Márcio Tadeu; de Carvalho, Andréa Teixeira; Cardoso, Valbert Nascimento; De Oliveira, Mônica Cristina

    2011-07-01

    Cisplatin (CDDP) is one of the most active cytotoxic agents and has been widely used in the treatment of peritoneal carcinomatosis by the intraperitoneal (i.p.) route. However, CDDP, a low-molecular-weight compound, is rapidly absorbed by the capillaries in the i.p. serosa and transferred to the bloodstream, inducing the appearance of systemic side-effects, such as nephrotoxicity. Furthermore, the i.p. CDDP chemotherapy is limited to patients whose residual tumor nodules are less than 0.5 cm in diameter after surgical debulking. The failure of i.p. therapy is attributed to the poor penetration of CDDP into larger tumors. One strategy to improve drug delivery in the peritoneal region and reduce toxicity is the use of drug delivery systems. The objective of the present work was to evaluate the biodistribution and antitumoral effect of long-circulating and pH-sensitive liposomes containing CDDP (SpHL-CDDP), as compared with free CDDP, after their i.p. administration in Ehrlich ascitic tumor-bearing mice. After administering a 6 mg/kg single i.p. bolus injection of either free CDDP or SpHL-CDDP, ascitic fluid (AF), blood and organs (kidneys, liver, spleen and lungs) were collected and analyzed for CDDP content. The area under the CDDP concentration-time curve (AUC) obtained for AF and blood after SpHL-CDDP administration was 3.3-fold larger and 1.3-fold lower, respectively, when compared with free CDDP treatment, thus indicating its high retention within the peritoneal cavity. The determination of the ratio between AUC in each tissue and that in blood (Kp) showed a lower accumulation of CDDP in kidneys after SpHL-CDDP treatment. The SpHL-CDDP treatment demonstrated a significant uptake by the liver and spleen. SpHL-CDDP treatment led to a higher survival rate of mice with initial or disseminated peritoneal carcinomatosis than CDDP treatment. These results indicate that SpHL-CDDP may be useful for i.p. chemotherapy due to their greater concentration in the peritoneal

  1. Hydroxysafflor yellow A inhibits angiogenesis of hepatocellular carcinoma via blocking ERK/MAPK and NF-κB signaling pathway in H22 tumor-bearing mice.

    PubMed

    Yang, Fangfang; Li, Jingmin; Zhu, Jinhui; Wang, Dong; Chen, Shaoshui; Bai, Xianyong

    2015-05-01

    Hydroxysafflor yellow A (HSYA), a flavonoid derived and isolated from traditional Chinese medicine Carthamus tinctorius L., possesses anti-tumor activity. However, its effects on hepatocellular carcinoma (HCC) have not been investigated. The proliferation and metastasis of HCC are dependent on angiogenesis, which also strongly links with several signal transduction pathways associated with cell proliferation and apoptosis. This study aimed to explore the effect of HSYA on vasculogenesis and to determine its molecular mechanism by investigating the expression of ERK/MAPK (p-c-Raf, c-Raf, p-ERK1/2, ERK1/2) and NF-κB (p65, IκB and p-IκB) signaling pathway in H22 tumor-bearing mice. The results showed that HSYA could considerably suppress tumor growth by inhibiting secretion of angiogenesis factors (vascular endothelial growth factor A, basic fibroblast growth factor) and vascular endothelial growth factor receptor1. At the moleculcould block ERK1/2 phosphorylation and then restrain the activation of NF-κB and its nuclear translocation by down-regulating the expression of p65 in the nucleus, up-regulating p65 level in the cytoplasm, inhibiting IκB phosphorylation and cytoplasmic degradation of IκB-α. Finally, we demonstrate that HSYA could suppress mRNA expression levels of cell proliferation-related genes (cyclinD1, c-myc, c-Fos) compared with negative control group. And best of all, HSYA could improve spleen/thymus indexes, which was evaluated as the marker of protective effect on the immune system. Our findings support HSYA as a promising candidate for the prevention and treatment of HCC. PMID:25720342

  2. Enhancement of fibroblast activation protein α-based vaccines and adenovirus boost immunity by cyclophosphamide through inhibiting IL-10 expression in 4T1 tumor bearing mice.

    PubMed

    Xia, Qiu; Geng, Fei; Zhang, Fang-Fang; Liu, Chen-Lu; Xu, Ping; Lu, Zhen-Zhen; Zhang, Hai-Hong; Kong, Wei; Yu, Xiang-Hui

    2016-08-31

    Fibroblast activation protein α (FAPα) is expressed in cancer-associated fibroblasts (CAFs) of more than 90% of malignant epithelia carcinomas. CAFs are the main type of cells in the tumor microenvironment which offer nutrition and protection to the tumor and regulate immunosuppression. To eliminate CAFs, a vaccine targeting FAPα may be used with a heterologous prime-boost strategy to enhance the FAPα-specific cellular immunity. Here, a FAP vaccine using a recombinant adenovirus (rAd) vector was constructed as well as a DNA vaccine reported in our previous work. Although the DNA prime-rAd boost strategy enhanced FAPα-specific immune responses, improvement of anti-tumor immunity effects was not observed. Examination of immunosuppressive factors revealed that high expression of the IL-10 cytokine was considered the main cause of the failure of the prime-boost strategy. However, heterologous vaccination in combination with a low-dose of cyclophosphamide (CY), which was reported to reduce IL-10 production and promote a shift from immunosuppression to immunopotentiation, resulted in enhanced effects in terms of numbers of effector T cells and tumor growth inhibition rates, compared to the CY alone or DNA alone group. Tumor growth was inhibited markedly when the prime-boost strategy was combined with CY in both the prophylactic and therapeutic settings and the survival time of 4T1 tumor bearing mice was also prolonged significantly. With the reduction of IL-10, enhancement of the anti-tumor effect by the prime-boost strategy was observed. These results suggest that FAPα-targeted rAd boosting in combination with CY is an attractive approach to overcoming immunosuppression in cancer vaccines. PMID:27498213

  3. Boron uptake in normal melanocytes and melanoma cells and boron biodistribution study in mice bearing B16F10 melanoma for boron neutron capture therapy.

    PubMed

    Faião-Flores, Fernanda; Coelho, Paulo Rogério Pinto; Arruda-Neto, João Dias Toledo; Camillo, Maria Aparecida Pires; Maria-Engler, Silvya Stuchi; Rici, Rose Eli Grassi; Sarkis, Jorge Eduardo Souza; Maria, Durvanei Augusto

    2012-08-01

    Information on (10)B distribution in normal tissues is crucial to any further development of boron neutron capture therapy (BNCT). The goal of this study was to investigate the in vitro and in vivo boron biodistribution in B16F10 murine melanoma and normal tissues as a model for human melanoma treatment by a simple and rapid colorimetric method, which was validated by HR-ICP-MS. The B16F10 melanoma cell line showed higher melanin content than human melanocytes, demonstrating a greater potential for boronophenylalanine uptake. The melanocytes showed a moderate viability decrease in the first few minutes after BNCT application, stabilizing after 75 min, whereas the B16F10 melanoma showed the greatest intracellular boron concentration at 150 min after application, indicating a different boron uptake of melanoma cells compared to normal melanocytes. Moreover, at this time, the increase in boron uptake in melanoma cells was approximately 1.6 times higher than that in normal melanocytes. The (10)B concentration in the blood of mice bearing B16F10 melanoma increased until 90 min after BNCT application and then decreased after 120 min, and remained low until the 240th minute. On the other hand, the (10)B concentration in tumors was increased from 90 min and maximal at 150 min after application, thus confirming the in vitro results. Therefore, the present in vitro and in vivo study of (10)B uptake in normal and tumor cells revealed important data that could enable BNCT to be possibly used as a treatment for melanoma, a chemoresistant cancer associated with high mortality.

  4. THRUST BEARING

    DOEpatents

    Heller, P.R.

    1958-09-16

    A thrust bearing suitable for use with a rotor or blower that is to rotate about a vertical axis is descrihed. A centrifagal jack is provided so thnt the device may opernte on one hearing at starting and lower speeds, and transfer the load to another bearing at higher speeds. A low viscosity fluid is used to lubricate the higher speed operation bearing, in connection with broad hearing -surfaces, the ability to withstand great loads, and a relatively high friction loss, as contraated to the lower speed operatio;n bearing which will withstand only light thrust loads but is sufficiently frictionfree to avoid bearing seizure during slow speed or startup operation. An axially aligned shaft pin provides the bearing surface for low rotational speeds, but at higher speed, weights operating against spring tension withdraw nthe shaft pin into the bearing proper and the rotor shaft comes in contact with the large bearing surfaces.

  5. Journal bearing

    DOEpatents

    Menke, John R.; Boeker, Gilbert F.

    1976-05-11

    1. An improved journal bearing comprising in combination a non-rotatable cylindrical bearing member having a first bearing surface, a rotatable cylindrical bearing member having a confronting second bearing surface having a plurality of bearing elements, a source of lubricant adjacent said bearing elements for supplying lubricant thereto, each bearing element consisting of a pair of elongated relatively shallowly depressed surfaces lying in a cylindrical surface co-axial with the non-depressed surface and diverging from one another in the direction of rotation and obliquely arranged with respect to the axis of rotation of said rotatable member to cause a flow of lubricant longitudinally along said depressed surfaces from their distal ends toward their proximal ends as said bearing members are rotated relative to one another, each depressed surface subtending a radial angle of less than 360.degree., and means for rotating said rotatable bearing member to cause the lubricant to flow across and along said depressed surfaces, the flow of lubricant being impeded by the non-depressed portions of said second bearing surface to cause an increase in the lubricant pressure.

  6. [Comparative S-adenosyl-L-methionine and S-adenosyl-L-homocysteine content in the tissues of experimental tumors in the process of their growth].

    PubMed

    Orlov, E N

    1980-01-01

    Content of S-adenosyl-l-methionine (SAM) in rat tissues of Pliss lymphosarcoma, of sarcoma 180 and in adenocarcinoma 755 of mice varied within the limits of 27-57 nM/g, 60-64 nM/g and 32-40 nM/g of wet tissue, respectively, content of S-adenosyl-l-homocysteine (SAH) varied in the tumors studied within the limits of 19-28, 16-21 and 11-20 nM/g, respectively. In the tumor bearing mice the content of SAM was unaltered in liver tissue during the growth of sarcoma 180 or adenocarcinoma 755. Development of Pliss lymphosarcoma in rats was accompanied by a decrease in content of SAM in liver tissue. When the rate of Pliss lymphosarcoma growth was decreased, the content of SAH in the tumor was unaltered but the level of SAM was decreased about 2-fold and the ratio SAH/SAM was increased, correspondingly, approximately 2-fold. If the rate of growth of mice adenocarcinoma 755 was elevated, content of SAM in the tumor was increased but the SAH level was markedly decreased and the ratio SAH/SAM was decreased about 2-fold. Concentrations of SAH and SAM were unaltered in mice sarcoma 180 with the linear rate of growth from 0.15 to 1.6 g. The data obtained suggest that the rate of growth of the tumors studied correlated with relative and absolute content of SAM and SAH.

  7. Grizzly bear

    USGS Publications Warehouse

    Schwartz, C.C.; Miller, S.D.; Haroldson, M.A.; Feldhamer, G.; Thompson, B.; Chapman, J.

    2003-01-01

    The grizzly bear inspires fear, awe, and respect in humans to a degree unmatched by any other North American wild mammal. Like other bear species, it can inflict serious injury and death on humans and sometimes does. Unlike the polar bear (Ursus maritimus) of the sparsely inhabited northern arctic, however, grizzly bears still live in areas visited by crowds of people, where presence of the grizzly remains physically real and emotionally dominant. A hike in the wilderness that includes grizzly bears is different from a stroll in a forest from which grizzly bears have been purged; nighttime conversations around the campfire and dreams in the tent reflect the presence of the great bear. Contributing to the aura of the grizzly bear is the mixture of myth and reality about its ferocity. unpredictable disposition, large size, strength, huge canines, long claws, keen senses, swiftness, and playfulness. They share characteristics with humans such as generalist life history strategies. extended periods of maternal care, and omnivorous diets. These factors capture the human imagination in ways distinct from other North American mammals. Precontact Native American legends reflected the same fascination with the grizzly bear as modern stories and legends (Rockwell 1991).

  8. Polar Bear

    USGS Publications Warehouse

    Amstrup, S.D.; ,; Lentfer, J.W.

    1988-01-01

    Polar bears are long-lived, late-maturing carnivores that have relatively low rates of reproduction and natural mortality. Their populations are susceptible to disturbance from human activities, such as the exploration and development of mineral resources or hunting. Polar bear populations have been an important renewable resource available to coastal communities throughout the Arctic for thousands of years.

  9. Application of a liquid chromatography-electrospray mass spectrometry (LC/MS) method to the biodistribution and excretion studies of novel 5'-chloro-2, 3-didehydroindolo (2', 3': 2, 3) betulinic acid (DRF-4012) in tumour-bearing mice.

    PubMed

    Mishra, Gautam; Singh, Manoj Kumar; Awasthi, Anshumali; Singh, Anu T; Jaggi, Manu; Ahmad, Farhan J

    2013-06-01

    Novel betulinic acid derivative 5'-chloro-2, 3-didehydroindolo [2', 3': 2, 3] betulinic acid (DRF-4012) is a new effective lupane type triterpenes with greater anticancer activity and efficacy than betulinic acid and currently under advanced preclinical investigation phase. In this study, a sensitive and rapid liquid chromatography-electrospray mass spectrometric (LC/MS) method has been developed for the determination of DRF-4012 in tumour-bearing mice plasma, urine, feces and tissues (liver, brain, lungs, heart, spleen, stomach, thigh muscle, kidneys, urinary bladder, small intestine and tumour). Biodistribution and excretion studies were performed for DRF-4012 nanoparticle (30 mg/kg body weight) after intravenous (i.v.) injection in tumour-bearing mice. DRF-4012 rapidly distributed throughout the body. After 0.5 h, tumour showed the second highest concentration, which was nearly half of the liver. After 4 and 24 h, the highest concentration of DRF-4012 was found in tumour indicating its retention in tumour site for a longer time. Excretion studies revealed that very low amount of unchanged DRF-4012 was observed in urine and primarily excreted through fecal route. This study may be useful to explain the manner in which DRF-4012 can inhibit tumour growth without apparent toxicity and preclinical/clinical evaluation of this potential antitumour agent.

  10. Magnetic Bearing

    NASA Technical Reports Server (NTRS)

    1996-01-01

    AVCON, Inc. produces advanced magnetic bearing systems for industrial use, offering a unique technological approach based on contract work done at Marshall Space Flight Center and Lewis Research Center. Designed for the turbopump of the Space Shuttle main engine, they are now used in applications such as electric power generation, petroleum refining, machine tool operation and natural gas pipelines. Magnetic bearings support moving machinery without physical contact; AVCON's homopolar approach is a hybrid of permanent and electromagnets which are one-third the weight, smaller and more power- efficient than previous magnetic bearings.

  11. Foil bearings

    NASA Astrophysics Data System (ADS)

    Elrod, David A.

    1993-11-01

    The rolling element bearings (REB's) which support many turbomachinery rotors offer high load capacity, low power requirements, and durability. Two disadvantages of REB's are: (1) rolling or sliding contact within the bearing has life-limiting consequences; and (2) REB's provide essentially no damping. The REB's in the Space Shuttle Main Engine (SSME) turbopumps must sustain high static and dynamic loads, at high speeds, with a cryogenic fluid as lubricant and coolant. The pump end ball bearings limit the life of the SSME high pressure oxygen turbopump (HPOTP). Compliant foil bearing (CFB) manufacturers have proposed replacing turbopump REB's with CFB's CFB's work well in aircraft air cycle machines, auxiliary power units, and refrigeration compressors. In a CFB, the rotor only contracts the foil support structure during start up and shut down. CFB damping is higher than REB damping. However, the load capacity of the CFB is low, compared to a REB. Furthermore, little stiffness and damping data exists for the CFB. A rotordynamic analysis for turbomachinery critical speeds and stability requires the input of bearing stiffness and damping coefficients. The two basic types of CFB are the tension-dominated bearing and the bending-dominated bearing. Many investigators have analyzed and measured characteristics of tension-dominated foil bearings, which are applied principally in magnetic tape recording. The bending-dominated CFB is used more in rotating machinery. This report describes the first phase of a structural analysis of a bending-dominated, multileaf CFB. A brief discussion of CFB literature is followed by a description and results of the present analysis.

  12. Foil bearings

    NASA Technical Reports Server (NTRS)

    Elrod, David A.

    1993-01-01

    The rolling element bearings (REB's) which support many turbomachinery rotors offer high load capacity, low power requirements, and durability. Two disadvantages of REB's are: (1) rolling or sliding contact within the bearing has life-limiting consequences; and (2) REB's provide essentially no damping. The REB's in the Space Shuttle Main Engine (SSME) turbopumps must sustain high static and dynamic loads, at high speeds, with a cryogenic fluid as lubricant and coolant. The pump end ball bearings limit the life of the SSME high pressure oxygen turbopump (HPOTP). Compliant foil bearing (CFB) manufacturers have proposed replacing turbopump REB's with CFB's CFB's work well in aircraft air cycle machines, auxiliary power units, and refrigeration compressors. In a CFB, the rotor only contracts the foil support structure during start up and shut down. CFB damping is higher than REB damping. However, the load capacity of the CFB is low, compared to a REB. Furthermore, little stiffness and damping data exists for the CFB. A rotordynamic analysis for turbomachinery critical speeds and stability requires the input of bearing stiffness and damping coefficients. The two basic types of CFB are the tension-dominated bearing and the bending-dominated bearing. Many investigators have analyzed and measured characteristics of tension-dominated foil bearings, which are applied principally in magnetic tape recording. The bending-dominated CFB is used more in rotating machinery. This report describes the first phase of a structural analysis of a bending-dominated, multileaf CFB. A brief discussion of CFB literature is followed by a description and results of the present analysis.

  13. Effect of diabetes on biodistribution, nephrotoxicity and antitumor activity of cisplatin in mice.

    PubMed

    da Silva Faria, Marcia C; Santos, Neife A G Dos; Carvalho Rodrigues, Maria A; Rodrigues, Jairo Lisboa; Barbosa Junior, Fernando; Santos, Antonio Cardozo Dos

    2015-03-01

    Both types of diabetes are associated with higher incidence of some types of cancer. Treating cancer in diabetic patients without aggravating diabetes-related complications is a challenge for clinicians. Additionally, little is known about how diabetes affects the treatment of cancer. One of the most effective chemotherapeutic drugs is cisplatin, which is nephrotoxic. Studies suggest that diabetes acts as a protective factor against the nephrotoxicity of cisplatin, but the mechanisms involved have not been elucidated yet. This renal protection has been attributed to decreased accumulation of cisplatin in the kidneys, which could be associated with deficient active transport of proximal tubular cells or to pharmacokinetic alterations caused by diabetes. However, it is uncertain if diabetes also compromises the antitumor activity of cisplatin. To address this issue, we developed a mouse model bearing cisplatin-induced nephrotoxicity, Sarcoma 180 and streptozotocin-induced diabetes. Four groups of treatment were defined: (i) control, (ii) diabetic, (iii) cisplatin and (iv) diabetic treated with cisplatin. The following parameters were evaluated: renal function, oxidative stress, apoptosis, renal histopathology, tumor remission, survival rate, genotoxicity and platinum concentration in tumor and several organs. Results indicate that diabetes protects against the renal damage induced by cisplatin, while also compromises its antitumor effectiveness. This is the first study to demonstrate this effect. PMID:25665769

  14. Seismic bearing

    NASA Astrophysics Data System (ADS)

    Power, Dennis

    2009-05-01

    Textron Systems (Textron) has been using geophones for target detection for many years. This sensing capability was utilized for detection and classification purposes only. Recently Textron has been evaluating multiaxis geophones to calculate bearings and track targets more specifically personnel. This capability will not only aid the system in locating personnel in bearing space or cartesian space but also enhance detection and reduce false alarms. Textron has been involved in the testing and evaluation of several sensors at multiple sites. One of the challenges of calculating seismic bearing is an adequate signal to noise ratio. The sensor signal to noise ratio is a function of sensor coupling to the ground, seismic propagation and range to target. The goals of testing at multiple sites are to gain a good understanding of the maximum and minimum ranges for bearing and detection and to exploit that information to tailor sensor system emplacement to achieve desired performance. Test sites include 10A Site Devens, MA, McKenna Airfield Ft. Benning, GA and Yuma Proving Ground Yuma, AZ. Geophone sensors evaluated include a 28 Hz triax spike, a 15 Hz triax spike and a hybrid triax spike consisting of a 10 Hz vertical geophone and two 28 Hz horizontal geophones. The algorithm uses raw seismic data to calculate the bearings. All evaluated sensors have triaxial geophone configuration mounted to a spike housing/fixture. The suite of sensors also compares various types of geophones to evaluate benefits in lower bandwidth. The data products of these tests include raw geophone signals, seismic features, seismic bearings, seismic detection and GPS position truth data. The analyses produce Probability of Detection vs range, bearing accuracy vs range, and seismic feature level vs range. These analysis products are compared across test sites and sensor types.

  15. Modulation of Immune Response of BALB/Mice Bearing Lymphoma L5178Y Treated with Bitter Yellow Juice of Aloe vera (L) in vivo.

    PubMed

    Oronzo-Barocio, Arturo; Zaitseva, Galina; Chavez-Anaya, Azucena; Arceta-Gonzalez, Veronika I.; Puebla-Perez, Ana Marija; Alfaro-Bustamante, Fernando; Zimina, Irina V.; Arion, Vitaly Ya.

    1999-04-01

    Aloe vera (L), a plant of African origin, has been introduced in Mexico since XVIth century. It has been used in the treatment of many diseases of immune system. In the present study we investigated a specific and non-specific immune response of BALB/c mice, healthy and immunosuppressed with murine lymphoma L5178Y, treated with bitter yellow juice (extract) of Aloe vera (L). We observed that the immunosuppressed mice, treated with the whole extract of the bitter yellow juice achieved restoration of immunological parameters in cellular immune response and phagocytosis. On the other hand, the humoral immunity was not restored. Also, in the healthy rodents treated with the extract, it caused the stimulation of specific and non-specific responses, the results had significant differences with the obtained ones in untreated mice.

  16. Ontogeny of the antibody-forming cell line in mice. IV. Appearance of cells bearing Fc receptors, complement receptors, and surface immunoglobulin.

    PubMed

    Rosenberg, Y J; Parish, C R

    1977-02-01

    The ontogeny of Ig, FcR, and CR-bearing cells in liver and spleen has been followed by using rosetting procedures. These studies demonstrated a sequential appearance of surface receptors during development. Two types of Ig+ cells could be distinguished according to their rosette morphology and adherence to carbonyl iron: 1) an adherent cell which bound few erythrocytes was found predominantly in fetal liver from 13 days gestation and 2) a nonadherent cell which bound larger numbers of erythrocytes appeared in small numbers in fetal liver from day-16 gestation but represented the major Ig+ cell type after birth. Changes in the proportions of receptor-bearing populations occurred at two particular periods during ontogeny. The first was at birth, where an increase in the proportion of FcR+ cells occurred and the proportion of type 2 Ig+ cells rose rapidly. This probably represented the first appearance of FcR+ B lymphocytes even though cells bearing FcR were detected in fetal liver of all ages (days 12 to 18). The second period was around 10 days after birth when the proportion of Ig+ cells again increased concomitant with the appearance of CR+ nonadherent cells.

  17. Vaccinia virus MUC1 immunization of mice: immune response and protection against the growth of murine tumors bearing the MUC1 antigen.

    PubMed

    Acres, R B; Hareuveni, M; Balloul, J M; Kieny, M P

    1993-08-01

    MUC1 is a mucin found on the apical surfaces of some normal mammalian mucin-secreting cells. It is characterized by heavy glycosylation and a 20-amino-acid tandem repeat segment. In most cases of human breast adenocarcinoma, this antigen is overexpressed. Moreover, abnormal glycosylation exposes a novel peptide epitope within the tandem repeat, such that antibodies to this epitope can distinguish normal from malignant adenocarcinomatous breast tissue. We have constructed a vaccinia virus (VV) that carries the cDNA for the MUC1 antigen. Murine and human cells infected with this virus express the MUC1 molecule, with three to four tandem repeats per molecule and with the tumor-associated epitopes exposed. Mice immunized with this virus produce antibodies that recognize MUC1 outside the tandem repeat, within the tandem repeat, and within the tumor-associated protein core epitope. Tumorigenic P815 (DBA) and 3T3 (BALB/c) cells have been transfected with MUC1. Thirty percent of DBA mice immunized with VV-MUC1 are protected from growth of P815-MUC1 tumors when implanted with 10(5) cells. Immunized BALB/c mice show a late development of transfected 3T3 tumor cells. Immunized mice show a moderate MUC1-specific IgG titer, but it cannot be correlated with subsequent tumor rejection. No evidence for a MUC1-specific cytotoxic T lymphocyte response has been found after immunization with VV-MUC1. PMID:8280702

  18. Restricted replication of herpes simplex virus in spinal ganglia of resistant mice is accompanied by an early infiltration of immunoglobulin G-bearing cells.

    PubMed Central

    Cook, M L; Stevens, J G

    1983-01-01

    In an attempt to define the nature of the difference in the susceptibility of C57BL/6 (resistant) and A/J (susceptible) mice to herpes simplex virus type 1, we initiated a study of virus progression through the nervous system. After inoculation of virus in a rear footpad, C57BL/6 mice were found to be more than 500-fold more resistant, but resistance did not extend to pseudorabies virus. In additional investigations, it was found that the virus was selectively restricted at the level of spinal ganglia in C57BL/6 mice. No intrinsic difference in the ability of this tissue from either mouse strain to replicate virus was found. However, by 4 days after infection, morphological investigations indicated that a mononuclear cell infiltrate was present surrounding infected neurons and satellite cells both earlier and in greater numbers in the ganglia of C57BL/6 mice. Immunohistochemical methods showed that most of these cells did not express Thy 1.2 antigen, but the vast majority bore immunoglobulin G. The mechanism by which these infiltrating cells could restrict virus spread is discussed. Images PMID:6302004

  19. Paullinia cupana Mart. var. sorbilis, guarana, increases survival of Ehrlich ascites carcinoma (EAC) bearing mice by decreasing cyclin-D1 expression and inducing a G0/G1 cell cycle arrest in EAC cells.

    PubMed

    Fukumasu, Heidge; Latorre, Andreia Oliveira; Zaidan-Dagli, Maria Lucia

    2011-01-01

    The objective of this work is to report the antiproliferative effect of P. cupana treatment in Ehrlich Ascites Carcinoma (EAC)-bearing animals. Female mice were treated with three doses of powdered P. cupana (100, 1000 and 2000 mg/kg) for 7 days, injected with 10(5) EAC cells and treated up to day 21. In addition, a survival experiment was carried out with the same protocol. P. cupana decreased the ascites volume (p = 0.0120), cell number (p = 0.0004) and hemorrhage (p = 0.0054). This occurred through a G1-phase arrest (p < 0.01) induced by a decreased gene expression of Cyclin D1 in EAC cells. Furthermore, P. cupana significantly increased the survival of EAC-bearing animals (p = 0.0012). In conclusion, the P. cupana growth control effect in this model was correlated with a decreased expression of cyclin D1 and a G1 phase arrest. These results reinforce the cancer therapeutic potential of this Brazilian plant.

  20. Effects of Some Natural Immunomodulatory Compounds in Combination with Thalidomide on Survival Rate and Tumor Size in Fibrosarcoma-Bearing Mice

    PubMed Central

    Aghebati Maleki, Reza; Shanehbandi, Dariush; Sadigh Eteghad, Saeed; Zarredar, Habib; Zare Shahneh, Fatemeh; Aghebati Maleki, Leili; Samavati, Mehrnosh; Asadi, Hamed; Mosavi, Seyed Ehsan; Habibzadeh, Afshin; Mohammadian, Mozhdeh; Baradaran, Behzad

    2014-01-01

    Purpose: Despite significant advances have been achieved in cancer therapy, response to conventional treatments like surgery, radiotherapy and chemotherapy varies among individuals. Immunotherapy is known to be an effective strategy for patients who are resistant to the currently available interventions. Methods: Ninety-six male Balb/c mice (aged 6-8 weeks) were selected and divided into twelve groups of eight. Approximately, 1×106of WEHI-164 cells were injected to each mouse for tumor genesis. Five immunotherapy treatments were considered in this study, including Heat Shock Proteins (HSP), Bacillus Calmette-Guérin (BCG), Bifidobacterium, Immuno-Modulator Drug (IMOD) and Thalidomide. After tumor formation, the groups were treated with one or more of these therapies. Tumor size and survival rate was regularly monitored. Results: Depending on the treatment group, tumor sizes were different. In some groups, combined treatments demonstrated more inhibitory effects on tumor growth rate. The mice in group (IMOD+ Thalidomide) had the lowest survival rate but group (BCG+ HSP+ Thalidomide) survived until the end of the experiment. Conclusion: The (HSP+ BCG+ Thalidomide) group exhibited satisfactory outcomes and two third of the mice in this group went into complete remission. Some combination therapies in test groups had significant impacts on survival and tumor growth rate. PMID:25364664

  1. Blood kinetics, tissue distribution, and radioimaging of anti-common chronic lymphatic leukemia antigen (cCLLa) monoclonal antibody CLL2 in mice transplanted with cCLLa-bearing human leukemia cells

    SciTech Connect

    Faguet, G.B.; Agee, J.F.; DiPiro, J.T. )

    1990-05-01

    The blood kinetics and biodistribution of anti-common chronic lymphatic leukemia antigen (cCLLa) monoclonal antibody (MoAb) CLL2 were assessed in mice bearing cCLLa+ tumors. The cCLLa is a 69-Kd glycoprotein antigen expressed selectively by malignant B cells in human CLL, hairy cell leukemia (HCL), and prolymphocytic leukemia. Immunoreactive 125I-CLL2 (5 micrograms/mouse, specific activity 4.3 microCi/micrograms) was injected intravenously in mice bearing HCL-derived EH xenografts, and blood kinetics and biodistribution were ascertained up to 16 days postinjection. Radioimages were also obtained up to 72 hours after injecting 10 micrograms/mouse (specific activity 50.1 microCi/micrograms) of 125I-CLL2. Distinct 125I-CLL2 blood kinetics were observed in EH engrafted compared with tumor-free mice including: a longer 125I-CLL2 T 1/2 (153 hours v 72 hours), and a considerably greater blood clearance (173 mg/h v 54.7 mg/h) with biexponential rather than monoexponential configuration; and a greater volume of antibody distribution (31,483 mg v 5,729 mg). These data suggest more rapid tissue uptake by grafted tumours. Preferential 125I-CLL2 uptake by EH tumours relative to normal tissues was observed beginning 24 hours postinjection (mean ratio, 4.2) with average peak tumor 125I-CLL2 levels of 428.7 pg/mg. 125I-CLL2 uptake selectivity by EH tumor cells was also supported by: (1) negligible 125I-CLL2 uptake by cCLLa- Molt-4 xenografts (average 29.1 pg/mg 24 hours postinjection); (2) background uptake of cCLLa-irrelevant MoAb 131I-LEU1 by CD5- EH xenografts (average 31.4 pg/mg 48 hours postinjection); and (3) by scintigraphy. The EH xenograft mouse model might be useful to ascertain preclinically the anti-tumor effect of anti-cCLLa MoAbs and of their conjugated derivatives.

  2. CUSHIONED BEARING

    DOEpatents

    Rushing, F.C.

    1960-09-01

    A vibration damping device effective to dampen vibrations occurring at the several critical speeds encountered in the operation of a high-speed centrifuge is described. A self-centering bearing mechanism is used to protect both the centrifuge shaft and the damping mechanism. The damping mechanism comprises spaced-apant, movable, and stationary sleeve members arranged concentrically of a rotating shaft with a fluid maintained between the members. The movable sleeve member is connected to the shaft for radial movement therewith.

  3. Tooling Converts Stock Bearings To Custom Bearings

    NASA Technical Reports Server (NTRS)

    Fleenor, E. N., Jr.

    1983-01-01

    Technique for reworking stock bearings saves time and produces helicopter-rotor bearings ground more precisely. Split tapered ring at one end of threaded bolt expands to hold inside of inner race bearing assembly; nut, at other end of bolt, adjusts amount of spring tension. Piece of hardware grasps bearing firmly without interfering with grinding operation. Operation produces bearing of higher quality than commercially available bearings.

  4. Non-extended cryoablation could be a new strategy in lung cancer management: An experiment on green fluorescent protein-labeled Lewis lung cancer-bearing mice.

    PubMed

    Zhou, Tian; Chen, Yujia; Li, Linyi; Qi, Hui; Shi, Jinping; Lu, Chongyi; Jiang, Sida; Geng, Tan; Yang, Meng; Li, Quanwang; Hu, Kaiwen

    2015-08-01

    Modern cryoablation has been performed in solid tumor management for more than two decades. Following the surgical spirits, it seems natural to pursue radical procedures in clinical practice, which results in unnecessary adverse effects. The attempt to use non-extended procedure made some marked achievements in practice but was criticized severely, because it was supposed to induce residual tumors, which would trigger the rapid development of cancer. Oncologists favored this procedure, however, claiming that non-extended cryoablation let lung cancer patients have higher quality of lives and longer survivals, in light of clinical observations. Therefore, this study was conducted trying to solve this controversy. In this study, fifty female C57BL/6J mice were grafted green fluorescent protein (GFP)-labeled Lewis lung cancer and randomized into two groups. The bidirectional diameters and fluorescence intensity of tumors, and the body weight of mice were recorded. Two weeks after the intervention, tumor volumes increased 20.95% in the cryoablation group, significantly different from that in the control group; the fluorescence intensity decreased 49.85% in the cryoablation group but increased 125.07% in the control group. Lung metastases could be observed in only 20% of mice in the cryosurgery group, contrasted to 64% in the control group. The non-extended lung cancer cryoablation does induce marginal tumor residuals, but will not trigger rapid tumor development. Inversely, the residual tumor cells are severely struck and the metastases are suppressed after the intervention. It could be a new strategy in lung cancer management, even for patients not in early stage.

  5. Connexin 43-dependent tumor-suppressing effect of the Bowman-Birk protease inhibitor on M5076 ovarian sarcoma-bearing mice.

    PubMed

    Sakurai, Noritaka; Suzuki, Kazuyuki; Nagaoka, Tetsuya; Saito, Teruyoshi; Yoshimura, Hisashi; Yano, Tomohiro; Sadzuka, Yasuyuki; Asano, Ryuji

    2008-01-01

    The present study was designed to confirm whether the Bowman-Birk inhibitor (BBI) induces an increase in p27 accumulation without S phase kinase-associated protein 2 (skp2) degradation by means of the expression of connexin (Cx) 43 as a gap junctional intercellular communication (GJIC)-dependent pathway in mice with M5076 ovarian sarcoma. M5076 ovarian sarcomas (1x105 cells/animal) were subcutaneously transplanted onto the backs of BDF1 mice receiving 10, 20 or 40 mg/kg of purified BBI intraperitoneally. Relative tumor weight (p<0.01, r=0.503) was negatively correlated with the dose of BBI. In contrast, the relative density of Cx43 mRNA (p<0.01, r=0.570) and Cx43 (p<0.01, r=0.718) was positively correlated with the dose of BBI, as were p21 (p<0.01, r=0.633), p27 (p<0.01, r=0.561) and skp2 (p<0.01, r=0.733). We therefore suggest that the anti-carcinogenic effects of BBI induce negative growth control by means of an increase in p27 accumulation caused by the expression of Cx43 as a GJIC pathway. PMID:21479471

  6. Dose estimation in B16 tumour bearing mice for future irradiation in the thermal column of the TRIGA reactor after B/Gd/LDL adduct infusion.

    PubMed

    Protti, N; Ballarini, F; Bortolussi, S; Bruschi, P; Stella, S; Geninatti, S; Alberti, D; Aime, S; Altieri, S

    2011-12-01

    To test the efficacy of a new (10)B-vector compound, the B/Gd/LDL adduct synthesised at Torino University, in vivo irradiations of murine tumours are in progress at the TRIGA Mark II reactor of the Pavia University. A localised B16 melanoma tumour is generated in C57BL/6 mice and subsequently infused with the adduct. During the irradiation, the mouse will be put in a shield to protect the whole body except the tumour in the back-neck area. To optimise the treatment set-up, MCNP simulations were performed. A very simplified mouse model was built using MCNP geometry capabilities, as well as the geometry of the shield made of 99% (10)B enriched boric acid. A hole in the shield is foreseen in correspondence of the back-neck region. Many configurations of the shield were tested in terms of neutron flux, dose distribution and mean induced activity in the tumour region and in the radiosensitive organs of the mouse. In the final set-up, up to five mice can be treated simultaneously in the reactor thermal column and the neutron fluence in the tumour region for 10 min of irradiation is of about 5×10(12) cm(-2). PMID:21459587

  7. Preparation of intravenous injection nanoformulation of VESylated gemcitabine by co-assembly with TPGS and its anti-tumor activity in pancreatic tumor-bearing mice.

    PubMed

    Xu, Yanyun; Meng, Haijing; Du, Fang; Lu, Wei; Liu, Shiyuan; Huang, Jin; Yu, Jiahui

    2015-11-30

    Our recent publication showed that VES-dFdC nanocapsules in pure water could be obtained via the self-assembling of VES-dFdC prodrug synthesized by coupling gemcitabine (dFdC) with vitamin E succinate (VES). To prepare the intravenous injection nanoformulation, we present here a novel strategy to improve the stability and drug concentration of VES-dFdC nanoformulation in PBS or isotonic solution. Particularly, D-α-tocopheryl polyethylene glycol succinate (TPGS), usually used as drug solubilizer and coincidentally contains the same VES moiety as VES-dFdC prodrug and PEG chain, is selected to co-assemble with VES-dFdC prodrug. The zeta potentials of all the TPGS/VES-dFdC co-assemblies were close to 0 mV, and their particle size measured by dynamic light scattering (DLS) decreased from 113 to 36 nm with increasing TPGS/VES-dFdC molar ratios from 0.15 to 1.5. Stable colloidal suspensions were obtained without aggregates in PBS at 4 °C in one month or isotonic solution at 37 °C in one week, and the weight concentration of VES-dFdC prodrug increased from 7 to 17 mg/mL when the molar ratios of TPGS/VES-dFdC ranged from 0.5/1 to 1.5/1. The concentration of VES-dFdC prodrug was high enough to be used as intravenous injection nanoformulation in nude mice. Interestingly, along with the increase of TPGS/VES-dFdC molar ratios from 0.3/1 to 1.5/1, the morphology of TPGS/VES-dFdC co-assemblies changed from loose nanocapsule to compact micelle revealed by transmission electron microscope (TEM). Finally, the co-assembly of TPGS/VES-dFdC (TPGS/VES-dFdC: 1/1) was selected as intravenous injection nanoformulation to evaluate the antitumor activity. Compared with native dFdC, TPGS/VES-dFdC nanoformulation with 0.2mmol/kg of dosage showed similar low toxicity in vivo, but 4.7 times high of tumor inhibition rate in nude mice with pre-established BxPC-3 tumors.

  8. Preparation of intravenous injection nanoformulation of VESylated gemcitabine by co-assembly with TPGS and its anti-tumor activity in pancreatic tumor-bearing mice.

    PubMed

    Xu, Yanyun; Meng, Haijing; Du, Fang; Lu, Wei; Liu, Shiyuan; Huang, Jin; Yu, Jiahui

    2015-11-30

    Our recent publication showed that VES-dFdC nanocapsules in pure water could be obtained via the self-assembling of VES-dFdC prodrug synthesized by coupling gemcitabine (dFdC) with vitamin E succinate (VES). To prepare the intravenous injection nanoformulation, we present here a novel strategy to improve the stability and drug concentration of VES-dFdC nanoformulation in PBS or isotonic solution. Particularly, D-α-tocopheryl polyethylene glycol succinate (TPGS), usually used as drug solubilizer and coincidentally contains the same VES moiety as VES-dFdC prodrug and PEG chain, is selected to co-assemble with VES-dFdC prodrug. The zeta potentials of all the TPGS/VES-dFdC co-assemblies were close to 0 mV, and their particle size measured by dynamic light scattering (DLS) decreased from 113 to 36 nm with increasing TPGS/VES-dFdC molar ratios from 0.15 to 1.5. Stable colloidal suspensions were obtained without aggregates in PBS at 4 °C in one month or isotonic solution at 37 °C in one week, and the weight concentration of VES-dFdC prodrug increased from 7 to 17 mg/mL when the molar ratios of TPGS/VES-dFdC ranged from 0.5/1 to 1.5/1. The concentration of VES-dFdC prodrug was high enough to be used as intravenous injection nanoformulation in nude mice. Interestingly, along with the increase of TPGS/VES-dFdC molar ratios from 0.3/1 to 1.5/1, the morphology of TPGS/VES-dFdC co-assemblies changed from loose nanocapsule to compact micelle revealed by transmission electron microscope (TEM). Finally, the co-assembly of TPGS/VES-dFdC (TPGS/VES-dFdC: 1/1) was selected as intravenous injection nanoformulation to evaluate the antitumor activity. Compared with native dFdC, TPGS/VES-dFdC nanoformulation with 0.2mmol/kg of dosage showed similar low toxicity in vivo, but 4.7 times high of tumor inhibition rate in nude mice with pre-established BxPC-3 tumors. PMID:26410754

  9. A Rapid and Sensitive HPLC Method for Quantitation of Paclitaxel in Biological Samples using Liquid-Liquid Extraction and UV Detection: Application to Pharmacokinetics and Tissues Distribution Study of Paclitaxel Loaded Targeted Polymeric Micelles in Tumor Bearing Mice.

    PubMed

    Rezazadeh, Mahboubeh; Emami, Jaber; Mostafavi, Abolfazl; Rostami, Mahboubeh; Hassanzadeh, Farshid; Sadeghi, Hojjat; Minaiyan, Mohsen; Lavasanifar, Afsaneh

    2015-01-01

    A simple, rapid, and sensitive reversed-phase HPLC method was developed and validated for determination of paclitaxel (PTX) in plasma, various organs and tumor tissues of tumor-bearing mice. Tissue specimens of liver, kidneys, spleen, lungs, heart and tumor were separately homogenized in normal saline. Plasma or tissue homogenate (250 µl) containing PTX and internal standard (diazepam) were extracted by diethyl ether (6 ml). The separation was achieved on a µ-Bondapak C18 HPLC column using sodium acetate buffer solution (0.01 M)/acetonitrile (58/42 v/v) at pH 5 ± 0.1 and flow rate of 1.9 mL/min. The effluent was monitored at 227 nm and column temperature was adjusted at 58ºC. The internal standard and PTX were eluted at 4.2 and 5.2 min, respectively and no interfering peaks were observed. Calibration curves were linear over the concentration range of 0.25-10 µg/ml of PTX in plasma and 0.3-20 µg/ml PTX in tissue homogenates with acceptable precision and accuracy (<15%). The mean recoveries of the drug after plasma extraction was 87.4% ± 3.6 while those of tissue homogenates ranged from 62.1± 4.5 to 75.5± 3.2 depending on the type of tissues studied. PTX was stable in samples with no evidence of degradation during 3 freeze-thaw cycles and 3 months storage at -70 °C. The developed HPLC method was applied to quantify PTX in the mouse plasma and tissues after intravenous administration of 10 mg equivalent PTX/Kg dose of PTX-loaded tocopherol succinate-chitosan-polyethylene glycol-folate (TS-CS-PEG-FA) micelles formulation or Anzatax® (Cremophor® EL- based formulation of PTX) to female Balb/c mice.

  10. Fluid lubricated bearing construction

    DOEpatents

    Dunning, John R.; Boorse, Henry A.; Boeker, Gilbert F.

    1976-01-01

    1. A fluid lubricated thrust bearing assembly comprising, in combination, a first bearing member having a plain bearing surface, a second bearing member having a bearing surface confronting the bearing surface of said first bearing member and provided with at least one spiral groove extending inwardly from the periphery of said second bearing member, one of said bearing members having an axial fluid-tight well, a source of fluid lubricant adjacent to the periphery of said second bearing member, and means for relatively rotating said bearing members to cause said lubricant to be drawn through said groove and to flow between said bearing surfaces, whereby a sufficient pressure is built up between said bearing surfaces and in said well to tend to separate said bearing surfaces.

  11. Pharmacokinetics in melanoma-bearing mice of 5-dihydroxyboryl-6-propyl-2-thiouracil (BPTU), a candidate compound for boron neutron capture therapy.

    PubMed Central

    Verrijk, R.; Smolders, I. J.; Huiskamp, R.; Gavin, P. R.; Philipp, K. H.; Begg, A. C.

    1994-01-01

    Blood pharmacokinetics and tissue distribution of 5-dihydroxyboryl-6-propyl-2-thiouracil (BPTU), a boron carrier with postulated melanin-seeking properties for boron neutron capture therapy, were determined in C57/BL mice with subcutaneous pigmented or non-pigmented B16 melanomas. Borocaptate sodium (BSH) was used as a boron compound without melanin-seeking properties in a comparative biodistribution study in the same animal tumour models. Administration of single doses showed that BPTU was retained better in the pigmented B16 tumour than in the non-pigmented variant. BPTU was found in large concentrations in kidney and liver. Brain boron was approximately 10-fold lower than tumour boron. On a molar basis, BPTU demonstrated higher affinity for B16 tumours than BSH. Owing to solubility limits, tumour boron concentrations in this mouse study were too low for effective application of BNCT. However, the high tumour-to-blood and tumour-to-normal tissues ratios indicate that, with appropriate formulation, BPTU could be a promising candidate for clinical BNCT. PMID:8142252

  12. Apigenin inhibits COX-2, PGE2, and EP1 and also initiates terminal differentiation in the epidermis of tumor bearing mice.

    PubMed

    Kiraly, Alex J; Soliman, Eman; Jenkins, Audrey; Van Dross, Rukiyah T

    2016-01-01

    Non-melanoma skin cancer (NMSC) is the most prevalent cancer in the United States. NMSC overexpresses cyclooxygenase-2 (COX-2). COX-2 synthesizes prostaglandins such as PGE2 which promote proliferation and tumorigenesis by engaging G-protein-coupled prostaglandin E receptors (EP). Apigenin is a bioflavonoid that blocks mouse skin tumorigenesis induced by the chemical carcinogens, 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). However, the effect of apigenin on the COX-2 pathway has not been examined in the DMBA/TPA skin tumor model. In the present study, apigenin decreased tumor multiplicity and incidence in DMBA/TPA-treated SKH-1 mice. Analysis of the non-tumor epidermis revealed that apigenin reduced COX-2, PGE2, EP1, and EP2 synthesis and also increased terminal differentiation. In contrast, apigenin did not inhibit the COX-2 pathway or promote terminal differentiation in the tumors. Since fewer tumors developed in apigenin-treated animals which contained reduced epidermal COX-2 levels, our data suggest that apigenin may avert skin tumor development by blocking COX-2. PMID:26802941

  13. Appearance of a syndrome similar to graft versus host reaction in C57 B1/6 mice bearing skin allogenic graft.

    PubMed

    Nedelea, M; Dima, S

    1975-01-01

    A syndrome similar to GVHR is described in mice of C57B1/6 strain during the WHT/Ht skin allografts rejection period. In all the cases the described thymus involution was associated with the hypertrophy of lymph nodes. Their volume increase is due to the high number of blastic pyroninophilic and plasma cells concomitant with small lymphocytes depletion in the cortical area, and with a very pronounced hypertrophy of medullary cords by presence of a high number of plasmocytes and blastic cells. These changes have been noticed only in some animals sacrified during the first days after grafting and never later one. In agreement with the scarce data of the literature, we think that the immunocompetent passenger lymphocyte comprised in the skin grafts constitute an immunologic organ able to induce a GVHR at the beginning of the period of graft survival on the host. This GVHR, generally mild and without clinical and microscopic signs, becomes obvious only in animals which, for unknown reasons, present a low immunologic defense capacity. In these animals the described process seems to be reversible.

  14. Peyer's patches and mesenteric lymph nodes are the sites of first appearance of IgE bearing B lymphocytes and hapten specific IgE antibody forming cells in BPO-KLH sensitized mice.

    PubMed

    Auci, D L; Chice, S M; Heusser, C; Athanassiades, T J; Durkin, H G

    1992-01-01

    Antigen specific IgE responses originate in gut associated lymphoid tissue (GALT) of mice sensitized with benzylpenicilloyl-keyhole limpet hemocyanin (BPO-KLH) in alum, regardless of the route (intraperitoneal [i.p.], oral [gavage], subcutaneous [s.c.], intramuscular [i.m.] or intravenous [i.v.]) used for immunization. When BALB/c mice were injected i.p. with BPO-KLH (10 micrograms) in alum, B lymphocytes bearing membrane bound IgE (sIgE+B cells) first appeared simultaneously in Peyer's patches (PP) and mesenteric lymph node (MLN) on day 8. BPO specific IgE antibody forming cells (AFC) also appeared in PP on day 8, but were not found in MLN until day 10. On day 8, no sIgE+B cells or IgE AFC were found in bone marrow (BM) or other lymphoid organs. The appearance of sIgE+B cells and IgE AFC in PP and MLN was transient; these cells were no longer detected in PP on days 14 and 24, respectively, or in MLN on days 14 and 36, respectively. sIgE+B cells and IgE AFC did not appear in spleen until day 12, where they were detected through day 70. Although sIgE+B cells were never found in BM, IgE AFC appeared in BM on day 18, where they were detected through day 70. No sIgE+B cells or IgE AFC were found in other lymph nodes (OLN) on days 0-70. Boosting did not induce the reappearance of sIgE+B cells or IgE AFC in PP, the reappearance of sIgE+B cells in MLN, the appearance of sIgE+B cells in BM, or the appearance of sIgE+B cells or IgE AFC in OLN.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Oil rich in carotenoids instead of vitamins C and E as a better option to reduce doxorubicin-induced damage to normal cells of Ehrlich tumor-bearing mice: hematological, toxicological and histopathological evaluations.

    PubMed

    Miranda-Vilela, Ana Luisa; Grisolia, Cesar K; Longo, João Paulo F; Peixoto, Raphael C A; de Almeida, Marcos Célio; Barbosa, Lilian Carla P; Roll, Mariana M; Portilho, Flávia A; Estevanato, Luciana L C; Bocca, Anamélia L; Báo, Sônia N; Lacava, Zulmira G M

    2014-11-01

    The development of therapeutic strategies to attenuate chemotherapy toxicity represents an area of great interest in cancer research, and among them is nutritional therapy based on antioxidants. As research on this topic is still controversial and scarce, we aim to investigate the effects of antioxidant supplementation with vitamin C, vitamin E or pequi oil, a carotenoid-rich oil extracted from pequi (Caryocar brasiliense), on doxorubicin (DX)-induced oxidative damage to normal cells in Ehrlich solid tumor-bearing mice. Tumor weight and volume, histopathology, morphometry and immunohistochemistry were used to assess the treatments' efficacy in containing tumor aggressiveness and regression, while possible toxicity of treatments was assessed by animals' weight, morphological analysis of the heart, liver and kidneys, hemogram, and serum levels of total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase, creatinine and urea. Although all the chemotherapeutic treatments increased internal necrosis area and reduced the positive Ki-67 cells compared to non-treated tumors, the treatments with pequi oil provided before tumor inoculation (PTDX) or in continuous and concurrent administration with doxorubicin (PTPDX) were more effective in containing tumor growth, besides increasing lymphocyte-dependent immunity and reducing the adverse side effects associated with DX-induced oxidative damage to normal cells, mainly the PTDX treatment. Vitamins C and E given before tumor inoculation and chemotherapy were not successful against doxorubicin-induced cardiotoxicity, besides increasing doxorubicin-induced nephrotoxicity, indicating that, at least for doxorubicin, pequi oil instead of vitamins C and E would be the best option to reduce its adverse effects.

  16. Passive magnetic bearing configurations

    DOEpatents

    Post, Richard F.

    2011-01-25

    A journal bearing provides vertical and radial stability to a rotor of a passive magnetic bearing system when the rotor is not rotating and when it is rotating. In the passive magnetic bearing system, the rotor has a vertical axis of rotation. Without the journal bearing, the rotor is vertically and radially unstable when stationary, and is vertically stable and radially unstable when rotating.

  17. Rolling-Element Bearings

    NASA Technical Reports Server (NTRS)

    Hamrock, B. J.; Anderson, W. J.

    1983-01-01

    Rolling element bearings are a precision, yet simple, machine element of great utility. A brief history of rolling element bearings is reviewed and the type of rolling element bearings, their geometry and kinematics, as well as the materials they are made from and the manufacturing processes they involve are described. Unloaded and unlubricated rolling element bearings, loaded but unlubricated rolling element bearings and loaded and lubricated rolling element bearings are considered. The recognition and understanding of elastohydrodynamic lubrication covered, represents one of the major development in rolling element bearings.

  18. Introduction to ball bearings

    NASA Technical Reports Server (NTRS)

    Hamrock, B. J.; Dowson, D.

    1981-01-01

    The purpose of a ball bearing is to provide a relative positioning and rotational freedom while transmitting a load between two structures, usually a shaft and a housing. For high rotational speeds (e.g., in gyroscope ball bearings) the purpose can be expanded to include rotational freedom with practically no wear in the bearing. This condition can be achieved by separating the bearing parts with a coherent film of fluid known as an elastohydrodynamic film. This film can be maintained not only when the bearing carries the load on a shaft, but also when the bearing is preloaded to position the shaft to within micro- or nano-inch accuracy and stability. Background information on ball bearings is provided, different types of ball bearings and their geometry and kinematics are defined, bearing materials, manufacturing processes, and separators are discussed. It is assumed, for the purposes of analysis, that the bearing carries no load.

  19. High efficiency magnetic bearings

    NASA Technical Reports Server (NTRS)

    Studer, Philip A.; Jayaraman, Chaitanya P.; Anand, Davinder K.; Kirk, James A.

    1993-01-01

    Research activities concerning high efficiency permanent magnet plus electromagnet (PM/EM) pancake magnetic bearings at the University of Maryland are reported. A description of the construction and working of the magnetic bearing is provided. Next, parameters needed to describe the bearing are explained. Then, methods developed for the design and testing of magnetic bearings are summarized. Finally, a new magnetic bearing which allows active torque control in the off axes directions is discussed.

  20. Experiments with needle bearings

    NASA Technical Reports Server (NTRS)

    Ferretti, Pericle

    1933-01-01

    Experiments and results are presented in testing needle bearings, especially in comparison with roller bearings. Reduction in coefficient of friction is discussed as well as experimental methods and recording devices.

  1. Axial Halbach Magnetic Bearings

    NASA Technical Reports Server (NTRS)

    Eichenberg, Dennis J.; Gallo, Christopher A.; Thompson, William K.

    2008-01-01

    Axial Halbach magnetic bearings have been investigated as part of an effort to develop increasingly reliable noncontact bearings for future high-speed rotary machines that may be used in such applications as aircraft, industrial, and land-vehicle power systems and in some medical and scientific instrumentation systems. Axial Halbach magnetic bearings are passive in the sense that unlike most other magnetic bearings that have been developed in recent years, they effect stable magnetic levitation without need for complex active control.

  2. Bearing puller facilitates removal and replacement of bearing assemblies

    NASA Technical Reports Server (NTRS)

    Schaus, R. B.

    1966-01-01

    Bearing puller removes ball bearing assemblies, which carry the rotor, from turbine type flowmeters. It matches the bearing configuration to facilitate removal of the bearing assemblies from the support members.

  3. Cryogenic Hybrid Magnetic Bearing

    NASA Technical Reports Server (NTRS)

    Meeks, Crawford R.; Dirusso, Eliseo; Brown, Gerald V.

    1994-01-01

    Cryogenic hybrid magnetic bearing is example of class of magnetic bearings in which permanent magnets and electromagnets used to suspend shafts. Electromagnets provide active control of position of shaft. Bearing operates at temperatures from -320 degrees F (-196 degrees C) to 650 degrees F (343 degrees C); designed for possible use in rocket-engine turbopumps, where effects of cryogenic environment and fluid severely limit lubrication of conventional ball bearings. This and similar bearings also suitable for terrestrial rotating machinery; for example, gas-turbine engines, high-vacuum pumps, canned pumps, precise gimbals that suspend sensors, and pumps that handle corrosive or gritty fluids.

  4. Examining T cells at vaccine sites of tumor-bearing hosts provides insights to dysfunctional T-cell immunity.

    PubMed

    Barr, Kristen M; Jing, Weiqing; Hallett, William H D; Gershan, Jill A; Johnson, Bryon D

    2013-01-01

    When tumor vaccines are administered as cancer immunotherapy, cellular interactions at the vaccine site are crucial to the generation of antitumor immunity. Examining interactions at the vaccine site could provide important insights to the success or failure of vaccination. Our laboratory previously showed that while administration of a cell-based vaccine to tumor-free mice leads to productive antineuroblastoma immunity, vaccination of tumor-bearing mice does not. The goal of this study was to examine immune effectors at the vaccine site to identify mechanisms responsible for the generation of ineffective antitumor immunity in tumor-bearing mice. The results of this study show that vaccine sites of tumor-bearing mice contained significantly fewer T cells than vaccine sites of tumor-free mice. Similar migration and proliferation of T cells was observed in the vaccine sites of tumor-bearing and tumor-free mice, but T cells in the sites of tumor-bearing mice were more apoptotic. T cells at the vaccine sites of both tumor-free and tumor-bearing mice had an effector-memory phenotype and expressed activation markers. Despite the activated phenotype, T cells from tumor-bearing mice elicited defective antitumor immune responses. Although T cells from vaccine sites of tumor-bearing mice were capable of producing inflammatory cytokines, the T cells from tumor-bearing mice produced lower levels of cytokines compared with T cells from the tumor-free mice. Remarkably, this defect seems to be systemic, affecting distal T cells in tumor-bearing mice. This study demonstrates that the defective vaccine-induced immune response to neuroblastoma in tumor-bearing hosts originates as a result of tumor burden, resulting in poor antitumor immunity.

  5. Origin and fate of IgE-bearing lymphocytes. II. Gut-associated lymphoid tissue as sites of first appearance of IgE-bearing B lymphocytes and hapten-specific IgE antibody-forming cells in mice immunized with benzylpenicilloyl-keyhole limpet hemocyanin by various routes: relation to asialo GM1 ganglioside+ cells and IgE/CD23 immune complexes.

    PubMed

    Auci, D L; Chice, S M; Heusser, C; Athanassiades, T J; Durkin, H G

    1992-10-01

    The organs in which B cells bearing membrane-bound IgE (sIgE+) and benzylpenicilloyl (BPO)-specific IgE antibody-forming cells (AFC) first appeared were determined in BALB/c mice given BPO-keyhole limpet hemocyanin (10 micrograms) in aluminum hydroxide by various routes (i.p, gavage, s.c., i.v., or i.m.). In mice immunized by the i.p. route, the numbers and location of sIgE+ B cells and asialo GM1 ganglioside (AsGm1+) cells, the location of IgE/CD23 immune complexes, and the numbers of BPO-specific IgE AFC in lymphoid organs were determined. With all routes of immunization, no sIgE+ B cells or BPO-specific IgE AFC were ever detected in any organ before day 8. On day 8, with the s.c., i.v., or i.m. routes, sIgE+ B cells and IgE AFC appeared exclusively in Peyer's patches (PP); with the i.p. or gavage routes, sIgE+ B cells simultaneously appeared in both PP and mesenteric lymph nodes, whereas IgE AFC appeared only in PP. In mice immunized by the i.p. route, IgE/CD23 immune complexes and strikingly increased numbers of AsGm1+ cells transiently appeared only in PP after the appearance and preceding the "disappearance" of the sIgE+ B cells and IgE AFC. The data suggest that specific IgE responses originate in gut-associated lymphoid tissue and appear later in spleen. The data also associate the appearance of IgE/CD23 immune complexes and AsGm1+ cells with the "disappearance" of sIgE+ B cells and IgE AFC from PP.

  6. Matrix effect and optimization of LC-MSn determination of trachylobane-360 in mice blood.

    PubMed

    Pita, João Carlos Lima Rodrigues; Gomes, Isis Fernandes; dos Santos, Socrates Golzio; Tavares, Josean Fechine; da Silva, Marcelo Sobral; Diniz, Margareth de Fátima Formiga Melo; Sobral, Marianna Vieira

    2014-11-01

    Xylopia langsdorffiana A. St.-Hil. & Tul. (Annonaceae) is popularly known as "pimenteira-da-terra". Various constituents have been isolated from this species, including diterpenes, such as 8(17), 12E, 14-labdatrien-18-oic acid, ent-atisan-7α, 16α-diol (xylodiol), ent-7α-hydroxytrachyloban-18-oic acid (trachylobane-318) and ent-7α-acetoxytrachyloban-18-oic acid, a crystalline solid with a molecular weight of 360 and molecular formula of C22H32O4 (trachylobane-360). When administered intraperitoneally to mice, trachylobane-360 (T-360) significantly inhibits growth of the solid tumor sarcoma 180 transplanted in mice, without causing alterations in biochemical, hematological and histopathological parameters that are frequently associated with the clinical use of antineoplastic. Furthermore, this diterpene blocks voltage-dependent calcium channels (Cav), showing spasmolytic activity. The present study shows that variables such as extraction solvent (methanol, acetonitrile and chloroform), centrifugation force (1000, 7000 and 14,000×g), and centrifugation time (5, 15 and 25min), are important in the liquid-liquid extraction of T-360 from male Swiss mice blood in HPLC-MSn studies. The study confirms matrix influence on recovery and detection of T-360. The recovery for T-360 was 37.02% using chloroform as better extractor solvent, while centrifuged at 14,000×g for 15min demonstrated the importance of the parameters chosen for the extraction/recovery process of analyte. The effect of mice blood matrix for T-360 was -51.23%. This method was optimized by repeating the extraction procedure and acidification of samples. These conditions were essential in increasing recovery (49.47%) by decreasing the matrix effect (-37.60%). The efficiency of the process, after optimization with two extractions and acidification, increased by 14.19% when compared to the initial method, from 18.05% to 32.24%. According to Marchi et al. (2010), the matrix effect does not necessarily need to

  7. Enzymes of creatine biosynthesis, arginine and methionine metabolism in normal and malignant cells.

    PubMed

    Bera, Soumen; Wallimann, Theo; Ray, Subhankar; Ray, Manju

    2008-12-01

    The creatine/creatine kinase system decreases drastically in sarcoma. In the present study, an investigation of catalytic activities, western blot and mRNA expression unambiguously demonstrates the prominent expression of the creatine-synthesizing enzymes l-arginine:glycine amidinotransferase and N-guanidinoacetate methyltransferase in sarcoma, Ehrlich ascites carcinoma and Sarcoma 180 cells, whereas both enzymes were virtually undetectable in normal muscle. Compared to that of normal animals, these enzymes remained unaffected in the kidney or liver of sarcoma-bearing mice. High activity and expression of mitochondrial arginase II in sarcoma indicated increased ornithine formation. Slightly or moderately higher levels of ornithine, guanidinoacetate and creatinine were observed in sarcoma compared to muscle. Despite the intrinsically low level of creatine in Ehrlich ascites carcinoma and Sarcoma 180 cells, these cells could significantly take up and release creatine, suggesting a functional creatine transport, as verified by measuring mRNA levels of creatine transporter. Transcript levels of arginase II, ornithine-decarboxylase, S-adenosyl-homocysteine hydrolase and methionine-synthase were significantly upregulated in sarcoma and in Ehrlich ascites carcinoma and Sarcoma 180 cells. Overall, the enzymes related to creatine and arginine/methionine metabolism were found to be significantly upregulated in malignant cells. However, the low levels of creatine kinase in the same malignant cells do not appear to be sufficient for the building up of an effective creatine/phosphocreatine pool. Instead of supporting creatine biosynthesis, l-arginine:glycine amidinotransferase and N-guanidinoacetate methyltransferase appear to be geared to support cancer cell metabolism in the direction of polyamine and methionine synthesis because both these compounds are in high demand in proliferating cancer cells.

  8. Bearings: Technology and needs

    NASA Technical Reports Server (NTRS)

    Anderson, W. J.

    1982-01-01

    A brief status report on bearing technology and present and near-term future problems that warrant research support is presented. For rolling element bearings a material with improved fracture toughness, life data in the low Lambda region, a comprehensive failure theory verified by life data and incorporated into dynamic analyses, and an improved corrosion resistant alloy are perceived as important needs. For hydrodynamic bearings better definition of cavitation boundaries and pressure distributions for squeeze film dampers, and geometry optimization for minimum power loss in turbulent film bearings are needed. For gas film bearings, foil bearing geometries that form more nearly optimum film shapes for maximum load capacity, and more effective surface protective coatings for high temperature operation are needed.

  9. Bear Spray Safety Program

    USGS Publications Warehouse

    Blome, C.D.; Kuzniar, R.L.

    2009-01-01

    A bear spray safety program for the U.S. Geological Survey (USGS) was officially initiated by the Firearms Safety Committee to address accident prevention and to promote personnel training in bear spray and its transportation, storage, and use for defense against wild animals. Used as part of a system including firearms, or used alone for those who choose not to carry a firearm, bear spray is recognized as an effective tool that can prevent injury in a wild animal attack.

  10. Linear magnetic bearing

    NASA Technical Reports Server (NTRS)

    Studer, P. A. (Inventor)

    1983-01-01

    A linear magnetic bearing system having electromagnetic vernier flux paths in shunt relation with permanent magnets, so that the vernier flux does not traverse the permanent magnet, is described. Novelty is believed to reside in providing a linear magnetic bearing having electromagnetic flux paths that bypass high reluctance permanent magnets. Particular novelty is believed to reside in providing a linear magnetic bearing with a pair of axially spaced elements having electromagnets for establishing vernier x and y axis control. The magnetic bearing system has possible use in connection with a long life reciprocating cryogenic refrigerator that may be used on the space shuttle.

  11. Bearing restoration by grinding

    NASA Technical Reports Server (NTRS)

    Hanau, H.; Parker, R. J.; Zaretsky, E. V.; Chen, S. M.; Bull, H. L.

    1976-01-01

    A joint program was undertaken by the NASA Lewis Research Center and the Army Aviation Systems Command to restore by grinding those rolling-element bearings which are currently being discarded at aircraft engine and transmission overhaul. Three bearing types were selected from the UH-1 helicopter engine (T-53) and transmission for the pilot program. No bearing failures occurred related to the restoration by grinding process. The risk and cost of a bearing restoration by grinding programs was analyzed. A microeconomic impact analysis was performed.

  12. Bearing fatigue investigation 3

    NASA Technical Reports Server (NTRS)

    Nahm, A. H.; Bamberger, E. N.; Signer, H. R.

    1982-01-01

    The operating characteristics of large diameter rolling-element bearings in the ultra high speed regimes expected in advanced turbine engines for high performance aircraft were investigated. A high temperature lubricant, DuPont Krytox 143 AC, was evaluated at bearing speeds to 3 million DN. Compared to the results of earlier, similar tests using a MIL-L-23699 (Type II) lubricant, bearings lubricated with the high density Krytox fluid showed significantly higher power requirements. Additionally, short bearing lives were observed when this fluid was used with AISI M50 bearings in an air atmosphere. The primary mode of failure was corrosion initiated surface distress (fatigue) on the raceways. The potential of a case-carburized bearing to sustain a combination of high-tangential and hertzian stresses without experiencing race fracture was also investigated. Limited full scale bearing tests of a 120 mm bore ball bearing at a speed of 25,000 rpm (3 million DN) indicated that a carburized material could sustain spalling fatigue without subsequent propagation to fracture. Planned life tests of the carburized material had to be aborted, however, because of apparent processing-induced material defects.

  13. Linear kinematic air bearing

    NASA Technical Reports Server (NTRS)

    Mayall, S. D.

    1974-01-01

    Bearing provides continuous, smooth movement of the cat's-eye mirror, eliminating wear and deterioration of bearing surface and resulting oscillation effects in servo system. Design features self-aligning configuration; single-point, pivotal pad mounting, having air passage through it; and design of pads that allows for precise control of discharge path of air from pads.

  14. Arcturus and the Bears

    NASA Astrophysics Data System (ADS)

    Antonello, E.

    2009-08-01

    Arcturus is the brightest star in Bootes. The ancient Greek name Arktouros means Bear Guard. The star, however, is not close to Ursa Maior (Big She-Bear) and Ursa Minor (Little She-Bear), as the name would suggest. This curious discrepancy could be explained by the star proper motion, assuming the name Bear Guard is a remote cultural heritage. The proper motion analysis could allow us to get an insight also into an ancient myth regarding Ursa Maior. Though we cannot explain scientifically such a myth, some interesting suggestions can be obtained about its possible origin, in the context of the present knowledge of the importance of the cult of the bear both during the Palaeolithic times and for several primitive populations of modern times, as shown by the ethnological studies.

  15. Anti-tumor Effects of Exo- and Endo-biopolymers Produced from Submerged Cultures of Three Different Mushrooms

    PubMed Central

    Jeong, Yong-Tae; Yang, Byung-Keun; Li, Chun-ru

    2008-01-01

    The anti-tumor effects of exo- (EX) and endo-biopolymers (EN) produced from submerged mycelial cultures of Ganoderma applanatum (GA), Collybia confluens (CC), and Pleurotus eryngii (PE) were studied using Sarcoma 180 bearing mice. Solid tumor growth was inhibited most effectively when 40 mg/kg body weight (BW) of GA-EX or PE-EN was administered to the intraperitoneal (i.p.) cavity of BALB/c mice. The spleen and liver indexes were increased in mice following i.p. administration of GA-EX and PE-EN fractions. GA-EX and PE-EN reduced the tumor formation by 30.7% and 29.4%, respectively. GA-EX and PE-EN increased the natural killer (NK) cell activity of splenocytes by 41.3% and 28.9%, respectively. PMID:23990743

  16. Good bearings reduce downtime

    SciTech Connect

    Kinney, J.; Foster, J.

    1982-12-01

    Points out that a poorly maintained $100 bearing can hold up the operation of a $1-million conveyor. Of all the moving parts in a coal conveyor system, few cost less or last longer than anti-friction bearings. Most modern conveyor systems are equipped with 2 types of bearings: troughing idlers, spaced at regular intervals to support the conveyor belt as it travels throughout the system, and the adaptermounted spherical roller bearing pillow blocks that are used in the head, tail, bend and takeup pulleys that drive, alter the direction of, or regulate tension in the belt to allow for repairs or splicing. Explains how pillow blocks should handle radial or axial loads, how to mount bearings correctly, and how rings prevent infiltration. Concludes that by making certain that the proper bearing types are built into the system initially, or used as replacements in case of failures, paying close attention to installation procedures and devoting adequate time to maintenance, conveyor system bearings can provide decades of problem-free service.

  17. Ball Bearing Mechanics

    NASA Technical Reports Server (NTRS)

    Hamrock, B. J.; Dowson, D.

    1981-01-01

    Load-deflection relationships for different types of elliptical contacts such as those found in a ball bearing are developed. Simplified expressions that allow quick calculations of deformation to be made simply from a knowledge of the applied load, the material properties, and the geometry of the contacting elements are presented. Ball bearings subjected to radial, thrust and combined ball loads are analyzed. A design criterion for fatigue life of ball bearings is developed. The section of a satisfactory lubricant, as well as describing systems that provide a constant flow of lubricant to the contact, is considered.

  18. Magnetic bearing update

    SciTech Connect

    Fowler, T.K.

    1995-05-25

    Stabilization of whirl instability by floppy, viscous bearing mounts is discussed and required material properties are estimated for the new tilt-whirl mode in eddy-current stabilized magnetic bearings. A relatively low Young`s modules Y {approximately} 10{sup 5} and high viscosity {zeta} {approximately} 10{sup 7} are required (both in MKS units), suggesting the need for careful mounting design. New information on periodic bearings shows that, thus far, Earshaw`s Theorem cannot be defeated by periodicity, despite the author`s earlier claims.

  19. Arkansas black bear hunter survey

    USGS Publications Warehouse

    Pharris, Larry D.; Clark, Joseph D.

    1987-01-01

    Questionnaires were mailed to black bear (Ursus americanus) hunters in Arkansas following the 1980-84 bear seasons to determine participation, hunter success, and number of bears observed by hunters. Man-days of hunting to harvest a bear ranged from 148 to 671 and hunter success ranged from 0.4% to 2.2%. With the exception of 1980, number of permits issued, man-days of bear hunting, and bears harvested appear affected by hunting permit cost. 

  20. Prevention and Inhibition of TC-1 Cell Growth in Tumor Bearing Mice by HPV16 E7 Protein in Fusion with Shiga Toxin B-Subunit from shigella dysenteriae

    PubMed Central

    Sadraeian, Mohammad; Khoshnood Mansoorkhani, Mohammad Javad; Mohkam, Milad; Rasoul-Amini, Sara; Hesaraki, Mahdi; Ghasemi, Younes

    2013-01-01

    Objective: For immunotherapy of human papillomavirus (HPV) -16-associated cervical cancers the E7 protein is considered a prime candidate. However it is a poor inducer of cytotoxic T-cell response, when being used as a singular antigen in protein vaccination. Hence, in this study we focused on the utilization of a vaccine delivery system for prevention or treatment of cervical cancer. Materials and Methods: In this experimental study, we designed and evaluated a novel fusion protein comprising HPV16 E7 antigen fused to Shiga toxin B-subunit (STxB) as both an antigen vector and an adjuvant. Then we designed two preventive and therapeutic tumor models to investigate the prevention and inhibition of TC-1 cell growth in female C57BL/6 mice, respectively. In each model, mice were immunized with the recombinant protein of E7-STxB or E7 without any adjuvant. Results: We demonstrated that prophylactic immunization of E7-STxB protected mice against TC-1 cells. Also in the therapeutic model, E7-STxB inhibited TC-1 tumor growth inlungs. The results were significant when compared with the immunization of E7 singularly. Conclusion: We concluded that immunization with the E7-STxB protein without any adjuvant could generate anti-tumor effect in mice challenged with TC-1 cells.This research verifies the clinical applications and the future prospects of developing HPV16 E7 therapeutic vaccines fused to immunoadjuvants. PMID:23862120

  1. Deformable bearing seat

    NASA Technical Reports Server (NTRS)

    Moreman, O. S., III (Inventor)

    1977-01-01

    A deformable bearing seat is described for seating a bearing assembly in a housing. The seat includes a seating surface in the housing having a first predetermined spheroidal contour when the housing is in an undeformed mode. The seating surface is deformable to a second predetermined spherically contoured surface when the housing is in a deformed mode. The seat is particularly adaptable for application to a rotating blade and mounting ring assembly in a gas turbine engine.

  2. Gear bearing drive

    NASA Technical Reports Server (NTRS)

    Weinberg, Brian (Inventor); Mavroidis, Constantinos (Inventor); Vranish, John M. (Inventor)

    2011-01-01

    A gear bearing drive provides a compact mechanism that operates as an actuator providing torque and as a joint providing support. The drive includes a gear arrangement integrating an external rotor DC motor within a sun gear. Locking surfaces maintain the components of the drive in alignment and provide support for axial loads and moments. The gear bearing drive has a variety of applications, including as a joint in robotic arms and prosthetic limbs.

  3. High speed hybrid bearing comprising a fluid bearing and a rolling bearing convected in series

    NASA Technical Reports Server (NTRS)

    Anderson, W. J. (Inventor)

    1973-01-01

    A description is given of an antifriction bearing and a process by which its fatigue life may be extended. The method involves a rotating shaft supported by a fluid bearing and a rolling element bearing coupled in series. Each bearing turns at a fraction of the rotational speed of the shaft. The fluid bearing is preferably conical, thereby providing thrust and radial load support in a single bearing structure.

  4. Load responsive hydrodynamic bearing

    DOEpatents

    Kalsi, Manmohan S.; Somogyi, Dezso; Dietle, Lannie L.

    2002-01-01

    A load responsive hydrodynamic bearing is provided in the form of a thrust bearing or journal bearing for supporting, guiding and lubricating a relatively rotatable member to minimize wear thereof responsive to relative rotation under severe load. In the space between spaced relatively rotatable members and in the presence of a liquid or grease lubricant, one or more continuous ring shaped integral generally circular bearing bodies each define at least one dynamic surface and a plurality of support regions. Each of the support regions defines a static surface which is oriented in generally opposed relation with the dynamic surface for contact with one of the relatively rotatable members. A plurality of flexing regions are defined by the generally circular body of the bearing and are integral with and located between adjacent support regions. Each of the flexing regions has a first beam-like element being connected by an integral flexible hinge with one of the support regions and a second beam-like element having an integral flexible hinge connection with an adjacent support region. A least one local weakening geometry of the flexing region is located intermediate the first and second beam-like elements. In response to application of load from one of the relatively rotatable elements to the bearing, the beam-like elements and the local weakening geometry become flexed, causing the dynamic surface to deform and establish a hydrodynamic geometry for wedging lubricant into the dynamic interface.

  5. Magnetic bearing and motor

    NASA Technical Reports Server (NTRS)

    Studer, P. A. (Inventor)

    1983-01-01

    A magnetic bearing for passively suspending a rotatable element subjected to axial and radial thrust forces is disclosed. The magnetic bearing employs a taut wire stretched along the longitudinal axis of the bearing between opposed end pieces and an intermediate magnetic section. The intermediate section is segmented to provide oppositely directed magnetic flux paths between the end pieces and may include either an axially polarized magnets interposed between the segments. The end pieces, separated from the intermediate section by air gaps, control distribution of magnetic flux between the intermediate section segments. Coaxial alignment of the end pieces with the intermediate section minimizes magnetic reluctance in the flux paths endowing the bearing with self-centering characteristics when subjected to radial loads. In an alternative embodiment, pairs of oppositely wound armature coils are concentrically interposed between segments of the intermediate section in concentric arcs adjacent to radially polarized magnets to equip a magnetic bearing as a torsion drive motor. The magnetic suspension bearing disclosed provides long term reliability without maintenance with application to long term space missions such as the VISSR/VAS scanning mirror instrument in the GOES program.

  6. Investigation of Pressurized Wave Bearings

    NASA Technical Reports Server (NTRS)

    Keith, Theo G., Jr.; Dimofte, Florin

    2003-01-01

    The wave bearing has been pioneered and developed by Dr. Dimofte over the past several years. This bearing will be the main focus of this research. It is believed that the wave bearing offers a number of advantages over the foil bearing, which is the bearing that NASA is currently pursuing for turbomachinery applications. The wave bearing is basically a journal bearing whose film thickness varies around the circumference approximately sinusoidally, with usually 3 or 4 waves. Being a rigid geometry bearing, it provides precise control of shaft centerlines. The wave profile also provides good load capacity and makes the bearing very stable. Manufacturing techniques have been devised that should allow the production of wave bearings almost as cheaply as conventional full-circular bearings.

  7. Climate Drives Polar Bear Origins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In their provocative analysis of northern bears (“Nuclear genomic sequences reveal that polar bears are an old and distinct bear lineage,” Reports, 20 April, p. 344), F. Hailer et al. use independent nuclear loci to show that polar bears originated during the middle Pleistocene, rather than during t...

  8. Fluid lubricated bearing assembly

    DOEpatents

    Boorse, Henry A.; Boeker, Gilbert F.; Menke, John R.

    1976-01-01

    1. A support for a loaded rotatable shaft comprising in combination on a housing having a fluid-tight cavity encasing an end portion of said shaft, a thrust bearing near the open end of said cavity for supporting the axial thrust of said shaft, said thrust bearing comprising a thrust plate mounted in said housing and a thrust collar mounted on said shaft, said thrust plate having a central opening the peripheral portion of which is hermetically sealed to said housing at the open end of said cavity, and means for supplying a fluid lubricant to said thrust bearing, said thrust bearing having a lubricant-conducting path connecting said lubricant supplying means with the space between said thrust plate and collar intermediate the peripheries thereof, the surfaces of said plate and collar being constructed and arranged to inhibit radial flow of lubricant and, on rotation of said thrust collar, to draw lubricant through said path between the bearing surfaces and to increase the pressure therebetween and in said cavity and thereby exert a supporting force on said end portion of said shaft.

  9. The Combined Effects of Pulsed Magnetic Radiation (Diapulse) and Chemotherapy on Tumor Bearing Mice. The Measurement of Rodent Palatal Explants as a Device for Measurement of the Biologic Effects of Nonionic Radiation (EMR)

    NASA Technical Reports Server (NTRS)

    Regelson, W.; West, B.; Depaola, D. P.

    1978-01-01

    Simultaneous treatment utilizing pulsed radiowave and cancer chemotherapy significantly extended the life span of mice with Lewis lung transplanted carcinoma. In comparison with nontreated controls, the combination of hydroxyurea and whole body nonionizing EM radiation (at 27.12 MHz) produced differential enhancement of longevity depending on hydroxyurea combined with highest power output achieved by pulsing the radiation 600 times per second; at a 3.9% duty cycle, peak watts = 975 produced the mean extension of life 67% greater than that of the group treated with hydroxyurea alone.

  10. Magnetic bearings for spacecraft

    NASA Technical Reports Server (NTRS)

    Studer, P. A.

    1972-01-01

    Magnetic bearings have been successfully applied to motorized rotor systems in the multi-kilogram range, at speeds up to 1200 radians per second. These engineering models also indicated the need for continued development in specific areas to make them feasible for spacecraft applications. Significant power reductions have recently been attained. A unique magnetic circuit, combining permanent magnets with electromagnetic control, has a bidirectional forcing capability with improved current sensitivity. The multi-dimensional nature of contact-free rotor support is discussed. Stable continuous radial suspension is provided by a rotationally symmetric permanent magnet circuit. Two bearings, on a common shaft, counteract the normal instability perpendicular to the rotational axis. The axial direction is servoed to prevent contact. A new bearing technology and a new field of application for magnetics is foreseen.

  11. Radial Halbach Magnetic Bearings

    NASA Technical Reports Server (NTRS)

    Eichenberg, Dennis J.; Gallo, Christopher A.; Thompson, William K.

    2009-01-01

    Radial Halbach magnetic bearings have been investigated as part of an effort to develop increasingly reliable noncontact bearings for future high-speed rotary machines that may be used in such applications as aircraft, industrial, and land-vehicle power systems and in some medical and scientific instrumentation systems. Radial Halbach magnetic bearings are based on the same principle as that of axial Halbach magnetic bearings, differing in geometry as the names of these two types of bearings suggest. Both radial and axial Halbach magnetic bearings are passive in the sense that unlike most other magnetic bearings that have been developed in recent years, they effect stable magnetic levitation without need for complex active control. Axial Halbach magnetic bearings were described in Axial Halbach Magnetic Bearings (LEW-18066-1), NASA Tech Briefs, Vol. 32, No. 7 (July 2008), page 85. In the remainder of this article, the description of the principle of operation from the cited prior article is recapitulated and updated to incorporate the present radial geometry. In simplest terms, the basic principle of levitation in an axial or radial Halbach magnetic bearing is that of the repulsive electromagnetic force between (1) a moving permanent magnet and (2) an electric current induced in a stationary electrical conductor by the motion of the magnetic field. An axial or radial Halbach bearing includes multiple permanent magnets arranged in a Halbach array ("Halbach array" is defined below) in a rotor and multiple conductors in the form of wire coils in a stator, all arranged so the rotary motion produces an axial or radial repulsion that is sufficient to levitate the rotor. A basic Halbach array (see Figure 1) consists of a row of permanent magnets, each oriented so that its magnetic field is at a right angle to that of the adjacent magnet, and the right-angle turns are sequenced so as to maximize the magnitude of the magnetic flux density on one side of the row while

  12. Partial tooth gear bearings

    NASA Technical Reports Server (NTRS)

    Vranish, John M. (Inventor)

    2010-01-01

    A partial gear bearing including an upper half, comprising peak partial teeth, and a lower, or bottom, half, comprising valley partial teeth. The upper half also has an integrated roller section between each of the peak partial teeth with a radius equal to the gear pitch radius of the radially outwardly extending peak partial teeth. Conversely, the lower half has an integrated roller section between each of the valley half teeth with a radius also equal to the gear pitch radius of the peak partial teeth. The valley partial teeth extend radially inwardly from its roller section. The peak and valley partial teeth are exactly out of phase with each other, as are the roller sections of the upper and lower halves. Essentially, the end roller bearing of the typical gear bearing has been integrated into the normal gear tooth pattern.

  13. Blood Pump Bearing System

    NASA Technical Reports Server (NTRS)

    Aber, Gregory S. (Inventor)

    2000-01-01

    An apparatus is provided for a blood pump bearing system within a pump housing to support long-term highspeed rotation of a rotor with an impeller blade having a plurality of individual magnets disposed thereon to provide a small radial air gap between the magnets and a stator of less than 0.025 inches. The bearing system may be mounted within a flow straightener, diffuser, or other pump element to support the shaft of a pump rotor. The bearing system includes a zirconia shaft having a radiused end. The radiused end has a first radius selected to be about three times greater than the radius of the zirconia shaft. The radiused end of the zirconia shaft engages a flat sapphire endstone. Due to the relative hardness of these materials a flat is quickly produced during break-in on the zirconia radiused end of precisely the size necessary to support thrust loads whereupon wear substantially ceases. Due to the selection of the first radius, the change in shaft end-play during pump break-in is limited to a total desired end-play of less than about 0.010 inches. Radial loads are supported by an olive hole ring jewel that makes near line contact around the circumference of the Ir shaft to support big speed rotation with little friction. The width of olive hole ring jewel is small to allow heat to conduct through to thereby prevent heat build-up in the bearing. A void defined by the bearing elements may fill with blood that then coagulates within the void. The coagulated blood is then conformed to the shape of the bearing surfaces.

  14. Blood Pump Bearing System

    NASA Technical Reports Server (NTRS)

    Aber, Gregory S. (Inventor)

    1999-01-01

    Methods and apparatus are provided for a blood pump bearing system within a pump housing to support long-term high-speed rotation of a rotor with an impeller blade having a plurality of individual magnets disposed thereon to provide a small radial air gap between the magnets and a stator of less than 0.025 inches. The bearing system may be mounted within a flow straightener, diffuser, or other pump element to support the shaft of a pump rotor. The bearing system includes a zirconia shaft having a radiused end. The radiused end has a first radius selected to be about three times greater than the radius of the zirconia shaft. The radiused end of the zirconia shaft engages a flat sapphire endstone. Due to the relative hardness of these materials a flat is quickly produced during break-in on the zirconia radiused end of precisely the size necessary to support thrust loads whereupon wear substantially ceases. Due to the selection of the first radius, the change in shaft end-play during pump break-in is limited to a total desired end-play of less than about 0.010 inches. Radial loads are supported by an olive hole ring jewel that makes near line contact around the circumference of the shaft to support high speed rotation with little friction. The width of olive hole ring jewel is small to allow heat to conduct through to thereby prevent heat build-up in the bearing. A void defined by the bearing elements may fill with blood that then coagulates within the void. The coagulated blood is then conformed to the shape of the bearing surfaces.

  15. Modular gear bearings

    NASA Technical Reports Server (NTRS)

    Vranish, John M. (Inventor)

    2009-01-01

    A gearing system using modular gear bearing components. Each component is composed of a core, one or more modules attached to the core and two or more fastening modules rigidly attaching the modules to the core. The modules, which are attached to the core, may consist of gears, rollers or gear bearing components. The core orientation affects the orientation of the modules attached to the core. This is achieved via the keying arrangement of the core and the component modules that attach to the core. Such an arrangement will also facilitate the phase tuning of gear modules with respect to the core and other gear modules attached to the core.

  16. Composite Bear Canister

    NASA Technical Reports Server (NTRS)

    Chung, W. Richard; Jara, Steve; Suffel, Susan

    2003-01-01

    To many national park campers and mountain climbers saving their foods in a safe and unbreakable storage container without worrying being attacked by a bear is a challenging task. In some parks, the park rangers have mandated that park visitors rent a bear canister for their food storage. Commercially available bear canisters are made of ABS plastic, weigh 2.8 pounds, and have a 180 cubic inch capacity for food storage. A new design with similar capacity was conducted in this study to reduce its weight and make it a stiffer and stronger canister. Two prototypes incorporating carbon prepreg with and without honeycomb constructions were manufactured using hand lay-up and vacuum bag forming techniques. A 6061-T6-aluminum ring was machined to dimensions in order to reinforce the opening area of the canister. Physical properties (weight and volume) along with mechanical properties (flexural strength and specific allowable moment) of the newly fabricated canisters are compared against the commercial ones. The composite canister weighs only 56% of the ABS one can withstand 9 times of the force greater. The advantages and limitations of using composite bear canisters will be discussed in the presentation.

  17. Hybrid superconductor magnet bearings

    SciTech Connect

    Chu, W.

    1995-04-01

    Hybrid superconductor magnet bearings (HSMB`s) utilize high temperature superconductors (HTS`s) together with permanent magnets to form a frictionless interface between relatively rotating parts. They are low mass, stable, and do not incur expenditure of energy during normal operation. There is no direct physical contact between rotor and stator, and hence there is no wear and tear. However, just as any other applications of HTS`s, it requires a very cold temperature to function. Whereas this might be perceived as a disadvantage on earth, it is of no great concern in space or on the moon. To astronomers, the moon is an excellent site for an observatory, but the cold and dusty vacuum environment on the moon precludes the use of mechanical bearings on the telescope mounts. Furthermore, drive mechanisms with very fine steps, and hence bearings with extremely low friction are needed to track a star from the moon, because the moon rotates very slowly. All aspects considered, the HSMB is about the only candidate that fits in naturally. Here, the authors present a design for one such bearing, capable of supporting a telescope that weighs about 3 lbs on Earth.

  18. Magnetic Bearings For Turbopumps

    NASA Technical Reports Server (NTRS)

    Meeks, Crawford R.; Mendez, Antonio J.

    1995-01-01

    Report presents study of feasibility of magnetic bearings in turbopumps. Liquid-oxygen turbopump in space shuttle main engine selected for study. Other potential applications include manned and unmanned spacecraft, gas turbines for commercial and military aircraft, turbomachinery for petro-chemical and gas operations, suspension systems for precise machinery, and precise pointing and tracking systems.

  19. History of ball bearings

    NASA Technical Reports Server (NTRS)

    Dowson, D.; Hamrock, B. J.

    1981-01-01

    The familiar precision rolling-element bearings of the twentieth century are products of exacting technology and sophisticated science. Their very effectiveness and basic simplicity of form may discourage further interest in their history and development. Yet the full story covers a large portion of recorded history and surprising evidence of an early recognition of the advantages of rolling motion over sliding action and progress toward the development of rolling-element bearings. The development of rolling-element bearings is followed from the earliest civilizations to the end of the eighteenth century. The influence of general technological developments, particularly those concerned with the movement of large building blocks, road transportation, instruments, water-raising equipment, and windmills are discussed, together with the emergence of studies of the nature of rolling friction and the impact of economic factors. By 1800 the essential features of ball and rolling-element bearings had emerged and it only remained for precision manufacture and mass production to confirm the value of these fascinating machine elements.

  20. The Teddy Bears' Disc.

    ERIC Educational Resources Information Center

    Laurillard, Diana

    1985-01-01

    Reports an evaluation of the Teddy Bear disc, an interactive videodisc developed at the Open University for a second-level course in metallurgy and materials technology. Findings from observation of students utilizing the videodisc are reviewed; successful design features and design problems are considered; and development costs are outlined. (MBR)

  1. Hybrid superconductor magnet bearings

    NASA Technical Reports Server (NTRS)

    Chu, Wei-Kan

    1995-01-01

    Hybrid superconductor magnet bearings (HSMB's) utilize high temperature superconductors (HTS's) together with permanent magnets to form a frictionless interface between relatively rotating parts. They are low mass, stable, and do not incur expenditure of energy during normal operation. There is no direct physical contact between rotor and stator, and hence there is no wear and tear. However, just as any other applications of HTS's, it requires a very cold temperature to function. Whereas this might be perceived as a disadvantage on earth, it is of no great concern in space or on the moon. To astronomers, the moon is an excellent site for an observatory, but the cold and dusty vacuum environment on the moon precludes the use of mechanical bearings on the telescope mounts. Furthermore, drive mechanisms with very fine steps, and hence bearings with extremely low friction are needed to track a star from the moon, because the moon rotates very slowly. All aspects considered, the HSMB is about the only candidate that fits in naturally. Here, we present a design for one such bearing, capable of supporting a telescope that weighs about 3 lbs on Earth.

  2. Magnetically leviated superconducting bearing

    DOEpatents

    Weinberger, Bernard R.; Lynds, Jr., Lahmer

    1993-01-01

    A magnetically levitated superconducting bearing includes a magnet (2) mounted on a shaft (12) that is rotatable around an axis of rotation and a Type II superconductor (6) supported on a stator (14) in proximity to the magnet (2). The superconductor (6) is positioned so that when it is cooled to its superconducting state in the presence of a magnetic field, it interacts with the magnet (2) to produce an attractive force that levitates the magnet (2) and supports a load on the shaft (12). The interaction between the superconductor (6) and magnet(2) also produces surface screening currents (8) that generate a repulsive force perpendicular to the load. The bearing also has means for maintaining the superconductor at a temperature below its critical temperature (16, 18). The bearing could also be constructed so the magnet (2) is supported on the stator (14) and the superconductor (6) is mounted on the shaft (12). The bearing can be operated by cooling the superconductor (6) to its superconducting state in the presence of a magnetic field.

  3. Optimal Synchronizability of Bearings

    NASA Astrophysics Data System (ADS)

    Araújo, N. A. M.; Seybold, H.; Baram, R. M.; Herrmann, H. J.; Andrade, J. S., Jr.

    2013-02-01

    Bearings are mechanical dissipative systems that, when perturbed, relax toward a synchronized (bearing) state. Here we find that bearings can be perceived as physical realizations of complex networks of oscillators with asymmetrically weighted couplings. Accordingly, these networks can exhibit optimal synchronization properties through fine-tuning of the local interaction strength as a function of node degree [Motter, Zhou, and Kurths, Phys. Rev. E 71, 016116 (2005)PLEEE81539-3755]. We show that, in analogy, the synchronizability of bearings can be maximized by counterbalancing the number of contacts and the inertia of their constituting rotor disks through the mass-radius relation, m˜rα, with an optimal exponent α=α× which converges to unity for a large number of rotors. Under this condition, and regardless of the presence of a long-tailed distribution of disk radii composing the mechanical system, the average participation per disk is maximized and the energy dissipation rate is homogeneously distributed among elementary rotors.

  4. Magnetic-Bearing Test Fixture

    NASA Technical Reports Server (NTRS)

    Groom, Nelson J.; Poole, William L.

    1991-01-01

    Microcomputer-controlled magnetic-bearing test fixture used to develop approaches to design of controls for magnetic bearing actuators designed and constructed. Includes load cells connected to bar, in turn, connected through screw positioners to geared drive motors. Position of equivalent suspended element sensed by position sensors and controlled by drive motors. Provides control of gap in magnetic bearing and of current in electromagnet coil. Measurements made include magnetic-bearing gaps, magnetic flux in bearing gaps, and bearing forces. Approaches to linearization and control developed by use of fixture applicable to wide range of small-gap suspension systems.

  5. Lubricant effects on bearing life

    NASA Technical Reports Server (NTRS)

    Zaretsky, Erwin V.

    1986-01-01

    Lubricant considerations for rolling-element bearings have within the last two decades taken on added importance in the design and operation of mechanical systems. The phenomenon which limits the useful life of bearings is rolling-element or surface pitting fatigue. The elastohydrodynamic (EHD) film thickness which separates the ball or roller surface from those of the raceways of the bearing directly affects bearing life. Chemical additives added to the lubricant can also significantly affect bearings life and reliability. The interaction of these physical and chemical effects is important to the design engineer and user of these systems. Design methods and lubricant selection for rolling-element bearings are presented and discussed.

  6. Biological comparison of 149Pm-, 166Ho-, and 177Lu-DOTA-biotin pretargeted by CC49 scFv-streptavidin fusion protein in xenograft-bearing nude mice.

    PubMed

    Lewis, Michael R; Zhang, Jiuli; Jia, Fang; Owen, Nellie K; Cutler, Cathy S; Embree, Mary F; Schultz, Jody; Theodore, Louis J; Ketring, Alan R; Jurisson, Silvia S; Axworthy, Donald B

    2004-02-01

    The radiolanthanides (149)Pm, (166)Ho, and (177)Lu possess a range of half-lives and alpha(-) beta(-) energies for targeted radiotherapy of cancer. (149)Pm-, (166)Ho-, and (177)Lu-DOTA-biotin were pretargeted to LS174T colorectal tumors in nude mice with CC49 scFvSA antibody-streptavidin fusion protein. Tumor uptakes of (149)Pm (22.9% ID/g), (166)Ho (30.2% ID/g), and (177)Lu (35.4% ID/g) peaked at 1-4 h. Rapid blood disappearance was accompanied by urinary excretion of 59-66% ID within 1 h. Biodistributions of these agents show promise for pretargeted radioimmunotherapy of cancer.

  7. Vygotsky and the Three Bears

    ERIC Educational Resources Information Center

    Kulczewski, Peggy

    2004-01-01

    Peggy Kulczewski, a kindergarten classroom teacher, remembers the day when students enjoyed a story she told them from the book "The Three Bears". The students' discussion about comparison of the bears was very helpful to the whole group.

  8. Magnetic bearings grow more attractive

    NASA Astrophysics Data System (ADS)

    1993-10-01

    Advances in materials and electronics have enabled designers to devise simpler, smaller magnetic bearings. As a result, costs have dropped, widening the applications for these very-low-friction devices. Avcon (Advanced Controls Technology) has patented a permanent-magnet bias actively controlled bearing. Here high-energy rare earth permanent-magnet materials supply the basic bearing load levitation, while servo-driven electromagnets generate stabilization and centering forces for motion contol. Previous heavy-duty magnetic bearings used electromagnets entirely for suspension and control, which led to large bearings and control systems with higher power requirements. Avcon has developed several types of permanent-magnet bias bearings. The simplest is the radial repulsion bearing. Avcon's homopolar permanent-magnet bias active bearing is the most versatile of the company's designs.

  9. Immunologic effects of arginine supplementation in tumor-bearing and non-tumor-bearing hosts.

    PubMed

    Reynolds, J V; Daly, J M; Shou, J; Sigal, R; Ziegler, M M; Naji, A

    1990-02-01

    Supplemental dietary arginine has anti-tumor properties but the degree and mechanisms are unclear. In non-tumor-bearing CBA/J mice (n = 60), 1% arginine supplementation significantly enhanced thymic weight, spleen cell mitogenesis, and interferon-activated natural killer cell activity; no further enhancement was observed with 2% or 4% supplementation. Supplemental 1% arginine, when compared with 1.7% glycine, enhanced interferon-induced natural killer cell activity, lymphokine-activated killer cell generation, and macrophage cytotoxicity. In A/J mice (n = 420), bearing either a moderately immunogenic (C1300) or weakly immunogenic (TBJ) murine neuroblastoma, 1% arginine significantly (p less than 0.05) retarded tumor growth and prolonged median survival time compared with glycine or no supplementation. Dietary arginine enhanced T-cell function and significantly increased responsiveness to autologous C1300 tumor in a mixed lymphocyte tumor cell culture (MLTC). The immunomodulatory effects of arginine provide nutritional and immunologic support of the tumor-bearing host and may be helpful when given concommitant with immunotherapy.

  10. Magnetic bearing and motor

    NASA Technical Reports Server (NTRS)

    Studer, Philip A. (Inventor)

    1983-01-01

    A magnetic bearing assembly (10) has an intermediate rotatable section (33) having an outer cylindrical member (30) coaxially suspended by a torsion wire (72) around an axially polarized cylindrical magnet (32). Axial alignment between the pole faces (40-43) of the intermediate section (33) and end surfaces (50-53) of opposed end bells (20, 22) provides a path of least reluctance across intervening air gaps (60-63) for the magnetic flux emanating from magnet (32). Radial dislocation increases the reluctance and creates a radial restoring force. Substitution of radially polarized magnets 107 fixed to a magnetically permeable cylinder (32') and insertion of pairs of armature coil windings (109-112) between the cylinder pair (33') provides an integral magnetic bearing and torsion motor (100) able to provide arcuately limited rotational drive.

  11. Centrifugally decoupling touchdown bearings

    DOEpatents

    Post, Richard F

    2014-06-24

    Centrifugally decoupling mechanical bearing systems provide thin tensioned metallic ribbons contained in a support structure. This assembly rotates around a stationary shaft being centered at low speeds by the action of the metal ribbons. Tension springs are connected on one end to the ribbons and on the other end to the support structure. The ribbons pass through slots in the inner ring of the support structure. The spring preloading thus insures contact (or near-contact) between the ribbons and the shaft at rotation speeds below the transition speed. Above this speed, however, the centrifugal force on the ribbons produces a tensile force on them that exceeds the spring tensile force so that the ribbons curve outward, effectively decoupling them from mechanical contact with the shaft. They still remain, however, in position to act as a touchdown bearing in case of abnormally high transverse accelerations.

  12. Passive magnetic bearing system

    SciTech Connect

    Post, Richard F.

    2014-09-02

    An axial stabilizer for the rotor of a magnetic bearing provides external control of stiffness through switching in external inductances. External control also allows the stabilizer to become a part of a passive/active magnetic bearing system that requires no external source of power and no position sensor. Stabilizers for displacements transverse to the axis of rotation are provided that require only a single cylindrical Halbach array in its operation, and thus are especially suited for use in high rotation speed applications, such as flywheel energy storage systems. The elimination of the need of an inner cylindrical array solves the difficult mechanical problem of supplying support against centrifugal forces for the magnets of that array. Compensation is provided for the temperature variation of the strength of the magnetic fields of the permanent magnets in the levitating magnet arrays.

  13. Frictionless Bearing Uses Permanent Magnets

    NASA Technical Reports Server (NTRS)

    1965-01-01

    The purpose of this innovation was to develop a frictionless bearing for high speed, light load applications. The device involves the incorporation of permanent magnets in the bearing design. The repulsion of like magnetic poles provides concentric support of the inner member so that no metallic contact occurs between the bearing surfaces.

  14. Rotating plug bearing and seal

    DOEpatents

    Wade, Elman E.

    1977-01-01

    A bearing and seal structure for nuclear reactors utilizing rotating plugs above the nuclear reactor vessel. The structure permits lubrication of bearings and seals of the rotating plugs without risk of the lubricant draining into the reactor vessel below. The structure permits lubrication by utilizing a rotating outer race bearing.

  15. Stacked magnet superconducting bearing

    SciTech Connect

    Rigney, T.K. II; Saville, M.P.

    1993-06-15

    A superconducting bearing is described, comprising: a plurality of permanent magnets magnetized end-to-end and stacked side-by-side in alternating polarity, such that flux lines flow between ends of adjacent magnets; isolating means, disposed between said adjacent magnets, for reducing flux leakage between opposing sides of said adjacent magnets; and a member made of superconducting material having at least one surface in communication with said flux lines.

  16. Magnetic translator bearings

    NASA Technical Reports Server (NTRS)

    Hockney, Richard L. (Inventor); Downer, James R. (Inventor); Eisenhaure, David B. (Inventor); Hawkey, Timothy J. (Inventor); Johnson, Bruce G. (Inventor)

    1990-01-01

    A magnetic bearing system for enabling translational motion includes a carriage and a shaft for movably supporting the carriage; a first magnetic bearing fixed to one of the carriage and shaft and slidably received in a first channel of the other of the carriage and shaft. The first channel is generally U shaped with two side walls and a back wall. The magnetic bearing includes a pair of spaced magnetic pole pieces, each pole piece having a pair of electromagnetic coils mounted on poles on opposite ends of the pole piece proximate the side walls, and a third electromagnetic coil mounted on a pole of the pole piece proximate the backwall; a motion sensor for sensing translational motion along two axes and rotationally about three axes of the carriage and shaft relative to each other; and a correction circuit responsive to the sensor for generating a correction signal to drive the coils to compensate for any misalignment sensed between the carriage and the shaft.

  17. Antitumor efficiency of D-alpha-tocopheryl polyethylene glycol 1000 succinate-b-poly(epsilon-caprolactone-ran-lactide) nanoparticle-based delivery of docetaxel in mice bearing cervical cancer.

    PubMed

    Wang, Zhongyuan; Zeng, Xiaowei; Ma, Yaping; Liu, Jian; Tang, Xiaolong; Gao, Yongfeng; Liu, Kewei; Zhang, Jinxie; Ming, Pinghong; Huang, Laiqiang; Mei, Lin

    2014-08-01

    Pharmaceutical nanotechnology holds potential in cancer chemotherapy. In this research, the docetaxel-loaded D-alpha-tocopheryl polyethylene glycol 1000 succinate-b-poly(epsilon-caprolactone-ran-lactide) (TPGS-b-(PCL-ran-PLA)) nanoparticles were prepared by a modified nanoprecipitation method and then the particle size, surface morphology, nanoparticle stability, in vitro drug release and cellular uptake of nanoparticles were characterized. Finally, we evaluated the therapeutic effects of nanoparticle formulation in comparison with Taxotere both in vitro and in vivo. The size of TPGS-b-(PCL-ran-PLA) nanoparticles was about 150 nm and much smaller than PCL nanoparticles (about 185 nm) and the absolute value of zeta potential was higher than PCL nanoparticles (16.49 mV vs. 13.17 mV). FESEM images further confirmed the morphology and size of nanoparticles. The drug-loaded nanoparticles were considered to be stable, showing no change in the particle size and surface charge during three-month storage of its aqueous solution. In vitro drug release of TPGS-b-(PCL-ran-PLA) nanoparticles was much faster than PCL and PCL-TPGS nanoparticles. The cumulative drug release of docetaxel-loaded TPGS-b-(PCL-ran-PLA), PCL-TPGS, and PCL NPs were 38.00%, 34.48% and 29.04%, respectively. TPGS-b-(PCL-ran-PLA) nanoparticles showed an obvious increase of cellular uptake. Due to the advantages of TPGS-b-(PCL-ran-PLA) nanoparticles, it could achieve significantly higher level of cytotoxicity in vitro and better inhibition effect of tumor growth on xenograft BALB/c nude mice tumor model than commercial Taxotere at the same dose (1.49-fold more effective). The TPGS-b-(PCL-ran-PLA) could be used as a novel and potential biodegradable polymeric material for nanoformulation in cervical cancer chemotherapy. PMID:25016651

  18. The bear that never was

    USGS Publications Warehouse

    Smith, T.S.; Amstrup, Steven C.; Herrero, Stephen

    2005-01-01

    From campfire stories to sensational books detailing gory attacks, Alaska's bears have long been maligned as deadly marauders capable of acquiring a taste for human flesh. Tall tales make for good storytelling but force bad reputations on the bears. When myth is compared to fact, the three North American's leading bear experts show that Alaska's three bear species are not the huge, unpredictable monsters they often are made out to be. Here, Smith, Amstrup, and Herrero examine the conventional wisdom people often hear regarding bears in the Great Land.

  19. Bearing, gearing, and lubrication technology

    NASA Technical Reports Server (NTRS)

    Anderson, W. J.

    1978-01-01

    Results of selected NASA research programs on rolling-element and fluid-film bearings, gears, and elastohydrodynamic lubrication are reported. Advances in rolling-element bearing material technology, which have resulted in a significant improvement in fatigue life, and which make possible new applications for rolling bearings, are discussed. Research on whirl-resistant, fluid-film bearings, suitable for very high-speed applications, is discussed. An improved method for predicting gear pitting life is reported. An improved formula for calculating the thickness of elastohydrodynamic films (the existence of which help to define the operating regime of concentrated contact mechanisms such as bearings, gears, and cams) is described.

  20. Bearing for liquid metal pump

    DOEpatents

    Dickinson, Robert J.; Wasko, John; Pennell, William E.

    1984-01-01

    A liquid metal pump bearing support comprises a series of tangentially oriented spokes that connect the bearing cylinder to the pump internals structure. The spokes may be arranged in a plurality of planes extending from the bearing cylinder to the pump internals with the spokes in one plane being arranged alternately with those in the next plane. The bearing support structure provides the pump with sufficient lateral support for the bearing structure together with the capability of accommodating differential thermal expansion without adversely affecting pump performance.

  1. Anti-backlash gear bearings

    NASA Technical Reports Server (NTRS)

    Vranish, John M. (Inventor)

    2009-01-01

    A gear bearing having a first gear and a second gear, each having a plurality of teeth. Each gear operates on two non-parallel surfaces of the opposing gear teeth to perform both gear and bearing functions simultaneously. The gears are moving at substantially the same speed at their contact points. The gears may be roller gear bearings or phase-shifted gear bearings, and may be arranged in a planet/sun system or used as a transmission. One preferred embodiment discloses and describes an anti-backlash feature to counter ''dead zones'' in the gear bearing movement.

  2. Hybrid Bearing Prognostic Test Rig

    NASA Technical Reports Server (NTRS)

    Dempsey, Paula J.; Certo, Joseph M.; Handschuh, Robert F.; Dimofte, Florin

    2005-01-01

    The NASA Glenn Research Center has developed a new Hybrid Bearing Prognostic Test Rig to evaluate the performance of sensors and algorithms in predicting failures of rolling element bearings for aeronautics and space applications. The failure progression of both conventional and hybrid (ceramic rolling elements, metal races) bearings can be tested from fault initiation to total failure. The effects of different lubricants on bearing life can also be evaluated. Test conditions monitored and recorded during the test include load, oil temperature, vibration, and oil debris. New diagnostic research instrumentation will also be evaluated for hybrid bearing damage detection. This paper summarizes the capabilities of this new test rig.

  3. Bearing construction for refrigeration compresssor

    DOEpatents

    Middleton, Marc G.; Nelson, Richard T.

    1988-01-01

    A hermetic refrigeration compressor has a cylinder block and a crankshaft rotatable about a vertical axis to reciprocate a piston in a cylinder on the cylinder block. A separate bearing housing is secured to the central portion of the cylinder block and extends vertically along the crankshaft, where it carries a pair of roller bearings to journal the crankshaft. The crankshaft has a radially extending flange which is journaled by a thrust-type roller bearing above the bearing housing to absorb the vertical forces on the crankshaft so that all three of the roller bearings are between the crankshaft and the bearing housing to maintain and control the close tolerances required by such bearings.

  4. Bearing construction for refrigeration compressor

    SciTech Connect

    Middleton, M.G.; Nelson, R.T.

    1988-01-12

    A hermetic refrigeration compressor has a cylinder block and a crankshaft rotatable about a vertical axis to reciprocate a piston in a cylinder on the cylinder block. A separate bearing housing is secured to the central portion of the cylinder block and extends vertically along the crankshaft, where it carries a pair of roller bearings to journal the crankshaft. The crankshaft has a radially extending flange which is journaled by a thrust-type roller bearing above the bearing housing to absorb the vertical forces on the crankshaft so that all three of the roller bearings are between the crankshaft and the bearing housing to maintain and control the close tolerances required by such bearings. 4 figs.

  5. Damping Bearings In High-Speed Turbomachines

    NASA Technical Reports Server (NTRS)

    Von Pragenau, George L.

    1994-01-01

    Paper presents comparison of damping bearings with traditional ball, roller, and hydrostatic bearings in high-speed cryogenic turbopumps. Concept of damping bearings described in "Damping Seals and Bearings for a Turbomachine" (MFS-28345).

  6. Effect of Bearing Cleaning on Long Term Bearing Life

    NASA Technical Reports Server (NTRS)

    Jett, Tim; Thom, R. L.

    1999-01-01

    For many years chlorofluorocarbon (CFC) based solvents, such as CFC-113 and 1,1,1, trichloroethane (TCA), were used as bearing cleaning solvents for space mechanism bearings. The 1995 ban on the production of ozone depleting chemicals (ODC) such as CFCs caused a change requiring the use of ODC-free cleaners for precision bearing cleaning. With this change the question arises; what effect if any do these new cleaners have on long term bearing life? The purpose of this study was to evaluate this effect. A one year test using 60 small electrical motors (two bearings per motor) was conducted in a high vacuum environment (2.0 x 10(exp -6) torr) at a temperature of 90 C. Prior to testing the bearings were cleaned with one of four cleaners. These cleaners included two aqueous based cleaners, a CFC based cleaner and supercritical carbon dioxide. Three space compatible greases were tested. After testing, the mass of each lubricated bearing was measured both pre and post test. Along with mass loss measurements a profilometer trace of each bearing was taken to measure post test wear of the bearings. In addition, the bearings were visually examined and analyzed using an optical microscope.

  7. Introgressive hybridization: brown bears as vectors for polar bear alleles.

    PubMed

    Hailer, Frank

    2015-03-01

    The dynamics and consequences of introgression can inform about numerous evolutionary processes. Biologists have therefore long been interested in hybridization. One challenge, however, lies in the identification of nonadmixed genotypes that can serve as a baseline for accurate quantification of admixture. In this issue of Molecular Ecology, Cahill et al. (2015) analyse a genomic data set of 28 polar bears, eight brown bears and one American black bear. Polar bear alleles are found to be introgressed into brown bears not only near a previously identified admixture zone on the Alaskan Admiralty, Baranof and Chichagof (ABC) Islands, but also far into the North American mainland. Elegantly contrasting admixture levels at autosomal and X chromosomal markers, Cahill and colleagues infer that male-biased dispersal has spread these introgressed alleles away from the Late Pleistocene contact zone. Compared to a previous study on the ABC Island population in which an Alaskan brown bear served as a putatively admixture-free reference, Cahill et al. (2015) utilize a newly sequenced Swedish brown bear as admixture baseline. This approach reveals that brown bears have been impacted by introgression from polar bears to a larger extent (up to 8.8% of their genome), than previously known, including the bear that had previously served as admixture baseline. No evidence for introgression of brown bear into polar bear is found, which the authors argue could be a consequence of selection. Besides adding new exciting pieces to the puzzle of polar/brown bear evolutionary history, the study by Cahill and colleagues highlights that wildlife genomics is moving from analysing single genomes towards a landscape genomics approach. PMID:25775930

  8. Introgressive hybridization: brown bears as vectors for polar bear alleles.

    PubMed

    Hailer, Frank

    2015-03-01

    The dynamics and consequences of introgression can inform about numerous evolutionary processes. Biologists have therefore long been interested in hybridization. One challenge, however, lies in the identification of nonadmixed genotypes that can serve as a baseline for accurate quantification of admixture. In this issue of Molecular Ecology, Cahill et al. (2015) analyse a genomic data set of 28 polar bears, eight brown bears and one American black bear. Polar bear alleles are found to be introgressed into brown bears not only near a previously identified admixture zone on the Alaskan Admiralty, Baranof and Chichagof (ABC) Islands, but also far into the North American mainland. Elegantly contrasting admixture levels at autosomal and X chromosomal markers, Cahill and colleagues infer that male-biased dispersal has spread these introgressed alleles away from the Late Pleistocene contact zone. Compared to a previous study on the ABC Island population in which an Alaskan brown bear served as a putatively admixture-free reference, Cahill et al. (2015) utilize a newly sequenced Swedish brown bear as admixture baseline. This approach reveals that brown bears have been impacted by introgression from polar bears to a larger extent (up to 8.8% of their genome), than previously known, including the bear that had previously served as admixture baseline. No evidence for introgression of brown bear into polar bear is found, which the authors argue could be a consequence of selection. Besides adding new exciting pieces to the puzzle of polar/brown bear evolutionary history, the study by Cahill and colleagues highlights that wildlife genomics is moving from analysing single genomes towards a landscape genomics approach.

  9. Gold-bearing skarns

    USGS Publications Warehouse

    Theodore, Ted G.; Orris, Greta J.; Hammerstrom, Jane M.; Bliss, James D.

    1991-01-01

    In recent years, a significant proportion of the mining industry's interest has been centered on discovery of gold deposits; this includes discovery of additional deposits where gold occurs in skarn, such as at Fortitude, Nevada, and at Red Dome, Australia. Under the classification of Au-bearing skarns, we have modeled these and similar gold-rich deposits that have a gold grade of at least 1 g/t and exhibit distinctive skarn mineralogy. Two subtypes, Au-skarns and byproduct Au-skarns, can be recognized on the basis of gold, silver, and base-metal grades, although many other geological factors apparently are still undistinguishable largely because of a lack of detailed studies of the Au-skarns. Median grades and tonnage for 40 Au-skarn deposits are 8.6 g/t Au, 5.0 g/t Ag, and 213,000 t. Median grades and tonnage for 50 byproduct and Au-skarn deposits are 3.7 g/t Au, 37 g/t Ag, and 330,000 t. Gold-bearing skarns are generally calcic exoskarns associated with intense retrograde hydrosilicate alteration. These skarns may contain economic amounts of numerous other commodities (Cu, Fe, Pb, Zn, As, Bi, W, Sb, Co, Cd, and S) as well as gold and silver. Most Au-bearing skarns are found in Paleozoic and Cenozoic orogenic-belt and island-arc settings and are associated with felsic to intermediate intrusive rocks of Paleozoic to Tertiary age. Native gold, electru, pyrite, pyrrhotite, chalcopyrite, arsenopyrite, sphalerite, galena, bismuth minerals, and magnetite or hematite are the most common opaque minerals. Gangue minerals typically include garnet (andradite-grossular), pyroxene (diopside-hedenbergite), wollastonite, chlorite, epidote, quartz, actinolite-tremolite, and (or) calcite.

  10. Linear magnetic bearings

    NASA Technical Reports Server (NTRS)

    Goldowskiy, M. P.

    1984-01-01

    A self regulating, nonfrictional, active magnetic bearing is disclosed which has an elongated cylindrical housing for containing a shaft type armature with quadrature positioned shaft position sensors and equidistantly positioned electromagnets located at one end of the housing. Each set of sensors is responsive to orthogonal displacement of the armature and is used to generate control signals to energize the electromagnets to center the armature. A bumper magnet assembly is located at one end of the housing for dampening any undesired axial movement of the armature or to axially move the armature either continuously or fixedly.

  11. Aerospace applications of magnetic bearings

    NASA Astrophysics Data System (ADS)

    Downer, James; Goldie, James; Gondhalekar, Vijay; Hockney, Richard

    1994-05-01

    Magnetic bearings have traditionally been considered for use in aerospace applications only where performance advantages have been the primary, if not only, consideration. Conventional wisdom has been that magnetic bearings have certain performance advantages which must be traded off against increased weight, volume, electric power consumption, and system complexity. These perceptions have hampered the use of magnetic bearings in many aerospace applications because weight, volume, and power are almost always primary considerations. This paper will review progress on several active aerospace magnetic bearings programs at SatCon Technology Corporation. The magnetic bearing programs at SatCon cover a broad spectrum of applications including: a magnetically-suspended spacecraft integrated power and attitude control system (IPACS), a magnetically-suspended momentum wheel, magnetic bearings for the gas generator rotor of a turboshaft engine, a vibration-attenuating magnetic bearing system for an airborne telescope, and magnetic bearings for the compressor of a space-rated heat pump system. The emphasis of these programs is to develop magnetic bearing technologies to the point where magnetic bearings can be truly useful, reliable, and well tested components for the aerospace community.

  12. Aerospace applications of magnetic bearings

    NASA Technical Reports Server (NTRS)

    Downer, James; Goldie, James; Gondhalekar, Vijay; Hockney, Richard

    1994-01-01

    Magnetic bearings have traditionally been considered for use in aerospace applications only where performance advantages have been the primary, if not only, consideration. Conventional wisdom has been that magnetic bearings have certain performance advantages which must be traded off against increased weight, volume, electric power consumption, and system complexity. These perceptions have hampered the use of magnetic bearings in many aerospace applications because weight, volume, and power are almost always primary considerations. This paper will review progress on several active aerospace magnetic bearings programs at SatCon Technology Corporation. The magnetic bearing programs at SatCon cover a broad spectrum of applications including: a magnetically-suspended spacecraft integrated power and attitude control system (IPACS), a magnetically-suspended momentum wheel, magnetic bearings for the gas generator rotor of a turboshaft engine, a vibration-attenuating magnetic bearing system for an airborne telescope, and magnetic bearings for the compressor of a space-rated heat pump system. The emphasis of these programs is to develop magnetic bearing technologies to the point where magnetic bearings can be truly useful, reliable, and well tested components for the aerospace community.

  13. Reduction in bearing size due to superconductors in magnetic bearings

    NASA Technical Reports Server (NTRS)

    Rao, Dantam K.; Lewis, Paul; Dill, James F.

    1991-01-01

    A design concept that reduces the size of magnetic bearings is assessed. The small size will enable magnetic bearings to fit into limited available bearing volume of cryogenic machinery. The design concept, called SUPERC, uses (high Tc) superconductors or high-purity aluminum conductors in windings instead of copper. The relatively high-current density of these conductors reduces the slot radial thickness for windings, which reduces the size of the bearings. MTI developed a sizing program called SUPERC that translates the high-current density of these conductors into smaller sized bearings. This program was used to size a superconducting bearing to carry a 500 lb. load. The sizes of magnetic bearings needed by various design concepts are as follows: SUPERC design concept = 3.75 in.; magnet-bias design concept = 5.25 in.; and all electromagnet design concept = 7.0 in. These results indicate that the SUPERC design concept can significantly reduce the size of the bearing. This reduction, in turn, reduces the weight and yields a lighter bearing. Since the superconductors have inherently near-zero resistance, they are also expected to save power needed for operation considerably.

  14. Effect of Bearing Cleaning on Long Term Bearing Life

    NASA Technical Reports Server (NTRS)

    Jett, Timothy Raymond; Thom, Robert L.

    1998-01-01

    For many years chlorofluorocarbon (CFC ) based solvents, such as Freon and 1,1,1, Trichloroethane (TCA), were used as bearing cleaning solvents for space mechanisms. The 1995 ban on the production of ozone depleting chemicals (ODC) such as CFCs caused a change to new ODC-free cleaners for the precision bearing cleaning. With this change the question arises what effect if any do these new cleaners have on long term bearing life. The purpose of this study was to evaluate this effect. A one year test using 60 small electrical motors (two bearings per motor) was conducted in a high vacuum environment (2.0* 10(exp -6) torr) at a temperature of 90C. Prior to testing the bearings were cleaned with one of four cleaners. These cleaners included two aqueous based cleaners, a CFC based cleaner and supercritical carbon dioxide. Three space compatible greases were tested. After testing the mass of each lubricated bearing was measured both pre and post test. Along with mass loss measurements a profilometer trace of each bearing was taken to measure post test wear of the bearings. In addition the bearings were visually examined and analyzed using an optical microscope.

  15. Robust and intelligent bearing estimation

    DOEpatents

    Claassen, John P.

    2000-01-01

    A method of bearing estimation comprising quadrature digital filtering of event observations, constructing a plurality of observation matrices each centered on a time-frequency interval, determining for each observation matrix a parameter such as degree of polarization, linearity of particle motion, degree of dyadicy, or signal-to-noise ratio, choosing observation matrices most likely to produce a set of best available bearing estimates, and estimating a bearing for each observation matrix of the chosen set.

  16. Towards new boron carriers for boron neutron capture therapy: metallacarboranes bearing cobalt, iron and chromium and their cholesterol conjugates.

    PubMed

    Białek-Pietras, Magdalena; Olejniczak, Agnieszka B; Tachikawa, Shoji; Nakamura, Hiroyuki; Leśnikowski, Zbigniew J

    2013-03-01

    A method for the synthesis of cholesterol-metallacarborane conjugates bearing cobalt, iron and chromium was developed. Effective incorporation of the cholesterol conjugate bearing cobalt into liposome membrane was revealed. Using the metallacarborane-encrusted liposomes as boron delivery system in vivo biodistribution experiments in tumor-bearing mice, high accumulation and selective delivery of boron into tumor tissues was observed. The results demonstrate that the cholesterol-metallacarborane conjugates can be considered as a potential candidate for boron delivery vehicle in BNCT.

  17. The polar bear phenomena

    SciTech Connect

    Maw, P.K. ); Lane, M.T.

    1990-02-01

    Results from measuring the thermal profile of polar bear pelts, reflectiveness of the pelts, and total thermal conversion data lead to the conclusion that the pelts from an ultra-efficient thermal diode for solar-thermal conversion. The transfer of the thermal energy from the surface of the fur to the skin where it is absorbed cannot be thermal, and therefore must be radiative. This process must have an efficiency of better than 90:0090 percent to account for measured values. The radiative transfer process is not known at present. To understand it, a detailed knowledge of the microscopic parameters of the pelts must be obtained. This is the current thrust of the polar solar research. If the process can be understood and synthesized,it will provide a major breakthrough in the area of solar-thermal energy conversion.

  18. Superconducting levitating bearing

    NASA Technical Reports Server (NTRS)

    Moon, Francis C. (Inventor)

    1996-01-01

    A superconducting bearing assembly includes a coil field source that may be superconducting and a superconducting structure. The coil field source assembly and superconducting structure are positioned so as to enable relative rotary movement therebetween. The structure and coil field source are brought to a supercooled temperature before a power supply induces a current in the coil field source. A Meissner-like effect is thereby obtained and little or no penetration of the field lines is seen in the superconducting structure. Also, the field that can be obtained from the superconducting coil is 2-8 times higher than that of permanent magnets. Since the magnetic pressure is proportioned to the square of the field, magnetic pressures from 4 to 64 times higher are achieved.

  19. The neuroimmune changes induced by cohabitation with an Ehrlich tumor-bearing cage mate rely on olfactory information.

    PubMed

    Alves, Glaucie J; Ribeiro, Alison; Palermo-Neto, João

    2012-01-01

    Cohabitation for 14 days with Ehrlich tumor-bearing mice was shown to increase locomotor activity, to decrease hypothalamic noradrenaline (NA) levels, to increase NA turnover and to decrease innate immune responses and decrease the animals' resistance to tumor growth. Cage mates of a B16F10 melanoma-bearer mice were also reported to show neuroimmune changes. Chemosignals released by Ehrlich tumor-bearing mice have been reported to be relevant for the neutrophil activity changes induced by cohabitation. The present experiment was designed to further analyze the effects of odor cues on neuroimmune changes induced by cohabitation with a sick cage mate. Specifically, the relevance of chemosignals released by an Ehrlich tumor-bearing mouse was assessed on the following: behavior (open-field and plus maze); hypothalamic NA levels and turnover; adrenaline (A) and NA plasmatic levels; and host resistance induced by tumor growth. To comply with such objectives, devices specifically constructed to analyze the influence of chemosignals released from tumor-bearing mice were employed. The results show that deprivation of odor cues released by Ehrlich tumor-bearing mice reversed the behavioral, neurochemical and immune changes induced by cohabitation. Mice use scents for intraspecies communication in many social contexts. Tumors produce volatile organic compounds released into the atmosphere through breath, sweat, and urine. Our results strongly suggest that volatile compounds released by Ehrlich tumor-injected mice are perceived by their conspecifics, inducing the neuroimmune changes reported for cohabitation with a sick companion.

  20. Formaldehyde and skin tumorigenesis in Sencar mice

    SciTech Connect

    Iversen, O.H.

    1988-01-01

    Previous experiments involving topical applications of formaldehyde on hairless mouse skin were repeated with SENCAR mice, which are bred for maximum sensitivity to chemical tumorigenesis. Most experimental groups consisted of 32 mice. Topical skin applications of either 100 ..mu..l acetone of about 200 ..mu..l 4% formaldehyde in water twice weekly, resulted in two tumor-bearing animals, each with one small, benign papilloma. A group of 96 mice, treated once with 51.2 ..mu..g DMBA in acetone, developed a total of 107 tumors in 40 tumor-bearing animals. Thus, DMBA is a strong, complete tumorigen also in SENCAR mice. Animals given 51.2 ..mu..g DMBA first and then treated twice weekly with 1% formaldehyde developed a total of 30 tumors in 8 tumor-bearing animals, whereas mice given 51.2 ..mu..g DMBA first, followed by twice weekly treatment with 4% formaldehyde, developed 51 tumors in 15 animals. When two widely accepted, statistical methods were used, there was no significant difference between the groups treated once with DMBA alone and that treated once with DMBA followed by 4% formaldehyde. The results in SENCAR mice confirm that formaldehyde has no skin tumorigenic or carcinogenic potency of its own. It seems doubtful whether it may act as a very weak enhancer of DMBA-induced tumorigenesis, but it has no significant influence on DMBA-induced carcinogenesis.

  1. Service Lives Of Restored Bearings

    NASA Technical Reports Server (NTRS)

    Zaretsky, Erwin V.

    1988-01-01

    Rebuilt units last almost as long as new ones. Report describes theoretical and experiemental studies of lifetimes of restored ball and cylindrical-roller bearings. Results of this and related studies have implications of economy and safety in modern high-speed machinery, especially in aircraft industry, where inspection and rejection or replacing of bearings are new standard practice.

  2. Permanent-Magnet Meissner Bearing

    NASA Technical Reports Server (NTRS)

    Robertson, Glen A.

    1994-01-01

    Permanent-magnet meissner bearing features inherently stable, self-centering conical configuration. Bearing made stiffer or less stiff by selection of magnets, springs, and spring adjustments. Cylindrical permanent magnets with axial magnetization stacked coaxially on rotor with alternating polarity. Typically, rare-earth magnets used. Magnets machined and fitted together to form conical outer surface.

  3. High-Performance Ball Bearing

    NASA Technical Reports Server (NTRS)

    Bursey, Roger W., Jr.; Haluck, David A.; Olinger, John B.; Owen, Samuel S.; Poole, William E.

    1995-01-01

    High-performance bearing features strong, lightweight, self-lubricating cage with self-lubricating liners in ball apertures. Designed to operate at high speed (tens of thousands of revolutions per minute) in cryogenic environment like liquid-oxygen or liquid-hydrogen turbopump. Includes inner race, outer race, and cage keeping bearing balls equally spaced.

  4. Nonlinear control of magnetic bearings

    NASA Technical Reports Server (NTRS)

    Pradeep, A. K.; Gurumoorthy, R.

    1994-01-01

    In this paper we present a variety of nonlinear controllers for the magnetic bearing that ensure both stability and robustness. We utilize techniques of discontinuous control to design novel control laws for the magnetic bearing. We present in particular sliding mode controllers, time optimal controllers, winding algorithm based controllers, nested switching controllers, fractional controllers, and synchronous switching controllers for the magnetic bearing. We show existence of solutions to systems governed by discontinuous control laws, and prove stability and robustness of the chosen control laws in a rigorous setting. We design sliding mode observers for the magnetic bearing and prove the convergence of the state estimates to their true values. We present simulation results of the performance of the magnetic bearing subject to the aforementioned control laws, and conclude with comments on design.

  5. Geophagy by yellowstone grizzly bears

    USGS Publications Warehouse

    Mattson, D.J.; Green, G.I.; Swalley, R.

    1999-01-01

    We documented 12 sites in the Yellowstone ecosystem where grizzly bears (Ursus arctos horribilis) had purposefully consumed soil (an activity known as geophagy). We also documented soil in numerous grizzly bear feces. Geophagy primarily occurred at sites barren of vegetation where surficial geology had been modified by geothermal activity. There was no evidence of ungulate use at most sites. Purposeful consumption of soil by bears peaked first from March to May and again from August to October, synchronous with peaks in consumption of ungulate meat and mushrooms. Geophageous soils were distinguished from ungulate mineral licks and soils in general by exceptionally high concentrations of potassium (K) and high concentrations of magnesium (Mg) and sulphur (S). Our results do not support the hypotheses that bears were consuming soil to detoxify secondary compounds in grazed foliage, as postulated for primates, or to supplement dietary sodium, as known for ungulates. Our results suggest that grizzly bears could have been consuming soil as an anti-diarrheal.

  6. Effects of bearing cleaning and lube environment on bearing performance

    NASA Technical Reports Server (NTRS)

    Ward, Peter C.

    1995-01-01

    Running torque data of SR6 ball bearings are presented for different temperatures and speeds. The data are discussed in contrast to generally used torque prediction models and point out the need to obtain empirical data in critical applications. Also, the effects of changing bearing washing techniques from old, universally used CFC-based systems to CFC-free aqueous/alkaline solutions are discussed. Data on wettability, torque and lubricant life using SR3 ball bearings are presented. In general, performance is improved using the new aqueous washing techniques.

  7. Ontogeny of B lymphocytes. II. Relative rates of appearance of lymphocytes bearing surface immunoglobulin and complement receptors.

    PubMed

    Gelfand, M C; Elfenbein, G J; Frank, M M; Paul, W E

    1974-05-01

    Many bursa-equivalent (B) lymphocytes of adult mice bear surface Ig and receptors for C3. The frequency of Ig-bearing cells increases rapidly immediately after birth, but these cells lack complement (C) receptors. Lymphocytes bearing C receptors are not found in the spleens of BALB/c, DBA/2, and C57BL/6 mice until 2 wk of age and do not attain substantial numbers until 3-4 wk of age. In AKR mice, a lag between appearance of Ig-bearing and complement receptor lymphocytes (CRL) is also observed but it is of much shorter duration. AKR mice have a frequency of CRL at 2 wk of age of 28% in comparison to a frequency of 4.8% for DBA/2 mice. The difference in frequency between young and adult mice and between "low" and "high CRL" strains cannot be explained by a nonspecific inability to form rosettes as similar results are obtained with soluble antigen-antibody-complement complexes. Analysis of CRL frequency in (AKR x DBA/2)F(1) mice and F(1) x parental backcross progeny suggests that two independent genes control the rate of appearance of CRL. Furthermore, the genetic difference in the ontogeny of CRL is recapitulated in the repopulation of the B-lymphocyte line in adult-irradiated mice restored with syngeneic bone marrow. Thus, the "CRL genes" described here appear to control B-cell differentiation throughout life.

  8. Magnetic Bearings at Draper Laboratory

    NASA Technical Reports Server (NTRS)

    Kondoleon, Anthony S.; Kelleher, William P.; Possel, Peter D.

    1996-01-01

    Magnetic bearings, unlike traditional mechanical bearings, consist of a series of components mated together to form a stabilized system. The correct design of the actuator and sensor will provide a cost effective device with low power requirements. The proper choice of a control system utilizes the variables necessary to control the system in an efficient manner. The specific application will determine the optimum design of the magnetic bearing system including the touch down bearing. Draper for the past 30 years has been a leader in all these fields. This paper summarizes the results carried out at Draper in the field of magnetic bearing development. A 3-D radial magnetic bearing is detailed in this paper. Data obtained from recently completed projects using this design are included. One project was a high radial load (1000 pound) application. The second was a high speed (35,000 rpm), low loss flywheel application. The development of a low loss axial magnetic bearing is also included in this paper.

  9. 49 CFR 229.69 - Side bearings.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ....69 Side bearings. (a) Friction side bearings with springs designed to carry weight may not have more than 25 percent of the springs in any one nest broken. (b) Friction side bearings may not be run...

  10. 49 CFR 229.69 - Side bearings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ....69 Side bearings. (a) Friction side bearings with springs designed to carry weight may not have more than 25 percent of the springs in any one nest broken. (b) Friction side bearings may not be run...

  11. 49 CFR 229.69 - Side bearings.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ....69 Side bearings. (a) Friction side bearings with springs designed to carry weight may not have more than 25 percent of the springs in any one nest broken. (b) Friction side bearings may not be run...

  12. 49 CFR 229.69 - Side bearings.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ....69 Side bearings. (a) Friction side bearings with springs designed to carry weight may not have more than 25 percent of the springs in any one nest broken. (b) Friction side bearings may not be run...

  13. 49 CFR 229.69 - Side bearings.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ....69 Side bearings. (a) Friction side bearings with springs designed to carry weight may not have more than 25 percent of the springs in any one nest broken. (b) Friction side bearings may not be run...

  14. Cytotoxic T lymphocyte-dependent tumor growth inhibition by a vascular endothelial growth factor-superantigen conjugate

    SciTech Connect

    Sun, Qingwen; Jiang, Songmin; Han, Baohui; Sun, Tongwen; Li, Zhengnan; Zhao, Lina; Gao, Qiang; Sun, Jialin

    2012-11-02

    Highlights: Black-Right-Pointing-Pointer We construct and purify a fusion protein VEGF-SEA. Black-Right-Pointing-Pointer VEGF-SEA strongly repressed the growth of murine solid sarcoma 180 (S180) tumors. Black-Right-Pointing-Pointer T cells driven by VEGF-SEA were accumulated around tumor cells bearing VEGFR by mice image model. Black-Right-Pointing-Pointer VEGF-SEA can serve as a tumor targeting agent and sequester CTLs into the tumor site. Black-Right-Pointing-Pointer The induced CTLs could release the cytokines, perforins and granzyme B to kill the tumor cells. -- Abstract: T cells are major lymphocytes in the blood and passengers across the tumor vasculature. If these T cells are retained in the tumor site, a therapeutic potential will be gained by turning them into tumor-reactive cytotoxic T lymphocytes (CTLs). A fusion protein composed of human vascular endothelial growth factor (VEGF) and staphylococcal enterotoxin A (SEA) with a D227A mutation strongly repressed the growth of murine solid sarcoma 180 (S180) tumors (control versus VEGF-SEA treated with 15 {mu}g, mean tumor weight: 1.128 g versus 0.252 g, difference = 0.876 g). CD4{sup +} and CD8{sup +} T cells driven by VEGF-SEA were accumulated around VEGFR expressing tumor cells and the induced CTLs could release the tumoricidal cytokines, such as interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). Meanwhile, intratumoral CTLs secreted cytolytic pore-forming perforin and granzyme B proteins around tumor cells, leading to the death of tumor cells. The labeled fusion proteins were gradually targeted to the tumor site in an imaging mice model. These results show that VEGF-SEA can serve as a tumor targeting agent and sequester active infiltrating CTLs into the tumor site to kill tumor cells, and could therefore be a potential therapeutical drug for a variety of cancers.

  15. Bears, Big and Little. Young Discovery Library Series.

    ERIC Educational Resources Information Center

    Pfeffer, Pierre

    This book is written for children 5 through 10. Part of a series designed to develop their curiosity, fascinate them and educate them, this volume describes: (1) the eight species of bears, including black bear, brown bear, grizzly bear, spectacled bear, sun bear, sloth bear, polar bear, and giant panda; (2) geographical habitats of bears; (3)…

  16. Random bearings and their stability.

    PubMed

    Mahmoodi Baram, Reza; Herrmann, Hans J

    2005-11-25

    Self-similar space-filling bearings have been proposed some time ago as models for the motion of tectonic plates and appearance of seismic gaps. These models have two features which, however, seem unrealistic, namely, high symmetry in the arrangement of the particles, and lack of a lower cutoff in the size of the particles. In this work, an algorithm for generating random bearings in both two and three dimensions is presented. Introducing a lower cutoff for the sizes of the particles, the instabilities of the bearing under an external force such as gravity, are studied. PMID:16384225

  17. The Gut Microbiota Modulates Energy Metabolism in the Hibernating Brown Bear Ursus arctos.

    PubMed

    Sommer, Felix; Ståhlman, Marcus; Ilkayeva, Olga; Arnemo, Jon M; Kindberg, Jonas; Josefsson, Johan; Newgard, Christopher B; Fröbert, Ole; Bäckhed, Fredrik

    2016-02-23

    Hibernation is an adaptation that helps many animals to conserve energy during food shortage in winter. Brown bears double their fat depots during summer and use these stored lipids during hibernation. Although bears seasonally become obese, they remain metabolically healthy. We analyzed the microbiota of free-ranging brown bears during their active phase and hibernation. Compared to the active phase, hibernation microbiota had reduced diversity, reduced levels of Firmicutes and Actinobacteria, and increased levels of Bacteroidetes. Several metabolites involved in lipid metabolism, including triglycerides, cholesterol, and bile acids, were also affected by hibernation. Transplantation of the bear microbiota from summer and winter to germ-free mice transferred some of the seasonal metabolic features and demonstrated that the summer microbiota promoted adiposity without impairing glucose tolerance, suggesting that seasonal variation in the microbiota may contribute to host energy metabolism in the hibernating brown bear. PMID:26854221

  18. Mixed-mu superconducting bearings

    SciTech Connect

    Hull, John R.; Mulcahy, Thomas M.

    1998-01-01

    A mixed-mu superconducting bearing including a ferrite structure disposed for rotation adjacent a stationary superconductor material structure and a stationary permanent magnet structure. The ferrite structure is levitated by said stationary permanent magnet structure.

  19. Mixed-mu superconducting bearings

    SciTech Connect

    Hull, J.R.; Mulcahy, T.M.

    1998-03-03

    A mixed-mu superconducting bearing is disclosed including a ferrite structure disposed for rotation adjacent a stationary superconductor material structure and a stationary permanent magnet structure. The ferrite structure is levitated by said stationary permanent magnet structure. 9 figs.

  20. A Passive Magnetic Bearing Flywheel

    NASA Technical Reports Server (NTRS)

    Siebert, Mark; Ebihara, Ben; Jansen, Ralph; Fusaro, Robert L.; Morales, Wilfredo; Kascak, Albert; Kenny, Andrew

    2002-01-01

    A 100 percent passive magnetic bearing flywheel rig employing no active control components was designed, constructed, and tested. The suspension clothe rotor was provided by two sets of radial permanent magnetic bearings operating in the repulsive mode. The axial support was provided by jewel bearings on both ends of the rotor. The rig was successfully operated to speeds of 5500 rpm, which is 65 percent above the first critical speed of 3336 rpm. Operation was not continued beyond this point because of the excessive noise generated by the air impeller and because of inadequate containment in case of failure. Radial and axial stiffnesses of the permanent magnetic bearings were experimentally measured and then compared to finite element results. The natural damping of the rotor was measured and a damping coefficient was calculated.

  1. Flex bearing UUEC, volume 2

    NASA Technical Reports Server (NTRS)

    Clapper, M. L.

    1993-01-01

    This volume, Volume 2, of this Flex Bearing UUEC Final Report documents findings and data pertaining to Team B's tasks. Team B was organized as one of two sub-teams of the Unplanned/Unintended Event or Condition (UUEC) board established per InterOffice Memorandum (IOM) A100-FY93-072. Team A determined the cause of the unacceptable unbonds (referred to as 'heat-affect' unbonds), including the initial, light rust film, in the FSM #3 flex bearing was overheating of the Forward End Ring (FER) during cure, specifically in zone 8 of the mold. Team A's findings are documented in Volume 1 of this report. Team B developed flight rationale for existing bearings, based on absence or presence of an unpropitious unbond condition like that in FSM #3's flex bearing.

  2. Myrmecophagy by Yellowstone grizzly bears

    USGS Publications Warehouse

    Mattson, D.J.

    2001-01-01

    I used data collected during a study of radio-marked grizzly bears (Ursus arctos horribilis) in the Yellowstone region from 1977 to 1992 to investigate myrmecophagy by this population. Although generally not an important source of energy for the bears (averaging 8 mm long) nested in logs over small ants (6 mm long) nested under stones. Optimal conditions for consumption of ants occurred on the warmest sites with ample substrate suitable for ant nests. For ants in mounds, this occurred at low elevations at non-forested sites. For ants in logs, this occurred at low elevations or on southerly aspects where there was abundant, large-diameter, well-decomposed woody debris under an open forest canopy. Grizzly bears selected moderately decomposed logs 4a??5 dm in diameter at midpoint. Ants will likely become a more important food for Yellowstone's grizzly bears as currently important foods decline, owing to disease and warming of the regional climate.

  3. ATM CMG bearing failure analysis

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The cause or causes for the failure of ATM CMG S/N 5 (Skylab 1) and the anomalies associated with ATM CMG S/N 6 (Skylab 2) were investigated. Skylab telemetry data were reviewed and presented in the form of parameter distributions. The theory that the problems were caused by marginal bearing lubrication was studied along with the effects of orbital conditions on lubricants. Bearing tests were performed to investigate the effect of lubricant or lack of lubricant in the ATM CMG bearings and the dispersion and migration of the lubricant. The vacuum and weightless conditions of space were simulated in the bearing tests. Analysis of the results of the tests conducted points to inadequate lubrication as the predominant factor causing the failure of ATM CMG S/N 5 (Skylab 1) and the anomalies associated with ATM CMG S/N 6 (Skylab 2).

  4. Polyurethane retainers for ball bearings

    NASA Technical Reports Server (NTRS)

    Christy, R. I.

    1973-01-01

    Evaluation of a new ball bearing retainer material is reported. A special composite polyurethane foam ball retainer has been developed that has virtually zero wear, is chemically inert to hydrocarbon lubricants, and stores up to 60 times as much lubricant per unit volume as the most commonly used retainer material, cotton phenolic. This new retainer concept shows promise of years of ball bearing operation without reoiling, based on life testing in high vacuum.

  5. Lateral dampers for thrust bearings

    NASA Technical Reports Server (NTRS)

    Hibner, D. H.; Szafir, D. R.

    1985-01-01

    The development of lateral damping schemes for thrust bearings was examined, ranking their applicability to various engine classes, selecting the best concept for each engine class and performing an in-depth evaluation. Five major engine classes were considered: large transport, military, small general aviation, turboshaft, and non-manrated. Damper concepts developed for evaluation were: curved beam, constrained and unconstrained elastomer, hybrid boost bearing, hydraulic thrust piston, conical squeeze film, and rolling element thrust face.

  6. Designing Rolling-Element Bearings

    NASA Technical Reports Server (NTRS)

    Moore, James D., Jr.

    2007-01-01

    Bearing Analysis Tool (BAT) is a computer program for designing rolling-element bearings for cryogenic turbomachines. BAT provides a graphical user interface (GUI) that guides the entry of data to develop mathematical models of bearings. The GUI breaks model data into logical subsets that are entered through logic-driven input screens. The software generates a threedimensional graphical model of a bearing as the data are entered. Most dataentry errors become immediately obvious in the graphical model. BAT provides for storage of all the data on a shaft/bearing system, enabling the creation of a library of proven designs. Data from the library can be transferred to subsequent projects by use of simple cut-and-paste routines. BAT includes a library of temperature- dependent cryogenic bearing-material properties for use in the mathematical models. BAT implements algorithms that (1) enable the user to select combinations of design and/or operating-condition parameters, and then (2) automatically optimize the design by performing trade studies over all of the parameter combinations. This feature enables optimization over a large trade space in a fraction of the time taken when using prior bearingmodel software.

  7. SSME Long-life Bearings

    NASA Technical Reports Server (NTRS)

    Butner, M. F.; Murphy, B. T.

    1986-01-01

    Hybrid hydrostatic/ball bearings for LH2 and LO2 service in turbopumps were studied as a means of improving speed and life capabilities. Four hybrid bearing configurations were designed with emphasis on achieving maximum stiffness and damping. Parallel load bearings were tested at steady-state and transient conditions with LH2 (externally fed) and LN2 (internally fed). The hydrostatic elements were tested with Freon 113 for empirical determination of dynamic characteristics. Tests using an eccentric journal for loading showed the externally and internally fed hydrostatic bearings to have significant separated coefficients of direct stiffness and damping. For the internally fed bearing, the strongly speed-dependent cross-coupling stiffness arising from fluid swirl, along with significant cross-coupling damping, resulted in low net effective stiffness and damping. The test method used can produce separated coefficients with a sufficiently elliptic journal orbit; otherwise, only net effective coefficients combining direct and cross-coupling terms can be determined. Testing with nonsynchronous excitation is recommended to avoid this restriction. Investigation of hard materials, including ceramics, is recommended as a means of eliminating the need for the rolling bearing for startup and shutdown support. The testing was performed in 1984 (LH2), 1985 (LN2) and 1985-86 (Freon).

  8. Gimbal bearing design considerations and friction control

    NASA Technical Reports Server (NTRS)

    Kramer, N. R.

    1979-01-01

    The design considerations of bearing selection, bearing fits, bearing installation, and thermal control are discussed for a gimbal with a high stiffness, low friction torque requirement. Tradeoffs between a quad set of small diameter spread apart or a large diameter bearing pair resulted in a cleaner, lighter, stiffer unit with the latter selection. Bearing fits were designed to eliminate clearances with tolerances of .00127 mm 00005 in) on the bearing shafts and housings. The problems in metrology are discussed and a perferred technique for measurement of small cross-section bearings described. A technique for installation to assure proper seating of the bearing is offered. Where transient thermal conditions are involved, a method of controlling bearing friction by active control of bearing temperature gradients including the use of bearing unload test curves is described.

  9. Testing and Lubrication for Single Race Bearings

    SciTech Connect

    Steinhoff, R.G.

    1998-03-04

    Three ES and H-compatible lubricants (Environment, Safety and Health) for single race bearing applications and one hybrid-material single race bearings were evaluated and compared against single race bearings with trichlorotrifluoroethane (Freon) deposition of low molecular weight polytetrafluoroethylene (PTFE) bearing lubricant extracted from Vydax{trademark}. Vydax is a product manufactured by DuPont consisting of various molecular weights of PTFE suspended in trichlorotrifluoroethane (Freon), which is an ozone-depleting solvent. Vydax has been used as a bearing lubricant in stronglink mechanisms since 1974. Hybrid bearings with silicon nitride balls and molded glass-nylon-Teflon retainers, bearings lubricated with titanium carbide (TiC) on the balls, bearings lubricated with sputtered MoS{sub 2} on races and retainers, and bearings lubricated with electrophoretically deposited MoS{sub 2} were evaluated. The bearings were maintained in a preloaded state in bearing cartridges during cycling and vibration tests. Bearings with electrophoretically deposited MoS{sub 2} performed as well as bearings lubricated with Vydax and were the best performing candidate. All candidates were suitable for low preload applications. Bearings with TiC coated balls and bearings lubricated with sputtered MoS{sub 2} on the races and retainers performed well at high preloads, though not as well as bearings lubricated with electrophoretic deposition of MoS{sub 2}. Bearings with silicon nitride balls were not suitable for high preload applications.

  10. Bear reintroduction: Lessons and challenges

    USGS Publications Warehouse

    Clark, Joseph D.; Huber, Djuro; Servheen, Christopher

    2002-01-01

    Reintroduction is defined as an attempt to establish a species in an area that was once part of its historical range, but from which it has been extirpated or become extinct. Historically, one of the most successful programs was the reintroduction of 254 American black bears (Ursus americanus) from Minnesota to the Interior Highlands of Arkansas in the 1960s; that population has grown to >2,500 today. More recent efforts have involved fewer but better monitored animals and have sometimes employed techniques to improve site fidelity and survival. In Pennsylvania, for example, pregnant female American black bears were successfully translocated from winter dens, the premise being that the adult females would be less likely to return because of the presence of young cubs. That winter-release technique was compared to summer trapping and release in Tennessee; winter releases resulted in greater survival and reduced post-release movements. Homing has not been a problem for small numbers of brown bears (Ursus arctos) reintroduced to the Cabinet-Yaak ecosystem in Montana and Idaho and to the mountains of Austria and France. Reintroduction success appears to be correlated with translocation distance and is greater for subadults and females. As with any small population, reintroduced bear populations are susceptible to environmental variation and stochastic demographic and genetic processes. Although managers have focused on these biological barriers, sociopolitical impediments to bear reintroduction are more difficult to overcome. Poor public acceptance and understanding of bears are the main reasons some reintroduction programs have been derailed. Consequently, the public should be involved in the reintroduction process from the outset; overcoming negative public perceptions about bear reintroduction will be our greatest challenge.

  11. 36 CFR 13.1236 - Bear orientation.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Bear orientation. 13.1236... Developed Area § 13.1236 Bear orientation. All persons visiting the BCDA must receive an NPS-approved Bear Orientation. Failure to receive an NPS-approved Bear Orientation is prohibited....

  12. 36 CFR 13.1236 - Bear orientation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Bear orientation. 13.1236... Developed Area § 13.1236 Bear orientation. All persons visiting the BCDA must receive an NPS-approved Bear Orientation. Failure to receive an NPS-approved Bear Orientation is prohibited....

  13. 36 CFR 13.1236 - Bear orientation.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Bear orientation. 13.1236... Developed Area § 13.1236 Bear orientation. All persons visiting the BCDA must receive an NPS-approved Bear Orientation. Failure to receive an NPS-approved Bear Orientation is prohibited....

  14. 36 CFR 13.1236 - Bear orientation.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Bear orientation. 13.1236... Developed Area § 13.1236 Bear orientation. All persons visiting the BCDA must receive an NPS-approved Bear Orientation. Failure to receive an NPS-approved Bear Orientation is prohibited....

  15. 36 CFR 13.1236 - Bear orientation.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false Bear orientation. 13.1236... Developed Area § 13.1236 Bear orientation. All persons visiting the BCDA must receive an NPS-approved Bear Orientation. Failure to receive an NPS-approved Bear Orientation is prohibited....

  16. Hydrostatic liquid-bearing for precision gyro

    NASA Technical Reports Server (NTRS)

    Sgambati, R. J.

    1971-01-01

    Unit with 2W power increase and slightly larger overall dimensions performs as well as or better than its gas-bearing counterpart. Liquid-bearings are built by reworking serviceable gas-bearing components /sleeves, endplates, and cylinders/. Hydrostatic bearing is self-centered, requiring no magnetic suspension or centering jewel.

  17. Liquid oxygen cooled bearing ignition potential assessment

    NASA Technical Reports Server (NTRS)

    Page, Arthur T.; Goode, Brian K.; Owen, James W.

    1990-01-01

    Space Shuttle Main Engine High Pressure Oxygen Turbopump bearings have shown evidence of heavy oxidation on the surfaces of the balls and races. Extensive analyses were performed to assess the ignition potential in the bearing system during normal and off-nominal operation. Test programs and analyses were used to determine the bearing thermal condition and bearing material ignition characteristics.

  18. Hydrostatic bearings for a turbine fluid flow metering device

    DOEpatents

    Fincke, James R.

    1982-01-01

    A rotor assembly fluid metering device has been improved by development of a hydrostatic bearing fluid system which provides bearing fluid at a common pressure to rotor assembly bearing surfaces. The bearing fluid distribution system produces a uniform film of fluid between bearing surfaces and allows rapid replacement of bearing fluid between bearing surfaces, thereby minimizing bearing wear and corrosion.

  19. Hydrostatic bearings for a turbine fluid flow metering device

    DOEpatents

    Fincke, J.R.

    1982-05-04

    A rotor assembly fluid metering device has been improved by development of a hydrostatic bearing fluid system which provides bearing fluid at a common pressure to rotor assembly bearing surfaces. The bearing fluid distribution system produces a uniform film of fluid between bearing surfaces and allows rapid replacement of bearing fluid between bearing surfaces, thereby minimizing bearing wear and corrosion. 3 figs.

  20. Cryogenic Magnetic Bearing Test Facility (CMBTF)

    NASA Technical Reports Server (NTRS)

    1992-01-01

    The Cryogenic Magnetic Bearing Test Facility (CMBTF) was designed and built to evaluate compact, lightweight magnetic bearings for use in the SSME's (space shuttle main engine) liquid oxygen and liquid hydrogen turbopumps. State of the art and tradeoff studies were conducted which indicated that a hybrid permanent magnet bias homopolar magnetic bearing design would be smaller, lighter, and much more efficient than conventional industrial bearings. A test bearing of this type was designed for the test rig for use at both room temperature and cryogenic temperature (-320 F). The bearing was fabricated from state-of-the-art materials and incorporated into the CMBTF. Testing at room temperature was accomplished at Avcon's facility. These preliminary tests indicated that this magnetic bearing is a feasible alternative to older bearing technologies. Analyses showed that the hybrid magnetic bearing is one-third the weight, considerably smaller, and uses less power than previous generations of magnetic bearings.

  1. Superconductor bearings, flywheels and transportation

    NASA Astrophysics Data System (ADS)

    Werfel, F. N.; Floegel-Delor, U.; Rothfeld, R.; Riedel, T.; Goebel, B.; Wippich, D.; Schirrmeister, P.

    2012-01-01

    This paper describes the present status of high temperature superconductors (HTS) and of bulk superconducting magnet devices, their use in bearings, in flywheel energy storage systems (FESS) and linear transport magnetic levitation (Maglev) systems. We report and review the concepts of multi-seeded REBCO bulk superconductor fabrication. The multi-grain bulks increase the averaged trapped magnetic flux density up to 40% compared to single-grain assembly in large-scale applications. HTS magnetic bearings with permanent magnet (PM) excitation were studied and scaled up to maximum forces of 10 kN axially and 4.5 kN radially. We examine the technology of the high-gradient magnetic bearing concept and verify it experimentally. A large HTS bearing is tested for stabilizing a 600 kg rotor of a 5 kWh/250 kW flywheel system. The flywheel rotor tests show the requirement for additional damping. Our compact flywheel system is compared with similar HTS-FESS projects. A small-scale compact YBCO bearing with in situ Stirling cryocooler is constructed and investigated for mobile applications. Next we show a successfully developed modular linear Maglev system for magnetic train operation. Each module levitates 0.25t at 10 mm distance during one-day operation without refilling LN2. More than 30 vacuum cryostats containing multi-seeded YBCO blocks are fabricated and are tested now in Germany, China and Brazil.

  2. 'Dodo' and 'Baby Bear' Trenches

    NASA Technical Reports Server (NTRS)

    2008-01-01

    NASA's Phoenix Mars Lander's Surface Stereo Imager took this image on Sol 11 (June 5, 2008), the eleventh day after landing. It shows the trenches dug by Phoenix's Robotic Arm. The trench on the left is informally called 'Dodo' and was dug as a test. The trench on the right is informally called 'Baby Bear.' The sample dug from Baby Bear will be delivered to the Phoenix's Thermal and Evolved-Gas Analyzer, or TEGA. The Baby Bear trench is 9 centimeters (3.1 inches) wide and 4 centimeters (1.6 inches) deep.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  3. Magnetic bearings with zero bias

    NASA Technical Reports Server (NTRS)

    Brown, Gerald V.; Grodsinsky, Carlos M.

    1991-01-01

    A magnetic bearing operating without a bias field has supported a shaft rotating at speeds up to 12,000 rpm with the usual four power supplies and with only two. A magnetic bearing is commonly operated with a bias current equal to half of the maximum current allowable in its coils. This linearizes the relation between net force and control current and improves the force slewing rate and hence the band width. The steady bias current dissipates power, even when no force is required from the bearing. The power wasted is equal to two-thirds of the power at maximum force output. Examined here is the zero bias idea. The advantages and disadvantages are noted.

  4. Air bearing vacuum seal assembly

    DOEpatents

    Booth, Rex

    1978-01-01

    An air bearing vacuum seal assembly capable of rotating at the speed of several thousand revolutions per minute using an air cushion to prevent the rotating and stationary parts from touching, and a two stage differential pumping arrangement to maintain the pressure gradient between the air cushion and the vacuum so that the leak rate into the vacuum is, for example, less than 1 .times. 10.sup.-4 Pa m.sup.3 /s. The air bearing vacuum seal has particular application for mounting rotating targets to an evacuated accelerator beam tube for bombardment of the targets with high-power charged particle beams in vacuum.

  5. Wave Journal Bearing. Part 1: Analysis

    NASA Technical Reports Server (NTRS)

    Dimofte, Florin

    1995-01-01

    A wave journal bearing concept features a waved inner bearing diameter of the non-rotating bearing side and it is an alternative to the plain journal bearing. The wave journal bearing has a significantly increased load capacity in comparison to the plain journal bearing operating at the same eccentricity. It also offers greater stability than the plain circular bearing under all operating conditions. The wave bearing's design is relatively simple and allows the shaft to rotate in either direction. Three wave bearings are sensitive to the direction of an applied stationary side load. Increasing the number of waves reduces the wave bearing's sensitivity to the direction of the applied load relative to the wave. However, the range in which the bearing performance can be varied decreases as the number of waves increases. Therefore, both the number and the amplitude of the waves must be properly selected to optimize the wave bearing design for a specific application. It is concluded that the stiffness of an air journal bearing, due to hydrodynamic effect, could be doubled and made to run stably by using a six or eight wave geometry with a wave amplitude approximately half of the bearing radial clearance.

  6. Satellite monitoring of black bear.

    NASA Technical Reports Server (NTRS)

    Craighead, J. J.; Craighead, F. C., Jr.; Varney, J. R.; Cote, C. E.

    1971-01-01

    Description of a feasibility experiment recently performed to test the use of a satellite system for telemetering environmental and physiological data from the winter den of a 'hibernating' black bear, Ursus americanus. The instrumentation procedure and evaluations of the equipment performance and sensory data obtained are discussed in detail.

  7. We still need Smokey Bear!

    USGS Publications Warehouse

    Keeley, Jon E.

    2001-01-01

    It was gratifying to see articles in recent issues of Fire Management Today clarifying the role of Smokey Bear in wildland fire management strategies (Baily 1999; Brown 1999). These articles clearly spelled out Smokey’s importance in reducing unplanned human-ignited wildland fires and rightly criticized attempts to detract from Smokey’s campaign (Williams 1995; see also Vogl 1973).

  8. Intelligent Engine Systems: Bearing System

    NASA Technical Reports Server (NTRS)

    Singh, Arnant P.

    2008-01-01

    The overall requirements necessary for sensing bearing distress and the related criteria to select a particular rotating sensor were established during the phase I. The current phase II efforts performed studies to evaluate the Robustness and Durability Enhancement of the rotating sensors, and to design, and develop the Built-in Telemetry System concepts for an aircraft engine differential sump. A generic test vehicle that can test the proposed bearing diagnostic system was designed, developed, and built. The Timken Company, who also assisted with testing the GE concept of using rotating sensors for the differential bearing diagnostics during previous phase, was selected as a subcontractor to assist General Electric (GE) for the design, and procurement of the test vehicle. A purchase order was prepared to define the different sub-tasks, and deliverables for this task. The University of Akron was selected to provide the necessary support for installing, and integrating the test vehicle with their newly designed test facility capable of simulating the operating environment for the planned testing. The planned testing with good and damaged bearings will be on hold pending further continuation of this effort during next phase.

  9. Beth Starts Like Brown Bear!

    ERIC Educational Resources Information Center

    Fawcett, Gay

    1994-01-01

    Recounts a reading teacher's illuminating experience with a first grader who enjoyed reading Bill Martin's "Brown Bear" books, despite being labeled as dyslexic. Dyslexia is an elusive condition that is biological in origin and distinct from other reading problems. New research shows that reading difficulties, including dyslexia, occur as part of…

  10. Inserts Automatically Lubricate Ball Bearings

    NASA Technical Reports Server (NTRS)

    Hager, J. A.

    1983-01-01

    Inserts on ball-separator ring of ball bearings provide continuous film of lubricant on ball surfaces. Inserts are machined or molded. Small inserts in ball pockets provide steady supply of lubricant. Technique is utilized on equipment for which maintenance is often poor and lubrication interval is uncertain, such as household appliances, automobiles, and marine engines.

  11. The correct "ball bearings" data.

    PubMed

    Caroni, C

    2002-12-01

    The famous data on fatigue failure times of ball bearings have been quoted incorrectly from Lieblein and Zelen's original paper. The correct data include censored values, as well as non-fatigue failures that must be handled appropriately. They could be described by a mixture of Weibull distributions, corresponding to different modes of failure.

  12. Robust and intelligent bearing estimation

    SciTech Connect

    Claassen, J.P.

    1998-07-01

    As the monitoring thresholds of global and regional networks are lowered, bearing estimates become more important to the processes which associate (sparse) detections and which locate events. Current methods of estimating bearings from observations by 3-component stations and arrays lack both accuracy and precision. Methods are required which will develop all the precision inherently available in the arrival, determine the measurability of the arrival, provide better estimates of the bias induced by the medium, permit estimates at lower SNRs, and provide physical insight into the effects of the medium on the estimates. Initial efforts have focused on 3-component stations since the precision is poorest there. An intelligent estimation process for 3-component stations has been developed and explored. The method, called SEE for Search, Estimate, and Evaluation, adaptively exploits all the inherent information in the arrival at every step of the process to achieve optimal results. In particular, the approach uses a consistent and robust mathematical framework to define the optimal time-frequency windows on which to make estimates, to make the bearing estimates themselves, and to withdraw metrics helpful in choosing the best estimate(s) or admitting that the bearing is immeasurable. The approach is conceptually superior to current methods, particular those which rely on real values signals. The method has been evaluated to a considerable extent in a seismically active region and has demonstrated remarkable utility by providing not only the best estimates possible but also insight into the physical processes affecting the estimates. It has been shown, for example, that the best frequency at which to make an estimate seldom corresponds to the frequency having the best detection SNR and sometimes the best time interval is not at the onset of the signal. The method is capable of measuring bearing dispersion, thereby withdrawing the bearing bias as a function of frequency

  13. TOOL ASSEMBLY WITH BI-DIRECTIONAL BEARING

    DOEpatents

    Longhurst, G.E.

    1961-07-11

    A two-direction motion bearing which is incorporated in a refueling nuclear fuel element trsnsfer tool assembly is described. A plurality of bi- directional bearing assembliesare fixed equi-distantly about the circumference of the transfer tool assembly to provide the tool assembly with a bearing surface- for both axial and rotational motion. Each bi-directional bearing assembly contains a plurality of circumferentially bulged rollers mounted in a unique arrangement which will provide a bearing surface for rotational movement of the tool assembly within a bore. The bi-direc tional bearing assembly itself is capable of rational motion and thus provides for longitudinal movement of the tool assembly.

  14. Alaskan brown bears, humans, and habituation

    USGS Publications Warehouse

    Smith, Thomas; Herrero, Stephen; DeBruyn, Terry D.

    2005-01-01

    We present a new paradigm for understanding habituation and the role it plays in brown bear (Ursus arctos) populations and interactions with humans in Alaska. We assert that 3 forms of habituation occur in Alaska: bear-to-bear, bear-to-human, and human-to-bear. We present data that supports our theory that bear density is an important factor influencing a bear’s overt reaction distance (ORD); that as bear density increases, overt reaction distance decreases, as does the likelihood of bear– human interactions. We maintain that the effects of bear-to-bear habituation are largely responsible for not only shaping bear aggregations but also for creating the relatively safe environment for bear viewing experienced at areas where there are high densities of brown bears. By promoting a better understanding of the forces that shape bear social interactions within populations and with humans that mingle with them, we can better manage human activities and minimize bear–human conflict.

  15. Journal and Wave Bearing Impedance Calculation Software

    NASA Technical Reports Server (NTRS)

    Hanford, Amanda; Campbell, Robert

    2012-01-01

    The wave bearing software suite is a MALTA application that computes bearing properties for user-specified wave bearing conditions, as well as plain journal bearings. Wave bearings are fluid film journal bearings with multi-lobed wave patterns around the circumference of the bearing surface. In this software suite, the dynamic coefficients are outputted in a way for easy implementation in a finite element model used in rotor dynamics analysis. The software has a graphical user interface (GUI) for inputting bearing geometry parameters, and uses MATLAB s structure interface for ease of interpreting data. This innovation was developed to provide the stiffness and damping components of wave bearing impedances. The computational method for computing bearing coefficients was originally designed for plain journal bearings and tilting pad bearings. Modifications to include a wave bearing profile consisted of changing the film thickness profile given by an equation, and writing an algorithm to locate the integration limits for each fluid region. Careful consideration was needed to implement the correct integration limits while computing the dynamic coefficients, depending on the form of the input/output variables specified in the algorithm.

  16. Short-bearing approximation for full journal bearings

    NASA Technical Reports Server (NTRS)

    Ocvirk, F W

    1952-01-01

    A short-bearing approximation of pressure distribution in the oil film is presented which is an extension of the pressure-distribution function of Michell and Cardullo and includes end-leakage effects. Equations giving applied load, attitude angle, location and magnitude of peak film pressure, friction, and required oil flow rate as functions of the eccentricity ratio are also given. The capacity number, a basic non dimensional quantity resulting from this analysis is the product of the Sommerfeld number and the square of the length-diameter ratio. Curves determined by this analysis are compared with previously published experimental data and theoretical curves of Sommerfeld and Cameron and Wood. Conclusions reached indicate that this approximation is of practical value for analysis of short bearings.

  17. Mobile bearing and fixed bearing total knee arthroplasty.

    PubMed

    Capella, Marcello; Dolfin, Marco; Saccia, Francesco

    2016-04-01

    The mobile bearing (MB) concept in total knee arthroplasty (TKA) was developed as an alternative to fixed bearing (FB) implants in order to reduce wear and improve range of motion (ROM), especially focused on younger patients. Unfortunately, its theoretical advantages are still controversial. In this paper we exhibit a review of the more recent literature available comparing FB and MB designs in biomechanical and clinical aspects, including observational studies, clinical trials, national and international registries analyses, randomized controlled trials, meta-analyses and Cochrane reviews. Except for some minor aspects, none of the studies published so far has reported a significant improvement related to MBs regarding patient satisfaction, clinical, functional and radiological outcome or medium and long-term survivorship. Thus the presumed superiority of MBs over FBs appears largely inconsistent. The routine use of MB is not currently supported by adequate evidences; implant choice should be therefore made on the basis of other factors, including cost and surgeon experience. PMID:27162777

  18. Mobile bearing and fixed bearing total knee arthroplasty

    PubMed Central

    Dolfin, Marco; Saccia, Francesco

    2016-01-01

    The mobile bearing (MB) concept in total knee arthroplasty (TKA) was developed as an alternative to fixed bearing (FB) implants in order to reduce wear and improve range of motion (ROM), especially focused on younger patients. Unfortunately, its theoretical advantages are still controversial. In this paper we exhibit a review of the more recent literature available comparing FB and MB designs in biomechanical and clinical aspects, including observational studies, clinical trials, national and international registries analyses, randomized controlled trials, meta-analyses and Cochrane reviews. Except for some minor aspects, none of the studies published so far has reported a significant improvement related to MBs regarding patient satisfaction, clinical, functional and radiological outcome or medium and long-term survivorship. Thus the presumed superiority of MBs over FBs appears largely inconsistent. The routine use of MB is not currently supported by adequate evidences; implant choice should be therefore made on the basis of other factors, including cost and surgeon experience. PMID:27162777

  19. A Preliminary Foil Gas Bearing Performance Map

    NASA Technical Reports Server (NTRS)

    DellaCorte, Christopher; Radil, Kevin C.; Bruckner, Robert J.; Howard, S. Adam

    2006-01-01

    Recent breakthrough improvements in foil gas bearing load capacity, high temperature tribological coatings and computer based modeling have enabled the development of increasingly larger and more advanced Oil-Free Turbomachinery systems. Successful integration of foil gas bearings into turbomachinery requires a step wise approach that includes conceptual design and feasibility studies, bearing testing, and rotor testing prior to full scale system level demonstrations. Unfortunately, the current level of understanding of foil gas bearings and especially their tribological behavior is often insufficient to avoid developmental problems thereby hampering commercialization of new applications. In this paper, a new approach loosely based upon accepted hydrodynamic theory, is developed which results in a "Foil Gas Bearing Performance Map" to guide the integration process. This performance map, which resembles a Stribeck curve for bearing friction, is useful in describing bearing operating regimes, performance safety margins, the effects of load on performance and limiting factors for foil gas bearings.

  20. Rolling Element Bearing Stiffness Matrix Determination (Presentation)

    SciTech Connect

    Guo, Y.; Parker, R.

    2014-01-01

    Current theoretical bearing models differ in their stiffness estimates because of different model assumptions. In this study, a finite element/contact mechanics model is developed for rolling element bearings with the focus of obtaining accurate bearing stiffness for a wide range of bearing types and parameters. A combined surface integral and finite element method is used to solve for the contact mechanics between the rolling elements and races. This model captures the time-dependent characteristics of the bearing contact due to the orbital motion of the rolling elements. A numerical method is developed to determine the full bearing stiffness matrix corresponding to two radial, one axial, and two angular coordinates; the rotation about the shaft axis is free by design. This proposed stiffness determination method is validated against experiments in the literature and compared to existing analytical models and widely used advanced computational methods. The fully-populated stiffness matrix demonstrates the coupling between bearing radial, axial, and tilting bearing deflections.

  1. Happy Birthday Smokey Bear from Joe Acaba

    NASA Video Gallery

    Expedition 32 Flight Engineer Joe Acaba wishes Smokey Bear a Happy Birthday. For 68 years Smokey Bear has been promoting fire safety and prevention through the message, “Only You Can Prevent Wild...

  2. Stable isotopes to detect food-conditioned bears and to evaluate human-bear management

    USGS Publications Warehouse

    Hopkins, John B.; Koch, Paul L.; Schwartz, Charles C.; Ferguson, Jake M.; Greenleaf, Schuyler S.; Kalinowski, Steven T.

    2012-01-01

    We used genetic and stable isotope analysis of hair from free-ranging black bears (Ursus americanus) in Yosemite National Park, California, USA to: 1) identify bears that consume human food, 2) estimate the diets of these bears, and 3) evaluate the Yosemite human–bear management program. Specifically, we analyzed the isotopic composition of hair from bears known a priori to be food-conditioned or non-food-conditioned and used these data to predict whether bears with an unknown management status were food-conditioned (FC) or non-food-conditioned (NFC). We used a stable isotope mixing model to estimate the proportional contribution of natural foods (plants and animals) versus human food in the diets of FC bears. We then used results from both analyses to evaluate proactive (population-level) and reactive (individual-level) human–bear management, and discussed new metrics to evaluate the overall human–bear management program in Yosemite. Our results indicated that 19 out of 145 (13%) unknown bears sampled from 2005 to 2007 were food-conditioned. The proportion of human food in the diets of known FC bears likely declined from 2001–2003 to 2005–2007, suggesting proactive management was successful in reducing the amount of human food available to bears. In contrast, reactive management was not successful in changing the management status of known FC bears to NFC bears, or in reducing the contribution of human food to the diets of FC bears. Nine known FC bears were recaptured on 14 occasions from 2001 to 2007; all bears were classified as FC during subsequent recaptures, and human–bear management did not reduce the amount of human food in the diets of FC bears. Based on our results, we suggest Yosemite continue implementing proactive human–bear management, reevaluate reactive management, and consider removing problem bears (those involved in repeated bear incidents) from the population.

  3. Cartridge Bearing System for Space Applications

    NASA Technical Reports Server (NTRS)

    Kingsbury, Edward P.; Hanson, Robert A.; Jones, William R.; Mohr, Terry W.

    1999-01-01

    Conventional spin axis ball bearings have been unreliable in spacecraft, often failing by two heretofore uncontrolled processes: ball retainer instability and lubricant breakdown. The Space Cartridge Bearing System (SCBS) addresses each of these mechanisms directly, leading to a bearing system with absolute freedom from retainer instability and negligible lubricant degradation rate. The result is a reliable plug-in bearing cartridge with a definite design life.

  4. Research In Diagnosing Bearing Defects From Vibrations

    NASA Technical Reports Server (NTRS)

    Zoladz, T.; Earhart, E.; Fiorucci, T.

    1995-01-01

    Report describes research in bearing-defect signature analysis - use of vibration-signal analysis to diagnose defects in roller and ball bearings. Experiments performed on bearings in good condition and other bearings in which various parts scratched to provide known defects correlated with vibration signals. Experiments performed on highly instrumented motor-driven rotor assembly at speeds up to 10,050 r/min, using accelerometers, velocity probes, and proximity sensors mounted at various locations on assembly to measure vibrations.

  5. Human impacts on bear habitat use

    USGS Publications Warehouse

    Mattson, David J.

    1990-01-01

    : Human effects on bear habitat use are mediated through food biomass changes, bear tolerance of humans and their impacts, and human tolerance of bears. Large-scale changes in bear food biomass have been caused by conversion of wildlands and waterways to intensive human use, and by the introduction of exotic pathogens. Bears consume virtually all human foods that have been established in former wildlands, but bear use has been limited by access. Air pollution has also affected bear food biomass on a small scale and is likely to have major future impacts on bear habitat through climatic warming. Major changes in disturbance cycles and landscape mosaics wrought by humans have further altered temporal and spatial pulses of bear food production. These changes have brought short-term benefits in places, but have also added long-term stresses to most bear populations. Although bears tend to avoid humans, they will also use exotic and native foods in close proximity to humans. Subadult males and adult females are more often impelled to forage closer to humans because of their energetic predicament and because more secure sites are often preempted by adult males. Although male bears are typically responsible for most livestock predation, adult females and subadult males are more likely to be habituated to humans because they tend to forage closer to humans. Elimination of human-habituated bears predictably reduces effective carrying capacity and is more likely to be a factor in preserving bear populations where humans are present in moderate-to-high densities. If humans desire to preserve viable bear populations, they will either have to accept increased risk of injury associated with preserving habituated animals, or continue to crop habituated bears while at the same time preserving large tracts of wildlands free from significant human intrusion.

  6. Mercury in polar bears from Alaska

    SciTech Connect

    Lentfer, J.W.; Galster, W.A.

    1987-04-01

    Alaskan polar bear (Ursus maritimus) muscle and liver samples collected in 1972 were analyzed for total mercury. Bears north of Alaska had more mercury than bears west of Alaska. The only difference between young and adult animals was in the northern area where adults had more mercury in liver tissue than young animals. Levels were probably not high enough to be a serious threat to bears.

  7. Antitumor and immunomodulatory activity of a polysaccharide from fungus Coprinus comatus (Mull.:Fr.) Gray.

    PubMed

    Jiang, Xiao-Gang; Lian, Ming-Xue; Han, Yan; Lv, She-Min

    2013-07-01

    In our study, a water-soluble polysaccharide (CCPa-1) was successfully purified from the fruiting bodies of Coprinus comatus by DEAE-cellulose and Sepharose CL-6B column chromatography. The molecular weight was evaluated to be 53.6 kDa as determined by high performance size exclusion chromatography (HPSEC). Sugar composition analysis revealed that CCPa-1 consisted primarily of galactose, glucose and arabinose in a molar ratio of 6.6:1.2:2.2. CCPa-1 could not only inhibit the growth of sarcoma 180 (S180) tumor transplanted in mice, but also increase the relative spleen/thymus indexes and body weight of tumor bearing mice. Moreover, Con A- or LPS-induced splenocyte proliferation was also enhanced after CCPa-1 administration in tumor-bearing mice. Furthermore, CCPa-1 significantly enhanced the Con A- or LPS-induced splenocyte proliferation and increased the production of TNF-α and IL-2. All the data demonstrated that CCPa-1 had a potential application as natural antitumor agent with immunomodulatory activity.

  8. Thin film superconductor magnetic bearings

    DOEpatents

    Weinberger, Bernard R.

    1995-12-26

    A superconductor magnetic bearing includes a shaft (10) that is subject to a load (L) and rotatable around an axis of rotation, a magnet (12) mounted to the shaft, and a stator (14) in proximity to the shaft. The stator (14) has a superconductor thin film assembly (16) positioned to interact with the magnet (12) to produce a levitation force on the shaft (10) that supports the load (L). The thin film assembly (16) includes at least two superconductor thin films (18) and at least one substrate (20). Each thin film (18) is positioned on a substrate (20) and all the thin films are positioned such that an applied magnetic field from the magnet (12) passes through all the thin films. A similar bearing in which the thin film assembly (16) is mounted on the shaft (10) and the magnet (12) is part of the stator (14) also can be constructed.

  9. 14 CFR 29.623 - Bearing factors.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Bearing factors. 29.623 Section 29.623... STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction General § 29.623 Bearing factors. (a... subject to pounding or vibration, must have a bearing factor large enough to provide for the effects...

  10. 49 CFR 229.64 - Plain bearings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Plain bearings. 229.64 Section 229.64 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION....64 Plain bearings. A plain bearing box shall contain visible free oil and may not be cracked to...

  11. 14 CFR 25.623 - Bearing factors.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Bearing factors. 25.623 Section 25.623... STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction General § 25.623 Bearing factors. (a) Except... subject to pounding or vibration, must have a bearing factor large enough to provide for the effects...

  12. 14 CFR 23.623 - Bearing factors.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Bearing factors. 23.623 Section 23.623... Bearing factors. (a) Each part that has clearance (free fit), and that is subject to pounding or vibration, must have a bearing factor large enough to provide for the effects of normal relative motion. (b)...

  13. 14 CFR 27.623 - Bearing factors.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Bearing factors. 27.623 Section 27.623... STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction General § 27.623 Bearing factors. (a) Except... subject to pounding or vibration, must have a bearing factor large enough to provide for the effects...

  14. 14 CFR 25.623 - Bearing factors.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Bearing factors. 25.623 Section 25.623... STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction General § 25.623 Bearing factors. (a) Except... subject to pounding or vibration, must have a bearing factor large enough to provide for the effects...

  15. Cool Polar Bears: Dabbing on the Texture

    ERIC Educational Resources Information Center

    O'Connell, Jean

    2011-01-01

    In this article, the author describes how her second-graders created their cool polar bears. The students used the elements of shape and texture to create the bears. They used Monet's technique of dabbing paint so as to give the bear some texture on his fur.

  16. 14 CFR 23.623 - Bearing factors.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Bearing factors. 23.623 Section 23.623... Bearing factors. (a) Each part that has clearance (free fit), and that is subject to pounding or vibration, must have a bearing factor large enough to provide for the effects of normal relative motion. (b)...

  17. 49 CFR 229.64 - Plain bearings.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Plain bearings. 229.64 Section 229.64 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION....64 Plain bearings. A plain bearing box shall contain visible free oil and may not be cracked to...

  18. 14 CFR 27.623 - Bearing factors.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Bearing factors. 27.623 Section 27.623... STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction General § 27.623 Bearing factors. (a) Except... subject to pounding or vibration, must have a bearing factor large enough to provide for the effects...

  19. 14 CFR 29.623 - Bearing factors.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Bearing factors. 29.623 Section 29.623... STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction General § 29.623 Bearing factors. (a... subject to pounding or vibration, must have a bearing factor large enough to provide for the effects...

  20. 14 CFR 29.623 - Bearing factors.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Bearing factors. 29.623 Section 29.623... STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction General § 29.623 Bearing factors. (a... subject to pounding or vibration, must have a bearing factor large enough to provide for the effects...

  1. 14 CFR 29.623 - Bearing factors.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Bearing factors. 29.623 Section 29.623... STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction General § 29.623 Bearing factors. (a... subject to pounding or vibration, must have a bearing factor large enough to provide for the effects...

  2. 49 CFR 229.64 - Plain bearings.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Plain bearings. 229.64 Section 229.64 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION....64 Plain bearings. A plain bearing box shall contain visible free oil and may not be cracked to...

  3. 14 CFR 25.623 - Bearing factors.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Bearing factors. 25.623 Section 25.623... STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction General § 25.623 Bearing factors. (a) Except... subject to pounding or vibration, must have a bearing factor large enough to provide for the effects...

  4. 14 CFR 23.623 - Bearing factors.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Bearing factors. 23.623 Section 23.623... Bearing factors. (a) Each part that has clearance (free fit), and that is subject to pounding or vibration, must have a bearing factor large enough to provide for the effects of normal relative motion. (b)...

  5. 14 CFR 23.623 - Bearing factors.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Bearing factors. 23.623 Section 23.623... Bearing factors. (a) Each part that has clearance (free fit), and that is subject to pounding or vibration, must have a bearing factor large enough to provide for the effects of normal relative motion. (b)...

  6. 14 CFR 23.623 - Bearing factors.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Bearing factors. 23.623 Section 23.623... Bearing factors. (a) Each part that has clearance (free fit), and that is subject to pounding or vibration, must have a bearing factor large enough to provide for the effects of normal relative motion. (b)...

  7. 14 CFR 25.623 - Bearing factors.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Bearing factors. 25.623 Section 25.623... STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction General § 25.623 Bearing factors. (a) Except... subject to pounding or vibration, must have a bearing factor large enough to provide for the effects...

  8. 14 CFR 27.623 - Bearing factors.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Bearing factors. 27.623 Section 27.623... STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction General § 27.623 Bearing factors. (a) Except... subject to pounding or vibration, must have a bearing factor large enough to provide for the effects...

  9. 49 CFR 229.64 - Plain bearings.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Plain bearings. 229.64 Section 229.64 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION....64 Plain bearings. A plain bearing box shall contain visible free oil and may not be cracked to...

  10. 14 CFR 27.623 - Bearing factors.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Bearing factors. 27.623 Section 27.623... STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction General § 27.623 Bearing factors. (a) Except... subject to pounding or vibration, must have a bearing factor large enough to provide for the effects...

  11. 14 CFR 27.623 - Bearing factors.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Bearing factors. 27.623 Section 27.623... STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction General § 27.623 Bearing factors. (a) Except... subject to pounding or vibration, must have a bearing factor large enough to provide for the effects...

  12. 49 CFR 229.64 - Plain bearings.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Plain bearings. 229.64 Section 229.64 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION....64 Plain bearings. A plain bearing box shall contain visible free oil and may not be cracked to...

  13. 14 CFR 25.623 - Bearing factors.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Bearing factors. 25.623 Section 25.623... STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction General § 25.623 Bearing factors. (a) Except... subject to pounding or vibration, must have a bearing factor large enough to provide for the effects...

  14. 14 CFR 29.623 - Bearing factors.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Bearing factors. 29.623 Section 29.623... STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction General § 29.623 Bearing factors. (a... subject to pounding or vibration, must have a bearing factor large enough to provide for the effects...

  15. Passive Thermal Management of Foil Bearings

    NASA Technical Reports Server (NTRS)

    Bruckner, Robert J. (Inventor)

    2015-01-01

    Systems and methods for passive thermal management of foil bearing systems are disclosed herein. The flow of the hydrodynamic film across the surface of bearing compliant foils may be disrupted to provide passive cooling and to improve the performance and reliability of the foil bearing system.

  16. Magnetic bearings for vibration control

    NASA Technical Reports Server (NTRS)

    Schweitzer, G.

    1985-01-01

    A survey is presented on the research of the Institute of Mechanics of the ETH in the field of vibration control with magnetic bearings. It shows a method for modelling an elastic rotor so that it can be represented by a low order model amenable to control techniques. It deals with the control law and spill-over effects, and it also discusses experimental results for an active resonance damper.

  17. Fault Tolerant Homopolar Magnetic Bearings

    NASA Technical Reports Server (NTRS)

    Li, Ming-Hsiu; Palazzolo, Alan; Kenny, Andrew; Provenza, Andrew; Beach, Raymond; Kascak, Albert

    2003-01-01

    Magnetic suspensions (MS) satisfy the long life and low loss conditions demanded by satellite and ISS based flywheels used for Energy Storage and Attitude Control (ACESE) service. This paper summarizes the development of a novel MS that improves reliability via fault tolerant operation. Specifically, flux coupling between poles of a homopolar magnetic bearing is shown to deliver desired forces even after termination of coil currents to a subset of failed poles . Linear, coordinate decoupled force-voltage relations are also maintained before and after failure by bias linearization. Current distribution matrices (CDM) which adjust the currents and fluxes following a pole set failure are determined for many faulted pole combinations. The CDM s and the system responses are obtained utilizing 1D magnetic circuit models with fringe and leakage factors derived from detailed, 3D, finite element field models. Reliability results are presented vs. detection/correction delay time and individual power amplifier reliability for 4, 6, and 7 pole configurations. Reliability is shown for two success criteria, i.e. (a) no catcher bearing contact following pole failures and (b) re-levitation off of the catcher bearings following pole failures. An advantage of the method presented over other redundant operation approaches is a significantly reduced requirement for backup hardware such as additional actuators or power amplifiers.

  18. Bearing strength of lunar soil.

    NASA Technical Reports Server (NTRS)

    Jaffe, L. D.

    1971-01-01

    Bearing load vs penetration curves have been measured on a 1.3 g sample of lunar soil from the scoop of the Surveyor 3 soil mechanics surface sampler, using a circular indentor 2 mm in diameter. Measurements were made in an Earth laboratory, in air. This sample provided a unique opportunity to evaluate earlier, remotely controlled, in-situ measurements of lunar surface bearing properties. Bearing capacity, measured at a penetration equal to the indentor diameter, varied from 0.02-0.04 N/sq cm at bulk densities of 1.15 g/cu cm to 30-100 N/sq cm at 1.9 g/cu cm. Deformation was by compression directly below the indentor at bulk densities below 1.61 g/cu cm, by outward displacement at bulk densities over 1.62 g/cu cm. Preliminary comparison of in-situ remote measurements with those on returned material indicates good agreement if the lunar regolith at Surveyor 3 has a bulk density of 1.6 g/cu cm at 2.5 cm depth.

  19. Cannibalism and predation on black bears by grizzly bears in the Yellowstone ecosystem, 1975-1990

    USGS Publications Warehouse

    Mattson, D.J.; Knight, R.R.; Blanchard, B.M.

    1992-01-01

    We documented one instance of an adult male grizzly bear preying upon a black bear and four instances where circumstantial evidence suggested that grizzly bears (two cubs-of-the-year, one yearling female that was injured, and one adult male) had been preyed upon by conspecifics. We also examined feces of grizzly bears for bear remains. Remains of bears tended to be more common in spring feces and did not differ in frequency between early and late years of the study. Our observations generally support existing hypotheses concerning cannibalism among bears.

  20. Heuristic explanation of journal bearing instability

    NASA Technical Reports Server (NTRS)

    Crandall, S. H.

    1982-01-01

    A fluid-filled journal bearing is viewed as a powerful pump circulating fluid around the annular space between the journal and the bearing. A small whirling motion of the journal generates a wave of thickness variation progressing around the channel. The hypothesis that the fluid flow drives the whirl whenever the mean of the pumped fluid velocity is greater than the peripheral speed of the thickness variation wave is discussed and compared with other simple explanations of journal bearing instability. It is shown that for non-cavitation long bearings the hypothesis predicts instability onset correctly for unloaded bearings but gradually overpredicts the onset speed as the load is increased.

  1. Ball Bearing Analysis with the ORBIS Tool

    NASA Technical Reports Server (NTRS)

    Halpin, Jacob D.

    2016-01-01

    Ball bearing design is critical to the success of aerospace mechanisms. Key bearing performance parameters, such as load capability, stiffness, torque, and life all depend on accurate determination of the internal load distribution. Hence, a good analytical bearing tool that provides both comprehensive capabilities and reliable results becomes a significant asset to the engineer. This paper introduces the ORBIS bearing tool. A discussion of key modeling assumptions and a technical overview is provided. Numerous validation studies and case studies using the ORBIS tool are presented. All results suggest the ORBIS code closely correlates to predictions on bearing internal load distributions, stiffness, deflection and stresses.

  2. Chromatographic (TLC) differentiation of grizzly bear and black bear scats

    USGS Publications Warehouse

    Picton, Harold D.; Kendall, Katherine C.

    1994-01-01

    While past work concluded that thin-layer chromatography (TLC) was inadequate for the separation of grizzly (Ursus arctos horribilis) and black bear (U. americanus) scats, our study found differences adequate for species separation. A key was constructed using 19 of 40 data points recorded on each(N)=356 profiles of 178) know-species scat. Accuracy was best for late summer scats (94%). Methods for specimen preparation, analysis, and reading the TLC profiles are discussed. Factors involved in scat variation were tested.

  3. Foil bearing research at Penn State

    NASA Astrophysics Data System (ADS)

    Carpino, Marc

    1993-11-01

    Foil journal bearings consist of a compliant metal shell or foil which supports a rigid journal by means of a fluid film. Foil bearings are considered to be a potential alternative to rolling element or traditional rigid surface bearings in cryogenic turbomachinery applications. The prediction of foil bearing performance requires the coupled solution of the foil deflection and the fluid flow in the bearing clearance between the rotor and the foil. The investigations being conducted in the Department of Mechanical Engineering at Penn State are focused in three areas: theoretical prediction of steady state bearing performance, modeling of the dynamic bearing characteristics to determine performance in rotor systems, and experimental verification of analysis codes. The current status and results from these efforts will be discussed.

  4. Design review of fluid film bearing testers

    NASA Technical Reports Server (NTRS)

    Scharrer, Joseph K.

    1993-01-01

    The designs of three existing testers (Hybrid Bearing Tester, OTV Bearing Tester, and Long Life Bearing Tester) owned by NASA were reviewed for their capability to serve as a multi-purpose cryogenic fluid film bearing tester. The primary tester function is the validation of analytical predictions for fluid film bearing steady state and dynamic performance. Evaluation criteria were established for test bearing configurations, test fluids, instrumentation, and test objectives. Each tester was evaluated with respect to these criteria. A determination was made of design improvements which would allow the testers to meet the stated criteria. The cost and time required to make the design changes were estimated. A recommendation based on the results of this study was made to proceed with the Hybrid Bearing Tester.

  5. Wave Journal Bearings Under Dynamic Loads

    NASA Technical Reports Server (NTRS)

    Hendricks, Robert C.; Dimofte, Florin

    2002-01-01

    The dynamic behavior of the wave journal bearing was determined by running a three-wave bearing with an eccentrically mounted shaft. A transient analysis was developed and used to predict numerical data for the experimental cases. The three-wave journal bearing ran stably under dynamic loads with orbits well inside the bearing clearance. The orbits were almost circular and nearly free of the influence of, but dynamically dependent on, bearing wave shape. Experimental observations for both the absolute bearing-housing-center orbits and the relative bearing-housing-center-to-shaft-center orbits agreed well with the predictions. Moreover, the subsynchronous whirl motion generated by the fluid film was found experimentally and predicted theoretically for certain speeds.

  6. Lubrication for high load duplex bearings

    SciTech Connect

    Steinhoff, R.G.

    1997-08-01

    Three ES and H-compatible lubricants (Environment, Safety and Health) for high load duplex bearing applications were evaluated and compared against trichlorotrifluoroethane (Freon) deposition of low molecular weight polytetrafluoroethylene (PTFE) bearing lubricant extracted from Vydax{trademark}. Vydax is a product manufactured by DuPont consisting of various molecular weights of PTFE suspended in trichlorotrifluoroethane (Freon) which is an ozone-depleting solvent. Bearings with Supercritical CO{sub 2} deposition of PTFE extracted from Vydax AR/IPA, bearings with titanium carbide coated balls, and bearings with diamond-like carbon races and retainers were evaluated. Bearings with Supercritical CO{sub 2} deposition of PTFE from Vydax AR/IPA performed as well as bearings with Freon deposition of PTFE from Freon-based Vydax.

  7. Determination of ball bearing dynamic stiffness

    NASA Technical Reports Server (NTRS)

    Beatty, R. F.; Rowan, B. F.

    1982-01-01

    The dynamic radial stiffness characteristics of rolling element bearings are currently determined by analytical methods that have not been experimentally verified. These bearing data are vital to rotating machinery design integrity because accurate critical speeds and rotor stability predictions are highly dependent on the bearing stiffness. A tester was designed capable of controlling the bearing axial preload, speed, and rotor unbalance. The rotor and support structures were constructed to permit critical speeds that are predominantly determined by a 57 mm test bearing. A curve of calculated critical speed versus stiffness was used to determine the actual bearing stiffness from the empirical data. The results of extensive testing are used to verify analytical predictions, increase confidence in existing bearing computer programs, and to serve as a data base for efforts to correct these programs.

  8. Pratt and Whitney cryogenic turbopump bearing experience

    NASA Technical Reports Server (NTRS)

    Poole, W. E.; Bursey, R. W., Jr.

    1988-01-01

    Successful, reusable bearings require lubrication, traditionally, a transfer film from sacrificial cage wear. Early testing included materials screening programs to identify suitable cryogenic cage materials. A specially developed element tester that simulated the function of a ball bearing cage was used. Suitable materials must provide lubrication with an acceptably low wear rate, without abrading contacting surfaces. The most promising materials were tested in full scale bearings at speeds up to 4 MDN. Teflon, filled with 40 percent bronze powder, was the best performing material. A variety of bearings were designed and successfully tested in LH2 and LOX. Bearings with bronze filled Teflon cages were successfully tested for 150 hrs. In overload tests, the same design was tested for 5 hrs at maximum Hertz stresses above 450 ksi and an additional 5 hrs with a maximum Hertz stress exceeding 500 ksi. Four bearings were tested in LOX for 25 hrs, with a maximum time per bearing of 10 hrs.

  9. Genomic evidence of geographically widespread effect of gene flow from polar bears into brown bears.

    PubMed

    Cahill, James A; Stirling, Ian; Kistler, Logan; Salamzade, Rauf; Ersmark, Erik; Fulton, Tara L; Stiller, Mathias; Green, Richard E; Shapiro, Beth

    2015-03-01

    Polar bears are an arctic, marine adapted species that is closely related to brown bears. Genome analyses have shown that polar bears are distinct and genetically homogeneous in comparison to brown bears. However, these analyses have also revealed a remarkable episode of polar bear gene flow into the population of brown bears that colonized the Admiralty, Baranof and Chichagof islands (ABC islands) of Alaska. Here, we present an analysis of data from a large panel of polar bear and brown bear genomes that includes brown bears from the ABC islands, the Alaskan mainland and Europe. Our results provide clear evidence that gene flow between the two species had a geographically wide impact, with polar bear DNA found within the genomes of brown bears living both on the ABC islands and in the Alaskan mainland. Intriguingly, while brown bear genomes contain up to 8.8% polar bear ancestry, polar bear genomes appear to be devoid of brown bear ancestry, suggesting the presence of a barrier to gene flow in that direction. PMID:25490862

  10. Genomic evidence of geographically widespread effect of gene flow from polar bears into brown bears

    PubMed Central

    Cahill, James A; Stirling, Ian; Kistler, Logan; Salamzade, Rauf; Ersmark, Erik; Fulton, Tara L; Stiller, Mathias; Green, Richard E; Shapiro, Beth

    2015-01-01

    Polar bears are an arctic, marine adapted species that is closely related to brown bears. Genome analyses have shown that polar bears are distinct and genetically homogeneous in comparison to brown bears. However, these analyses have also revealed a remarkable episode of polar bear gene flow into the population of brown bears that colonized the Admiralty, Baranof and Chichagof islands (ABC islands) of Alaska. Here, we present an analysis of data from a large panel of polar bear and brown bear genomes that includes brown bears from the ABC islands, the Alaskan mainland and Europe. Our results provide clear evidence that gene flow between the two species had a geographically wide impact, with polar bear DNA found within the genomes of brown bears living both on the ABC islands and in the Alaskan mainland. Intriguingly, while brown bear genomes contain up to 8.8% polar bear ancestry, polar bear genomes appear to be devoid of brown bear ancestry, suggesting the presence of a barrier to gene flow in that direction. PMID:25490862

  11. Genomic evidence of geographically widespread effect of gene flow from polar bears into brown bears.

    PubMed

    Cahill, James A; Stirling, Ian; Kistler, Logan; Salamzade, Rauf; Ersmark, Erik; Fulton, Tara L; Stiller, Mathias; Green, Richard E; Shapiro, Beth

    2015-03-01

    Polar bears are an arctic, marine adapted species that is closely related to brown bears. Genome analyses have shown that polar bears are distinct and genetically homogeneous in comparison to brown bears. However, these analyses have also revealed a remarkable episode of polar bear gene flow into the population of brown bears that colonized the Admiralty, Baranof and Chichagof islands (ABC islands) of Alaska. Here, we present an analysis of data from a large panel of polar bear and brown bear genomes that includes brown bears from the ABC islands, the Alaskan mainland and Europe. Our results provide clear evidence that gene flow between the two species had a geographically wide impact, with polar bear DNA found within the genomes of brown bears living both on the ABC islands and in the Alaskan mainland. Intriguingly, while brown bear genomes contain up to 8.8% polar bear ancestry, polar bear genomes appear to be devoid of brown bear ancestry, suggesting the presence of a barrier to gene flow in that direction.

  12. Development and Evaluation of Titanium Spacesuit Bearings

    NASA Technical Reports Server (NTRS)

    Rhodes, Richard; Battisti, Brian; Ytuarte, Raymond, Jr.; Schultz, Bradley

    2016-01-01

    The Z-2 Prototype Planetary Extravehicular Space Suit Assembly is a continuation of NASA's Z-series of spacesuits, designed with the intent of meeting a wide variety of exploration mission objectives, including human exploration of the Martian surface. Incorporating titanium bearings into the Z-series space suit architecture allows us to reduce mass by an estimated 23 lbs per suit system compared to the previously used stainless steel bearing race designs, without compromising suit functionality. There are two obstacles to overcome when using titanium for a bearing race- 1) titanium is flammable when exposed to the oxygen wetted environment inside the space suit and 2) titanium's poor wear properties are often challenging to overcome in tribology applications. In order to evaluate the ignitability of a titanium space suit bearing, a series of tests were conducted at White Sands Test Facility (WSTF) that introduced the bearings to an extreme test profile, with multiple failures imbedded into the test bearings. The testing showed no signs of ignition in the most extreme test cases; however, substantial wear of the bearing races was observed. In order to design a bearing that can last an entire exploration mission (approx. 3 years), design parameters for maximum contact stress need to be identified. To identify these design parameters, bearing test rigs were developed that allow for the quick evaluation of various bearing ball loads, ball diameters, lubricants, and surface treatments. This test data will allow designers to minimize the titanium bearing mass for a specific material and lubricant combination and design around a cycle life requirement for an exploration mission. This paper reviews the current research and testing that has been performed on titanium bearing races to evaluate the use of such materials in an enriched oxygen environment and to optimize the bearing assembly mass and tribological properties to accommodate for the high bearing cycle life for an

  13. Use of nude mice in experimental neutron capture therapy with 10B-BPA

    SciTech Connect

    Tamaoki, N.; Ueda, M.; Tamauchi, S.; Yamamoto, K.; Mishima, Y. )

    1989-07-01

    Mouse B16 melanoma allografts in nude mice were successfully treated by thermal neutron irradiation after IP injection of 10B-paraboronophenylalanine hydrochloride. The tumor growth was significantly suppressed for 4 weeks after irradiation, compared with animals given neutron irradiation alone. Tumor-bearing nude mice were shown to be useful for evaluating the treatment for melanoma.

  14. Hydrostatic bearings for a turbine fluid flow metering device

    DOEpatents

    Fincke, J.R.

    1980-05-02

    A rotor assembly fluid metering device has been improved by development of a hydrostatic bearing fluid system which provides bearing fluid at a common pressure to rotor assembly bearing surfaces. The bearing fluid distribution system produces a uniform film of fluid distribution system produces a uniform film of fluid between bearing surfaces and allows rapid replacement of bearing fluid between bearing surfaces, thereby minimizing bearing wear and corrosion.

  15. Restoration of Immune Responsiveness to Glioma by Vaccination of Mice with Established Brain Gliomas with a Semi-Allogeneic Vaccine.

    PubMed

    Gattoni-Celli, Sebastiano; Young, M Rita I

    2016-01-01

    Prior studies had shown the clinical efficacy of a semi-allogeneic glioma vaccine in mice with lethal GL261 gliomas. This was confirmed in the present study. As subcutaneous vaccination resulted in protection against tumor in the brain, the present study assessed the impact of this vaccination of mice bearing established GL261 brain gliomas on their cytokine production upon in vitro exposure to tumor-derived products. Mice with established GL261 brain gliomas were vaccinated subcutaneously with H-2(b) GL261 glioma cells fused with H-2(d) RAG-neo cells or with a mock vaccine of phosphate-buffered saline. The results of these analyses show that the presence of GL261 tumor-conditioned medium resulted in increased production of Th1, inflammatory and inhibitory cytokines by spleen cells from control mice and from vaccinated glioma-bearing mice. In contrast, spleen cells of tumor-bearing, mock-vaccinated mice produced lower levels of cytokines in the presence of tumor-conditioned media. However, these results also show that there was not a heightened level of cytokine production in the presence of tumor-conditioned medium by spleen cells of vaccinated mice over the production by spleen cells of control mice. Overall, these results show that vaccination slows growth of the GL261 tumors to the point where GL261-vaccinated mice do not show the signs of morbidly or splenic dysfunction exhibited by unvaccinated, late stage glioma-bearing mice. PMID:27598146

  16. Restoration of Immune Responsiveness to Glioma by Vaccination of Mice with Established Brain Gliomas with a Semi-Allogeneic Vaccine

    PubMed Central

    Gattoni-Celli, Sebastiano; Young, M. Rita I.

    2016-01-01

    Prior studies had shown the clinical efficacy of a semi-allogeneic glioma vaccine in mice with lethal GL261 gliomas. This was confirmed in the present study. As subcutaneous vaccination resulted in protection against tumor in the brain, the present study assessed the impact of this vaccination of mice bearing established GL261 brain gliomas on their cytokine production upon in vitro exposure to tumor-derived products. Mice with established GL261 brain gliomas were vaccinated subcutaneously with H-2b GL261 glioma cells fused with H-2d RAG-neo cells or with a mock vaccine of phosphate-buffered saline. The results of these analyses show that the presence of GL261 tumor-conditioned medium resulted in increased production of Th1, inflammatory and inhibitory cytokines by spleen cells from control mice and from vaccinated glioma-bearing mice. In contrast, spleen cells of tumor-bearing, mock-vaccinated mice produced lower levels of cytokines in the presence of tumor-conditioned media. However, these results also show that there was not a heightened level of cytokine production in the presence of tumor-conditioned medium by spleen cells of vaccinated mice over the production by spleen cells of control mice. Overall, these results show that vaccination slows growth of the GL261 tumors to the point where GL261-vaccinated mice do not show the signs of morbidly or splenic dysfunction exhibited by unvaccinated, late stage glioma-bearing mice. PMID:27598146

  17. Precision magnetic suspension linear bearing

    NASA Technical Reports Server (NTRS)

    Trumper, David L.; Queen, Michael A.

    1992-01-01

    We have shown the design and analyzed the electromechanics of a linear motor suitable for independently controlling two suspension degrees of freedom. This motor, at least on paper, meets the requirements for driving an X-Y stage of 10 Kg mass with about 4 m/sq sec acceleration, with travel of several hundred millimeters in X and Y, and with reasonable power dissipation. A conceptual design for such a stage is presented. The theoretical feasibility of linear and planar bearings using single or multiple magnetic suspension linear motors is demonstrated.

  18. Monitoring grizzly bear population trends

    USGS Publications Warehouse

    Eberhardt, L.L.; Knight, R.R.; Blanchard, B.M.

    1986-01-01

    A simple different equation model was developed to provide additional perspective on observed mortality and trend data on Yellowstone grizzly bears (Ursus arctos horribilis). Records of mortalities of adult females from 1959 to 1985 were utilized, in conjunction with data on females with cubs. The overall downward trend of observed numbers of females with cubs generally agrees with the model calculations but does not adequately reflect mortality from 1970 to 1974. The model may be useful in developing a composite index of population trend.

  19. Anti-metastatic effects of the sulfated polysaccharide ascophyllan isolated from Ascophyllum nodosum on B16 melanoma.

    PubMed

    Abu, Ryogo; Jiang, Zedong; Ueno, Mikinori; Isaka, Shogo; Nakazono, Satoru; Okimura, Takasi; Cho, Kichul; Yamaguchi, Kenichi; Kim, Daekyung; Oda, Tatsuya

    2015-03-20

    We previously found that ascophyllan, a sulfated polysaccharide isolated from brown seaweed Ascophyllum nodosum, exhibited antitumor activity in sarcoma-180 tumor-bearing mice. In this study, we found that ascophyllan inhibited the migration and adhesion of B16 melanoma cells by reducing the expression of N-cadherin and enhancing the expression of E-cadherin in a concentration-dependent manner. Transwell invasion assay revealed that ascophyllan suppressed the invasion ability of B16 cells. It also inhibited the expression of matrix metalloprotease-9 (MMP-9) mRNA and the secretion of MMP-9 protein in B16 cells, a process that may involve the extracellular signal-regulated kinase (ERK) signaling pathway. Furthermore, ascophyllan administered intraperitoneally at 25 mg/kg showed anti-metastatic activity in a mouse model of metastasis induced by intravenous injection of B16 cells, and the number of lung surface metastatic nodules in ascophyllan-treated mice was significantly reduced compared to that in the untreated control mice. Since splenic natural killer cell activity enhanced in the mice injected with ascophyllan intraperitoneally, we suggest that ascophyllan may exhibit in vivo anti-metastatic activity on B16 melanoma cells through activation of the host immune system in addition to a direct action on cancer cells.

  20. Anti-metastatic effects of the sulfated polysaccharide ascophyllan isolated from Ascophyllum nodosum on B16 melanoma.

    PubMed

    Abu, Ryogo; Jiang, Zedong; Ueno, Mikinori; Isaka, Shogo; Nakazono, Satoru; Okimura, Takasi; Cho, Kichul; Yamaguchi, Kenichi; Kim, Daekyung; Oda, Tatsuya

    2015-03-20

    We previously found that ascophyllan, a sulfated polysaccharide isolated from brown seaweed Ascophyllum nodosum, exhibited antitumor activity in sarcoma-180 tumor-bearing mice. In this study, we found that ascophyllan inhibited the migration and adhesion of B16 melanoma cells by reducing the expression of N-cadherin and enhancing the expression of E-cadherin in a concentration-dependent manner. Transwell invasion assay revealed that ascophyllan suppressed the invasion ability of B16 cells. It also inhibited the expression of matrix metalloprotease-9 (MMP-9) mRNA and the secretion of MMP-9 protein in B16 cells, a process that may involve the extracellular signal-regulated kinase (ERK) signaling pathway. Furthermore, ascophyllan administered intraperitoneally at 25 mg/kg showed anti-metastatic activity in a mouse model of metastasis induced by intravenous injection of B16 cells, and the number of lung surface metastatic nodules in ascophyllan-treated mice was significantly reduced compared to that in the untreated control mice. Since splenic natural killer cell activity enhanced in the mice injected with ascophyllan intraperitoneally, we suggest that ascophyllan may exhibit in vivo anti-metastatic activity on B16 melanoma cells through activation of the host immune system in addition to a direct action on cancer cells. PMID:25623538

  1. Current Status of Hybrid Bearing Damage Detection

    NASA Technical Reports Server (NTRS)

    Dempsey, Paula J.; Certo, Joseph M.; Morales, Wilfredo

    2004-01-01

    Advances in material development and processing have led to the introduction of ceramic hybrid bearings for many applications. The introduction of silicon nitride hybrid bearings into the high pressure oxidizer turbopump, on the space shuttle main engine, led NASA to solve a highly persistent and troublesome bearing problem. Hybrid bearings consist of ceramic balls and steel races. The majority of hybrid bearings utilize Si3N4 balls. The aerospace industry is currently studying the use of hybrid bearings and naturally the failure modes of these bearings become an issue in light of the limited data available. In today s turbine engines and helicopter transmissions, the health of the bearings is detected by the properties of the debris found in the lubrication line when damage begins to occur. Current oil debris sensor technology relies on the magnetic properties of the debris to detect damage. Since the ceramic rolling elements of hybrid bearings have no metallic properties, a new sensing system must be developed to indicate the system health if ceramic components are to be safely implemented in aerospace applications. The ceramic oil debris sensor must be capable of detecting ceramic and metallic component damage with sufficient reliability and forewarning to prevent a catastrophic failure. The objective of this research is to provide a background summary on what is currently known about hybrid bearing failure modes and to report preliminary results on the detection of silicon nitride debris, in oil, using a commercial particle counter.

  2. Turbocharger bearing retention and lubrication system

    SciTech Connect

    Gutknecht, D.A.

    1991-12-31

    This patent describes exhausts gas driven turbocharger. It comprises a housing, a shaft within the housing having a longitudinal axis of rotation and a pair of ends, a compressor wheel mounted within the housing on one end of the shaft for rotation therewith, a turbine wheel mounted within the housing on the other end of the shaft for rotation therewith, means for communicating air to the compressor wheel, means for communicating exhaust gas to the turbine wheel to cause the latter to rotate the shaft and the compressor wheel mounted thereon to compress the air communicated to the compressor wheel, and bearing means mounting the shaft for rotation relative to the housing, the bearing means including a bearing outer ring, a bearing inner ring, and ball bearing elements supporting the bearing outer ring on the bearing inner ring, a bearing locating aperture in the bearing outer ring, and an elongated bearing location pin having a longitudinal axis of symmetry extending transversely to the longitudinal axis of the shaft.

  3. Interference Fit Life Factors for Roller Bearings

    NASA Technical Reports Server (NTRS)

    Oswald, Fred B.; Zaretsky, Erwin V.; Poplawski, Joseph V.

    2008-01-01

    The effect of hoop stresses in reducing cylindrical roller bearing fatigue life was determined for various classes of inner ring interference fit. Calculations were performed for up to seven interference fit classes for each of ten bearing sizes. Each fit was taken at tightest, average and loosest values within the fit class for RBEC-5 tolerance, thus requiring 486 separate analyses. The hoop stresses were superimposed on the Hertzian principal stresses created by the applied radial load to calculate roller bearing fatigue life. The method was developed through a series of equations to calculate the life reduction for cylindrical roller bearings based on interference fit. All calculated lives are for zero initial bearing internal clearance. Any reduction in bearing clearance due to interference fit was compensated by increasing the initial (unmounted) clearance. Results are presented as tables and charts of life factors for bearings with light, moderate and heavy loads and interference fits ranging from extremely light to extremely heavy and for bearing accuracy class RBEC 5 (ISO class 5). Interference fits on the inner bearing ring of a cylindrical roller bearing can significantly reduce bearing fatigue life. In general, life factors are smaller (lower life) for bearings running under light load where the unfactored life is highest. The various bearing series within a particular bore size had almost identical interference fit life factors for a particular fit. The tightest fit at the high end of the RBEC-5 tolerance band defined in ANSI/ABMA shaft fit tables produces a life factor of approximately 0.40 for an inner-race maximum Hertz stress of 1200 MPa (175 ksi) and a life factor of 0.60 for an inner-race maximum Hertz stress of 2200 MPa (320 ksi). Interference fits also impact the maximum Hertz stress-life relation.

  4. Of Mice & Men: Advancements in the Understanding of Down Syndrome

    ERIC Educational Resources Information Center

    Silverman, Wayne

    2007-01-01

    Mice have become the model of choice for studies of Down syndrome due to the fact that mouse chromosome 16 bears a striking resemblance to human chromosome 21. This has allowed researchers to create various mouse models of Down syndrome, but this is a tricky business on many levels. Great expertise is required to manipulate DNA to create these…

  5. Prospects for Yellowstone grizzly bears

    USGS Publications Warehouse

    Knight, R.R.; Eberhardt, L.L.

    1987-01-01

    Recent analyses of data on the grizzly bear (Ursus arctos horribilis) population of Yellowstone National Park and its environs suggest the likelihood of a continuing decline in numbers if losses of fully adult females are not reduced. The size of the population is not known, and a simple projection model has been used to identify some inconsistencies in the available index data. Population dynamics calculations, based on Lotka's equation or a stochastic model, indicate a continuing decrease in numbers, although continued observations through radio-telemetry are needed to verify these trends. The margin between stabilizing the population and a continued decrease appears to be roughly the loss of 2 fully adult female bears per year. At present, the risk of extirpation of this population over the next 30 years appears to be small. Continued monitoring of survivorship will be needed, particularly because "recovery" of the population may be mainly characterized by a shift in the pattern of mortality, from adults to subadults, and not necessarily a reduction in absolute number of losses.

  6. Rolling bearing stiffness in arbitrary direction

    NASA Astrophysics Data System (ADS)

    Luo, Zhusan; Sun, Xinde; Wu, Linfeng

    1992-06-01

    This paper presents a new concept of rolling bearing stiffness in arbitrary direction, which is necessary to the investigation of rotor-bearing dynamics. It includes the axial stiffness and the arbitrary radial stiffness of the rolling bearing. Based on elasticity theory and the geometrical parameters of the bearing, the approximate formulas of the axial stiffness, the arbitrary radial stiffness, and the inner ring displacements are derived. Furthermore, the paper also discusses the effects of the loads, the radial clearance, and the load distribution parameters on the rolling bearing stiffness. In order to verify the model and the computer program, an example of a ball bearing is analyzed in detail. It shows that the model and the program are reliable and the results are consistent with the data supplied by the U.S. Air Force Aeropropulsion Laboratory.

  7. Magnetic bearings-state of the art

    NASA Technical Reports Server (NTRS)

    Fleming, David P.

    1991-01-01

    Magnetic bearings have existed for many years, at least in theory. Earnshaw's theorem, formulated in 1842, concerns stability of magnetic suspensions, and states that not all axes of a bearing can be stable without some means of active control. In Beam's widely referenced experiments, a tiny (1/64 in diameter) rotor was rotated to the astonishing speed of 800,000 rps while it was suspended in a magnetic field. Despite a long history, magnetic bearings have only begun to see practical application since about 1980. The development that finally made magnetic bearings practical was solid state electronics, enabling power supplies and controls to be reduced in size to where they are now comparable in volume to the bearings themselves. An attempt is made to document the current (1991) state of the art of magnetic bearings. The referenced papers are large drawn from two conferences publications published in 1988 and 1990 respectively.

  8. Two High-Temperature Foil Journal Bearings

    NASA Technical Reports Server (NTRS)

    Zak, Michail

    2006-01-01

    An enlarged, high-temperature-compliant foil bearing has been built and tested to demonstrate the feasibility of such bearings for use in aircraft gas turbine engines. Foil bearings are attractive for use in some machines in which (1) speeds of rotation, temperatures, or both exceed maximum allowable values for rolling-element bearings; (2) conventional lubricants decompose at high operating temperatures; and/or (3) it is necessary or desirable not to rely on conventional lubrication systems. In a foil bearing, the lubricant is the working fluid (e.g., air or a mixture of combustion gases) in the space between the journal and the shaft in the machine in which the bearing is installed.

  9. Magnetic Bearings for Inertial Energy Storage

    NASA Technical Reports Server (NTRS)

    Studer, P. A.

    1983-01-01

    The selection of a noncontacting bearing technique with no wear out phenomena and which is vacuum compatible which is the decisive factor in selecting magnetic bearings for kinetic energy storage was investigated. Unlimited cycle life without degradation is a primary goal. Storage efficiency is a key parameter which is defined as the ratio of the energy remaining to energy stored after a fixed time interval at no load conditions. Magnetic bearings, although noncontacting, are not perfectly frictionless in that magnetic losses due to eddy currents and hysteresis can occur. Practical magnetic bearings, however, deviate from perfect symmetry and have discontinuities and asymmetric flux paths either by design or when controlled in the presence of disturbances, which cause losses. These losses can be kept smaller in the bearings than in a high power motor/generator, however, are a significant factor in selecting the magnetic bearing type.

  10. Magnetic bearings - State of the art

    NASA Astrophysics Data System (ADS)

    Fleming, David P.

    Magnetic bearings have existed for many years, at least in theory. Earnshaw's theorem, formulated in 1842, concerns stability of magnetic suspensions, and states that not all axes of a bearing can be stable without some means of active control. In Beam's widely referenced experiments, a tiny (1/64 in diameter) rotor was rotated to the astonishing speed of 800,000 rps while it was suspended in a magnetic field. Despite a long history, magnetic bearings have only begun to see practical application since about 1980. The development that finally made magnetic bearings practical was solid state electronics, enabling power supplies and controls to be reduced in size to where they are now comparable in volume to the bearings themselves. An attempt is made to document the current (1991) state of the art of magnetic bearings. The referenced papers are large drawn from two conferences publications published in 1988 and 1990 respectively.

  11. Cryogenic Fluid Film Bearing Tester Development Study

    NASA Technical Reports Server (NTRS)

    Scharrer, Joseph K. (Editor); Murphy, Brian T.; Hawkins, Lawrence A.

    1993-01-01

    Conceptual designs were developed for the determination of rotordynamic coefficients of cryogenic fluid film bearings. The designs encompassed the use of magnetic and conventional excitation sources as well as the use of magnetic bearings as support bearings. Test article configurations reviewed included overhung, floating housing, and fixed housing. Uncertainty and forced response analyses were performed to assess quality of data and suitability of each for testing a variety of fluid film bearing designs. Development cost and schedule estimates were developed for each design. Facility requirements were reviewed and compared with existing MSFC capability. The recommended configuration consisted of a fixed test article housing centrally located between two magnetic bearings. The magnetic bearings would also serve as the excitation source.

  12. Effects of climate change on polar bears.

    PubMed

    Wiig, Øystein; Aars, Jon; Born, Erik W

    2008-01-01

    In this article, we review the effects on polar bears of global warming that have already been observed, and try to evaluate what may happen to the polar bears in the future. Many researchers have predicted a wide range of impacts of climate change on polar bear demography and conditions. A predicted major reduction in sea ice habitat will reduce the availability of ice associated seals, the main prey of polar bears, and a loss and fragmentation of polar bear habitat will ultimately lead to large future reductions in most subpopulations. It is likely that polar bears will be lost from many areas where they are common today and also that the total population will change into a few more distinctly isolated populations.

  13. Powder-Metallurgical Bearings For Turbopumps

    NASA Technical Reports Server (NTRS)

    Bhat, B. N.; Humphries, T. S.; Thom, R. L.; Moxson, V.; Friedman, G. I.; Dolan, F. J.; Shipley, R. J.

    1993-01-01

    Bearings fabricated by powder metallurgy developed for use in machines subjected to extremes of temperature, rolling-contact cyclic stresses, and oxidizing or otherwise corrosive fluids. Bearings also extend operating lives of other machines in which bearings required to resist extreme thermal, mechanical, and chemical stresses. One alloy exhibiting outstanding properties was MRC-2001. Resistance to fatigue, stress corrosion cracking, and wear found superior to that of 440C stainless steel.

  14. Complex networks from space-filling bearings.

    PubMed

    Kranz, J J; Araújo, N A M; Andrade, J S; Herrmann, H J

    2015-07-01

    Two-dimensional space-filling bearings are dense packings of disks that can rotate without slip. We consider the entire first family of bearings for loops of four disks and propose a hierarchical construction of their contact network. We provide analytic expressions for the clustering coefficient and degree distribution, revealing bipartite scale-free behavior with a tunable degree exponent depending on the bearing parameters. We also analyze their average shortest path and percolation properties.

  15. Cantilever mounted resilient pad gas bearing

    NASA Technical Reports Server (NTRS)

    Etsion, I. (Inventor)

    1978-01-01

    A gas-lubricated bearing is described, employing at least one pad mounted on a rectangular cantilever beam to produce a lubricating wedge between the face of the pad and a moving surface. The load-carrying and stiffness characteristics of the pad are related to the dimensions and modulus of elasticity of the beam. The bearing is applicable to a wide variety of types of hydrodynamic bearings.

  16. A miniature tilting pad gas lubricated bearing

    NASA Astrophysics Data System (ADS)

    Sixsmith, H.; Swift, W. L.

    1983-12-01

    This paper describes the design and development of a miniature tilting pad gas bearing developed for use in very small turbomachines. The bearings have been developed for cryogenic turboexpanders with shaft diameters down to about 0.3 cm and rotational speeds up to one million rpm. Cryogenic expansion turbines incorporating this type of bearing should be suitable for refrigeration rates down to about 10 w.

  17. A miniature tilting pad gas lubricated bearing

    NASA Technical Reports Server (NTRS)

    Sixsmith, H.; Swift, W. L.

    1983-01-01

    This paper describes the design and development of a miniature tilting pad gas bearing developed for use in very small turbomachines. The bearings have been developed for cryogenic turboexpanders with shaft diameters down to about 0.3 cm and rotational speeds up to one million rpm. Cryogenic expansion turbines incorporating this type of bearing should be suitable for refrigeration rates down to about 10 w.

  18. Bearing strength of the lunar soil

    NASA Technical Reports Server (NTRS)

    Jaffe, L. D.

    1972-01-01

    A discussion is presented on the bearing strength and bearing load-penetration relations in lunar soil. These were measured in air as a function of bulk density. It was found that the relation between bulk density and the logarithm of the bearing capacity is about linear. Shapes of the load vs penetration curves were observed to be similar to those obtained with particulate material of terrestrial origin.

  19. Effect of Rolling Bearing Refurbishment and Restoration on Bearing Life and Reliability

    NASA Technical Reports Server (NTRS)

    Zaretsky, Erwin V.; Branzai, Emanuel V.

    2005-01-01

    For nearly four decades it has been a practice in commercial and military aircraft application that rolling-element bearings removed at maintenance or overhaul be reworked and returned to service. The work presented extends previously reported bearing life analysis to consider the depth (Z(45)) to maximum shear stress (45) on stressed volume removal and the effect of replacing the rolling elements with a new set. A simple algebraic relationship was established to determine the L(10) life of bearing races subject to bearing rework. Depending on the extent of rework and based upon theoretical analysis, representative life factors (LF) for bearings subject to rework ranged from 0.87 to 0.99 the lives of new bearings. Based on bearing endurance data, 92 percent of the bearing sets that would be subject to rework would result in L(10) lives equaling and/or exceeding that predicted for new bearings with the remaining 8 percent having the potential to achieve the analytically predicted life of new bearings when one of the rings is replaced at rework.. The potential savings from bearing rework varies from 53 to 82 percent that of new bearings depending on the cost, size and complexity of the bearing.

  20. Permanent Magnetic Bearing for Spacecraft Applications

    NASA Technical Reports Server (NTRS)

    Morales, Winfredo; Fusaro, Robert; Kascak, Albert

    2008-01-01

    A permanent, totally passive magnetic bearing rig was designed, constructed, and tested. The suspension of the rotor was provided by two sets of radial permanent magnetic bearings operating in the repulsive mode. The axial support was provided by jewel bearings on both ends of the rotor. The rig was successfully operated to speeds of 5500 rpm using an air impeller. Radial and axial stiffnesses of the permanent magnetic bearings were experimentally measured and then compared to finite element results. The natural damping of the rotor was measured and a damping coefficient was calculated.

  1. Surficial deposits in the Bear Lake Basin

    USGS Publications Warehouse

    Reheis, Marith C.; Laabs, Benjamin J.C.; Forester, Richard M.; McGeehin, John P.; Kaufman, Darrell S.; Bright, Jordon

    2005-01-01

    Mapping and dating of surficial deposits in the Bear Lake drainage basin were undertaken to provide a geologic context for interpretation of cores taken from deposits beneath Bear Lake, which sometimes receives water and sediment from the glaciated Bear River and sometimes only from the small drainage basin of Bear Lake itself. Analyses of core sediments by others are directed at (1) constructing a high-resolution climate record for the Bear Lake area during the late Pleistocene and Holocene, and (2) investigating the sources and weathering history of sediments in the drainage basin. Surficial deposits in the upper Bear River and Bear Lake drainage basins are different in their overall compositions, although they do overlap. In the upper Bear River drainage, Quaternary deposits derived from glaciation of the Uinta Range contain abundant detritus weathered from Precambrian quartzite, whereas unglaciated tributaries downstream mainly contribute finer sediment weathered from much younger, more friable sedimentary rocks. In contrast, carbonate rocks capped by a carapace of Tertiary sediments dominate the Bear Lake drainage basin.

  2. Technical Development Path for Foil Gas Bearings

    NASA Technical Reports Server (NTRS)

    DellaCorte, Christopher

    2008-01-01

    Foil gas bearings are in widespread commercial use in air cycle machines, turbocompressors and microturbine generators and are emerging in more challenging applications such as turbochargers, auxiliary power units and propulsion gas turbines. Though not well known, foil bearing technology is well over fifty years old. Recent technological developments indicate that their full potential has yet to be realized. This paper investigates the key technological developments that have characterized foil bearing advances. It is expected that a better understanding of foil gas bearing development path will aid in future development and progress towards more advanced applications.

  3. An increase of B cells in the tumor-bearing state has the potential to induce anti-tumor immunity.

    PubMed

    Ito, O; Harada, M; Takenoyama, M; Sumichika, H; Matsuzaki, G; Nomoto, K

    1996-01-01

    We investigated the role of an increased amount of B cells in the tumor-bearing state. The proportion of B cells increased concomitantly with tumor development in the regional lymph nodes (LN) of BALB/c mice bearing Meth A fibrosarcoma (Meth A). Tumor development was accompanied by an increased level of IgG antibodies against Meth A. CD4+ T cells of the regional LN in the early tumor-bearing stage produced significant levels of interferon-gamma and interleukin-4 in response to in vitro stimulation with coated anti-CD3 monoclonal antibody, whereas such capacities decreased in the late tumor-bearing stage. In a tumor-neutralizing assay, the growth of Meth A was significantly suppressed by a co-inoculation with splenic B cells from BALB/c mice in the late tumor-bearing state. This suppression of Meth A growth was tumor-specific and was abolished by the in vivo depletion of either CD4+ or CD8+ T cells. These findings thus suggest that tumor development was accompanied by an increase of B cells and tumor-specific IgG production, but such kinetic changes were not the result of a preferential activation of Th2 type CD4+ T cells. Furthermore, our results indicate that the increase of B cells in the tumor-bearing state has the potential to induce anti-tumor-specific T cell immunity.

  4. Experimental Evaluation of Journal Bearing Stability and New Gas Bearing Material

    NASA Technical Reports Server (NTRS)

    Keith, Theo G., Jr.; Dimofte, Florin

    2001-01-01

    It has been estimated that the noise levels in aircraft engine transmissions can be reduced by as much as 10 dB through the use of journal bearings. The potential benefits of lower noise levels include reduced wear, longer gear life and enhanced comfort for passengers and crew. Based on this concept the journal-thrust wave bearing was analyzed and its performance was evaluated. Numerical codes, developed over the past 30 years by Dr. Dimofte, were used to predict the performance of the bearing. The wave bearing is a fluid film bearing and therefore was analyzed using the Reynolds pressure equation. The formulation includes turbulent flow concepts and possesses a viscosity-temperature correction. The centrifugal growth of the bearing diameter and the deformation of the bearing under gear loads were also incorporated into the code. An experimental rig was developed to test the journal-thrust wave bearing.

  5. Nuclear genomic sequences reveal that polar bears are an old and distinct bear lineage.

    PubMed

    Hailer, Frank; Kutschera, Verena E; Hallström, Björn M; Klassert, Denise; Fain, Steven R; Leonard, Jennifer A; Arnason, Ulfur; Janke, Axel

    2012-04-20

    Recent studies have shown that the polar bear matriline (mitochondrial DNA) evolved from a brown bear lineage since the late Pleistocene, potentially indicating rapid speciation and adaption to arctic conditions. Here, we present a high-resolution data set from multiple independent loci across the nuclear genomes of a broad sample of polar, brown, and black bears. Bayesian coalescent analyses place polar bears outside the brown bear clade and date the divergence much earlier, in the middle Pleistocene, about 600 (338 to 934) thousand years ago. This provides more time for polar bear evolution and confirms previous suggestions that polar bears carry introgressed brown bear mitochondrial DNA due to past hybridization. Our results highlight that multilocus genomic analyses are crucial for an accurate understanding of evolutionary history.

  6. Dynamic modelling and response characteristics of a magnetic bearing rotor system including auxiliary bearings

    NASA Technical Reports Server (NTRS)

    Free, April M.; Flowers, George T.; Trent, Victor S.

    1993-01-01

    Auxiliary bearings are a critical feature of any magnetic bearing system. They protect the soft iron core of the magnetic bearing during an overload or failure. An auxiliary bearing typically consists of a rolling element bearing or bushing with a clearance gap between the rotor and the inner race of the support. The dynamics of such systems can be quite complex. It is desired to develop a rotor-dynamic model and assess the dynamic behavior of a magnetic bearing rotor system which includes the effects of auxiliary bearings. Of particular interest is the effects of introducing sideloading into such a system during failure of the magnetic bearing. A model is developed from an experimental test facility and a number of simulation studies are performed. These results are presented and discussed.

  7. Dynamic modelling and response characteristics of a magnetic bearing rotor system with auxiliary bearings

    NASA Technical Reports Server (NTRS)

    Free, April M.; Flowers, George T.; Trent, Victor S.

    1995-01-01

    Auxiliary bearings are a critical feature of any magnetic bearing system. They protect the soft iron core of the magnetic bearing during an overload or failure. An auxiliary bearing typically consists of a rolling element bearing or bushing with a clearance gap between the rotor and the inner race of the support. The dynamics of such systems can be quite complex. It is desired to develop a rotordynamic model which describes the dynamic behavior of a flexible rotor system with magnetic bearings including auxiliary bearings. The model is based upon an experimental test facility. Some simulation studies are presented to illustrate the behavior of the model. In particular, the effects of introducing sideloading from the magnetic bearing when one coil fails is studied.

  8. Gearbox Reliability Collaborative Bearing Calibration

    SciTech Connect

    van Dam, J.

    2011-10-01

    NREL has initiated the Gearbox Reliability Collaborative (GRC) to investigate the root cause of the low wind turbine gearbox reliability. The GRC follows a multi-pronged approach based on a collaborative of manufacturers, owners, researchers and consultants. The project combines analysis, field testing, dynamometer testing, condition monitoring, and the development and population of a gearbox failure database. At the core of the project are two 750kW gearboxes that have been redesigned and rebuilt so that they are representative of the multi-megawatt gearbox topology currently used in the industry. These gearboxes are heavily instrumented and are tested in the field and on the dynamometer. This report discusses the bearing calibrations of the gearboxes.

  9. Movements of Yellowstone grizzly bears

    USGS Publications Warehouse

    Blanchard, Bonnie M.; Knight, Richard R.

    1991-01-01

    Ninety-seven grizzly bears Ursus arctos horribilis were radio-located 6299 times during 1975–1987. Annual range sizes differed by sex, age, reproductive status and amount of precipitation. Females exhibited greater fidelity to seasonal and annual ranges than males. Weaned female offspring generally remained in the vicinity of the maternal range, while weaned males often made substantial movements to unexplored country. Average total home range size was 884 km2 for females and 3757 km2 for males. Males consistently exhibited greater indices of movement and range sizes than females. All cohorts had larger mean ranges during this study than during the period 1959–1969 when the population had access to open garbage dumps. Movements and elevational distribution of all cohorts were related to availability of whitebark pine Pinus albicaulis seeds. We hypothesized that females with cubs-of-the-year and yearlings were displaced from most productive habitats during seasons and years of limited food availability.

  10. 77 FR 70423 - Black Bear Hydro Partners, LLC and Black Bear Development Holdings, LLC and Black Bear SO, LLC...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-26

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Black Bear Hydro Partners, LLC and Black Bear Development Holdings, LLC and... partial the transfer of licenses for the Orono Hydroelectric Project, FERC No. 2710, and the...

  11. Evaluation of bearing configurations using the single bearing tester in liquid nitrogen

    NASA Technical Reports Server (NTRS)

    Jett, T.; Hall, P.; Thom, R.

    1991-01-01

    Various bearing configurations were tested using the Marshall Space Flight Center single bearing tester with LN2 as the cryogenic coolant. The baseline was one Rocketdyne phase one high pressure oxidizer turbopump (HPOTP) pump end 45-mm bore bearing. The bearing configurations that were tested included a Salox/M cage configuration, a silicon nitride ball configuration, an elongated cage configuration, and a Bray 601 grease configuration.

  12. Role of outer membrane protein H (OmpH)- and OmpA-specific monoclonal antibodies from hybridoma tumors in protection of mice against Pasteurella multocida.

    PubMed Central

    Vasfi Marandi, M; Mittal, K R

    1997-01-01

    Two major outer membrane proteins of Pasteurella multocida, designated OmpH and OmpA, were characterized and shown to be related to the families of porin and heat-modifiable proteins, respectively. The backpack hybridoma tumor system in BALB/c mice was used to continuously deliver immunoglobulin G2b (IgG2b) monoclonal antibodies (MAbs) specific for OmpH (MAb MT1) and OmpA (MAb MT4.1). MAbs were detected in serum and peritoneal lavage samples of mice bearing hybridoma tumors by an enzyme-linked immunosorbent assay and an immunoblot assay. Highly significant protection was observed in mice bearing MT1 hybridoma tumors against both intraperitoneal and intranasal challenge infections with homologous nontoxigenic P. multocida strains possessing MAb MT1-reacting epitopes, whereas the mice bearing MT4.1 hybridoma tumors were not protected. The numbers of P. multocida organisms in the lungs of mice bearing MT1 hybridoma tumors were significantly less than those in lungs of mice bearing MT4.1 hybridoma tumors at 48 h postchallenge. These results indicate that the OmpH-specific MAb inhibited proliferation of P. multocida in the lungs. MAb MT1 was unable to kill P. multocida in vitro in the presence of complement. However, an enhanced phagocytosis by polymorphonuclear cells (PMNs) was observed in mice bearing MT1 hybridoma tumors. P. multocida induced a more extensive and rapid influx of PMNs into the peritoneal cavity of mice bearing MT1 hybridoma tumors than of mice bearing MT4.1 hybridoma tumors. The results of this study demonstrate for the first time that IgG MAbs against OmpH of P. multocida are involved in the protection of mice against lethal challenge infection by means of opsonization and inhibition of proliferation of P. multocida as a result of increased influx of PMNs into the infection site. PMID:9353026

  13. Unbalance Response Prediction for Rotors on Ball Bearings Using Speed and Load Dependent Nonlinear Bearing Stiffness

    NASA Technical Reports Server (NTRS)

    Fleming, David P.; Poplawski, J. V.

    2003-01-01

    Rolling-element bearing forces vary nonlinearly with bearing deflection. Thus an accurate rotordynamic analysis requires that bearing forces corresponding to the actual bearing deflection be utilized. For this work bearing forces were calculated by COBRA-AHS, a recently developed rolling-element bearing analysis code. Bearing stiffness was found to be a strong function of bearing deflection, with higher deflection producing markedly higher stiffness. Curves fitted to the bearing data for a range of speeds and loads were supplied to a flexible rotor unbalance response analysis. The rotordynamic analysis showed that vibration response varied nonlinearly with the amount of rotor imbalance. Moreover, the increase in stiffness as critical speeds were approached caused a large increase in rotor and bearing vibration amplitude over part of the speed range compared to the case of constant bearing stiffness. Regions of bistable operation were possible, in which the amplitude at a given speed was much larger during rotor acceleration than during deceleration. A moderate amount of damping will eliminate the bistable region, but this damping is not inherent in ball bearings.

  14. Phylogeography of mitochondrial DNA variation in brown bears and polar bears

    USGS Publications Warehouse

    Shields, Gerald F.; Adams, Deborah; Garner, Gerald; Labelle, Martine; Pietsch, Jacy; Ramsay, Malcolm; Schwartz, Charles; Titus, Kimberly; Williamson, Scott

    2000-01-01

    We analyzed 286 nucleotides of the middle portion of the mitochondrial cytochrome b gene of 61 brown bears from three locations in Alaska and 55 polar bears from Arctic Canada and Arctic Siberia to test our earlier observations of paraphyly between polar bears and brown bears as well as to test the extreme uniqueness of mitochondrial DNA types of brown bears on Admiralty, Baranof, and Chichagof (ABC) islands of southeastern Alaska. We also investigated the phylogeography of brown bears of Alaska's Kenai Peninsula in relation to other Alaskan brown bears because the former are being threatened by increased human development. We predicted that: (1) mtDNA paraphyly between brown bears and polar bears would be upheld, (2) the mtDNA uniqueness of brown bears of the ABC islands would be upheld, and (3) brown bears of the Kenai Peninsula would belong to either clade II or clade III of brown bears of our earlier studies of mtDNA. All of our predictions were upheld through the analysis of these additional samples.

  15. Damage Mechanics Approach for Bearing Lifetime Prognostics

    NASA Astrophysics Data System (ADS)

    Qiu, Jing; Seth, Brij B.; Liang, Steven Y.; Zhang, Cheng

    2002-09-01

    The ability to achieve accurate bearing prognostics is critical to the optimal maintenance of rotating machinery in the interest of cost and productivity. However, techniques to real time predict the lifetime of a bearing under practical operating conditions have not been well developed. In this paper, a stiffness-based prognostic model for bearing systems based on vibration response analysis and damage mechanics is discussed. As the bearing system is considered as a single-degree-of-freedom vibratory system, its natural frequency and its acceleration amplitude at the natural frequency can be related to the system stiffness. On the other hand, the relationship between failure lifetime, running time and stiffness variation can be established from the damage mechanics. Combining the above two, the natural frequency and the acceleration amplitude of a bearing system can be related to its running time and failure lifetime. Thus, the failure lifetime of a bearing system can be predicted on-line based on vibration measurement. Experiments have been performed on a tapered roller bearing life testing stand under various operation conditions to calibrate and to validate the proposed model. The comparison between model-calculated data and experimental results indicates that this model can be used to effectively predict the failure lifetime and the remaining life of a bearing system.

  16. 33 CFR 117.543 - Bear Creek.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Bear Creek. 117.543 Section 117.543 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Maryland § 117.543 Bear Creek. (a) The draws of the...

  17. 33 CFR 117.543 - Bear Creek.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Bear Creek. 117.543 Section 117.543 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Maryland § 117.543 Bear Creek. (a) The draws of the...

  18. 33 CFR 117.543 - Bear Creek.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Bear Creek. 117.543 Section 117.543 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Maryland § 117.543 Bear Creek. (a) The draw of the...

  19. 33 CFR 117.543 - Bear Creek.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Bear Creek. 117.543 Section 117.543 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Maryland § 117.543 Bear Creek. (a) The draw of the...

  20. 33 CFR 117.543 - Bear Creek.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Bear Creek. 117.543 Section 117.543 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Maryland § 117.543 Bear Creek. (a) The draw of the...