Sample records for l1210 mouse leukemia

  1. Pharmacological effect of aminoferrocene in mice with L1210 leukemia.

    PubMed

    Chekhun, V F; Mokhir, A; Daum, S; Todor, I N; Lukianova, N Yu; Shvets, Yu V; Burlaka, A P

    2015-06-01

    To study the cytostatic and some biological effects of aminoferrocene using mice with L1210 lymphoid leukemia. Experiments were performed on BDF1 male mice (DBA/2, female × C57Bl/6, male) with transplantable L1210 lymphoid leukemia. Determination of antitumor activity of Benzyl-Fc Boron (Bn), it was injected intraperitoneally 6 times daily, starting on day 2 after L1210 leukemia cell transplantation. Doses of Bn such as 26; 260 and 2600 μg/kg were used. The determination of intracellular content of cardiolipin, thiols, reactive oxygen species (ROS) and also analysis of Annexin V positivity and mitochondrial transmembrane potential (JC-1 staining) were performed with use of flow cytometry. The levels of "free iron" complexes, transferrin active forms and the rate of NO generation were measured by EPR-specroscopy. Six daily injections of Bn at a dose of 26 μg/kg resulted in an increased survival of mice with L1210 leukemia by 28% (p < 0.05). Bn led to an increase of apoptotic cells number and ROS amount in leukemia cells. Besides, Bn caused a decrease of cardiolipin and nonprotein thiol compounds content. The membrane electrochemical potential of cell mitochondria was decreased also after Bn administration. Studies using EPR-spectroscopy revealed a significant increase in a level of "free iron", content of transferrin active species and generation rate of NO by inducible NO-synthase in L1210 cells after aminoferrocene administration. Our data indicate that Benzyl-Fc Boron can be promising candidate for realizing a new strategy of anticancer therapy with the use of ROS-inducing agents.

  2. Lunasin, with an arginine-glycine-aspartic acid motif, causes apoptosis to L1210 leukemia cells by activation of caspase-3.

    PubMed

    de Mejia, Elvira Gonzalez; Wang, Wenyi; Dia, Vermont P

    2010-03-01

    Lunasin is a novel chemopreventive peptide featuring a cell adhesion motif composed of arginine-glycine-aspartate (RGD) which has been associated to cytotoxicity to established cell lines. The objectives of this study were to determine the effect of lunasin on the viability of L1210 leukemia cells and to understand the underlying mechanisms involved. Pure lunasin and lunasin enriched soy flour (LES) caused cytotoxicity to L1210 leukemia cells with IC(50) of 14 and 16 microM (lunasin equivalent), respectively. Simulated gastrointestinal digestion showed that 25% of the original amount of lunasin survived 3 h of pepsin digestion and 3% of lunasin remained after sequential pepsin-pancreatin digestion for a total of 6 h. Cell cycle analysis showed that lunasin caused a dose-dependent G2 cell cycle arrest and apoptosis. Treatment of L1210 leukemia cells with 1 mg/mL of LES for 18 h led to an increase in the amount of apoptotic cells from 2 to 40%. Compared to untreated cells, treatment with 1 mg/mL LES showed a 6-fold increase on the expressions of caspases-8 and -9, and and a 12-fold increase on the expression of caspase-3. These results showed for the first time that lunasin, a naturally occurring peptide containing an RGD motif, caused apoptosis to L1210 leukemia cells through caspase-3 activation.

  3. Murine and human leukemias.

    PubMed

    Burchenal, J H

    1975-01-01

    Essentially all the drugs which are active against human leukemias and lymphomas are active against one type or another of the rodent leukemias and lymphomas. Leukemia L1210 has been generally the most successful screening tool for clinically active compounds. Leukemia P388, however, seems to be better in detecting active antibiotics and natural products and P1534 is particularly sensitive to the Vinca alkaloids, while L5178Y, EARAD, and 6C3HED are useful in detecting the activities of various asparaginase containing fractions. Cell cultures of these leukemias can demonstrate mechanism of drug action and quantitate resistance. Spontaneous AKR leukemia is a model of the advanced human disease. In these leukemias vincristine and prednisone produce a 4 log cell kill. Cytoxan and arabinosyl cytosine (Ara-C) are also effective. On the other hand drugs such as mercaptopurine (6MP) and methotrexate which are highly active in the maintenance phase of acute lymphocytic leukemia (ALL) and in L1210 have little or no activity against the AKR spontaneous system. Mouse leukemias can also detect schedule dependence, synergistic combinations, cross resistance, oral activity, and the ability of drugs to pass the blood brain barrier. A case in point is the Ara-C analog 2,2'-anhydro-arabinofuranosyl-5-fluorocytosine (AAFC) which is not schedule dependent, is active orally, is potentiated by thioguanine, and is effective against intracerebrally inoculated mouse leukemia. AAFC and its analogs might thus be a considerable improvement over Ara-C which is at the present time the most important component of the combination treatment of acute myelogenous leukemia (AML).

  4. Permeabilization of the plasma membrane of L1210 mouse leukemia cells using lithotripter shock waves.

    PubMed

    Gambihler, S; Delius, M; Ellwart, J W

    1994-09-01

    Permeabilization of L1210 cells by lithotripter shock waves in vitro was monitored by evaluating the accumulation of fluorescein-labeled dextrans with a relative molecular mass ranging from 3,900-2,000,000. Incubation with labeled dextran alone caused a dose- and time-dependent increase in cellular fluorescence as determined by flow cytometry, with a vesicular distribution pattern in the cells consistent with endocytotic uptake. Shock wave exposure prior to incubation with labeled dextran revealed similar fluorescence intensities compared to incubation with labeled dextran alone. When cells were exposed to shock waves in the presence of labeled dextran, mean cellular fluorescence was further increased, indicating additional internalization of the probe. Confocal laser scanning microscopy confirmed intracellular fluorescence of labeled dextran with a diffuse distribution pattern. Fluorescence-activated cell sorting with subsequent determination of proliferation revealed that permeabilized cells were viable and able to proliferate. Permeabilization of the membrane of L1210 cells by shock waves in vitro allowed loading of dextrans with a relative molecular mass up to 2,000,000. Permeabilization of tumor cells by shock waves provides a useful tool for introducing molecules into cells which might be of interest for drug targeting in tumor therapy in vivo.

  5. Comparative Study of 6-Mercaptopurine Metabolism in Human Leukemic Leukocytes and L1210 Cells

    PubMed Central

    Higuchi, Tomihiko; Nakamura, Toru; Uchino, Haruto; Wakisaka, Gyoichi

    1977-01-01

    Leukocytes from patients with leukemia and L1210 cells from mice were examined for the rate of formation and cellular concentration of phosphoribosylpyrophosphate, the rate of thioinosinic acid formation, and a number of selected enzymes involved in purine nucleotide synthesis. The amount of thioinosinic acid formed in L1210 cells was much higher than that in human leukemic leukocytes. In cell extracts, the synthesis of thioinosinic acid was similar in both cell types, and the amount of purine phosphoribosyltransferase was not rate limiting in either case. Much higher concentrations and rates of formation of phosphoribosylpyrophosphate were found in L1210 cells than in human leukemic leukocytes. The difference in response to 6-mercaptopurine between L1210 cells and human leukemic leukocytes might be attributed to their difference in supply of phosphoribosylpyrophosphate. Phosphoribosylpyrophosphate-amidotransferase was found to be high in L1210 cells, but was not detected in human leukemic leukocytes. PMID:921247

  6. Diethylglyoxal bis(guanylhydrazone), a potent inhibitor of mammalian S-adenosylmethionine decarboxylase. Effects on cell proliferation and polyamine metabolism in L1210 leukemia cells.

    PubMed

    Svensson, F; Kockum, I; Persson, L

    1993-07-21

    The polyamines are cell constituents essential for growth and differentiation. S-Adenosylmethionine decarboxylase (AdoMetDC) catalyzes a key step in the polyamine biosynthetic pathway. Methylglyoxal bis(guanylhydrazone) (MGBG) is an anti-leukemic agent with a strong inhibitory effect against AdoMetDC. However, the lack of specificity limits the usefulness of MGBG. In the present report we have used an analog of MGBG, diethylglyoxal bis(guanylhydrazone) (DEGBG), with a much greater specificity and potency against AdoMetDC, to investigate the effects of AdoMetDC inhibition on cell proliferation and polyamine metabolism in mouse L1210 leukemia cells. DEGBG was shown to effectively inhibit AdoMetDC activity in exponentially growing L1210 cells. The inhibition of AdoMetDC was reflected in a marked decrease in the cellular concentrations of spermidine and spermine. The concentration of putrescine, on the other hand, was greatly increased. Treatment with DEGBG resulted in a compensatory increase in the synthesis of AdoMetDC demonstrating an efficient feedback control. Cells seeded in the presence of DEGBG ceased to grow after a lag period of 1-2 days, indicating that the cells contained an excess of polyamines which were sufficient for one or two cell cycles in the absence of polyamine synthesis. The present results indicate that analogs of MGBG, having a greater specificity against AdoMetDC, might be valuable for studies concerning polyamines and cell proliferation.

  7. Triorganotin Derivatives Induce Cell Death Effects on L1210 Leukemia Cells at Submicromolar Concentrations Independently of P-glycoprotein Expression.

    PubMed

    Bohacova, Viera; Seres, Mario; Pavlikova, Lucia; Kontar, Szilvia; Cagala, Martin; Bobal, Pavel; Otevrel, Jan; Brtko, Julius; Sulova, Zdena; Breier, Albert

    2018-05-01

    The acceleration of drug efflux activity realized by plasma membrane transporters in neoplastic cells, particularly by P-glycoprotein (P-gp, ABCB1 member of the ABC transporter family), represents a frequently observed molecular cause of multidrug resistance (MDR). This multiple resistance represents a real obstacle in the effective chemotherapy of neoplastic diseases. Therefore, identifying cytotoxic substances that are also effective in P-gp overexpressing cells may be useful for the rational design of substances for the treatment of malignancies with developed MDR. Here, we showed that triorganotin derivatives—tributyltin-chloride (TBT-Cl), tributyltin-bromide (TBT-Br), tributyltin-iodide (TBT-I) and tributyltin-isothiocyanate (TBT-NCS) or triphenyltin-chloride (TPT-Cl) and triphenyltin-isothiocyanate (TPT-NCS)—could induce the death of L1210 mice leukemia cells at a submicromolar concentration independently of P-gp overexpression. The median lethal concentration obtained for triorganotin derivatives did not exceed 0.5 µM in the induction of cell death of either P-gp negative or P-gp positive L1210 cells. Apoptosis related to regulatory pathway of Bcl-2 family proteins seems to be the predominant mode of cell death in either P-gp negative or P-gp positive L1210 cells. TBT-Cl and TBT-Br were more efficient with L1210 cells overexpressing P-gp than with their counterpart P-gp negative cells. In contrast, TBT-I and TPT-NCS induced a more pronounced cell death effect on P-gp negative cells than on P-gp positive cells. Triorganotin derivatives did not affect P-gp efflux in native cells measured by calcein retention within the cells. Taken together, we assumed that triorganotin derivatives represent substances suitable for suppressing the viability of P-gp positive malignant cells.

  8. Potentiating action of 5-fluorouracil when used in combination with platinium compounds and cyclophosphamide in treatment of advanced L1210 leukemia.

    PubMed

    Gale, G R; Atkins, L M; Schwartz, P; Meischen, S J

    1978-01-01

    Nine new organoplatinum (Pt) compounds, cyclophosphamide (CY), and 5-fluorouracil (FU) were used singly and in combination in treatment of advanced L1210 leukemia in C57BL/6 X DBA/2 hybrid mice. In each experiment the Pt + CY dual combination was minimally supra-additive at the doses chosen. However, eight of the nine Pt + CY + FU combination regimens enhanced markedly the increased life span of treated mice as compared with the corresponding dual Pt + CY combination. Collectively, the cure rate (greater than 60-day survival) was less than 6% with the various Pt + CY combinations, and was increased to over 63% upon inclusion of FU in the regimens.

  9. Ethylglyoxal bis(guanylhydrazone) as an inhibitor of polyamine biosynthesis in L1210 leukemia cells.

    PubMed

    Seppänen, P; Ruohola, H; Jänne, J

    1984-04-16

    Ethylglyoxal bis(guanylhydrazone), a close derivative of the known anti-cancer drug methylglyoxal bis(guanylhydrazone), is also a powerful inhibitor of S-adenosylmethionine decarboxylase (EC 4.1.1.50), the enzyme needed for the synthesis of spermidine and spermine. There were, however, marked differences between the ethyl and methyl derivatives of glyoxal bis(guanylhydrazone) when tested in cultured L1210 cells. The cellular accumulation of ethylglyoxal bis(guanylhydrazone) represented only a fraction (20-25%) of that of the methyl derivative. Moreover, polyamine depletion, which is known to strikingly stimulate the uptake of methylglyoxal bis(guanylhydrazone), decreased, if anything, the uptake of ethylglyoxal bis(guanylhydrazone) by L1210 cells. The compound produced spermidine and spermine depletion fully comparable to that achieved with methylglyoxal bis(guanylhydrazone) at micromolar concentrations. Ethylglyoxal bis(guanylhydrazone) was growth-inhibitory to L1210 cells and produced an additive antiproliferative action when used together with 2-difluoromethylornithine. Ethylglyoxal bis(guanylhydrazone) was distinctly less effective than methylglyoxal bis(guanylhydrazone) in releasing bound polyamines from isolated cell organelles in vitro. Ethylglyoxal bis(guanylhydrazone) was also devoid of the early and profound mitochondrial toxicity typical to methylglyoxal bis(guanylhydrazone). These findings may indicate that this compound is a more specific inhibitor of polyamine biosynthesis with less intracellular polyamine 'receptor-site' activity than methylglyoxal bis(guanylhydrazone).

  10. Equivalent chemotherapy efficacy against leukemia in mice treated with topical vasoconstrictors to prevent cancer therapy side effects.

    PubMed

    Graul-Conroy, Amanda; Hicks, Emily J; Fahl, William E

    2016-06-15

    Topically applied vasoconstrictor is a new strategy to prevent oral mucositis and alopecia, two complications of chemotherapy and stem-cell transplant. We sought to determine whether mice treated with topical vasoconstrictor minutes before chemotherapy to suppress L1210 leukemia would develop a vasoconstrictor-induced L1210 cell sanctuary, and with it, significantly worse survival outcomes. B6D2F1 mice received 10(4) mouse L1210 leukemia cells via retro-orbital intravenous injection and were then divided into treatment groups, which included: (i) no further treatment, (ii) a single, sub-curative, intraperitoneal dose of cyclophosphamide (90 µg/gm bw) 24 hr after L1210 cell inoculation, (iii) topical epinephrine (25-400 mM) to clipped dorsal backs 20 min before cyclophosphamide or (iv) orotopical phenylephrine (16-130 mM), epinephrine (10 mM) or norepinephrine (25 mM) 20 min before cyclophosphamide. All mice were then followed until day of death. Differences in median survival time and percent survival between mice receiving cyclophosphamide alone and mice treated with either orotopical phenylephrine, epinephrine or norepinephrine; or topical epinephrine before cyclophosphamide were not significantly different. A discernible leukemia sanctuary was not created by topical vasoconstrictor treatment prior to chemotherapy; there was no significant difference in leukemia progression between untreated mice and those treated with either orotopical or topical vasoconstrictor before chemotherapy. We have opened a Phase I/IIa dose escalation trial to evaluate the safety and efficacy of orotopical phenylephrine in preventing oral mucositis in subjects undergoing hematopoietic stem cell transplant conditioning with cyclophosphamide plus total body irradiation. This could provide a cost-effective and convenient method to prevent oral mucositis. © 2016 UICC.

  11. Characterization of the methotrexate transport pathway in murine L1210 leukemia cells: Involvement of a membrane receptor and a cytosolic protein

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Price, E.M.; Ratnam, M.; Rodeman, K.M.

    1988-10-04

    A radioiodinated photoaffinity analogue of methotrexate, N{sup {alpha}}-(4-amino-4-deoxy-10-methyl-pteroyl)-N{sup {epsilon}}-(4-azidosalicylyl)-L-lysine (APA-ASA-Lys), was recently used to identify the plasma membrane derived binding protein involved in the transport of this folate antagonist into murine L1210 cells. The labeled protein has an apparent molecular weight of 46K-48K when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but no such labeling occurs in a methotrexate transport-defective cell line (L1210/R81). Labeling of the total cytosolic protein from disrupted cells, followed by electrophoresis and autoradiography, showed, among other proteins, a 21K band, corresponding to dihydrofolate reductase (DHFR), in both the parent and R81 cells and a 38K bandmore » only in the parent cells. However, when whole cells were UV irradiated at various times at 37{degree}C following addition of radiolabeled APA-ASA-Lys, the 38K protein and DHFR were the only cytosolic proteins labeled in the parent cells, while the intact R81 cells showed no labeled cytosolic protein, since the photoprobe is not transported. Further, when the parent cells were treated with a pulse of radiolabeled photoprobe, followed by UV irradiation at different times at 37{degree}C, the probe appeared sequentially on the 48K membrane protein and both the 38K cytosolic protein and dihydrofolate reductase. A 48K protein could be detected in both parent L1210 cells and the R81 cells on Western blots using antisera to a membrane folate binding protein from human placenta. These results suggest a vectorial transport of APA-ASA-Lys or methotrexate and reduced folate coenzymes into murine L1210 cells mediated by a 48K integral membrane protein and a 38K cytosolic or peripheral membrane protein. The 38K protein may help in the trafficking of reduced folate coenzymes, shuttling them to various cytosolic targets.« less

  12. Successful immunotherapy with micrococcus, BCG or related polysaccharides on L1210 leukaemia after BCNU chemotherapy.

    PubMed Central

    Verloes, R.; Atassi, G.; Dumont, P.; Kanarek, L.

    1981-01-01

    The experiments aimed at evaluating the optimal parameters in the chemo-immunotherapeutic treatment of the L1210 lymphoid leukaemia grafted to [female BALB/c (H2d) X male DBA/2 (H2d)]F1 hybrid mice, hereafter referred to as CDF1 mice. In vitro irradiation of leukaemic ascites cells by X- or gamma-rays and subsequent inoculation in mice showed that optimum immunogenicity is radiation dose-dependent. Grafting mice with 10(7) leukaemic ascites cells irradiated at optimum dose (80 GyX- or gamma-rays) delays mortality of the animals when challenged later with untreated L1210 cells, but is unable to cure mice. By contrast, specific immunoprophylaxis induced by Micrococcus, complement-triggering polysaccharides or BCG and irradiated leukaemic cells was able to protect mice against grafts of 10(4) L1210 cells. The i.p. route was notably superior to the i.v. route. When mice bearing advanced L1210 tumour were treated by chemotherapy (12 mg/kg of BCNU) on Day 6.5 after grafting 10(4) L1210 cells and subsequently treated by immunotherapy, a very high percentage (up to 90%) of mice with 10(8) leukaemic cells could be cured by repeated 1mg injections of bacterium or polysaccharide, and challenge with irradiated leukaemic cells was unnecessary. Because of the high cure rate obtained, the very regular response pattern and the non-pathogenicity, the bacterium Micrococcus lysodeikticus would seem a promising new candidate for chemo-immunotherapeutic antitumour strategies. PMID:7470382

  13. Lethality to leukemia cell lines of DNA interstrand cross-links generated by Cloretazine derived alkylating species

    PubMed Central

    Penketh, Philip G.; Baumann, Raymond P.; Ishiguro, Kimiko; Shyam, Krishnamurthy; Seow, Helen A.; Sartorelli, Alan C.

    2010-01-01

    Cloretazine [1, 2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]-hydrazine; VNP40101M; 101M] is a relatively new prodrug with activity in elderly acute myelogenous leukemia patients. Its therapeutic action is due largely to the production of 1-(3-cytosinyl),2-(1-guanyl)ethane cross-links (G-C ethane cross-links) in DNA. The number of cross-links produced in three experimental leukemia lines (L1210, U937 and HL-60) were fewer than 10 per genome at their respective LC50 concentrations. Only 1 in approximately 20,000 90CE molecules produce a cross-link in the AGT (O6-alkylguanine-DNA alkyltransferase) negative L1210 and U937 cell lines and 1 in 400,000 in the AGT positive HL-60 cell line. PMID:18479747

  14. Podoscyphic acid, a new inhibitor of avian myeloblastosis virus and Moloney murine leukemia virus reverse transcriptase from a Podoscypha species.

    PubMed

    Erkel, G; Anke, T; Velten, R; Steglich, W

    1991-01-01

    A novel enzyme inhibitor of RNA-directed DNA-polymerases of avian myeloblastosis and murine leukemia virus was isolated from fermentations of an tasmanian Podoscypha species. Its structure was elucidated by spectroscopic methods and oxidative degradation as (E)-4,5-dioxo-2-hexadecenoic acid (1). The enzyme inhibitor, which was named podoscyphic acid, did not inhibit DNA and RNA synthesis in permeabilized L 1210 cells nor did it affect RNA synthesis in isolated nuclei of L 1210 cells. 1 inhibits protein synthesis in whole L 1210 cells and rabbit reticulocyte lysate and shows very weak antimicrobial and cytotoxic properties. The testing of ethyl (E)-4,5-dioxo-2-hexadecenoate (2) and (E)-4-oxo-2-tetradecenoic acid (11) revealed the importance of the free gamma-oxoacrylic acid unit for the biological activities of 1.

  15. Genetic mapping of xenotropic murine leukemia virus-inducing loci in five mouse strains

    PubMed Central

    1980-01-01

    A single mendelian gene was identified for induction of the endogenous xenotropic murine leukemia virus in five mouse strains (C57BL/10, C57L, C57BR, AKR, and BALB/c). This locus, designated Bxv-1, mapped to the same site on chromosome 1 in all strains: Id-1-Pep-3-[Bxv-1-Lp]. Thus, inducibility loci for xenotropic virus are more limited in number and chromosomal distribution than ecotropic inducibility loci. Virus expression in mice with Bxv-1 was induced by treatment of fibroblasts with 5-iododeoxyuridine or by exposure of spleen cells to a B cell mitogen, bacterial lipopolysaccharide. An analysis of the hamster X mouse somatic cell hybrids indicated that chromosome 1, alone, was sufficient for virus induction. PMID:6249881

  16. Genetic mapping of xenotropic murine leukemia virus-inducing loci in five mouse strains.

    PubMed

    Kozak, C A; Rowe, W P

    1980-07-01

    A single mendelian gene was identified for induction of the endogenous xenotropic murine leukemia virus in five mouse strains (C57BL/10, C57L, C57BR, AKR, and BALB/c). This locus, designated Bxv-1, mapped to the same site on chromosome 1 in all strains: Id-1-Pep-3-[Bxv-1-Lp]. Thus, inducibility loci for xenotropic virus are more limited in number and chromosomal distribution than ecotropic inducibility loci. Virus expression in mice with Bxv-1 was induced by treatment of fibroblasts with 5-iododeoxyuridine or by exposure of spleen cells to a B cell mitogen, bacterial lipopolysaccharide. An analysis of the hamster X mouse somatic cell hybrids indicated that chromosome 1, alone, was sufficient for virus induction.

  17. Evidence for a Stable Intermediate in Leukemia Virus Activation in AKR Mouse Embryo Cells

    PubMed Central

    Ihle, James N.; Kenney, Francis T.; Tennant, Raymond W.

    1974-01-01

    Analysis of the requirement for serum in the activation of the endogenous leukemia virus expression in AKR mouse embryo cells by 5-iododeoxyuridine shows that activation can be dissociated into two discrete serum-dependent events. The first involves incorporation of 5-iododeoxyuridine into DNA and results in the formation of a stable “activation intermediate” resembling the provirus formed during infection of stationary mouse embryo cells with exogenous leukemia virus. The second event, resulting in expression of the activation intermediate as synthesis of virus proteins, requires DNA replication but not 5-iododeoxyuridine. PMID:4604455

  18. Carnitine prevents the early mitochondrial damage induced by methylglyoxal bis(guanylhydrazone) in L1210 leukaemia cells.

    PubMed

    Nikula, P; Ruohola, H; Alhonen-Hongisto, L; Jänne, J

    1985-06-01

    We previously found that the anti-cancer drug methylglyoxal bis(guanylhydrazone) (mitoguazone) depresses carnitine-dependent oxidation of long-chain fatty acids in cultured mouse leukaemia cells [Nikula, Alhonen-Hongisto, Seppänen & Jänne (1984) Biochem. Biophys. Res. Commun. 120, 9-14]. We have now investigated whether carnitine also influences the development of the well-known mitochondrial damage produced by the drug in L1210 leukaemia cells. Palmitate oxidation was distinctly inhibited in tumour cells exposed to 5 microM-methylglyoxal bis(guanylhydrazone) for only 7 h. Electron-microscopic examination of the drug-exposed cells revealed that more than half of the mitochondria were severely damaged. Similar exposure of the leukaemia cells to the drug in the presence of carnitine not only abolished the inhibition of fatty acid oxidation but almost completely prevented the drug-induced mitochondrial damage. The protection provided by carnitine appeared to depend on the intracellular concentration of methylglyoxal bis(guanylhydrazone), since the mitochondria-sparing effect disappeared at higher drug concentrations.

  19. Different expressions and DNA methylation patterns of lysophosphatidic acid receptor genes in mouse tumor cells.

    PubMed

    Okabe, Kyoko; Hayashi, Mai; Wakabayashi, Naoko; Yamawaki, Yasuna; Teranishi, Miki; Fukushima, Nobuyuki; Tsujiuchi, Toshifumi

    2010-01-01

    Lysophosphatidic acid (LPA) receptors act as several biological effectors through LPA, which is a bioactive phospholipid. Recently, aberrant expressions of LPA receptor genes due to DNA methylation have been detected in several tumor cells. In this study, we measured expression levels and DNA methylation status of LPA receptor genes in mouse tumor cells, LL/2 lung carcinoma, B16F0 melanoma, FM3A mammary carcinoma and L1210 leukemia cells, compared with normal tissues. Total RNAs were extracted and RT-PCR analysis was performed. For DNA methylation status, bisulfite sequencing analysis was carried out, comparing outcomes with other tumor cells and normal tissues. The expressions of LPA1 gene were shown in LL/2, but not in B16F0, FM3A and L1210 cells. While the LPA2 gene was expressed in all 4 tumor cells, the LPA3 gene was unexpressed in them. The LPA1 and LPA3 unexpressed cells were highly methylated, although normal tissues were all unmethylated. The DNA methylation status was correlated with gene expression levels in cancer cells. The present results demonstrate that DNA methylation patterns of LPA receptor genes are dependent on cancer cell types, suggesting that LPA receptors may be new molecular targets for therapeutic approaches and chemoprevention. Copyright © 2011 S. Karger AG, Basel.

  20. Mouse chromosomal mapping of a murine leukemia virus integration region (Mis-1) first identified in rat thymic leukemia.

    PubMed Central

    Jolicoeur, P; Villeneuve, L; Rassart, E; Kozak, C

    1985-01-01

    We have previously identified a region of genomic DNA which constitutes the site of frequent provirus integration in rat thymomas induced by Moloney murine leukemia virus (Lemay and Jolicoeur, Proc. Natl. Acad. Sci. USA 81:38-42, 1984). This genetic locus is now designated Mis-1 (Moloney integration site). Cellular sequences homologous to Mis-1 are present in mouse DNA. Using a series of hamster-mouse somatic cell hybrids, we mapped the Mis-1 locus to mouse chromosome 15. Frequent chromosome 15 aberrations have been described in mouse thymomas. Mis-1 represents a putative new oncogene which might be involved in the initiation or maintenance or both of these neoplasms. Images PMID:4068142

  1. Carnitine prevents the early mitochondrial damage induced by methylglyoxal bis(guanylhydrazone) in L1210 leukaemia cells.

    PubMed Central

    Nikula, P; Ruohola, H; Alhonen-Hongisto, L; Jänne, J

    1985-01-01

    We previously found that the anti-cancer drug methylglyoxal bis(guanylhydrazone) (mitoguazone) depresses carnitine-dependent oxidation of long-chain fatty acids in cultured mouse leukaemia cells [Nikula, Alhonen-Hongisto, Seppänen & Jänne (1984) Biochem. Biophys. Res. Commun. 120, 9-14]. We have now investigated whether carnitine also influences the development of the well-known mitochondrial damage produced by the drug in L1210 leukaemia cells. Palmitate oxidation was distinctly inhibited in tumour cells exposed to 5 microM-methylglyoxal bis(guanylhydrazone) for only 7 h. Electron-microscopic examination of the drug-exposed cells revealed that more than half of the mitochondria were severely damaged. Similar exposure of the leukaemia cells to the drug in the presence of carnitine not only abolished the inhibition of fatty acid oxidation but almost completely prevented the drug-induced mitochondrial damage. The protection provided by carnitine appeared to depend on the intracellular concentration of methylglyoxal bis(guanylhydrazone), since the mitochondria-sparing effect disappeared at higher drug concentrations. Images Fig. 1. PMID:3837667

  2. Thrombopoietin/MPL signaling confers growth and survival capacity to CD41-positive cells in a mouse model of Evi1 leukemia.

    PubMed

    Nishikawa, Satoshi; Arai, Shunya; Masamoto, Yosuke; Kagoya, Yuki; Toya, Takashi; Watanabe-Okochi, Naoko; Kurokawa, Mineo

    2014-12-04

    Ecotropic viral integration site 1 (Evi1) is a transcription factor that is highly expressed in hematopoietic stem cells and is crucial for their self-renewal capacity. Aberrant expression of Evi1 is observed in 5% to 10% of de novo acute myeloid leukemia (AML) patients and predicts poor prognosis, reflecting multiple leukemogenic properties of Evi1. Here, we show that thrombopoietin (THPO) signaling is implicated in growth and survival of Evi1-expressing cells using a mouse model of Evi1 leukemia. We first identified that the expression of megakaryocytic surface molecules such as ITGA2B (CD41) and the THPO receptor, MPL, positively correlates with EVI1 expression in AML patients. In agreement with this finding, a subpopulation of bone marrow and spleen cells derived from Evi1 leukemia mice expressed both CD41 and Mpl. CD41(+) Evi1 leukemia cells induced secondary leukemia more efficiently than CD41(-) cells in a serial bone marrow transplantation assay. Importantly, the CD41(+) cells predominantly expressing Mpl effectively proliferated and survived on OP9 stromal cells in the presence of THPO via upregulating BCL-xL expression, suggesting an essential role of the THPO/MPL/BCL-xL cascade in enhancing the progression of Evi1 leukemia. These observations provide a novel aspect of the diverse functions of Evi1 in leukemogenesis. © 2014 by The American Society of Hematology.

  3. [Expression of Notch Gene and Its Role of Anti-apoptosis and Drug-resistance of Cells in Chronic Lymphocytic Leukemia].

    PubMed

    Zhang, Jin-Yan; Zhang, Ju-Shun; Xu, Zhen-Shu

    2015-08-01

    To investigate the expression of Notch gene in chronic lymphocytic leukemia cells and to explore the change of Notch protein after the therapy with cytosine arabinoside or dexmethasone, and the mechanism of Notch mediated anti-apoptosis and drug-resistance in chronic lymphocytic leukemia cells. The mononuclear cells from bone marrow or peripheral blood of chronic lymphocytic leukemia patients (24 cases) and healthy donors (14 cases) were collected, then the expression of Notch gene, BCL-2, as well as NF-κB gene were detected by real-time fluorescent quantitative PCR (qRT-PCR) at the level of transcription. The change of Notch protein in L1210 cell lines after therapy with cytosine arabinoside and dexmethasone was determined by Western blot. mRNA expression levels of Notch1, Notch2, BCL-2 and NF-κB gene in CLL group were significantly higher than those in healthy control group (0.8556 ± 0.8726 vs 0.6731 ± 0.5334, P = 0.0182; 1.2273 ± 0.8207 vs 0.6577 ± 0.6424, P < 0.0001; 8.0960 ± 7.5661 vs 0.5969 ± 0.4976, P < 0.0001; 1.0966 ± 0.6925 vs 0.5373 ± 0.7180, P < 0.0001, respectively), but no significant difference was found between Notch3 and Notch4 gene (1.1914 ± 2.4219 vs 0.8713 ± 0.7937, P = 0.3427; 0.8174 ± 1.0869 vs 0.9752 ± 1.3446, P = 0.2402, respectively). Notch1 protein expression in L1210 cells were significantly decreased after treating with cytosine arabinoside of low and middle concentrations, but increased after treating with cytosine arabinoside of high concentration or prolonging time of cytosine arabinoside of middle con-centration. Notch1 protein expression in L1210 cells dereased after treating with dexamethasone, but did not be changed with the different concentrations and different times of dexmethason. The transcription level of Notch gene in CLL patients significantly higher than that in normal controls. The Notch1 protein expression is down-regulated in process of inhibiting L1210 cell proliferation by Ara-C and dexmethason. Notch

  4. A new inhibitor of synovial phospholipase A2 from fermentations of Penicillium sp. 62-92.

    PubMed

    Witter, L; Anke, T; Sterner, O

    1998-01-01

    Penidiamide, a new tripetide containing dehydrotryptamine, glycine and anthranilic acid linked together by two amide bonds, and oxindole were isolated from submerged cultures of Penicillium sp. 62-92. Both compounds preferentially inhibited human synovial phospholipase A2, penidiamide with an IC50 of 30 microM and oxindole of 380 microM. With the exception of U 937 cells (leukemia, human), no cytotoxic activities were detected against HL-60- (leukemia, human), HeLa S3- (epitheloid carcinoma, human), BHK 21- (kidney fibroblasts, hamster), and L1210-cells (leukemia, mouse). No antimicrobial activity was detected for oxindole, and only weak antibacterial activity for penidiamide. The structure of penidiamide was elucidated by spectroscopic methods.

  5. Modulation of thymus-leukemia antigens on mouse leukemia cells induced by IgG, but not IgM, antibody.

    PubMed

    Stackpole, C W

    1980-04-01

    Exposure of mouse leukemia cells bearing thymus-leukemia (TL) surface antigens to whole TL alloantiserum has previously been shown to desensitize the cells to subsequent lysis by guinea pig complement (C) and fresh antiserum (antigenic modulation) and to correlate with the ability of cells to escape immune destruction in mice immunized against TL antigens. Tested in vitro, IgG of TL.1,2,3,5 antiserum modulated RADA1 leukemia cells (TL.1,2,3,5) completely within 2 hours at 37 degrees C when fully sensitizing amounts were used, with normal mouse serum as a source of C3. Similar results were obtained with IgG1, IgG2a, and IgG2b fractions of TL antiserum. An IgG2a monoclonal TL.3 antibody also completely modulated TL.3 antigens and partially modulated all antigens detected with TL.1,2,3,5 antiserum. IgM anti-TL.1,2,3,5 failed to modulate RADA1 cells even after 6 hours in vitro when fully sensitizing amounts of antibody were used. An IgM monoclonal TL antibody also failed to induce modulation. Modulation did occur on cells incubated with fully sensitizing amounts of IgG and IgM TL.1,2,3,5 antibody simultaneously, and nearly all cell-bound immunoglobulins were IgG. In mice passively immunized with IgG TL antibody, RADA1 cells modulated completely within 24 hours, whereas no modulation occurred during 4 days in mice immunized with IgM antibody. However, in both instances, tumor cells grew actively, which indicated that tumor escape did not depend on achievement of a modulated state.

  6. 7 CFR 1210.327 - Powers.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Powers. 1210.327 Section 1210.327 Agriculture... PLAN Watermelon Research and Promotion Plan National Watermelon Promotion Board § 1210.327 Powers. The Board shall have the following powers subject to § 1210.363: (a) To administer the provisions of this...

  7. 21 CFR 1210.18 - Scoring.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Scoring. 1210.18 Section 1210.18 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER... MILK ACT Inspection and Testing § 1210.18 Scoring. Scoring of sanitary conditions required by §§ 1210...

  8. 21 CFR 1210.18 - Scoring.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Scoring. 1210.18 Section 1210.18 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER... MILK ACT Inspection and Testing § 1210.18 Scoring. Scoring of sanitary conditions required by §§ 1210...

  9. 16 CFR 1210.15 - Specifications.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Specifications. 1210.15 Section 1210.15 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Certification Requirements § 1210.15 Specifications. (a) Requirement...

  10. 7 CFR 1210.324 - Vacancies.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Vacancies. 1210.324 Section 1210.324 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... PLAN Watermelon Research and Promotion Plan National Watermelon Promotion Board § 1210.324 Vacancies...

  11. 7 CFR 1210.343 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false [Reserved] 1210.343 Section 1210.343 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... PLAN Watermelon Research and Promotion Plan Expenses and Assessments § 1210.343 [Reserved] ...

  12. 7 CFR 1210.323 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Acceptance. 1210.323 Section 1210.323 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... PLAN Watermelon Research and Promotion Plan National Watermelon Promotion Board § 1210.323 Acceptance...

  13. 7 CFR 1210.305 - Watermelon.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Watermelon. 1210.305 Section 1210.305 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... PLAN Watermelon Research and Promotion Plan Definitions § 1210.305 Watermelon. Watermelon means all...

  14. 7 CFR 1210.327 - Powers.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan National Watermelon Promotion Board § 1210.327 Powers. The... 7 Agriculture 10 2010-01-01 2010-01-01 false Powers. 1210.327 Section 1210.327 Agriculture...

  15. 7 CFR 1210.312 - Promotion.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Promotion. 1210.312 Section 1210.312 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.312 Promotion. Promotion means any...

  16. 7 CFR 1210.313 - Research.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Research. 1210.313 Section 1210.313 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.313 Research. Research means any type of...

  17. 7 CFR 1210.313 - Research.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Research. 1210.313 Section 1210.313 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.313 Research. Research means any type of...

  18. 7 CFR 1210.313 - Research.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Research. 1210.313 Section 1210.313 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.313 Research. Research means any type of...

  19. 7 CFR 1210.313 - Research.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Research. 1210.313 Section 1210.313 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.313 Research. Research means any type of...

  20. 7 CFR 1210.313 - Research.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Research. 1210.313 Section 1210.313 Agriculture... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.313 Research. Research means any type of...

  1. 7 CFR 1210.308 - Handler.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Handler. 1210.308 Section 1210.308 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... PLAN Watermelon Research and Promotion Plan Definitions § 1210.308 Handler. Handler means any person...

  2. 7 CFR 1210.314 - Importer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Importer. 1210.314 Section 1210.314 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... PLAN Watermelon Research and Promotion Plan Definitions § 1210.314 Importer. Importer means any person...

  3. 7 CFR 1210.306 - Producer.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Producer. 1210.306 Section 1210.306 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... PLAN Watermelon Research and Promotion Plan Definitions § 1210.306 Producer. Producer means any person...

  4. 7 CFR 1210.604 - Subagents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Subagents. 1210.604 Section 1210.604 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... PLAN Referendum Procedures § 1210.604 Subagents. The referendum agent may appoint any individual or...

  5. 7 CFR 1210.309 - Person.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Person. 1210.309 Section 1210.309 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... PLAN Watermelon Research and Promotion Plan Definitions § 1210.309 Person. Person means any individual...

  6. 7 CFR 1210.302 - Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Act. 1210.302 Section 1210.302 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... PLAN Watermelon Research and Promotion Plan Definitions § 1210.302 Act. Act means the Watermelon...

  7. 7 CFR 1210.303 - Plan.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Plan. 1210.303 Section 1210.303 Agriculture... PLAN Watermelon Research and Promotion Plan Definitions § 1210.303 Plan. Plan means this watermelon research and promotion Plan issued by the Secretary pursuant to the Act. ...

  8. 7 CFR 1210.304 - Board.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Board. 1210.304 Section 1210.304 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... PLAN Watermelon Research and Promotion Plan Definitions § 1210.304 Board. Board means the National...

  9. [Effect of topical application of a recombinant adenovirus carrying promyelocytic leukemia gene in a psoriasis-like mouse model].

    PubMed

    Wang, Qiongyu; Zhang, Aijun; Ma, Huiqun; Wang, Shijie; Ma, Yunyun; Zou, Xingwei; Li, Ruilian

    2013-03-01

    To investigate the effects of topical treatment with adenovirus-mediated promyelocytic leukemia gene (PML) gene in a psoriasis-like mouse model. The effect of adenovirus-mediated PML gene on the granular layer of mouse tail scale epidermis and epithelial mitosis were observed on longitudinal histological sections prepared from the tail skin and vaginal epithelium of the mice. Adenovirus-mediated PML gene significantly inhibited mitosis of mouse vaginal epithelial cells and promoted the formation of granular layer in mouse tail scale epidermis. The therapeutic effect of PML gene in the psoriasis-like mouse model may be associated with increased granular cells and suppressed epidemic cell proliferation.

  10. Retinoic Acid and Arsenic Synergize to Eradicate Leukemic Cells in a Mouse Model of Acute Promyelocytic Leukemia

    PubMed Central

    Lallemand-Breitenbach, Valérie; Guillemin, Marie-Claude; Janin, Anne; Daniel, Marie-Thérèse; Degos, Laurent; Kogan, Scott C.; Michael Bishop, J.; de Thé, Hugues

    1999-01-01

    In acute promyelocytic leukemia (APL) patients, retinoic acid (RA) triggers differentiation while arsenic trioxide (arsenic) induces both a partial differentiation and apoptosis. Although their mechanisms of action are believed to be distinct, these two drugs both induce the catabolism of the oncogenic promyelocytic leukemia (PML)/RARα fusion protein. While APL cell lines resistant to one agent are sensitive to the other, the benefit of combining RA and arsenic in cell culture is controversial, and thus far, no data are available in patients. Using syngenic grafts of leukemic blasts from PML/RARα transgenic mice as a model for APL, we demonstrate that arsenic induces apoptosis and modest differentiation, and prolongs mouse survival. Furthermore, combining arsenic with RA accelerates tumor regression through enhanced differentiation and apoptosis. Although RA or arsenic alone only prolongs survival two- to threefold, associating the two drugs leads to tumor clearance after a 9-mo relapse-free period. These studies establishing RA/arsenic synergy in vivo prompt the use of combined arsenic/RA treatments in APL patients and exemplify how mouse models of human leukemia can be used to design or optimize therapies. PMID:10190895

  11. 7 CFR 1210.301 - Secretary.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Secretary. 1210.301 Section 1210.301 Agriculture... PLAN Watermelon Research and Promotion Plan Definitions § 1210.301 Secretary. Secretary means the Secretary of Agriculture of the United States or any officer or employee of the Department to whom authority...

  12. 7 CFR 1210.301 - Secretary.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Secretary. 1210.301 Section 1210.301 Agriculture... PLAN Watermelon Research and Promotion Plan Definitions § 1210.301 Secretary. Secretary means the Secretary of Agriculture of the United States or any officer or employee of the Department to whom authority...

  13. 7 CFR 1210.301 - Secretary.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Secretary. 1210.301 Section 1210.301 Agriculture... PLAN Watermelon Research and Promotion Plan Definitions § 1210.301 Secretary. Secretary means the Secretary of Agriculture of the United States or any officer or employee of the Department to whom authority...

  14. 7 CFR 1210.301 - Secretary.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Secretary. 1210.301 Section 1210.301 Agriculture... PLAN Watermelon Research and Promotion Plan Definitions § 1210.301 Secretary. Secretary means the Secretary of Agriculture of the United States or any officer or employee of the Department to whom authority...

  15. 7 CFR 1210.301 - Secretary.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Secretary. 1210.301 Section 1210.301 Agriculture... PLAN Watermelon Research and Promotion Plan Definitions § 1210.301 Secretary. Secretary means the Secretary of Agriculture of the United States or any officer or employee of the Department to whom authority...

  16. 21 CFR 1210.13 - Tuberculin test.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Tuberculin test. 1210.13 Section 1210.13 Food and... IMPORT MILK ACT Inspection and Testing § 1210.13 Tuberculin test. (a) Except as provided in § 1210.27 any... United States shall be free from tuberculosis, as determined by a tuberculin test applied by an official...

  17. 7 CFR 1210.350 - Reports.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Reports. 1210.350 Section 1210.350 Agriculture... PLAN Watermelon Research and Promotion Plan Reports, Books, and Records § 1210.350 Reports. (a) Each... watermelons produced and handled by the handler. Handlers shall report to the Board at such times and in such...

  18. 7 CFR 1210.350 - Reports.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Reports. 1210.350 Section 1210.350 Agriculture... PLAN Watermelon Research and Promotion Plan Reports, Books, and Records § 1210.350 Reports. (a) Each... watermelons produced and handled by the handler. Handlers shall report to the Board at such times and in such...

  19. Induction of apoptosis and cell cycle arrest in L-1210 murine lymphoblastic leukaemia cells by (2E)-3-(2-naphthyl)-1-(3'-methoxy-4'-hydroxy-phenyl)-2-propen-1-one.

    PubMed

    Pedrini, Fernanda Spezia; Chiaradia, Louise Domeneghini; Licínio, Marley Aparecida; de Moraes, Ana Carolina Rabello; Curta, Juliana Costa; Costa, Aline; Mascarello, Alessandra; Creczinsky-Pasa, Tânia Beatriz; Nunes, Ricardo José; Yunes, Rosendo Augusto; Santos-Silva, Maria Cláudia

    2010-09-01

    New compounds with biological targets and less cytotoxicity to normal cells are necessary for cancer therapy. In this work ten synthetic chalcones derived from 2-naphtaldehyde were evaluated for their cytotoxic effect in murine acute lymphoblastic leukemia cells L-1210. A series of ten chalcones derived from 2-naphtaldehyde and corresponding acetophenones were prepared by aldolic condensation, using methanol as solvent under basic conditions, at room temperature for 24 h. The cell viability was determined by MTT colorimeter method. The cell cycle phase analysis was carried out by flow cytometry after propidium iodide staining. The apoptosis induction was assessed by exposure to phosphatidylserine (ANNEXIN V-FITC). Cytometric analysis was performed to evaluate the expression of p53, Bcl-2 and Bax protein. The caspase-3 expression was studied by immunoblotting analysis. A preliminary screening of a series of ten chalcones derived from 2-naphtaldehyde showed that chalcone 8, (2E)-3-(2-naphtyl)-1-(3'-methoxy-4'-hydroxy-phenyl)-2-propen-1-one, had the highest cytotoxic effect (IC50 of 54 microM), but not in normal human lymphocytes. To better understand the cytotoxic mechanism of chalcone 8, its effect on cell cycle and apoptosis was assessed. Our results showed that chalcone 8 caused cell cycle arrest in the G2/M phase and a significant increase in the proportion of cells in the subG0/G1 phase. Our results also demonstrated that chalcone 8 promoted a modification in Bax:Bcl-2 ratio and increased p53 expression and caspase-3 activation. The studied chalcone 8 has cytotoxic effect against L-1210 lymphoblastic leukaemic cells, and this effect is associated with increase of p-53 and Bax expression.

  20. 16 CFR 1210.12 - Certificate of compliance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 1210.12 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Certification Requirements § 1210.12 Certificate of compliance. (a..., based on a reasonable testing program or a test of each product, as required by §§ 1210.13-1210.14 and...

  1. 16 CFR 1210.14 - Qualification testing.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Qualification testing. 1210.14 Section 1210.14 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Certification Requirements § 1210.14 Qualification testing. (a...

  2. 16 CFR 1210.16 - Production testing.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Production testing. 1210.16 Section 1210.16 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Certification Requirements § 1210.16 Production testing. (a) General...

  3. 7 CFR 1210.315 - United States.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false United States. 1210.315 Section 1210.315 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... PLAN Watermelon Research and Promotion Plan Definitions § 1210.315 United States. United States means...

  4. 7 CFR 1210.315 - United States.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false United States. 1210.315 Section 1210.315 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... PLAN Watermelon Research and Promotion Plan Definitions § 1210.315 United States. United States means...

  5. 7 CFR 1210.315 - United States.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false United States. 1210.315 Section 1210.315 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... PLAN Watermelon Research and Promotion Plan Definitions § 1210.315 United States. United States means...

  6. 7 CFR 1210.315 - United States.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false United States. 1210.315 Section 1210.315 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... PLAN Watermelon Research and Promotion Plan Definitions § 1210.315 United States. United States means...

  7. 16 CFR § 1210.15 - Specifications.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Specifications. § 1210.15 Section § 1210.15 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Certification Requirements § 1210.15 Specifications. (a...

  8. 16 CFR 1210.13 - Certification tests.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Certification tests. 1210.13 Section 1210.13 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Certification Requirements § 1210.13 Certification tests. (a) General. As...

  9. 7 CFR 1210.344 - Operating reserve.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Operating reserve. 1210.344 Section 1210.344 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... PROMOTION PLAN Watermelon Research and Promotion Plan Expenses and Assessments § 1210.344 Operating reserve...

  10. 16 CFR 1210.13 - Certification tests.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Certification tests. 1210.13 Section 1210.13 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Certification Requirements § 1210.13 Certification tests. (a) General. As...

  11. Production of feline leukemia inhibitory factor with biological activity in Escherichia coli.

    PubMed

    Kanegi, R; Hatoya, S; Tsujimoto, Y; Takenaka, S; Nishimura, T; Wijewardana, V; Sugiura, K; Takahashi, M; Kawate, N; Tamada, H; Inaba, T

    2016-07-15

    Leukemia inhibitory factor (LIF) is a cytokine which is essential for oocyte and embryo development, embryonic stem cell, and induced pluripotent stem cell maintenance. Leukemia inhibitory factor improves the maturation of oocytes in the human and the mouse. However, feline LIF (fLIF) cloning and effects on oocytes during IVM have not been reported. Thus, we cloned complete cDNA of fLIF and examined its biological activity and effects on oocytes during IVM in the domestic cat. The aminoacid sequence of fLIF revealed a homology of 81% or 92% with that of mouse or human. The fLIF produced by pCold TF DNA in Escherichia coli was readily soluble and after purification showed bioactivity in maintaining the undifferentiated state of mouse embryonic stem cells and enhancing the proliferation of human erythrocyte leukemia cells. Furthermore, 10- and 100-ng/mL fLIF induced cumulus expansion with or without FSH and EGF (P < 0.05). The rate of metaphase II oocytes was also improved with 100-ng/mL fLIF (P < 0.05). We therefore confirmed the successful production for the first time of biologically active fLIF and revealed its effects on oocytes during IVM in the domestic cat. Feline LIF will further improve reproduction and stem cell research in the feline family. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. 16 CFR 1210.16 - Production testing.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... in the manufacturing process, the assembly process, the equipment used to manufacture the product, or... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Production testing. 1210.16 Section 1210.16... STANDARD FOR CIGARETTE LIGHTERS Certification Requirements § 1210.16 Production testing. (a) General...

  13. 16 CFR 1210.13 - Certification tests.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Certification tests. 1210.13 Section 1210.13... STANDARD FOR CIGARETTE LIGHTERS Certification Requirements § 1210.13 Certification tests. (a) General. As... reasonable testing programs shall include qualification tests, which must be performed on surrogates of each...

  14. 21 CFR 582.1210 - Calcium oxide.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Calcium oxide. 582.1210 Section 582.1210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1210 Calcium oxide. (a) Product. Calcium oxide. (b) Conditions of use. This substance is generally...

  15. 21 CFR 582.1210 - Calcium oxide.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium oxide. 582.1210 Section 582.1210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1210 Calcium oxide. (a) Product. Calcium oxide. (b) Conditions of use. This substance is generally...

  16. 21 CFR 582.1210 - Calcium oxide.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Calcium oxide. 582.1210 Section 582.1210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1210 Calcium oxide. (a) Product. Calcium oxide. (b) Conditions of use. This substance is generally...

  17. 21 CFR 582.1210 - Calcium oxide.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Calcium oxide. 582.1210 Section 582.1210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1210 Calcium oxide. (a) Product. Calcium oxide. (b) Conditions of use. This substance is generally...

  18. 21 CFR 582.1210 - Calcium oxide.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Calcium oxide. 582.1210 Section 582.1210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1210 Calcium oxide. (a) Product. Calcium oxide. (b) Conditions of use. This substance is generally...

  19. 7 CFR 1210.315 - United States.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false United States. 1210.315 Section 1210.315 Agriculture... PLAN Watermelon Research and Promotion Plan Definitions § 1210.315 United States. United States means each of the several States and the District of Columbia. [60 FR 10797, Feb. 28, 1995] National...

  20. 21 CFR 1210.21 - Permit number.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Permit number. 1210.21 Section 1210.21 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS... IMPORT MILK ACT Permit Control § 1210.21 Permit number. Each permit issued under the Federal Import Milk...

  1. 21 CFR 1210.21 - Permit number.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Permit number. 1210.21 Section 1210.21 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS... IMPORT MILK ACT Permit Control § 1210.21 Permit number. Each permit issued under the Federal Import Milk...

  2. 16 CFR 1210.4 - Test protocol.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Test protocol. 1210.4 Section 1210.4... STANDARD FOR CIGARETTE LIGHTERS Requirements for Child Resistance § 1210.4 Test protocol. (a) Child test panel. (1) The test to determine if a lighter is resistant to successful operation by children uses a...

  3. 21 CFR 184.1210 - Calcium oxide.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Calcium oxide. 184.1210 Section 184.1210 Food and....1210 Calcium oxide. (a) Calcium oxide (CaO, CAS Reg. No. 1305-78-8) is also known as lime, quick lime, burnt lime, or calx. It is produced from calcium carbonate, limestone, or oyster shells by calcination...

  4. 21 CFR 1210.21 - Permit number.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Permit number. 1210.21 Section 1210.21 Food and... IMPORT MILK ACT Permit Control § 1210.21 Permit number. Each permit issued under the Federal Import Milk Act, including each temporary permit, shall bear an individual number. The right to the use of such...

  5. 21 CFR 1210.21 - Permit number.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Permit number. 1210.21 Section 1210.21 Food and... IMPORT MILK ACT Permit Control § 1210.21 Permit number. Each permit issued under the Federal Import Milk Act, including each temporary permit, shall bear an individual number. The right to the use of such...

  6. 21 CFR 1210.21 - Permit number.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Permit number. 1210.21 Section 1210.21 Food and... IMPORT MILK ACT Permit Control § 1210.21 Permit number. Each permit issued under the Federal Import Milk Act, including each temporary permit, shall bear an individual number. The right to the use of such...

  7. Sequence Diversity, Intersubgroup Relationships, and Origins of the Mouse Leukemia Gammaretroviruses of Laboratory and Wild Mice.

    PubMed

    Bamunusinghe, Devinka; Naghashfar, Zohreh; Buckler-White, Alicia; Plishka, Ronald; Baliji, Surendranath; Liu, Qingping; Kassner, Joshua; Oler, Andrew J; Hartley, Janet; Kozak, Christine A

    2016-04-01

    Mouse leukemia viruses (MLVs) are found in the common inbred strains of laboratory mice and in the house mouse subspecies ofMus musculus Receptor usage and envelope (env) sequence variation define three MLV host range subgroups in laboratory mice: ecotropic, polytropic, and xenotropic MLVs (E-, P-, and X-MLVs, respectively). These exogenous MLVs derive from endogenous retroviruses (ERVs) that were acquired by the wild mouse progenitors of laboratory mice about 1 million years ago. We analyzed the genomes of seven MLVs isolated from Eurasian and American wild mice and three previously sequenced MLVs to describe their relationships and identify their possible ERV progenitors. The phylogenetic tree based on the receptor-determining regions ofenvproduced expected host range clusters, but these clusters are not maintained in trees generated from other virus regions. Colinear alignments of the viral genomes identified segmental homologies to ERVs of different host range subgroups. Six MLVs show close relationships to a small xenotropic ERV subgroup largely confined to the inbred mouse Y chromosome.envvariations define three E-MLV subtypes, one of which carries duplications of various sizes, sequences, and locations in the proline-rich region ofenv Outside theenvregion, all E-MLVs are related to different nonecotropic MLVs. These results document the diversity in gammaretroviruses isolated from globally distributedMussubspecies, provide insight into their origins and relationships, and indicate that recombination has had an important role in the evolution of these mutagenic and pathogenic agents. Laboratory mice carry mouse leukemia viruses (MLVs) of three host range groups which were acquired from their wild mouse progenitors. We sequenced the complete genomes of seven infectious MLVs isolated from geographically separated Eurasian and American wild mice and compared them with endogenous germ line retroviruses (ERVs) acquired early in house mouse evolution. We did this

  8. Assessment in vitro of the genotoxicity, antigenotoxicity and antioxidant of Ceratonia siliqua L. extracts in murine leukaemia cells L1210 by comet assay.

    PubMed

    Sassi, Aïcha; Bouhlel, Ines; Mustapha, Nadia; Mokdad-Bzeouich, Imen; Chaabane, Fadwa; Ghedira, Kamel; Chekir-Ghedira, Leila

    2016-06-01

    Genotoxicity of Ceratonia siliqua extracts, was investigated by assessing their capacity to induce nucleus DNA degradation of murine leukaemia cells L1210, using the "Comet assay". The ability of total oligomer flavonoids (TOF) and aqueous extracts to protect cell DNA against oxidative stress induced by H2O2, was performed by pre- co or post-treatment of cells with the before mentioned extracts for different periods preceding exposure to H2O2 stress. No significant genotoxic effect was detected at different exposure times, except at the lowest concentration of TOF extract (16.25 μg/ml). It appears that extracts decreased DNA damage, induced by H2O2. Both of TOF and aqueous extracts exhibited cellular antioxidant capacity, with EC50 values of respectively <16.25 and < 35 μg/ml, as well as, a protective capacity against lipidperoxidation inducing using L1210 cells line as a cellular model. MDA inhibition percentages reached 88.43% and 90.52% with respectively 35.5 μg/ml of TOF extract and 70 μg/ml of aqueous extract. Antioxidant properties of carob leaf extracts revealed by our study make a good antioxidant protection and thus a good candidate as food addition component. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. 21 CFR 184.1210 - Calcium oxide.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium oxide. 184.1210 Section 184.1210 Food and... Substances Affirmed as GRAS § 184.1210 Calcium oxide. (a) Calcium oxide (CaO, CAS Reg. No. 1305-78-8) is also known as lime, quick lime, burnt lime, or calx. It is produced from calcium carbonate, limestone, or...

  10. 21 CFR 184.1210 - Calcium oxide.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Calcium oxide. 184.1210 Section 184.1210 Food and... Substances Affirmed as GRAS § 184.1210 Calcium oxide. (a) Calcium oxide (CaO, CAS Reg. No. 1305-78-8) is also known as lime, quick lime, burnt lime, or calx. It is produced from calcium carbonate, limestone, or...

  11. 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

  12. 16 CFR 1210.18 - Refusal of importation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Refusal of importation. 1210.18 Section 1210.18 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Certification Requirements § 1210.18 Refusal of importation. (a...

  13. 10 CFR 603.1210 - Articles of collaboration.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Articles of collaboration. 603.1210 Section 603.1210 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Definitions of Terms Used in this Part § 603.1210 Articles of collaboration. An agreement among the...

  14. 10 CFR 603.1210 - Articles of collaboration.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Articles of collaboration. 603.1210 Section 603.1210 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Definitions of Terms Used in this Part § 603.1210 Articles of collaboration. An agreement among the...

  15. 10 CFR 603.1210 - Articles of collaboration.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Articles of collaboration. 603.1210 Section 603.1210 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Definitions of Terms Used in this Part § 603.1210 Articles of collaboration. An agreement among the...

  16. 10 CFR 603.1210 - Articles of collaboration.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Articles of collaboration. 603.1210 Section 603.1210 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Definitions of Terms Used in this Part § 603.1210 Articles of collaboration. An agreement among the...

  17. 10 CFR 603.1210 - Articles of collaboration.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Articles of collaboration. 603.1210 Section 603.1210 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Definitions of Terms Used in this Part § 603.1210 Articles of collaboration. An agreement among the...

  18. 7 CFR 1210.321 - Nominations and selection.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Nominations and selection. 1210.321 Section 1210.321 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... PROMOTION PLAN Watermelon Research and Promotion Plan National Watermelon Promotion Board § 1210.321...

  19. 36 CFR 1210.37 - Property trust relationship.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Property trust relationship. 1210.37 Section 1210.37 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS... Standards § 1210.37 Property trust relationship. Real property, equipment, intangible property and debt...

  20. 16 CFR 1210.15 - Specifications.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Certification Requirements § 1210.15 Specifications. (a) Requirement... described in a written product specification. (Section 1210.4(c) requires that six surrogate lighters be...

  1. 16 CFR § 1210.14 - Qualification testing.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Qualification testing. § 1210.14 Section § 1210.14 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Certification Requirements § 1210.14 Qualification testing. (a...

  2. 21 CFR 870.1210 - Continuous flush catheter.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Continuous flush catheter. 870.1210 Section 870.1210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Diagnostic Devices § 870.1210 Continuous flush...

  3. 16 CFR § 1210.13 - Certification tests.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Certification tests. § 1210.13 Section § 1210.13 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Certification Requirements § 1210.13 Certification tests. (a...

  4. 16 CFR § 1210.16 - Production testing.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Production testing. § 1210.16 Section § 1210.16 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Certification Requirements § 1210.16 Production testing. (a...

  5. 7 CFR 1210.322 - Term of office.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Term of office. 1210.322 Section 1210.322 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... PLAN Watermelon Research and Promotion Plan National Watermelon Promotion Board § 1210.322 Term of...

  6. 21 CFR 870.1210 - Continuous flush catheter.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Continuous flush catheter. 870.1210 Section 870.1210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Diagnostic Devices § 870.1210 Continuous flush...

  7. 7 CFR 1210.602 - Voting.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Voting. 1210.602 Section 1210.602 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... each producer in a landlord-tenant relationship or a divided ownership arrangement involving totally...

  8. 7 CFR 1210.340 - Budget and expenses.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Budget and expenses. 1210.340 Section 1210.340... PROMOTION PLAN Watermelon Research and Promotion Plan Expenses and Assessments § 1210.340 Budget and... shall prepare and recommend a budget on a fiscal period basis of its anticipated expenses and...

  9. 7 CFR 1210.325 - Procedure.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Procedure. 1210.325 Section 1210.325 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... mail, telegraph, telephone, or by other means of communication; Provided, That each member receives an...

  10. 7 CFR 1210.325 - Procedure.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Procedure. 1210.325 Section 1210.325 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... mail, telegraph, telephone, or by other means of communication; Provided, That each member receives an...

  11. 36 CFR 13.1210 - Firearms.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ....1210 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Katmai National Park and Preserve General Provisions § 13.1210 Firearms. The superintendent may designate areas or routes within Katmai National Park where...

  12. 7 CFR 1210.362 - Influencing government action.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Influencing government action. 1210.362 Section 1210... RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Miscellaneous § 1210.362 Influencing government action. No funds received by the Board under this Plan shall in any manner be used for the purpose...

  13. 7 CFR 1210.362 - Influencing government action.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Influencing government action. 1210.362 Section 1210... RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Miscellaneous § 1210.362 Influencing government action. No funds received by the Board under this Plan shall in any manner be used for the purpose...

  14. 7 CFR 1210.351 - Books and records.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Books and records. 1210.351 Section 1210.351... PROMOTION PLAN Watermelon Research and Promotion Plan Reports, Books, and Records § 1210.351 Books and... make available for inspection by employees of the Board or Secretary, such books and records as are...

  15. 7 CFR 1210.351 - Books and records.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Books and records. 1210.351 Section 1210.351... PROMOTION PLAN Watermelon Research and Promotion Plan Reports, Books, and Records § 1210.351 Books and... make available for inspection by employees of the Board or Secretary, such books and records as are...

  16. 7 CFR 1210.351 - Books and records.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Books and records. 1210.351 Section 1210.351... PROMOTION PLAN Watermelon Research and Promotion Plan Reports, Books, and Records § 1210.351 Books and... make available for inspection by employees of the Board or Secretary, such books and records as are...

  17. 7 CFR 1210.351 - Books and records.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Books and records. 1210.351 Section 1210.351... PROMOTION PLAN Watermelon Research and Promotion Plan Reports, Books, and Records § 1210.351 Books and... make available for inspection by employees of the Board or Secretary, such books and records as are...

  18. 7 CFR 1210.351 - Books and records.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Books and records. 1210.351 Section 1210.351... PROMOTION PLAN Watermelon Research and Promotion Plan Reports, Books, and Records § 1210.351 Books and... make available for inspection by employees of the Board or Secretary, such books and records as are...

  19. 21 CFR 862.1210 - Creatine test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Creatine test system. 862.1210 Section 862.1210....1210 Creatine test system. (a) Identification. A creatine test system is a device intended to measure creatine (a substance synthesized in the liver and pancreas and found in biological fluids) in plasma...

  20. 7 CFR 1210.307 - Handle.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Handle. 1210.307 Section 1210.307 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS..., process, sell, transport, purchase, or in any other way to place or cause watermelons to which one has...

  1. 9 CFR 12.10 - Stipulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Stipulations. 12.10 Section 12.10 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE RULES OF PRACTICE GOVERNING PROCEEDINGS UNDER THE HORSE PROTECTION ACT Supplemental Rules of...

  2. 7 CFR 1210.605 - Ballots.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Ballots. 1210.605 Section 1210.605 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS..., the agent or subagent shall endorse above their signature, on the ballot, a statement to the effect...

  3. Immunohistochemical detection of Ym1/Ym2 chitinase-like lectins associated with hyalinosis and polypoid adenomas of the transitional epithelium in a mouse with acute myeloid leukemia.

    PubMed

    Marchesi, F; Minucci, S; Pelicci, P G; Gobbi, A; Scanziani, E

    2006-09-01

    An 8-month-old PML/RARalpha knock-in female mouse developed a promyelocytic-like myeloid leukemia with an expected latency. At necropsy, besides the typical findings associated with myeloid leukemia, a severe unilateral hydronephrosis was observed. By histopathologic examination, 2 polypoid adenomas arising from the transitional epithelium of the renal pelvis and ureter were detected. The epithelial cells of the polypoid adenomas showed accumulation of hyaline eosinophilic material within the cytoplasm. Large amounts of extracellular eosinophilic crystals were also associated with the transitional cell adenomas. Immunohistochemical analysis revealed that the eosinophilic intracytoplasmic material and the extracellular eosinophilic crystals were composed of Ym proteins. A unilateral hyaline droplet tubular nephropathy was associated with the myeloid leukemia. Expression of Ym proteins characterized both the neoplastic myeloid infiltrates and the tubular hyaline droplets. In the present PML/RARalpha knock-in female mouse, the accumulation of Ym proteins associated with the myeloid leukemia and with the polypoid adenomas of the transitional epithelium underlies 2 distinct pathogenetic mechanisms.

  4. 16 CFR 1210.2 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... STANDARD FOR CIGARETTE LIGHTERS Requirements for Child Resistance § 1210.2 Definitions. As used in this part 1210: (a) Cigarette lighter. See lighter. (b) Disposable lighter—means a lighter that either is..., is $2.25. (c) Lighter, also referred to as cigarette lighter, means a flame-producing product...

  5. 21 CFR 1210.1 - Authority.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Authority. 1210.1 Section 1210.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION REGULATIONS UNDER THE FEDERAL IMPORT...

  6. 36 CFR 1210.43 - Competition.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Competition. 1210.43 Section..., HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Post-Award Requirements Procurement Standards § 1210.43 Competition. All procurement transactions shall be conducted in a manner to provide, to the maximum extent...

  7. 21 CFR 1210.2 - Scope of act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Scope of act. 1210.2 Section 1210.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER... MILK ACT General Provisions § 1210.2 Scope of act. The provisions of the act apply to all milk and...

  8. 21 CFR 1210.2 - Scope of act.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Scope of act. 1210.2 Section 1210.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER... MILK ACT General Provisions § 1210.2 Scope of act. The provisions of the act apply to all milk and...

  9. [Combination chemotherapy of experimental leukemia].

    PubMed

    Emanuel', N M; Konovalova, N P; D'iachkovskaia, R F

    1977-01-01

    In the present work an attempt was made to gain greater therapeutic effect of diazane coupled with adriamycin and sarcolysin. Leucemias L-1210 and La served as a model. In leucosis La diazane was injected once in 5 days. Either an additional injection of adriamycin two days prior to diazane injection or sarcolysin injected simultaneously with diazane enabled the authors to obtain a distinct synergestic effect. In leucemia L-1210 a simultaneous administration of diazane and sarcolysin also contributes to considerably longer survival of leucemic animals. Such combinations are likely to be promising in their clinical use.

  10. Effects of leukemia inhibitory factor and basic fibroblast growth factor on free radicals and endogenous stem cell proliferation in a mouse model of cerebral infarction.

    PubMed

    Huang, Weihui; Li, Yadan; Lin, Yufeng; Ye, Xue; Zang, Dawei

    2012-07-05

    The present study established a mouse model of cerebral infarction by middle cerebral artery occlusion, and monitored the effect of 25 μg/kg leukemia inhibitory factor and (or) basic fibroblast growth factor administration 2 hours after model establishment. Results showed that following administration, the number of endogenous neural stem cells in the infarct area significantly increased, malondialdehyde content in brain tissue homogenates significantly decreased, nitric oxide content, glutathione peroxidase and superoxide dismutase activity significantly elevated, and mouse motor function significantly improved as confirmed by the rotarod and bar grab tests. In particular, the effect of leukemia inhibitory factor in combination with basic fibroblast growth factor was the most significant. Results indicate that leukemia inhibitory factor and basic fibroblast growth factor can improve the microenvironment after cerebral infarction by altering free radical levels, improving the quantity of endogenous neural stem cells, and promoting neurological function of mice with cerebral infarction.

  11. A new class of nitrosoureas. 4. Synthesis and antitumor activity of disaccharide derivatives of 3,3-disubstituted 1-(2-chloroethyl)-1-nitrosoureas.

    PubMed

    Tsujihara, K; Ozeki, M; Morikawa, T; Kawamori, M; Akaike, Y; Arai, Y

    1982-04-01

    A series of 33 N-(2-chloroethyl)-N-nitrosocarbamoyl derivatives of N-substituted glycosylamines has been prepared and tested for antitumor activities. The compounds were obtained by reaction of glycosylamines with isocyanate, followed by nitrosation with N2O4. Structure-activity relationships of these trisubstituted nitrosoureas were investigated by varying the N-substituents and disaccharide groups and by comparing them with the corresponding disubstituted analogues. A large number of the nitrosoureas bearing a maltosyl group exhibited strong antitumor activities against leukemia L1210 and Ehrlich ascites carcinoma, and 60-day survivors against leukemia L1210 were found at the optimal dose for these derivatives. In contrast, the lactosyl and the melibiosyl derivatives were almost inactive. The most interesting compound in this series, the 3-isobutyl-3-maltosyl derivative (37), was tested against leukemia L1210 by single and multiple treatment. Its therapeutic ratio (96.3) obtained by multiple treatment is 3 times larger than that (31.5) obtained by single treatment, suggesting a possible clinical utility of 37 by multiple treatment. The favorable effect of a maltosyl moiety in this class of compounds is discussed.

  12. 7 CFR 12.10 - Scheme or device.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Scheme or device. 12.10 Section 12.10 Agriculture... § 12.10 Scheme or device. All or any part of the benefits listed in § 12.4 otherwise due a person from... scheme or device designed to evade, or which has the effect of evading, the provisions of this part. Such...

  13. 7 CFR 12.10 - Scheme or device.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 1 2014-01-01 2014-01-01 false Scheme or device. 12.10 Section 12.10 Agriculture... § 12.10 Scheme or device. All or any part of the benefits listed in § 12.4 otherwise due a person from... scheme or device designed to evade, or which has the effect of evading, the provisions of this part. Such...

  14. 7 CFR 12.10 - Scheme or device.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 1 2013-01-01 2013-01-01 false Scheme or device. 12.10 Section 12.10 Agriculture... § 12.10 Scheme or device. All or any part of the benefits listed in § 12.4 otherwise due a person from... scheme or device designed to evade, or which has the effect of evading, the provisions of this part. Such...

  15. 7 CFR 12.10 - Scheme or device.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 1 2011-01-01 2011-01-01 false Scheme or device. 12.10 Section 12.10 Agriculture... § 12.10 Scheme or device. All or any part of the benefits listed in § 12.4 otherwise due a person from... scheme or device designed to evade, or which has the effect of evading, the provisions of this part. Such...

  16. 7 CFR 12.10 - Scheme or device.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 1 2012-01-01 2012-01-01 false Scheme or device. 12.10 Section 12.10 Agriculture... § 12.10 Scheme or device. All or any part of the benefits listed in § 12.4 otherwise due a person from... scheme or device designed to evade, or which has the effect of evading, the provisions of this part. Such...

  17. Quantitation of human thymus/leukemia-associated antigen by radioimmunoassay in different forms of leukemia.

    PubMed

    Chechik, B E; Jason, J; Shore, A; Baker, M; Dosch, H M; Gelfand, E W

    1979-12-01

    Using a radioimmunoassay, increased levels of a human thymus/leukemia-associated antigen (HThy-L) have been detected in leukemic cells and plasma from most patients with E-rosette-positive acute lymphoblastic leukemia (ALL) and a number of patients with E-rosette-negative ALL, acute myeloblastic leukemia (AML), acute monomyelocytic leukemia (AMML), and acute undifferentiated leukemia (AVL). Low levels of HThy-L have been demonstrated in white cells from patients with chronic myelocytic leukemia (stable phase) and in mononuclear cells from patients with chronic lymphatic leukemia. The relationship between HThy-L and differentiation of hematopoietic cells is discussed.

  18. The OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse model

    PubMed Central

    Mercher, Thomas; Raffel, Glen D.; Moore, Sandra A.; Cornejo, Melanie G.; Baudry-Bluteau, Dominique; Cagnard, Nicolas; Jesneck, Jonathan L.; Pikman, Yana; Cullen, Dana; Williams, Ifor R.; Akashi, Koichi; Shigematsu, Hirokazu; Bourquin, Jean-Pierre; Giovannini, Marco; Vainchenker, William; Levine, Ross L.; Lee, Benjamin H.; Bernard, Olivier A.; Gilliland, D. Gary

    2009-01-01

    Acute megakaryoblastic leukemia (AMKL) is a form of acute myeloid leukemia (AML) associated with a poor prognosis. The genetics and pathophysiology of AMKL are not well understood. We generated a knockin mouse model of the one twenty-two–megakaryocytic acute leukemia (OTT-MAL) fusion oncogene that results from the t(1;22)(p13;q13) translocation specifically associated with a subtype of pediatric AMKL. We report here that OTT-MAL expression deregulated transcriptional activity of the canonical Notch signaling pathway transcription factor recombination signal binding protein for immunoglobulin κ J region (RBPJ) and caused abnormal fetal megakaryopoiesis. Furthermore, cooperation between OTT-MAL and an activating mutation of the thrombopoietin receptor myeloproliferative leukemia virus oncogene (MPL) efficiently induced a short-latency AMKL that recapitulated all the features of human AMKL, including megakaryoblast hyperproliferation and maturation block, thrombocytopenia, organomegaly, and extensive fibrosis. Our results establish that concomitant activation of RBPJ (Notch signaling) and MPL (cytokine signaling) transforms cells of the megakaryocytic lineage and suggest that specific targeting of these pathways could be of therapeutic value for human AMKL. PMID:19287095

  19. 7 CFR 1210.360 - Right of the Secretary.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Right of the Secretary. 1210.360 Section 1210.360 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... PROMOTION PLAN Watermelon Research and Promotion Plan Miscellaneous § 1210.360 Right of the Secretary. All...

  20. Genetically engineered mouse models of human B-cell precursor leukemias.

    PubMed

    Hauer, Julia; Borkhardt, Arndt; Sánchez-García, Isidro; Cobaleda, César

    2014-01-01

    B-cell precursor acute lymphoblastic leukemias (pB-ALLs) are the most frequent type of malignancies of the childhood, and also affect an important proportion of adult patients. In spite of their apparent homogeneity, pB-ALL comprises a group of diseases very different both clinically and pathologically, and with very diverse outcomes as a consequence of their biology, and underlying molecular alterations. Their understanding (as a prerequisite for their cure) will require a sustained multidisciplinary effort from professionals coming from many different fields. Among all the available tools for pB-ALL research, the use of animal models stands, as of today, as the most powerful approach, not only for the understanding of the origin and evolution of the disease, but also for the development of new therapies. In this review we go over the most relevant (historically, technically or biologically) genetically engineered mouse models (GEMMs) of human pB-ALLs that have been generated over the last 20 years. Our final aim is to outline the most relevant guidelines that should be followed to generate an "ideal" animal model that could become a standard for the study of human pB-ALL leukemia, and which could be shared among research groups and drug development companies in order to unify criteria for studies like drug testing, analysis of the influence of environmental risk factors, or studying the role of both low-penetrance mutations and cancer susceptibility alterations.

  1. 16 CFR § 1210.18 - Refusal of importation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Refusal of importation. § 1210.18 Section § 1210.18 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Certification Requirements § 1210.18 Refusal of importation. (a...

  2. 36 CFR 1210.3 - Effect on other issuances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Effect on other issuances. 1210.3 Section 1210.3 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION... EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS General § 1210.3 Effect on other issuances. For...

  3. 45 CFR 1210.3-10 - Reinstatement of Volunteer.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Reinstatement of Volunteer. 1210.3-10 Section 1210... COMMUNITY SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early Termination § 1210.3-10 Reinstatement of Volunteer. (a) If the Regional Director or Director of VISTA...

  4. 45 CFR 1210.3-10 - Reinstatement of Volunteer.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 4 2014-10-01 2014-10-01 false Reinstatement of Volunteer. 1210.3-10 Section 1210... COMMUNITY SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early Termination § 1210.3-10 Reinstatement of Volunteer. (a) If the Regional Director or Director of VISTA...

  5. 45 CFR 1210.3-10 - Reinstatement of Volunteer.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 4 2013-10-01 2013-10-01 false Reinstatement of Volunteer. 1210.3-10 Section 1210... COMMUNITY SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early Termination § 1210.3-10 Reinstatement of Volunteer. (a) If the Regional Director or Director of VISTA...

  6. 45 CFR 1210.3-10 - Reinstatement of Volunteer.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 4 2012-10-01 2012-10-01 false Reinstatement of Volunteer. 1210.3-10 Section 1210... COMMUNITY SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early Termination § 1210.3-10 Reinstatement of Volunteer. (a) If the Regional Director or Director of VISTA...

  7. 45 CFR 1210.3-10 - Reinstatement of Volunteer.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 4 2011-10-01 2011-10-01 false Reinstatement of Volunteer. 1210.3-10 Section 1210... COMMUNITY SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early Termination § 1210.3-10 Reinstatement of Volunteer. (a) If the Regional Director or Director of VISTA...

  8. 16 CFR 1210.3 - Requirements for cigarette lighters.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Requirements for cigarette lighters. 1210.3... REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Requirements for Child Resistance § 1210.3 Requirements for cigarette lighters. (a) A lighter subject to this part 1210 shall be resistant to successful operation by at...

  9. 16 CFR 1210.3 - Requirements for cigarette lighters.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Requirements for cigarette lighters. 1210.3... REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Requirements for Child Resistance § 1210.3 Requirements for cigarette lighters. (a) A lighter subject to this part 1210 shall be resistant to successful operation by at...

  10. 16 CFR 1210.3 - Requirements for cigarette lighters.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Requirements for cigarette lighters. 1210.3... REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Requirements for Child Resistance § 1210.3 Requirements for cigarette lighters. (a) A lighter subject to this part 1210 shall be resistant to successful operation by at...

  11. 16 CFR 1210.3 - Requirements for cigarette lighters.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Requirements for cigarette lighters. 1210.3... REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Requirements for Child Resistance § 1210.3 Requirements for cigarette lighters. (a) A lighter subject to this part 1210 shall be resistant to successful operation by at...

  12. 16 CFR 1210.14 - Qualification testing.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ....14 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Certification Requirements § 1210.14 Qualification testing. (a... accordance with § 1210.4. (b) Product modifications. If any changes are made to a product after initial...

  13. 21 CFR 1210.23 - Permits granted on certificates.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Permits granted on certificates. 1210.23 Section 1210.23 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... FEDERAL IMPORT MILK ACT Permit Control § 1210.23 Permits granted on certificates. In the discretion of the...

  14. 21 CFR 1210.23 - Permits granted on certificates.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Permits granted on certificates. 1210.23 Section 1210.23 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... FEDERAL IMPORT MILK ACT Permit Control § 1210.23 Permits granted on certificates. In the discretion of the...

  15. 7 CFR 1210.607 - Confidential information.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Confidential information. 1210.607 Section 1210.607 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... contents and all other information or reports furnished to, compiled by, or in possession of, the...

  16. 7 CFR 1210.607 - Confidential information.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Confidential information. 1210.607 Section 1210.607 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... contents and all other information or reports furnished to, compiled by, or in possession of, the...

  17. 7 CFR 1210.607 - Confidential information.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Confidential information. 1210.607 Section 1210.607 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... contents and all other information or reports furnished to, compiled by, or in possession of, the...

  18. 7 CFR 1210.607 - Confidential information.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Confidential information. 1210.607 Section 1210.607 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... contents and all other information or reports furnished to, compiled by, or in possession of, the...

  19. 7 CFR 1210.607 - Confidential information.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Confidential information. 1210.607 Section 1210.607 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... contents and all other information or reports furnished to, compiled by, or in possession of, the...

  20. 7 CFR 1210.352 - Confidential treatment.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Confidential treatment. 1210.352 Section 1210.352 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... treatment. (a) All information obtained from the books, records, or reports required to be maintained under...

  1. Mouse bone marrow-derived mesenchymal stem cells inhibit leukemia/lymphoma cell proliferation in vitro and in a mouse model of allogeneic bone marrow transplant

    PubMed Central

    SONG, NINGXIA; GAO, LEI; QIU, HUIYING; HUANG, CHONGMEI; CHENG, HUI; ZHOU, HONG; LV, SHUQING; CHEN, LI; WANG, JIANMIN

    2015-01-01

    The allogeneic hematopoietic stem cell (HSC) transplantation of mesenchymal stem cells (MSCs) contributes to the reconstitution of hematopoiesis by ameliorating acute graft-versus-host disease (aGVHD). However, the role of MSCs in graft-versus-leukemia remains to be determined. In the present study, we co-cultured C57BL/6 mouse bone marrow (BM)-derived MSCs with A20 murine B lymphoma, FBL3 murine erythroleukemia and P388 murine acute lymphocytic leukemia cells. Cell proliferation, apoptosis, cell cycle progression and the amount of cytokine secretion were then measured using a Cell Counting kit-8, Annexin V/propidium iodide staining, flow cytometry and ELISA, respectively. We also established a model of allogeneic bone marrow transplantation (BMT) using BALB/c mice. Following the administration of A20 cells and MSCs, we recorded the symptoms and the survival of the mice for 4 weeks, assessed the T cell subsets present in peripheral blood, and, after the mice were sacrifice, we determined the infiltration of MSCs into the organs by histological staining. Our results revealed that the MSCs inhibited the proliferation of the mouse lymphoma and leukemia cells in vitro, leading to cell cycle arrest and reducing the secretion of interleukin (IL)-10. In our model of allogeneic BMT, the intravenous injection of MSCs into the mice injected wth A20 cells decreased the incidence of lymphoma, improved survival, increased the fraction of CD3+CD8+ T cells, decreased the fraction of CD3+CD4+ T cells and CD4+CD25+ T cells in peripheral blood, and ameliorated the manifestation of aGVHD. The results from the present study indicate that MSCs may be safe and effective when used in allogeneic BMT for the treatment of hemotological malignancies. PMID:25901937

  2. Mouse bone marrow-derived mesenchymal stem cells inhibit leukemia/lymphoma cell proliferation in vitro and in a mouse model of allogeneic bone marrow transplant.

    PubMed

    Song, Ningxia; Gao, Lei; Qiu, Huiying; Huang, Chongmei; Cheng, Hui; Zhou, Hong; Lv, Shuqing; Chen, Li; Wang, Jianmin

    2015-07-01

    The allogeneic hematopoietic stem cell (HSC) transplantation of mesenchymal stem cells (MSCs) contributes to the reconstitution of hematopoiesis by ameliorating acute graft‑versus‑host disease (aGVHD). However, the role of MSCs in graft‑versus‑leukemia remains to be determined. In the present study, we co‑cultured C57BL/6 mouse bone marrow (BM)‑derived MSCs with A20 murine B lymphoma, FBL3 murine erythroleukemia and P388 murine acute lymphocytic leukemia cells. Cell proliferation, apoptosis, cell cycle progression and the amount of cytokine secretion were then measured using a Cell Counting kit‑8, Annexin V/propidium iodide staining, flow cytometry and ELISA, respectively. We also established a model of allogeneic bone marrow transplantation (BMT) using BALB/c mice. Following the administration of A20 cells and MSCs, we recorded the symptoms and the survival of the mice for 4 weeks, assessed the T cell subsets present in peripheral blood, and, after the mice were sacrifice, we determined the infiltration of MSCs into the organs by histological staining. Our results revealed that the MSCs inhibited the proliferation of the mouse lymphoma and leukemia cells in vitro, leading to cell cycle arrest and reducing the secretion of interleukin (IL)‑10. In our model of allogeneic BMT, the intravenous injection of MSCs into the mice injected wth A20 cells decreased the incidence of lymphoma, improved survival, increased the fraction of CD3+CD8+ T cells, decreased the fraction of CD3+CD4+ T cells and CD4+CD25+ T cells in peripheral blood, and ameliorated the manifestation of aGVHD. The results from the present study indicate that MSCs may be safe and effective when used in allogeneic BMT for the treatment of hemotological malignancies.

  3. Chlorozotocin

    PubMed Central

    Panasci, Lawrence C.; Green, Dianna; Schein, Philip S.

    1979-01-01

    Chlorozotocin is a chloroethyl nitrosourea with a glucose carrier that has curative activity for the murine L1210 leukemia, but is nonmyelosuppressive in mice. To determine the mechanism for this unique property of reduced bone marrow toxicity, comparative studies were conducted with chlorozotocin and CCNU, a myelotoxic chloroethyl nitrosourea. Suspensions of L1210 leukemia and murine bone marrow cells were incubated for 2 h with 0.1 mM [14C]-chloroethyl chlorozotocin or CCNU. Chlorozotocin demonstrated a fourfold increased covalent binding of the chloroethyl group to L1210 nuclei when compared to equimolar CCNU. Chlorozotocin alkylation of L1210 cells resulted in the binding of 57 pmol of [14C]ethyl group/mg of DNA, which represented a 2.3-fold increased alkylation when compared to CCNU. In marked contrast, the binding of the chloroethyl group to bone marrow nuclei was equivalent for both drugs. In addition, chlorozotocin alkylation of murine bone marrow DNA, 45 pmol of [14C]ethyl group/mg of DNA, was equivalent to that of CCNU. The ratio of L1210:bone marrow DNA alkylation was 1.3 for chlorozotocin compared to 0.6 for CCNU. The intracellular carbamoylation of L1210 and bone marrow protein by CCNU was 400- to 600-fold greater than that produced by chlorozotocin. After a 2-h exposure to 0.1, 0.05, or 0.01 mM drug, both chlorozotocin and CCNU produced a reduction in the cloning efficiency of L1210 cells that was dose dependent. However, chlorozotocin was significantly more cytotoxic than CCNU at all three molar concentrations (P < 0.01). Chlorozotocin, 0.1 mM, reduced L1210 DNA synthesis to 1% of control by 48 h, in contrast to 16% with equimolar CCNU (P < 0.01). In mice bearing 105 L1210 cells, chlorozotocin produced its optimal antitumor activity (332% increased life span [ILS]) at doses of 48-64 μmol/kg, with >50% indefinite survivors. In contrast, CCNU at the same molar doses resulted in only a 191% ILS; a CCNU dose of 128 μmol/kg was required for comparable

  4. 21 CFR 1210.12 - Physical examination of cows.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Physical examination of cows. 1210.12 Section 1210... FEDERAL IMPORT MILK ACT Inspection and Testing § 1210.12 Physical examination of cows. (a) Physical.... (b) The result of the physical examination shall be set forth in the form prescribed by the Secretary. ...

  5. 21 CFR 1210.12 - Physical examination of cows.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Physical examination of cows. 1210.12 Section 1210... FEDERAL IMPORT MILK ACT Inspection and Testing § 1210.12 Physical examination of cows. (a) Physical.... (b) The result of the physical examination shall be set forth in the form prescribed by the Secretary. ...

  6. 21 CFR 1210.12 - Physical examination of cows.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Physical examination of cows. 1210.12 Section 1210... FEDERAL IMPORT MILK ACT Inspection and Testing § 1210.12 Physical examination of cows. (a) Physical.... (b) The result of the physical examination shall be set forth in the form prescribed by the Secretary. ...

  7. 21 CFR 1210.12 - Physical examination of cows.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Physical examination of cows. 1210.12 Section 1210... FEDERAL IMPORT MILK ACT Inspection and Testing § 1210.12 Physical examination of cows. (a) Physical.... (b) The result of the physical examination shall be set forth in the form prescribed by the Secretary. ...

  8. 7 CFR 1210.361 - Personal liability.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Personal liability. 1210.361 Section 1210.361 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... others, in any way whatsoever to any person for errors in judgment, mistakes, or other acts, either of...

  9. 7 CFR 1210.401 - District conventions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false District conventions. 1210.401 Section 1210.401 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... multi-State districts, no one State shall have nominees for more than three of the four district...

  10. 16 CFR 1210.12 - Certificate of compliance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... SAFETY STANDARD FOR CIGARETTE LIGHTERS Certification Requirements § 1210.12 Certificate of compliance. (a... Product Safety Standard for Cigarette Lighters (16 CFR 1210),” (2) The name and address of the...

  11. 21 CFR 1210.12 - Physical examination of cows.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Physical examination of cows. 1210.12 Section 1210... FEDERAL IMPORT MILK ACT Inspection and Testing § 1210.12 Physical examination of cows. (a) Physical examination of any and all cows in herds producing milk or cream which is to be shipped or transported into...

  12. 32 CFR 37.1210 - Advanced research.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 1 2011-07-01 2011-07-01 false Advanced research. 37.1210 Section 37.1210... research. Research that creates new technology or demonstrates the viability of applying existing technology to new products and processes in a general way. Advanced research is most closely analogous to...

  13. 32 CFR 37.1210 - Advanced research.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 1 2013-07-01 2013-07-01 false Advanced research. 37.1210 Section 37.1210... research. Research that creates new technology or demonstrates the viability of applying existing technology to new products and processes in a general way. Advanced research is most closely analogous to...

  14. 32 CFR 37.1210 - Advanced research.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Advanced research. 37.1210 Section 37.1210... research. Research that creates new technology or demonstrates the viability of applying existing technology to new products and processes in a general way. Advanced research is most closely analogous to...

  15. 32 CFR 37.1210 - Advanced research.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 1 2014-07-01 2014-07-01 false Advanced research. 37.1210 Section 37.1210... research. Research that creates new technology or demonstrates the viability of applying existing technology to new products and processes in a general way. Advanced research is most closely analogous to...

  16. 32 CFR 37.1210 - Advanced research.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 1 2012-07-01 2012-07-01 false Advanced research. 37.1210 Section 37.1210... research. Research that creates new technology or demonstrates the viability of applying existing technology to new products and processes in a general way. Advanced research is most closely analogous to...

  17. 21 CFR 1210.13 - Tuberculin test.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tuberculin test. 1210.13 Section 1210.13 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION REGULATIONS UNDER THE FEDERAL...

  18. 21 CFR 1210.13 - Tuberculin test.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Tuberculin test. 1210.13 Section 1210.13 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION REGULATIONS UNDER THE FEDERAL...

  19. 21 CFR 1210.13 - Tuberculin test.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Tuberculin test. 1210.13 Section 1210.13 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION REGULATIONS UNDER THE FEDERAL...

  20. 36 CFR 1210.48 - Contract provisions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... instances in which a contractor violates or breaches the contract terms, and provide for such remedial... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Contract provisions. 1210.48... § 1210.48 Contract provisions. The recipient shall include, in addition to provisions to define a sound...

  1. L-Asparaginase encapsulated intact erythrocytes for treatment of acute lymphoblastic leukemia (ALL).

    PubMed

    Kwon, Young Min; Chung, Hee Sun; Moon, Cheol; Yockman, James; Park, Yoon Jeong; Gitlin, Scott D; David, Allan E; Yang, Victor C

    2009-11-03

    As a primary drug for the treatment of acute lymphoblastic leukemia (ALL), encapsulation of L-asparaginase (ASNase) into red blood cells (RBC) has been popular to circumvent immunogenicity from the exogenous protein. Unlike existing methods that perturbs RBC membranes, we introduce a novel method of RBC-incorporation of proteins using the membrane-translocating low molecular weight protamine (LMWP). Confocal study of fluorescence-labeled LMWP-ovalbumin, as a model protein conjugate, has shown significant fluorescence inside RBCs. Surface morphology by scanning electron microscopy of the RBCs loaded with LMWP-ASNase was indistinguishable with normal RBCs. These drug loaded RBCs also closely resembled the profile of the native erythrocytes in terms of osmotic fragility, oxygen dissociation and hematological parameters. The in vivo half-life of enzyme activity after administering 8 units of RBC/LMWP-ASNase in DBA/2 mice was prolonged to 4.5+/-0.5 days whereas that of RBCs loaded with ASNase via a hypotonic method was 2.4+/-0.7 days. Furthermore, the mean survival time of DBA/2 mice bearing mouse lymphoma cell L5178Y was improved by approximately 44% compared to the saline control group after treatment with the RBC loaded enzymes. From these data, an innovative, novel method for encapsulating proteins into intact and fully functional erythrocytes was established for potential treatment of ALL.

  2. 16 CFR 1210.1 - Scope, application, and effective date.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Scope, application, and effective date. 1210.1 Section 1210.1 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Requirements for Child Resistance § 1210.1 Scope...

  3. Synchrony in human, mouse and bacterial cell cultures--a comparison

    NASA Technical Reports Server (NTRS)

    Helmstetter, Charles E.; Thornton, Maureen; Romero, Ana; Eward, K. Leigh

    2003-01-01

    Growth characteristics of synchronous human MOLT-4, human U-937 and mouse L1210 cultures produced with a new minimally-disturbing technology were compared to each other and to synchronous Escherichia coli B/r. Based on measurements of cell concentrations during synchronous growth, synchrony persisted in similar fashion for all cells. Cell size and DNA distributions in the mammalian cultures also progressed synchronously and reproducibly for multiple cell cycles. The results demonstrate that unambiguous multi-cycle synchrony, critical for verifying the absence of significant growth imbalances induced by the synchronization procedure, is feasible with these cell lines, and possibly others.

  4. 36 CFR 1210.24 - Program income.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Program income. 1210.24... Management § 1210.24 Program income. (a) The NHPRC applies the standards set forth in this section in requiring recipient organizations to account for program income related to projects financed in whole or in...

  5. Effects of Mg2+ and adenine nucleotides on thymidylate synthetase from different mouse tumors.

    PubMed

    Rode, W; Jastreboff, M M

    1984-01-01

    Magnesium ions variably influenced activity of highly purified thymidylate synthetase preparations from different mouse tumors, activating the enzyme from Ehrlich ascites carcinoma (EAC) cells and inhibiting the enzyme from L1210 and L5178Y cells and from 5-fluorodeoxyuridine (FdUrd)-resistant EAC cells. In the presence of Mg2+ in a concentration resulting in either maximum activation or inhibition (25-30 mM) the enzymes from both the sensitive and FdUrd-resistant EAC lines and L5178Y cells were activated by ATP. Under the same conditions of Mg2+ concentration ADP and AMP inhibited the enzyme from the parental but not from the FdUrd-resistant EAC cells.

  6. 47 CFR 27.1210 - Remote control operation.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Remote control operation. 27.1210 Section 27.1210 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Broadband Radio Service and Educational Broadband Service § 27...

  7. 47 CFR 27.1210 - Remote control operation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Remote control operation. 27.1210 Section 27.1210 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Broadband Radio Service and Educational Broadband Service § 27...

  8. 47 CFR 27.1210 - Remote control operation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 2 2012-10-01 2012-10-01 false Remote control operation. 27.1210 Section 27.1210 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Broadband Radio Service and Educational Broadband Service § 27...

  9. 47 CFR 27.1210 - Remote control operation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false Remote control operation. 27.1210 Section 27.1210 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Broadband Radio Service and Educational Broadband Service § 27...

  10. 47 CFR 27.1210 - Remote control operation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Remote control operation. 27.1210 Section 27.1210 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Broadband Radio Service and Educational Broadband Service § 27...

  11. 16 CFR § 1210.3 - Requirements for cigarette lighters.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Requirements for cigarette lighters. § 1210... ACT REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Requirements for Child Resistance § 1210.3 Requirements for cigarette lighters. (a) A lighter subject to this part 1210 shall be resistant to successful...

  12. 23 CFR 1210.4 - Adoption of zero tolerance law.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 23 Highways 1 2011-04-01 2011-04-01 false Adoption of zero tolerance law. 1210.4 Section 1210.4... TRANSPORTATION GUIDELINES OPERATION OF MOTOR VEHICLES BY INTOXICATED MINORS § 1210.4 Adoption of zero tolerance... that license suspensions or revocations are authorized for any violation of the State zero tolerance...

  13. 23 CFR 1210.4 - Adoption of zero tolerance law.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 23 Highways 1 2013-04-01 2013-04-01 false Adoption of zero tolerance law. 1210.4 Section 1210.4... TRANSPORTATION GUIDELINES OPERATION OF MOTOR VEHICLES BY INTOXICATED MINORS § 1210.4 Adoption of zero tolerance... that license suspensions or revocations are authorized for any violation of the State zero tolerance...

  14. 23 CFR 1210.4 - Adoption of zero tolerance law.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 23 Highways 1 2012-04-01 2012-04-01 false Adoption of zero tolerance law. 1210.4 Section 1210.4... TRANSPORTATION GUIDELINES OPERATION OF MOTOR VEHICLES BY INTOXICATED MINORS § 1210.4 Adoption of zero tolerance... that license suspensions or revocations are authorized for any violation of the State zero tolerance...

  15. 23 CFR 1210.4 - Adoption of zero tolerance law.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 23 Highways 1 2014-04-01 2014-04-01 false Adoption of zero tolerance law. 1210.4 Section 1210.4... TRANSPORTATION GUIDELINES OPERATION OF MOTOR VEHICLES BY INTOXICATED MINORS § 1210.4 Adoption of zero tolerance... that license suspensions or revocations are authorized for any violation of the State zero tolerance...

  16. 23 CFR 1210.4 - Adoption of zero tolerance law.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Adoption of zero tolerance law. 1210.4 Section 1210.4... TRANSPORTATION GUIDELINES OPERATION OF MOTOR VEHICLES BY INTOXICATED MINORS § 1210.4 Adoption of zero tolerance... that license suspensions or revocations are authorized for any violation of the State zero tolerance...

  17. 21 CFR 1210.13 - Tuberculin test.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... IMPORT MILK ACT Inspection and Testing § 1210.13 Tuberculin test. (a) Except as provided in § 1210.27 any and all animals in herds producing milk or cream which is to be shipped or transported raw into the... any event, shall have been made within 1 year previous to the time of the importation. All animals...

  18. 16 CFR § 1210.12 - Certificate of compliance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Certification Requirements § 1210.12 Certificate of... Product Safety Standard for Cigarette Lighters (16 CFR 1210),” (2) The name and address of the...

  19. 36 CFR 1210.11 - Pre-award policies.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... RULES UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Pre-Award Requirements § 1210.11 Pre-award policies... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false Pre-award policies. 1210.11...

  20. 21 CFR 862.1210 - Creatine test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Creatine test system. 862.1210 Section 862.1210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862...

  1. 7 CFR 1210.362 - Influencing government action.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Influencing government action. 1210.362 Section 1210.362 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING... government action. No funds received by the Board under this Plan shall in any manner be used for the purpose...

  2. 21 CFR 862.1210 - Creatine test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Creatine test system. 862.1210 Section 862.1210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862...

  3. 21 CFR 862.1210 - Creatine test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Creatine test system. 862.1210 Section 862.1210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862...

  4. 21 CFR 862.1210 - Creatine test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Creatine test system. 862.1210 Section 862.1210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862...

  5. 7 CFR 1210.540 - OMB assigned numbers.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false OMB assigned numbers. 1210.540 Section 1210.540 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... Management and Budget (OMB) under the provisions of 44 U.S.C. chapter 35 and have been assigned OMB Control...

  6. 42 CFR 493.1210 - Condition: Routine chemistry.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Routine chemistry. 493.1210 Section 493....1210 Condition: Routine chemistry. If the laboratory provides services in the subspecialty of Routine chemistry, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, § 493.1267...

  7. 40 CFR 721.1210 - Benzene, (2-chloroethoxy)-.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Benzene, (2-chloroethoxy)-. 721.1210... Substances § 721.1210 Benzene, (2-chloroethoxy)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as benzene, (2-chloroethoxy)- (PMN P-87-1471) is subject to...

  8. 40 CFR 721.1210 - Benzene, (2-chloroethoxy)-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Benzene, (2-chloroethoxy)-. 721.1210... Substances § 721.1210 Benzene, (2-chloroethoxy)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as benzene, (2-chloroethoxy)- (PMN P-87-1471) is subject to...

  9. 40 CFR 721.1210 - Benzene, (2-chloroethoxy)-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Benzene, (2-chloroethoxy)-. 721.1210... Substances § 721.1210 Benzene, (2-chloroethoxy)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as benzene, (2-chloroethoxy)- (PMN P-87-1471) is subject to...

  10. 40 CFR 721.1210 - Benzene, (2-chloroethoxy)-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Benzene, (2-chloroethoxy)-. 721.1210... Substances § 721.1210 Benzene, (2-chloroethoxy)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as benzene, (2-chloroethoxy)- (PMN P-87-1471) is subject to...

  11. 40 CFR 721.1210 - Benzene, (2-chloroethoxy)-.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Benzene, (2-chloroethoxy)-. 721.1210... Substances § 721.1210 Benzene, (2-chloroethoxy)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as benzene, (2-chloroethoxy)- (PMN P-87-1471) is subject to...

  12. 42 CFR 493.1210 - Condition: Routine chemistry.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Condition: Routine chemistry. 493.1210 Section 493....1210 Condition: Routine chemistry. If the laboratory provides services in the subspecialty of Routine chemistry, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, § 493.1267...

  13. 42 CFR 493.1210 - Condition: Routine chemistry.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Condition: Routine chemistry. 493.1210 Section 493....1210 Condition: Routine chemistry. If the laboratory provides services in the subspecialty of Routine chemistry, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, § 493.1267...

  14. 42 CFR 493.1210 - Condition: Routine chemistry.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Condition: Routine chemistry. 493.1210 Section 493....1210 Condition: Routine chemistry. If the laboratory provides services in the subspecialty of Routine chemistry, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, § 493.1267...

  15. 42 CFR 493.1210 - Condition: Routine chemistry.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Condition: Routine chemistry. 493.1210 Section 493....1210 Condition: Routine chemistry. If the laboratory provides services in the subspecialty of Routine chemistry, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, § 493.1267...

  16. 36 CFR 1210.20 - Purpose of financial and program management.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Financial and Program Management § 1210.20 Purpose of financial and program management. Sections 1210.21 through 1210.28 prescribe standards for financial management systems, methods for making payments and... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Purpose of financial and...

  17. 36 CFR § 1210.24 - Program income.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true Program income. § 1210.24 Section § 1210.24 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION.... However, Patent and Trademark Amendments (35 U.S.C. 18) apply to inventions made under an experimental...

  18. 21 CFR 1210.25 - Permits for pasteurized milk or cream.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Permits for pasteurized milk or cream. 1210.25 Section 1210.25 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... UNDER THE FEDERAL IMPORT MILK ACT Permit Control § 1210.25 Permits for pasteurized milk or cream...

  19. 21 CFR 1210.25 - Permits for pasteurized milk or cream.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Permits for pasteurized milk or cream. 1210.25 Section 1210.25 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... UNDER THE FEDERAL IMPORT MILK ACT Permit Control § 1210.25 Permits for pasteurized milk or cream...

  20. 45 CFR 1210.3-8 - Termination file and Examiner's report.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 4 2012-10-01 2012-10-01 false Termination file and Examiner's report. 1210.3-8 Section 1210.3-8 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early Termination § 1210.3-8...

  1. 7 CFR 1210.505 - Department of Agriculture costs.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Department of Agriculture costs. 1210.505 Section 1210.505 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON...

  2. 7 CFR 1210.505 - Department of Agriculture costs.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Department of Agriculture costs. 1210.505 Section 1210.505 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON...

  3. 7 CFR 1210.505 - Department of Agriculture costs.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Department of Agriculture costs. 1210.505 Section 1210.505 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON...

  4. 7 CFR 1210.505 - Department of Agriculture costs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Department of Agriculture costs. 1210.505 Section 1210.505 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON...

  5. 7 CFR 1210.505 - Department of Agriculture costs.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Department of Agriculture costs. 1210.505 Section 1210.505 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON...

  6. 5 CFR 890.1210 - Reconsideration and appeal rights.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Reconsideration and appeal rights. 890.1210 Section 890.1210 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Benefits for United States Hostages in Iraq...

  7. 5 CFR 890.1210 - Reconsideration and appeal rights.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 2 2014-01-01 2014-01-01 false Reconsideration and appeal rights. 890.1210 Section 890.1210 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Benefits for United States Hostages in Iraq...

  8. In vivo antitumor activity of 4-amino 4-methyl 2-pentyne 1-al, an inhibitor of aldehyde dehydrogenase.

    PubMed

    Quemener, V; Quash, G; Moulinoux, J P; Penlap, V; Ripoll, H; Havouis, R; Doutheau, A; Goré, J

    1989-01-01

    4-amino-4-methyl-2-pentyne-1-al (AMPAL), a new irreversible inhibitor of aldehyde dehydrogenase (ALDH) has been assayed for its in vitro and in vivo antitumor activity. In vitro, AMPAL inhibits the proliferation and the ALDH activity of L1210 and RBL5 cell lines. In vivo, AMPAL significantly increases the mean survival time of mice i.p. grafted with leukemia (L1210, P815, MBL2, EL4, RBL5 cell lines) or carcinoma cells (Krebs cell line), without haematopoetic toxicity. No carcinostatic effect was observed against the P388 leukemia and the 3LL Lewis lung carcinoma. A possible relationship between the ALDH isoenzyme activity of the tumor and its sensitivity to AMPAL is discussed in the light of previous reports concerning the role of aldehydes in cell growth control.

  9. Comparative sequence analysis of a region on human chromosome 13q14, frequently deleted in B-cell chronic lymphocytic leukemia, and its homologous region on mouse chromosome 14.

    PubMed

    Kapanadze, B; Makeeva, N; Corcoran, M; Jareborg, N; Hammarsund, M; Baranova, A; Zabarovsky, E; Vorontsova, O; Merup, M; Gahrton, G; Jansson, M; Yankovsky, N; Einhorn, S; Oscier, D; Grandér, D; Sangfelt, O

    2000-12-15

    Previous studies have indicated the presence of a putative tumor suppressor gene on human chromosome 13q14, commonly deleted in patients with B-cell chronic lymphocytic leukemia (B-CLL). We have recently identified a minimally deleted region encompassing parts of two adjacent genes, termed LEU1 and LEU2 (leukemia-associated genes 1 and 2), and several additional transcripts. In addition, 50 kb centromeric to this region we have identified another gene, LEU5/RFP2. To elucidate further the complex genomic organization of this region, we have identified, mapped, and sequenced the homologous region in the mouse. Fluorescence in situ hybridization analysis demonstrated that the region maps to mouse chromosome 14. The overall organization and gene order in this region were found to be highly conserved in the mouse. Sequence comparison between the human deletion hotspot region and its homologous mouse region revealed a high degree of sequence conservation with an overall score of 74%. However, our data also show that in terms of transcribed sequences, only two of those, human LEU2 and LEU5/RFP2, are clearly conserved, strengthening the case for these genes as putative candidate B-CLL tumor suppressor genes.

  10. 5 CFR 831.1210 - Annuity rights after a disability annuity terminates.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Annuity rights after a disability annuity terminates. 831.1210 Section 831.1210 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Disability Retirement § 831.1210 Annuity rights after a...

  11. 5 CFR 831.1210 - Annuity rights after a disability annuity terminates.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Annuity rights after a disability annuity terminates. 831.1210 Section 831.1210 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Disability Retirement § 831.1210 Annuity rights after a...

  12. 45 CFR 156.1210 - Confirmation of HHS payment and collections reports.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... reports. 156.1210 Section 156.1210 Public Welfare Department of Health and Human Services REQUIREMENTS RELATING TO HEALTH CARE ACCESS HEALTH INSURANCE ISSUER STANDARDS UNDER THE AFFORDABLE CARE ACT, INCLUDING STANDARDS RELATED TO EXCHANGES Qualified Health Plan Issuer Responsibilities § 156.1210 Confirmation of HHS...

  13. 21 CFR 1210.26 - Permits for raw milk or cream.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Permits for raw milk or cream. 1210.26 Section... FEDERAL IMPORT MILK ACT Permit Control § 1210.26 Permits for raw milk or cream. Except as provided in § 1210.27, permits to ship or transport raw milk or cream into the United States will be granted only...

  14. 21 CFR 1210.26 - Permits for raw milk or cream.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Permits for raw milk or cream. 1210.26 Section... FEDERAL IMPORT MILK ACT Permit Control § 1210.26 Permits for raw milk or cream. Except as provided in § 1210.27, permits to ship or transport raw milk or cream into the United States will be granted only...

  15. Alemtuzumab and Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2014-03-20

    Acute Undifferentiated Leukemia; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; L1 Adult Acute Lymphoblastic Leukemia; L1 Childhood Acute Lymphoblastic Leukemia; L2 Adult Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  16. 36 CFR 1210.45 - Cost and price analysis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Cost and price analysis. 1210.45 Section 1210.45 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION... in various ways, including the comparison of price quotations submitted, market prices and similar...

  17. 40 CFR 60.1210 - What pollutants are regulated by this subpart?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... subpart? 60.1210 Section 60.1210 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Modification or Reconstruction is Commenced After June 6, 2001 Emission Limits § 60.1210 What pollutants are.... (1) Hydrogen chloride. (2) Nitrogen oxides. (3) Sulfur dioxide. (d) Other. (1) Carbon monoxide. (2...

  18. 40 CFR 60.1210 - What pollutants are regulated by this subpart?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... subpart? 60.1210 Section 60.1210 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Modification or Reconstruction is Commenced After June 6, 2001 Emission Limits § 60.1210 What pollutants are.... (1) Hydrogen chloride. (2) Nitrogen oxides. (3) Sulfur dioxide. (d) Other. (1) Carbon monoxide. (2...

  19. Endogenous murine leukemia virus-encoded proteins in radiation leukemias of BALB/c mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tress, E.; Pierotti, M.; DeLeo, A.B.

    1982-02-01

    To explore the role of endogenous retroviruses in radiation-induced leukemogenesis in the mouse, we have examined virus-encoded proteins in nine BALB/c leukemias by pulsechase labeling procedures and serological typing with monospecific and monoclonal antibodies. The major gag precursor protein, Pr65/sup gag/, was observed in all cases, but only three leukemias expressed detectable amounts of the glycosylated gag species, gP95/sup gag/, or its precursor, Pr75/sup gag/. No evidence was found for synthesis of gag-host fusion proteins. None of the leukemias released infectious xenotropic or dualtropic virus, but all nine expressed at least one env protein with xenotropic properties. In two instancesmore » a monoclonal antibody, 35/56, which is specific for the NuLV G/sub IX/ antigen, displayed a distinctive reactivity with this class of env protein, although this antibody is unreactive with replicating xenotropic viruses. An ecotropic/xenotropic recombinant env protein with the same 35/56 phenotype was observed in a leukemia induced by a strongly leukemogenic virus isolated from a BALB/c radiation leukemia.« less

  20. Radiation-induced leukemia: Comparative studies in mouse and man

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Haas, M.

    1991-01-01

    We now have a clear understanding of the mechanism by which radiation-induced (T-cell) leukemia occurs. In irradiated mice (radiation-induced thymic leukemia) and in man (acute lymphoblastic T-cell leukemia, T-ALL) the mechanism of leukemogenesis is surprisingly similar. Expressed in the most elementary terms, T-cell leukemia occurs when T-cell differentiation is inhibited by a mutation, and pre-T cells attempt but fail to differentiate in the thymus. Instead of leaving the thymus for the periphery as functional T-cells they continue to proliferate in the thymus. The proliferating pre- (pro-) T-cells constitute the (early) acute T-cell leukemia (A-TCL). This model for the mechanism ofmore » T-cell leukemogenesis accounts for all the properties of both murine and human A-TCL. Important support for the model has recently come from work by Ilan Kirsch and others, who have shown that mutations/deletions in the genes SCL (TAL), SIL, and LCK constitute primary events in the development of T-ALL, by inhibiting differentiation of thymic pre- (pro-) T-cells. This mechanism of T-cell leukemogenesis brings several specific questions into focus: How do early A-TCL cells progress to become potently tumorigenic and poorly treatable Is it feasible to genetically suppress early and/or progressed A-TCL cells What is the mechanism by which the differentiation-inhibited (leukemic) pre-T cells proliferate During the first grant year we have worked on aspects of all three questions.« less

  1. 7 CFR 1210.516 - Exemption for organic watermelons.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Exemption for organic watermelons. 1210.516 Section... RESEARCH AND PROMOTION PLAN Rules and Regulations Assessments § 1210.516 Exemption for organic watermelons. (a) A producer who produces only products that are eligible to be labeled as 100 percent organic...

  2. 30 CFR 1210.352 - Special forms and reports.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Special forms and reports. 1210.352 Section 1210.352 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL... the requirements of the Paperwork Reduction Act of 1980 and other applicable laws. [56 FR 57286, Nov...

  3. 30 CFR 1210.352 - Special forms and reports.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Special forms and reports. 1210.352 Section 1210.352 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL... the requirements of the Paperwork Reduction Act of 1980 and other applicable laws. [56 FR 57286, Nov...

  4. 30 CFR 1210.352 - Special forms and reports.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Special forms and reports. 1210.352 Section 1210.352 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL... the requirements of the Paperwork Reduction Act of 1980 and other applicable laws. [56 FR 57286, Nov...

  5. 21 CFR 1210.15 - Pasteurization; equipment and methods.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Section 1210.15 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... UNDER THE FEDERAL IMPORT MILK ACT Inspection and Testing § 1210.15 Pasteurization; equipment and methods. All dairy farms and plants at which any milk or cream is pasteurized for shipment or transportation...

  6. 21 CFR 1210.15 - Pasteurization; equipment and methods.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Section 1210.15 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... UNDER THE FEDERAL IMPORT MILK ACT Inspection and Testing § 1210.15 Pasteurization; equipment and methods. All dairy farms and plants at which any milk or cream is pasteurized for shipment or transportation...

  7. 7 CFR 1210.516 - Exemption for organic watermelons.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Exemption for organic watermelons. 1210.516 Section... RESEARCH AND PROMOTION PLAN Rules and Regulations Assessments § 1210.516 Exemption for organic watermelons. (a) A producer who produces only products that are eligible to be labeled as 100 percent organic...

  8. 7 CFR 1210.516 - Exemption for organic watermelons.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Exemption for organic watermelons. 1210.516 Section... RESEARCH AND PROMOTION PLAN Rules and Regulations Assessments § 1210.516 Exemption for organic watermelons. (a) A producer who produces only products that are eligible to be labeled as 100 percent organic...

  9. 7 CFR 1210.516 - Exemption for organic watermelons.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Exemption for organic watermelons. 1210.516 Section... RESEARCH AND PROMOTION PLAN Rules and Regulations Assessments § 1210.516 Exemption for organic watermelons. (a) A producer who produces only products that are eligible to be labeled as 100 percent organic...

  10. 18 CFR 12.10 - Reporting safety-related incidents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...-related incidents. 12.10 Section 12.10 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT SAFETY OF WATER POWER PROJECTS AND... providing a copy of a clipping from a newspaper article, if available. (4) For the purposes of this...

  11. 36 CFR 1210.23 - Cost sharing or matching.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... 1210.23 Section 1210.23 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS... records at the time of donation. (2) The current fair market value. However, when there is sufficient justification, the NHPRC may approve the use of the current fair market value of the donated property, even if...

  12. 40 CFR 63.1210 - What are the notification requirements?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...? 63.1210 Section 63.1210 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES National Emission Standards for Hazardous Air Pollutants from Hazardous Waste Combustors Notification...

  13. 40 CFR 63.1210 - What are the notification requirements?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...? 63.1210 Section 63.1210 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES National Emission Standards for Hazardous Air Pollutants from Hazardous Waste Combustors Notification...

  14. 21 CFR 1210.14 - Sanitary inspection of plants.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 1210.14 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... FEDERAL IMPORT MILK ACT Inspection and Testing § 1210.14 Sanitary inspection of plants. The sanitary conditions of any plant handling milk or cream any part of which is to be shipped or transported into the...

  15. 7 CFR 1210.365 - Effect of termination or amendment.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Effect of termination or amendment. 1210.365 Section 1210.365 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON...

  16. 21 CFR 1210.14 - Sanitary inspection of plants.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Sanitary inspection of plants. 1210.14 Section... FEDERAL IMPORT MILK ACT Inspection and Testing § 1210.14 Sanitary inspection of plants. The sanitary conditions of any plant handling milk or cream any part of which is to be shipped or transported into the...

  17. 21 CFR 1210.14 - Sanitary inspection of plants.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Sanitary inspection of plants. 1210.14 Section... FEDERAL IMPORT MILK ACT Inspection and Testing § 1210.14 Sanitary inspection of plants. The sanitary conditions of any plant handling milk or cream any part of which is to be shipped or transported into the...

  18. 21 CFR 1210.14 - Sanitary inspection of plants.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Sanitary inspection of plants. 1210.14 Section... FEDERAL IMPORT MILK ACT Inspection and Testing § 1210.14 Sanitary inspection of plants. The sanitary conditions of any plant handling milk or cream any part of which is to be shipped or transported into the...

  19. 21 CFR 1210.14 - Sanitary inspection of plants.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Sanitary inspection of plants. 1210.14 Section... FEDERAL IMPORT MILK ACT Inspection and Testing § 1210.14 Sanitary inspection of plants. The sanitary conditions of any plant handling milk or cream any part of which is to be shipped or transported into the...

  20. Nonstructural Protein L* Species Specificity Supports a Mouse Origin for Vilyuisk Human Encephalitis Virus.

    PubMed

    Drappier, Melissa; Opperdoes, Fred R; Michiels, Thomas

    2017-07-15

    Vilyuisk human encephalitis virus (VHEV) is a picornavirus related to Theiler's murine encephalomyelitis virus (TMEV). VHEV was isolated from human material passaged in mice. Whether this VHEV is of human or mouse origin is therefore unclear. We took advantage of the species-specific activity of the nonstructural L* protein of theiloviruses to track the origin of TMEV isolates. TMEV L* inhibits RNase L, the effector enzyme of the interferon pathway. By using coimmunoprecipitation and functional RNase L assays, the species specificity of RNase L antagonism was tested for L* from mouse (DA) and rat (RTV-1) TMEV strains as well as for VHEV. Coimmunoprecipitation and functional assay data confirmed the species specificity of L* activity and showed that L* from rat strain RTV-1 inhibited rat but not mouse or human RNase L. Next, we showed that the VHEV L* protein was phylogenetically related to L* of mouse viruses and that it failed to inhibit human RNase L but readily antagonized mouse RNase L, unambiguously showing the mouse origin of VHEV. IMPORTANCE Defining the natural host of a virus can be a thorny issue, especially when the virus was isolated only once or when the isolation story is complex. The species Theilovirus includes Theiler's murine encephalomyelitis virus (TMEV), infecting mice and rats, and Saffold virus (SAFV), infecting humans. One TMEV strain, Vilyuisk human encephalitis virus (VHEV), however, was isolated from mice that were inoculated with cerebrospinal fluid of a patient presenting with chronic encephalitis. It is therefore unclear whether VHEV was derived from the human sample or from the inoculated mouse. The L* protein encoded by TMEV inhibits RNase L, a cellular enzyme involved in innate immunity, in a species-specific manner. Using binding and functional assays, we show that this species specificity even allows discrimination between TMEV strains of mouse and of rat origins. The VHEV L* protein clearly inhibited mouse but not human RNase L

  1. mTORC1 is essential for leukemia propagation but not stem cell self-renewal

    PubMed Central

    Hoshii, Takayuki; Tadokoro, Yuko; Naka, Kazuhito; Ooshio, Takako; Muraguchi, Teruyuki; Sugiyama, Naoyuki; Soga, Tomoyoshi; Araki, Kimi; Yamamura, Ken-ichi; Hirao, Atsushi

    2012-01-01

    Although dysregulation of mTOR complex 1 (mTORC1) promotes leukemogenesis, how mTORC1 affects established leukemia is unclear. We investigated the role of mTORC1 in mouse hematopoiesis using a mouse model of conditional deletion of Raptor, an essential component of mTORC1. Raptor deficiency impaired granulocyte and B cell development but did not alter survival or proliferation of hematopoietic progenitor cells. In a mouse model of acute myeloid leukemia (AML), Raptor deficiency significantly suppressed leukemia progression by causing apoptosis of differentiated, but not undifferentiated, leukemia cells. mTORC1 did not control cell cycle or cell growth in undifferentiated AML cells in vivo. Transplantation of Raptor-deficient undifferentiated AML cells in a limiting dilution revealed that mTORC1 is essential for leukemia initiation. Strikingly, a subset of AML cells with undifferentiated phenotypes survived long-term in the absence of mTORC1 activity. We further demonstrated that the reactivation of mTORC1 in those cells restored their leukemia-initiating capacity. Thus, AML cells lacking mTORC1 activity can self-renew as AML stem cells. Our findings provide mechanistic insight into how residual tumor cells circumvent anticancer therapies and drive tumor recurrence. PMID:22622041

  2. 30 CFR 1210.40 - Will ONRR keep the information I provide confidential?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... confidential? 1210.40 Section 1210.40 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE FORMS AND REPORTS General Provisions § 1210.40 Will ONRR keep the... to the extent permitted by law as specified at 43 CFR part 2. ...

  3. 30 CFR 1210.40 - Will ONRR keep the information I provide confidential?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... confidential? 1210.40 Section 1210.40 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE FORMS AND REPORTS General Provisions § 1210.40 Will ONRR keep the... to the extent permitted by law as specified at 43 CFR part 2. ...

  4. 30 CFR 1210.40 - Will ONRR keep the information I provide confidential?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... confidential? 1210.40 Section 1210.40 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE FORMS AND REPORTS General Provisions § 1210.40 Will ONRR keep the... to the extent permitted by law as specified at 43 CFR part 2. ...

  5. lncRNA requirements for mouse acute myeloid leukemia and normal differentiation

    PubMed Central

    Knott, Simon RV; Munera Maravilla, Ester; Jackson, Benjamin T; Wild, Sophia A; Kovacevic, Tatjana; Stork, Eva Maria; Zhou, Meng; Erard, Nicolas; Lee, Emily; Kelley, David R; Roth, Mareike; Barbosa, Inês AM; Zuber, Johannes; Rinn, John L

    2017-01-01

    A substantial fraction of the genome is transcribed in a cell-type-specific manner, producing long non-coding RNAs (lncRNAs), rather than protein-coding transcripts. Here, we systematically characterize transcriptional dynamics during hematopoiesis and in hematological malignancies. Our analysis of annotated and de novo assembled lncRNAs showed many are regulated during differentiation and mis-regulated in disease. We assessed lncRNA function via an in vivo RNAi screen in a model of acute myeloid leukemia. This identified several lncRNAs essential for leukemia maintenance, and found that a number act by promoting leukemia stem cell signatures. Leukemia blasts show a myeloid differentiation phenotype when these lncRNAs were depleted, and our data indicates that this effect is mediated via effects on the MYC oncogene. Bone marrow reconstitutions showed that a lncRNA expressed across all progenitors was required for the myeloid lineage, whereas the other leukemia-induced lncRNAs were dispensable in the normal setting. PMID:28875933

  6. lncRNA requirements for mouse acute myeloid leukemia and normal differentiation.

    PubMed

    Delás, M Joaquina; Sabin, Leah R; Dolzhenko, Egor; Knott, Simon Rv; Munera Maravilla, Ester; Jackson, Benjamin T; Wild, Sophia A; Kovacevic, Tatjana; Stork, Eva Maria; Zhou, Meng; Erard, Nicolas; Lee, Emily; Kelley, David R; Roth, Mareike; Barbosa, Inês Am; Zuber, Johannes; Rinn, John L; Smith, Andrew D; Hannon, Gregory J

    2017-09-06

    A substantial fraction of the genome is transcribed in a cell-type-specific manner, producing long non-coding RNAs (lncRNAs), rather than protein-coding transcripts. Here, we systematically characterize transcriptional dynamics during hematopoiesis and in hematological malignancies. Our analysis of annotated and de novo assembled lncRNAs showed many are regulated during differentiation and mis-regulated in disease. We assessed lncRNA function via an in vivo RNAi screen in a model of acute myeloid leukemia. This identified several lncRNAs essential for leukemia maintenance, and found that a number act by promoting leukemia stem cell signatures. Leukemia blasts show a myeloid differentiation phenotype when these lncRNAs were depleted, and our data indicates that this effect is mediated via effects on the MYC oncogene. Bone marrow reconstitutions showed that a lncRNA expressed across all progenitors was required for the myeloid lineage, whereas the other leukemia-induced lncRNAs were dispensable in the normal setting.

  7. An Advanced Preclinical Mouse Model for Acute Myeloid Leukemia Using Patients' Cells of Various Genetic Subgroups and In Vivo Bioluminescence Imaging

    PubMed Central

    Vick, Binje; Rothenberg, Maja; Sandhöfer, Nadine; Carlet, Michela; Finkenzeller, Cornelia; Krupka, Christina; Grunert, Michaela; Trumpp, Andreas; Corbacioglu, Selim; Ebinger, Martin; André, Maya C.; Hiddemann, Wolfgang; Schneider, Stephanie; Subklewe, Marion; Metzeler, Klaus H.; Spiekermann, Karsten; Jeremias, Irmela

    2015-01-01

    Acute myeloid leukemia (AML) is a clinically and molecularly heterogeneous disease with poor outcome. Adequate model systems are required for preclinical studies to improve understanding of AML biology and to develop novel, rational treatment approaches. Xenografts in immunodeficient mice allow performing functional studies on patient-derived AML cells. We have established an improved model system that integrates serial retransplantation of patient-derived xenograft (PDX) cells in mice, genetic manipulation by lentiviral transduction, and essential quality controls by immunophenotyping and targeted resequencing of driver genes. 17/29 samples showed primary engraftment, 10/17 samples could be retransplanted and some of them allowed virtually indefinite serial transplantation. 5/6 samples were successfully transduced using lentiviruses. Neither serial transplantation nor genetic engineering markedly altered sample characteristics analyzed. Transgene expression was stable in PDX AML cells. Example given, recombinant luciferase enabled bioluminescence in vivo imaging and highly sensitive and reliable disease monitoring; imaging visualized minimal disease at 1 PDX cell in 10000 mouse bone marrow cells and facilitated quantifying leukemia initiating cells. We conclude that serial expansion, genetic engineering and imaging represent valuable tools to improve the individualized xenograft mouse model of AML. Prospectively, these advancements enable repetitive, clinically relevant studies on AML biology and preclinical treatment trials on genetically defined and heterogeneous subgroups. PMID:25793878

  8. 7 CFR 1210.307 - Handle.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.307 Handle. Handle means to grade, pack...

  9. 7 CFR 1210.307 - Handle.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.307 Handle. Handle means to grade, pack...

  10. 7 CFR 1210.307 - Handle.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.307 Handle. Handle means to grade, pack...

  11. 7 CFR 1210.307 - Handle.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.307 Handle. Handle means to grade, pack...

  12. Behavior of a cloned murine interferon alpha/beta receptor expressed in homospecific or heterospecific background.

    PubMed

    Uzé, G; Lutfalla, G; Bandu, M T; Proudhon, D; Mogensen, K E

    1992-05-15

    A murine interferon (IFN) alpha/beta receptor was cloned from the IFN-sensitive L1210 cell line on the basis of its homology with the human receptor. A combination of methods that includes the screening of random-primed and oligo(dT)-primed cDNA libraries and polymerase chain reactions with a single-side specificity was used. At the amino acid level, the murine IFN-alpha/beta shows 46% identity with its human counterpart. Both human WISH cells presenting a low sensitivity to mouse IFN and a murine L1210 mutant subline that does not express the receptor have been stably transfected with the murine IFN-alpha/beta receptor. Whereas transfected human cells became sensitive to a limited number of mouse IFN-alpha/beta subtypes, the transfected murine L1210 mutant was found to be fully complemented and became sensitive to all mouse IFN-alpha/beta subtypes tested, including those that were not active on transfected human cells. These results strongly suggest that the receptor described here is implicated in the mediation of the activities of all murine IFN-alpha/beta subtypes.

  13. 30 CFR 1210.51 - Who must submit royalty reports?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Who must submit royalty reports? 1210.51 Section 1210.51 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR Natural Resources Revenue FORMS AND REPORTS Royalty Reports-Oil, Gas, and Geothermal Resources...

  14. 7 CFR 1210.310 - Fiscal period and marketing year.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Fiscal period and marketing year. 1210.310 Section 1210.310 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon...

  15. 7 CFR 1210.532 - Confidential books, records, and reports.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Confidential books, records, and reports. 1210.532... WATERMELON RESEARCH AND PROMOTION PLAN Rules and Regulations Records § 1210.532 Confidential books, records, and reports. All information obtained from the books, records, and reports of handlers and importers...

  16. 7 CFR 1210.532 - Confidential books, records, and reports.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Confidential books, records, and reports. 1210.532... WATERMELON RESEARCH AND PROMOTION PLAN Rules and Regulations Records § 1210.532 Confidential books, records, and reports. All information obtained from the books, records, and reports of handlers and importers...

  17. 7 CFR 1210.532 - Confidential books, records, and reports.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Confidential books, records, and reports. 1210.532... WATERMELON RESEARCH AND PROMOTION PLAN Rules and Regulations Records § 1210.532 Confidential books, records, and reports. All information obtained from the books, records, and reports of handlers and importers...

  18. 7 CFR 1210.532 - Confidential books, records, and reports.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Confidential books, records, and reports. 1210.532... WATERMELON RESEARCH AND PROMOTION PLAN Rules and Regulations Records § 1210.532 Confidential books, records, and reports. All information obtained from the books, records, and reports of handlers and importers...

  19. 7 CFR 1210.532 - Confidential books, records, and reports.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Confidential books, records, and reports. 1210.532... WATERMELON RESEARCH AND PROMOTION PLAN Rules and Regulations Records § 1210.532 Confidential books, records, and reports. All information obtained from the books, records, and reports of handlers and importers...

  20. Mechanisms of acquired resistance to the quinazoline thymidylate synthase inhibitor ZD1694 (Tomudex) in one mouse and three human cell lines.

    PubMed Central

    Jackman, A. L.; Kelland, L. R.; Kimbell, R.; Brown, M.; Gibson, W.; Aherne, G. W.; Hardcastle, A.; Boyle, F. T.

    1995-01-01

    Four cell lines, the mouse L1210 leukaemia, the human W1L2 lymphoblastoid and two human ovarian (CH1 and 41M) cell lines, were made resistant to ZD1694 (Tomudex) by continual exposure to incremental doses of the drug. A 500-fold increase in thymidylate synthase (TS) activity is the primary mechanism of resistance to ZD1694 in the W1L2:RD1694 cell line, which is consequently highly cross-resistant to other folate-based TS inhibitors, including BW1843U89, LY231514 and AG337, but sensitive to antifolates with other enzyme targets. The CH1:RD1694 cell line is 14-fold resistant to ZD1694, largely accounted for by the 4.2-fold increase in TS activity. Cross-resistance was observed to other TS inhibitors, including 5-fluorodeoxyuridine (FdUrd). 41M:RD1694 cells, when exposed to 0.1 microM [3H]ZD1694, accumulated approximately 20-fold less 3H-labelled material over 24 h than the parental line. Data are consistent with this being the result of impaired transport of the drug via the reduced folate/methotrexate carrier. Resistance was therefore observed to methotrexate but not to CB3717, a compound known to use this transport mechanism poorly. The mouse L1210:RD1694 cell line does not accumulate ZD1694 or Methotrexate (MTX) polyglutamates. Folylpolyglutamate synthetase substrate activity (using ZD1694 as the substrate) was decreased to approximately 13% of that observed in the parental line. Cross-resistance was found to those compounds known to be active through polyglutamation. PMID:7537518

  1. 21 CFR 1210.10 - Availability for examination and inspection.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ....10 Section 1210.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... REGULATIONS UNDER THE FEDERAL IMPORT MILK ACT Inspection and Testing § 1210.10 Availability for examination and inspection. Dairy farms and plants from which milk or cream is shipped or transported into the...

  2. 21 CFR 1210.10 - Availability for examination and inspection.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ....10 Section 1210.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... REGULATIONS UNDER THE FEDERAL IMPORT MILK ACT Inspection and Testing § 1210.10 Availability for examination and inspection. Dairy farms and plants from which milk or cream is shipped or transported into the...

  3. 36 CFR Appendix A to Part 1210 - Contract Provisions

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Pt. 1210, App. A Appendix A to Part 1210—Contract Provisions All contracts, awarded by a recipient including small purchases, shall contain the following... not apply to the purchases of supplies or materials or articles ordinarily available on the open...

  4. 16 CFR 1210.11 - General.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... CIGARETTE LIGHTERS Certification Requirements § 1210.11 General. Section 14(a) of the Consumer Product... certify that their products comply with the Safety Standard for Cigarette Lighters. This subpart B...

  5. 25 CFR 11.1210 - Duration and renewal of a regular protection order.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Duration and renewal of a regular protection order. 11.1210 Section 11.1210 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAW AND ORDER COURTS OF INDIAN OFFENSES AND LAW AND ORDER CODE Child Protection and Domestic Violence Procedures § 11.1210...

  6. 20 CFR 418.1210 - What is not a major life-changing event?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false What is not a major life-changing event? 418.1210 Section 418.1210 Employees' Benefits SOCIAL SECURITY ADMINISTRATION MEDICARE SUBSIDIES Medicare... Adjusted Gross Income § 418.1210 What is not a major life-changing event? We will not consider events other...

  7. 25 CFR 11.1210 - Duration and renewal of a regular protection order.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Duration and renewal of a regular protection order. 11.1210 Section 11.1210 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAW AND ORDER COURTS OF INDIAN OFFENSES AND LAW AND ORDER CODE Child Protection and Domestic Violence Procedures § 11.1210...

  8. 20 CFR 418.1210 - What is not a major life-changing event?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false What is not a major life-changing event? 418.1210 Section 418.1210 Employees' Benefits SOCIAL SECURITY ADMINISTRATION MEDICARE SUBSIDIES Medicare... Adjusted Gross Income § 418.1210 What is not a major life-changing event? We will not consider events other...

  9. 21 CFR 1210.11 - Sanitary inspection of dairy farms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Section 1210.11 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... UNDER THE FEDERAL IMPORT MILK ACT Inspection and Testing § 1210.11 Sanitary inspection of dairy farms. The sanitary conditions of any dairy farm producing milk or cream to be shipped or transported into...

  10. 21 CFR 1210.17 - Authority to sample and inspect.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 1210.17 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... FEDERAL IMPORT MILK ACT Inspection and Testing § 1210.17 Authority to sample and inspect. Inspectors engaged in the enforcement of the Federal Import Milk Act are empowered to test for temperature, to take...

  11. 21 CFR 1210.11 - Sanitary inspection of dairy farms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Section 1210.11 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... UNDER THE FEDERAL IMPORT MILK ACT Inspection and Testing § 1210.11 Sanitary inspection of dairy farms. The sanitary conditions of any dairy farm producing milk or cream to be shipped or transported into...

  12. 21 CFR 1210.17 - Authority to sample and inspect.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 1210.17 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... FEDERAL IMPORT MILK ACT Inspection and Testing § 1210.17 Authority to sample and inspect. Inspectors engaged in the enforcement of the Federal Import Milk Act are empowered to test for temperature, to take...

  13. 16 CFR 1210.20 - Stockpiling.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... STANDARD FOR CIGARETTE LIGHTERS Stockpiling § 1210.20 Stockpiling. (a) Definition. Stockpiling means to... cigarette lighters shall not manufacture or import lighters that do not comply with the requirements of this...

  14. 16 CFR 1210.20 - Stockpiling.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... STANDARD FOR CIGARETTE LIGHTERS Stockpiling § 1210.20 Stockpiling. (a) Definition. Stockpiling means to... cigarette lighters shall not manufacture or import lighters that do not comply with the requirements of this...

  15. Diethylglyoxal bis(guanylhydrazone): a novel highly potent inhibitor of S-adenosylmethionine decarboxylase with promising properties for potential chemotherapeutic use.

    PubMed

    Elo, H; Mutikainen, I; Alhonen-Hongisto, L; Laine, R; Jänne, J

    1988-07-01

    Diethylglyoxal bis(guanylhydrazone) (DEGBG), a novel analog of the antileukemic agent methylglyoxal bis(guanylhydrazone) (MGBG) was synthesized. It was found to be the most powerful inhibitor of yeast S-adenosylmethionine decarboxylase (AdoMetDC) so far studied (Ki approx. 9 nM). This property, together with the finding that the compound is a weaker inhibitor of intestinal diamine oxidase than are MGBG and its glyoxal, ethylglyoxal and ethylmethylglyoxal analogs, makes the compound a promising candidate as a polyamine antimetabolite for chemotherapy studies. DEGBG was also found to potentiate the antiproliferative effect of the ornithine decarboxylase inhibitor alpha-difluoromethyl ornithine against mouse L1210 leukemia cells in vitro. DEGBG increased several-fold the intracellular putrescine concentration of cultured L1210 cells, just as MGBG and its ethylglyoxal analog are known to do. The results strongly suggest that DEGBG is worth further studies. Combined with previous studies, they also made possible the construction of some empirical rules concerning the structure-activity relationships of bis(guanylhydrazone) type inhibitors of AdoMetDC. The identity of DEGBG was confirmed by a single-crystal X-ray analysis and by 1H- and 13C-NMR spectroscopy. It consisted of the same isomer as MGBG and several of its analogs are known to consist of.

  16. Graft-versus-Leukemia Effect Following Hematopoietic Stem Cell Transplantation for Leukemia

    PubMed Central

    Dickinson, Anne M.; Norden, Jean; Li, Shuang; Hromadnikova, Ilona; Schmid, Christoph; Schmetzer, Helga; Jochem-Kolb, Hans

    2017-01-01

    The success of hematopoietic stem cell transplantation (HSCT) lies with the ability of the engrafting immune system to remove residual leukemia cells via a graft-versus-leukemia effect (GvL), caused either spontaneously post-HSCT or via donor lymphocyte infusion. GvL effects can also be initiated by allogenic mismatched natural killer cells, antigen-specific T cells, and activated dendritic cells of leukemic origin. The history and further application of this GvL effect and the main mechanisms will be discussed and reviewed in this chapter. PMID:28638379

  17. 45 CFR 1210.4 - Early termination procedures for National Grant Trainees and Volunteers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Trainees and Volunteers. 1210.4 Section 1210.4 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES National Grant Trainees and Volunteers § 1210.4 Early termination procedures for...

  18. 45 CFR 1210.4 - Early termination procedures for National Grant Trainees and Volunteers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Trainees and Volunteers. 1210.4 Section 1210.4 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES National Grant Trainees and Volunteers § 1210.4 Early termination procedures for...

  19. 45 CFR 1210.4 - Early termination procedures for National Grant Trainees and Volunteers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Trainees and Volunteers. 1210.4 Section 1210.4 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES National Grant Trainees and Volunteers § 1210.4 Early termination procedures for...

  20. 30 CFR 1210.02 - To whom do these regulations apply?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 3 2012-07-01 2012-07-01 false To whom do these regulations apply? 1210.02 Section 1210.02 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL... regulations, laws, and the lease terms. ...

  1. 30 CFR 1210.02 - To whom do these regulations apply?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 3 2013-07-01 2013-07-01 false To whom do these regulations apply? 1210.02 Section 1210.02 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL... regulations, laws, and the lease terms. ...

  2. 30 CFR 1210.02 - To whom do these regulations apply?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 3 2014-07-01 2014-07-01 false To whom do these regulations apply? 1210.02 Section 1210.02 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL... regulations, laws, and the lease terms. ...

  3. In Vitro Activity of E1210, a Novel Antifungal, against Clinically Important Yeasts and Molds▿

    PubMed Central

    Miyazaki, Mamiko; Horii, Takaaki; Hata, Katsura; Watanabe, Nao-aki; Nakamoto, Kazutaka; Tanaka, Keigo; Shirotori, Syuji; Murai, Norio; Inoue, Satoshi; Matsukura, Masayuki; Abe, Shinya; Yoshimatsu, Kentaro; Asada, Makoto

    2011-01-01

    E1210 is a new antifungal compound with a novel mechanism of action and broad spectrum of antifungal activity. We investigated the in vitro antifungal activities of E1210 compared to those of fluconazole, itraconazole, voriconazole, amphotericin B, and micafungin against clinical fungal isolates. E1210 showed potent activities against most Candida spp. (MIC90 of ≤0.008 to 0.06 μg/ml), except for Candida krusei (MICs of 2 to >32 μg/ml). E1210 showed equally potent activities against fluconazole-resistant and fluconazole-susceptible Candida strains. E1210 also had potent activities against various filamentous fungi, including Aspergillus fumigatus (MIC90 of 0.13 μg/ml). E1210 was also active against Fusarium solani and some black molds. Of note, E1210 showed the greatest activities against Pseudallescheria boydii (MICs of 0.03 to 0.13 μg/ml), Scedosporium prolificans (MIC of 0.03 μg/ml), and Paecilomyces lilacinus (MICs of 0.06 μg/ml) among the compounds tested. The antifungal action of E1210 was fungistatic, but E1210 showed no trailing growth of Candida albicans, which has often been observed with fluconazole. In a cytotoxicity assay using human HK-2 cells, E1210 showed toxicity as low as that of fluconazole. Based on these results, E1210 is likely to be a promising antifungal agent for the treatment of invasive fungal infections. PMID:21825291

  4. Requirement for Dot1l in murine postnatal hematopoiesis and leukemogenesis by MLL translocation

    PubMed Central

    Jo, Stephanie Y.; Granowicz, Eric M.; Maillard, Ivan; Thomas, Dafydd

    2011-01-01

    Disruptor of telomeric silencing 1-like (Dot1l) is a histone 3 lysine 79 methyltransferase. Studies of constitutive Dot1l knockout mice show that Dot1l is essential for embryonic development and prenatal hematopoiesis. DOT1L also interacts with translocation partners of Mixed Lineage Leukemia (MLL) gene, which is commonly translocated in human leukemia. However, the requirement of Dot1l in postnatal hematopoiesis and leukemogenesis of MLL translocation proteins has not been conclusively shown. With a conditional Dot1l knockout mouse model, we examined the consequences of Dot1l loss in postnatal hematopoiesis and MLL translocation leukemia. Deletion of Dot1l led to pancytopenia and failure of hematopoietic homeostasis, and Dot1l-deficient cells minimally reconstituted recipient bone marrow in competitive transplantation experiments. In addition, MLL-AF9 cells required Dot1l for oncogenic transformation, whereas cells with other leukemic oncogenes, such as Hoxa9/Meis1 and E2A-HLF, did not. These findings illustrate a crucial role of Dot1l in normal hematopoiesis and leukemogenesis of specific oncogenes. PMID:21398221

  5. 30 CFR 1210.20 - What if I disagree with the burden hour estimates?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... estimates? 1210.20 Section 1210.20 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE FORMS AND REPORTS General Provisions § 1210.20 What if I disagree with....gov/Laws_R_D/FRNotices/FRInfColl.htm-. Send comments on the accuracy of these burden estimates or...

  6. 30 CFR 1210.20 - What if I disagree with the burden hour estimates?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... estimates? 1210.20 Section 1210.20 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE FORMS AND REPORTS General Provisions § 1210.20 What if I disagree with....gov/Laws_R_D/FRNotices/FRInfColl.htm-. Send comments on the accuracy of these burden estimates or...

  7. 30 CFR 1210.20 - What if I disagree with the burden hour estimates?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... estimates? 1210.20 Section 1210.20 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE FORMS AND REPORTS General Provisions § 1210.20 What if I disagree with....gov/Laws_R_D/FRNotices/FRInfColl.htm-. Send comments on the accuracy of these burden estimates or...

  8. A non-invasive approach to monitor chronic lymphocytic leukemia engraftment in a xenograft mouse model using ultra-small superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI).

    PubMed

    Valdora, Francesca; Cutrona, Giovanna; Matis, Serena; Morabito, Fortunato; Massucco, Carlotta; Emionite, Laura; Boccardo, Simona; Basso, Luca; Recchia, Anna Grazia; Salvi, Sandra; Rosa, Francesca; Gentile, Massimo; Ravina, Marco; Pace, Daniele; Castronovo, Angela; Cilli, Michele; Truini, Mauro; Calabrese, Massimo; Neri, Antonino; Neumaier, Carlo Emanuele; Fais, Franco; Baio, Gabriella; Ferrarini, Manlio

    2016-11-01

    Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia among adults. Despite its indolent nature, CLL remains an incurable disease. Herein we aimed to monitor CLL disease engraftment and, progression/regression in a xenograft CLL mouse model using ultra-small superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI). Spleen contrast enhancement, quantified as percentage change in signal intensity upon USPIO administration, demonstrated a difference due to a reduced USPIO uptake, in the spleens of mice injected with CLL cells (NSG-CLL, n=71) compared to controls (NSG-CTR, n=17). These differences were statistically significant both after 2 and 4weeks from CLL cells injection. In addition comparison of mice treated with rituximab with untreated controls for changes in spleen iron uptake confirmed that it is possible to monitor treatment efficacy in this mouse model of CLL using USPIO-enhanced MRI. Further applications could include the preclinical in vivo monitoring of new therapies and the clinical evaluation of CLL patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. 7 CFR 1210.600 - General.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... PLAN Referendum Procedures § 1210.600 General. Referenda to determine whether eligible producers... Research and Promotion Plan shall be conducted in accordance with this subpart. ...

  10. Mouse Models of Human T Lymphotropic Virus Type-1–Associated Adult T-Cell Leukemia/Lymphoma

    PubMed Central

    Zimmerman, B.; Niewiesk, S.; Lairmore, M. D.

    2011-01-01

    Human T-lymphotropic virus type-1 (HTLV-1), the first human retrovirus discovered, is the causative agent of adult T-cell leukemia/lymphoma (ATL) and a number of lymphocyte-mediated inflammatory conditions including HTLV-1–associated myelopathy/tropical spastic paraparesis. Development of animal models to study the pathogenesis of HTLV-1–associated diseases has been problematic. Mechanisms of early infection and cell-to-cell transmission can be studied in rabbits and nonhuman primates, but lesion development and reagents are limited in these species. The mouse provides a cost-effective, highly reproducible model in which to study factors related to lymphoma development and the preclinical efficacy of potential therapies against ATL. The ability to manipulate transgenic mice has provided important insight into viral genes responsible for lymphocyte transformation. Expansion of various strains of immunodeficient mice has accelerated the testing of drugs and targeted therapy against ATL. This review compares various mouse models to illustrate recent advances in the understanding of HTLV-1–associated ATL development and how improvements in these models are critical to the future development of targeted therapies against this aggressive T-cell lymphoma. PMID:20442421

  11. 30 CFR 1210.52 - What royalty reports must I submit?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false What royalty reports must I submit? 1210.52 Section 1210.52 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR Natural Resources Revenue FORMS AND REPORTS Royalty Reports-Oil, Gas, and Geothermal Resources...

  12. 30 CFR 1210.60 - What definitions apply to this subpart?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false What definitions apply to this subpart? 1210.60 Section 1210.60 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR Natural Resources Revenue FORMS AND REPORTS Royalty Reports-Oil, Gas, and Geothermal Resources...

  13. 45 CFR 1210.3-9 - Decision by Director of VISTA.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 4 2013-10-01 2013-10-01 false Decision by Director of VISTA. 1210.3-9 Section 1210.3-9 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early...

  14. 45 CFR 1210.3-9 - Decision by Director of VISTA.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 4 2012-10-01 2012-10-01 false Decision by Director of VISTA. 1210.3-9 Section 1210.3-9 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early...

  15. 45 CFR 1210.3-9 - Decision by Director of VISTA.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 4 2011-10-01 2011-10-01 false Decision by Director of VISTA. 1210.3-9 Section 1210.3-9 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early...

  16. 45 CFR 1210.3-9 - Decision by Director of VISTA.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 4 2014-10-01 2014-10-01 false Decision by Director of VISTA. 1210.3-9 Section 1210.3-9 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early...

  17. 45 CFR 1210.3-9 - Decision by Director of VISTA.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Decision by Director of VISTA. 1210.3-9 Section 1210.3-9 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early...

  18. Nanoparticle targeted therapy against childhood acute lymphoblastic leukemia

    NASA Astrophysics Data System (ADS)

    Satake, Noriko; Lee, Joyce; Xiao, Kai; Luo, Juntao; Sarangi, Susmita; Chang, Astra; McLaughlin, Bridget; Zhou, Ping; Kenney, Elaina; Kraynov, Liliya; Arnott, Sarah; McGee, Jeannine; Nolta, Jan; Lam, Kit

    2011-06-01

    The goal of our project is to develop a unique ligand-conjugated nanoparticle (NP) therapy against childhood acute lymphoblastic leukemia (ALL). LLP2A, discovered by Dr. Kit Lam, is a high-affinity and high-specificity peptidomimetic ligand against an activated α4β1 integrin. Our study using 11 fresh primary ALL samples (10 precursor B ALL and 1 T ALL) showed that childhood ALL cells expressed activated α4β1 integrin and bound to LLP2A. Normal hematopoietic cells such as activated lymphocytes and monocytes expressed activated α4β1 integrin; however, normal hematopoietic stem cells showed low expression of α4β1 integrin. Therefore, we believe that LLP2A can be used as a targeted therapy for childhood ALL. The Lam lab has developed novel telodendrimer-based nanoparticles (NPs) which can carry drugs efficiently. We have also developed a human leukemia mouse model using immunodeficient NOD/SCID/IL2Rγ null mice engrafted with primary childhood ALL cells from our patients. LLP2A-conjugated NPs will be evaluated both in vitro and in vivo using primary leukemia cells and this mouse model. NPs will be loaded first with DiD near infra-red dye, and then with the chemotherapeutic agents daunorubicin or vincristine. Both drugs are mainstays of current chemotherapy for childhood ALL. Targeting properties of LLP2A-conjugated NPs will be evaluated by fluorescent microscopy, flow cytometry, MTS assay, and mouse survival after treatment. We expect that LLP2A-conjugated NPs will be preferentially delivered and endocytosed to leukemia cells as an effective targeted therapy.

  19. Protracted Administration of L-Asparaginase in Maintenance Phase Is the Risk Factor for Hyperglycemia in Older Patients with Pediatric Acute Lymphoblastic Leukemia

    PubMed Central

    Yoshida, Hideki; Imamura, Toshihiko; Saito, Akiko M.; Takahashi, Yoshihiro; Suenobu, So-ichi; Hasegawa, Daiichiro; Deguchi, Takao; Hashii, Yoshiko; Kawasaki, Hirohide; Endo, Mikiya; Hori, Hiroki; Suzuki, Nobuhiro; Kosaka, Yoshiyuki; Kato, Koji; Yumura-Yagi, Keiko; Hara, Junichi; Oda, Megumi; Sato, Atsushi; Horibe, Keizo

    2015-01-01

    Although L-asparaginase related hyperglycemia is well known adverse event, it is not studied whether the profile of this adverse event is affected by intensification of L-asparaginase administration. Here, we analyzed the profile of L-asparaginase related hyperglycemia in a 1,176 patients with pediatric acute lymphoblastic leukemia treated according to the Japan Association of Childhood Leukemia Study ALL-02 protocol using protracted L-asparaginase administration in maintenance phase. We determined that a total of 75 L-asparaginase related hyperglycemia events occurred in 69 patients. Although 17 events (17/1176, 1.4%) developed in induction phase, which was lower incidence than those (10–15%) in previous reports, 45 events developed during the maintenance phase with protracted L-asparaginase administration. Multivariate analysis showed that older age at onset (≥10 years) was a sole independent risk factor for L-asparaginase-related hyperglycemia (P<0.01), especially in maintenance phase. Contrary to the previous reports, obesity was not associated with L-asparaginase-related hyperglycemia. These findings suggest that protracted administration of L-asparaginase is the risk factor for hyperglycemia when treating adolescent and young adult acute lymphoblastic leukemia patients. PMID:26317422

  20. The cytological manifestation of gene amplification in multidrug-resistant mouse leukemia P388 sublines is correlated with amplicon content

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Il`inskaya, G.V.; Kopnin, B.P.; Demidova, N.S.

    1995-10-01

    Previously, we showed that development of multidrug resistance (MDR) in mouse P388 leukemia cells is often associated with the appearance of newly-formed chromosomelike structures that contain amplified copies of the mdr1 gene. In the present study, we compared amplicon content in P388 sublines showing different types of these structures. A strong correlation between the formation of specific acentric markers consisting of two identical arms and the absence of the sorcin gene coamplification was found. In all the sublines containing other types of chromosomelike structures, the sorcin gene is coamplified. 9 refs., 2 figs., 1 tab.

  1. 36 CFR 1210.31 - Insurance coverage.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Post-Award Requirements Property Standards § 1210.31 Insurance coverage. Recipients shall, at a minimum, provide the equivalent insurance coverage for...

  2. 36 CFR 1210.31 - Insurance coverage.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Post-Award Requirements Property Standards § 1210.31 Insurance coverage. Recipients shall, at a minimum, provide the equivalent insurance coverage for...

  3. 36 CFR 1210.31 - Insurance coverage.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Post-Award Requirements Property Standards § 1210.31 Insurance coverage. Recipients shall, at a minimum, provide the equivalent insurance coverage for...

  4. 36 CFR 1210.31 - Insurance coverage.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Post-Award Requirements Property Standards § 1210.31 Insurance coverage. Recipients shall, at a minimum, provide the equivalent insurance coverage for...

  5. 2 CFR 1.210 - Applicability to Federal agencies and others.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 2 Grants and Agreements 1 2010-01-01 2010-01-01 false Applicability to Federal agencies and others. 1.210 Section 1.210 Grants and Agreements ABOUT TITLE 2 OF THE CODE OF FEDERAL REGULATIONS AND... may apply to— (1) The agency's awarding or administering officials; (2) Non-Federal entities that...

  6. Two decades of leukemia oncoprotein epistasis: the MLL1 paradigm for epigenetic deregulation in leukemia

    PubMed Central

    Li, Bin E.; Ernst, Patricia

    2015-01-01

    MLL1, located on human chromosome 11, is disrupted in distinct recurrent chromosomal translocations in several leukemia subsets. Studying the MLL1 gene and its oncogenic variants has provided a paradigm for understanding cancer initiation and maintenance through aberrant epigenetic gene regulation. Here we review the historical development of model systems to recapitulate oncogenic MLL1-rearrangement (MLL-r) alleles encoding mixed-lineage leukemia fusion proteins (MLL-FPs) or internal gene rearrangement products. These largely mouse and human cell/xenograft systems have been generated and used to understand how MLL-r alleles affect diverse pathways to result in a highly penetrant, drug-resistant leukemia. The particular features of the animal models influenced the conclusions of mechanisms of transformation. We discuss significant downstream enablers, inhibitors, effectors, and collaborators of MLL-r leukemia, including molecules that directly interact with MLL-FPs and endogenous mixed-lineage leukemia protein, direct target genes of MLL-FPs, and other pathways that have proven to be influential in supporting or suppressing the leukemogenic activity of MLL-FPs. The use of animal models has been complemented with patient sample, genome-wide analyses to delineate the important genomic and epigenomic changes that occur in distinct subsets of MLL-r leukemia. Collectively, these studies have resulted in rapid progress toward developing new strategies for targeting MLL-r leukemia and general cell-biological principles that may broadly inform targeting aberrant epigenetic regulators in other cancers. PMID:25264566

  7. Behavior of a cloned murine interferon alpha/beta receptor expressed in homospecific or heterospecific background.

    PubMed Central

    Uzé, G; Lutfalla, G; Bandu, M T; Proudhon, D; Mogensen, K E

    1992-01-01

    A murine interferon (IFN) alpha/beta receptor was cloned from the IFN-sensitive L1210 cell line on the basis of its homology with the human receptor. A combination of methods that includes the screening of random-primed and oligo(dT)-primed cDNA libraries and polymerase chain reactions with a single-side specificity was used. At the amino acid level, the murine IFN-alpha/beta shows 46% identity with its human counterpart. Both human WISH cells presenting a low sensitivity to mouse IFN and a murine L1210 mutant subline that does not express the receptor have been stably transfected with the murine IFN-alpha/beta receptor. Whereas transfected human cells became sensitive to a limited number of mouse IFN-alpha/beta subtypes, the transfected murine L1210 mutant was found to be fully complemented and became sensitive to all mouse IFN-alpha/beta subtypes tested, including those that were not active on transfected human cells. These results strongly suggest that the receptor described here is implicated in the mediation of the activities of all murine IFN-alpha/beta subtypes. Images PMID:1533935

  8. Combination Chemotherapy and Imatinib Mesylate in Treating Children With Relapsed Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2013-10-07

    L1 Childhood Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; Non-T, Non-B Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

  9. All-trans-retinoic acid enhances apoptosis induction by tyrosine kinase inhibitors in the eosinophilic leukemia-derived EoL-1 cell line.

    PubMed

    Robert, Carine; Apàti, Agota; Chomienne, Christine; Papp, Béla

    2008-02-01

    Imatinib and retinoids induce apoptosis in FIP1L1/PDGFRalpha-positive EoL-1 leukemia cells. Although imatinib induces complete remission in most FIP1L1/PDGFRalpha-positive patients, response to imatinib is sometimes suboptimal. In order to enhance the potency of the molecularly targeted therapy of eosinophilic leukemia, we investigated the effect of retinoids combined with tyrosine kinase inhibitors on EoL-1 cells. We demonstrate that retinoids combined with tyrosine kinase inhibitors lead to enhanced apoptosis induction in EoL-1 cells. Our results suggest that tyrosine kinase inhibitors combined with retinoids may constitute a valuable therapeutic approach for sensitive neoplasias that may display enhanced anti-leukemic potency when compared to single drug treatments.

  10. 21 CFR 1210.3 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER... MILK ACT General Provisions § 1210.3 Definitions. (a) Secretary. Secretary means the Secretary of Health and Human Services. (b) Commissioner. Commissioner means the Commissioner of Food and Drugs. (c...

  11. 7 CFR 1210.366 - Separability.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... PLAN Watermelon Research and Promotion Plan Miscellaneous § 1210.366 Separability. If any provision of this Plan is declared invalid or the applicability thereof to any person or circumstance is held...

  12. Mouse xenograft modeling of human adult acute lymphoblastic leukemia provides mechanistic insights into adult LIC biology

    PubMed Central

    Dey, Aditi; Castleton, Anna Z.; Schwab, Claire; Samuel, Edward; Sivakumaran, Janani; Beaton, Brendan; Zareian, Nahid; Zhang, Christie Yu; Rai, Lena; Enver, Tariq; Moorman, Anthony V.; Fielding, Adele K.

    2014-01-01

    The distinct nature of acute lymphoblastic leukemia (ALL) in adults, evidenced by inferior treatment outcome and different genetic landscape, mandates specific studies of disease-initiating mechanisms. In this study, we used NOD/LtSz-scid IL2Rγ nullc (NSG) mouse xenotransplantation approaches to elucidate leukemia-initiating cell (LIC) biology in primary adult precursor B (pre-B) ALL to optimize disease modeling. In contrast with xenografting studies of pediatric ALL, we found that modification of the NSG host environment using preconditioning total body irradiation (TBI) was indispensable for efficient engraftment of adult non-t(4;11) pre-B ALL, whereas t(4;11) pre-B ALL was successfully reconstituted without this adaptation. Furthermore, TBI-based xenotransplantation of non-t(4;11) pre-B ALL enabled detection of a high frequency of LICs (<1:6900) and permitted frank leukemic engraftment from a remission sample containing drug-resistant minimal residual disease. Investigation of TBI-sensitive stromal-derived factor-1/chemokine receptor type 4 signaling revealed greater functional dependence of non-t(4;11) pre-B ALL on this niche-based interaction, providing a possible basis for the differential engraftment behavior. Thus, our studies establish the optimal conditions for experimental modeling of human adult pre-B ALL and demonstrate the critical protumorogenic role of microenvironment-derived SDF-1 in regulating adult pre-B LIC activity that may present a therapeutic opportunity. PMID:24825861

  13. 16 CFR § 1210.20 - Stockpiling.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... STANDARD FOR CIGARETTE LIGHTERS Stockpiling § 1210.20 Stockpiling. (a) Definition. Stockpiling means to... cigarette lighters shall not manufacture or import lighters that do not comply with the requirements of this...

  14. 7 CFR 1210.328 - Duties.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., advertising or promotion, and the payment of the costs thereof with funds received pursuant to this Plan; (e... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan National Watermelon Promotion Board § 1210.328 Duties. The...

  15. Activation of a promyelocytic leukemia-tumor protein 53 axis underlies acute promyelocytic leukemia cure.

    PubMed

    Ablain, Julien; Rice, Kim; Soilihi, Hassane; de Reynies, Aurélien; Minucci, Saverio; de Thé, Hugues

    2014-02-01

    Acute promyelocytic leukemia (APL) is driven by the promyelocytic leukemia (PML)-retinoic acid receptor-α (PML-RARA) fusion protein, which interferes with nuclear receptor signaling and PML nuclear body (NB) assembly. APL is the only malignancy definitively cured by targeted therapies: retinoic acid (RA) and/or arsenic trioxide, which both trigger PML-RARA degradation through nonoverlapping pathways. Yet, the cellular and molecular determinants of treatment efficacy remain disputed. We demonstrate that a functional Pml-transformation-related protein 53 (Trp53) axis is required to eradicate leukemia-initiating cells in a mouse model of APL. Upon RA-induced PML-RARA degradation, normal Pml elicits NB reformation and induces a Trp53 response exhibiting features of senescence but not apoptosis, ultimately abrogating APL-initiating activity. Apart from triggering PML-RARA degradation, arsenic trioxide also targets normal PML to enhance NB reformation, which may explain its clinical potency, alone or with RA. This Pml-Trp53 checkpoint initiated by therapy-triggered NB restoration is specific for PML-RARA-driven APL, but not the RA-resistant promyelocytic leukemia zinc finger (PLZF)-RARA variant. Yet, as NB biogenesis is druggable, it could be therapeutically exploited in non-APL malignancies.

  16. 16 CFR § 1210.11 - General.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... STANDARD FOR CIGARETTE LIGHTERS Certification Requirements § 1210.11 General. Section 14(a) of the Consumer... to certify that their products comply with the Safety Standard for Cigarette Lighters. This subpart B...

  17. 30 CFR 1210.54 - Must I submit this royalty report electronically?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Must I submit this royalty report electronically? 1210.54 Section 1210.54 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR Natural Resources Revenue FORMS AND REPORTS Royalty Reports-Oil, Gas, and...

  18. 30 CFR 1210.207 - How will information submissions be kept confidential?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... confidential? 1210.207 Section 1210.207 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE FORMS AND REPORTS Production and Royalty Reports-Solid Minerals... lessee, except as otherwise provided by law or regulation. [66 FR 45771, Aug. 30, 2001. Redesignated at...

  19. 30 CFR 1210.207 - How will information submissions be kept confidential?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... confidential? 1210.207 Section 1210.207 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE FORMS AND REPORTS Production and Royalty Reports-Solid Minerals... lessee, except as otherwise provided by law or regulation. [66 FR 45771, Aug. 30, 2001. Redesignated at...

  20. 30 CFR 1210.207 - How will information submissions be kept confidential?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... confidential? 1210.207 Section 1210.207 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE, DEPARTMENT OF THE INTERIOR NATURAL RESOURCES REVENUE FORMS AND REPORTS Production and Royalty Reports-Solid Minerals... lessee, except as otherwise provided by law or regulation. [66 FR 45771, Aug. 30, 2001. Redesignated at...

  1. 36 CFR 1210.61 - Termination.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Post-Award Requirements Termination and Enforcement § 1210.61... agree upon the termination conditions, including the effective date and, in the case of partial... setting forth the reasons for such termination, the effective date, and, in the case of partial...

  2. 36 CFR 1210.22 - Payment.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Post-Award Requirements Financial and Program Management... financial management systems that meet the standards for fund control and accountability as established in § 1210.21. Cash advances to a recipient organization shall be limited to the minimum amounts needed and...

  3. 21 CFR 1210.1 - Authority.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... health” shall be known and referred to as “the Federal Import Milk Act.” ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER... MILK ACT General Provisions § 1210.1 Authority. For the purposes of the regulations in this part the...

  4. 7 CFR 1210.341 - Assessments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... PLAN Watermelon Research and Promotion Plan Expenses and Assessments § 1210.341 Assessments. (a) During... those that are exempt under this Plan, and such other information as may be prescribed by the Board. (d...

  5. 16 CFR 1210.11 - General.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Certification Requirements § 1210.11 General. Section 14(a) of the Consumer Product... product that is subject to a consumer product safety standard and that is distributed in commerce to issue...

  6. 7 CFR 1.210 - Purpose.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Secretary of Agriculture ADMINISTRATIVE REGULATIONS Appearance of USDA Employees as Witnesses in Judicial or Administrative Proceedings § 1.210 Purpose. This subpart sets forth procedures governing the appearance of USDA... employment with USDA. These regulations do not apply to appearances by USDA employees as witnesses in...

  7. 7 CFR 1.210 - Purpose.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Secretary of Agriculture ADMINISTRATIVE REGULATIONS Appearance of USDA Employees as Witnesses in Judicial or Administrative Proceedings § 1.210 Purpose. This subpart sets forth procedures governing the appearance of USDA... employment with USDA. These regulations do not apply to appearances by USDA employees as witnesses in...

  8. 7 CFR 1.210 - Purpose.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Secretary of Agriculture ADMINISTRATIVE REGULATIONS Appearance of USDA Employees as Witnesses in Judicial or Administrative Proceedings § 1.210 Purpose. This subpart sets forth procedures governing the appearance of USDA... employment with USDA. These regulations do not apply to appearances by USDA employees as witnesses in...

  9. 7 CFR 1.210 - Purpose.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Secretary of Agriculture ADMINISTRATIVE REGULATIONS Appearance of USDA Employees as Witnesses in Judicial or Administrative Proceedings § 1.210 Purpose. This subpart sets forth procedures governing the appearance of USDA... employment with USDA. These regulations do not apply to appearances by USDA employees as witnesses in...

  10. 7 CFR 1.210 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Secretary of Agriculture ADMINISTRATIVE REGULATIONS Appearance of USDA Employees as Witnesses in Judicial or Administrative Proceedings § 1.210 Purpose. This subpart sets forth procedures governing the appearance of USDA... employment with USDA. These regulations do not apply to appearances by USDA employees as witnesses in...

  11. 30 CFR 1210.55 - May I submit this royalty report manually?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false May I submit this royalty report manually? 1210.55 Section 1210.55 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR Natural Resources Revenue FORMS AND REPORTS Royalty Reports-Oil, Gas, and Geothermal...

  12. 36 CFR 1210.34 - Equipment.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 1210.34 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION GENERAL RULES... data, including date of disposal and sales price or the method used to determine current fair market... the following standards. For equipment with a current per unit fair market value of $5,000 or more...

  13. Apoptosis- and differentiation-inducing activities of jacaric acid, a conjugated linolenic acid isomer, on human eosinophilic leukemia EoL-1 cells.

    PubMed

    Liu, Wai-Nam; Leung, Kwok-Nam

    2014-11-01

    Conjugated linolenic acids (CLNAs) are a group of naturally occurring positional and geometrical isomers of the C18 polyunsaturated essential fatty acid, linolenic acid (LNA), with three conjugated double bonds (C18:3). Although previous research has demonstrated the growth-inhibitory effects of CLNA on a wide variety of cancer cell lines in vitro, their action mechanisms and therapeutic potential on human myeloid leukemia cells remain poorly understood. In the present study, we found that jacaric acid (8Z,10E,12Z-octadecatrienoic acid), a CLNA isomer which is present in jacaranda seed oil, inhibited the in vitro growth of human eosinophilic leukemia EoL-1 cells in a time- and concentration-dependent manner. Mechanistic studies showed that jacaric acid triggered cell cycle arrest of EoL-1 cells at the G0/G1 phase and induced apoptosis of the EoL-1 cells, as measured by the Cell Death Detection ELISAPLUS kit, Annexin V assay and JC-1 dye staining. Notably, the jacaric acid-treated EoL-1 cells also underwent differentiation as revealed by morphological and phenotypic analysis. Collectively, our results demonstrated the capability of jacaric acid to inhibit the growth of EoL-1 cells in vitro through triggering cell cycle arrest and by inducing apoptosis and differentiation of the leukemia cells. Therefore, jacaric acid might be developed as a potential candidate for the treatment of certain forms of myeloid leukemia with minimal toxicity and few side effects.

  14. Myeloid leukemia factor 1 stabilizes tumor suppressor C/EBPα to prevent Trib1-driven acute myeloid leukemia.

    PubMed

    Nakamae, Ikuko; Kato, Jun-Ya; Yokoyama, Takashi; Ito, Hidenori; Yoneda-Kato, Noriko

    2017-09-12

    C/EBPα is a key transcription factor regulating myeloid differentiation and leukemogenesis. The Trib1-COP1 complex is an E3 ubiquitin ligase that targets C/EBPα for degradation, and its overexpression specifically induces acute myeloid leukemia (AML). Here we show that myeloid leukemia factor 1 (MLF1) stabilizes C/EBPα protein levels by inhibiting the ligase activity of the Trib1-COP1 complex. MLF1 directly interacts with COP1 in the nucleus and interferes with the formation of the Trib1-COP1 complex, thereby blocking its ability to polyubiquitinate C/EBPα for degradation. MLF1 overexpression suppressed the Trib1-induced growth advantage in a murine bone marrow (BM) culture and Trib1-induced AML development in BM-transplanted mouse models. MLF1 was expressed in hematopoietic stem cells and myeloid progenitors (common myeloid progenitors and granulocyte-macrophage progenitors) in normal hematopoiesis, which is consistent with the distribution of C/EBPα. An MLF1 deficiency conferred a more immature phenotype on Trib1-induced AML development. A higher expression ratio of Trib1 to MLF1 was a key determinant for AML development in mouse models, which was also confirmed in human patient samples with acute leukemia. These results indicate that MLF1 is a positive regulator that is critical for C/EBPα stability in the early phases of hematopoiesis and leukemogenesis.

  15. Myeloid leukemia factor 1 stabilizes tumor suppressor C/EBPα to prevent Trib1-driven acute myeloid leukemia

    PubMed Central

    Nakamae, Ikuko; Kato, Jun-ya; Yokoyama, Takashi; Ito, Hidenori

    2017-01-01

    C/EBPα is a key transcription factor regulating myeloid differentiation and leukemogenesis. The Trib1-COP1 complex is an E3 ubiquitin ligase that targets C/EBPα for degradation, and its overexpression specifically induces acute myeloid leukemia (AML). Here we show that myeloid leukemia factor 1 (MLF1) stabilizes C/EBPα protein levels by inhibiting the ligase activity of the Trib1-COP1 complex. MLF1 directly interacts with COP1 in the nucleus and interferes with the formation of the Trib1-COP1 complex, thereby blocking its ability to polyubiquitinate C/EBPα for degradation. MLF1 overexpression suppressed the Trib1-induced growth advantage in a murine bone marrow (BM) culture and Trib1-induced AML development in BM-transplanted mouse models. MLF1 was expressed in hematopoietic stem cells and myeloid progenitors (common myeloid progenitors and granulocyte-macrophage progenitors) in normal hematopoiesis, which is consistent with the distribution of C/EBPα. An MLF1 deficiency conferred a more immature phenotype on Trib1-induced AML development. A higher expression ratio of Trib1 to MLF1 was a key determinant for AML development in mouse models, which was also confirmed in human patient samples with acute leukemia. These results indicate that MLF1 is a positive regulator that is critical for C/EBPα stability in the early phases of hematopoiesis and leukemogenesis. PMID:29296815

  16. The role of cell size in density gradient electrophoretic separation of mouse leukemia cells according to position in the cell cycle

    NASA Technical Reports Server (NTRS)

    Plank, L. D.; Kunze, M. E.; Todd, P. W.

    1985-01-01

    Cultured mouse leukemia cells line L5178Y were subjected to upward electrophoresis in a density gradient and the slower migrating cell populations were enriched in G2 cells. It is indicated that this cell line does not change electrophoretic mobility through the cell cycle. The possibility that increased sedimentation downward on the part of the larger G2 cells caused this separation was explored. Two different cell populations were investigated. The log phase population was found to migrate upward faster than the G2 population, and a similar difference between their velocities and calculated on the basis of a 1 um diameter difference between the two cell populations. The G2 and G1 enriched populations were isolated by Ficoll density gradient sedimentation. The bottom fraction was enriched in G2 cells and the top fraction was enriched with G1 cells, especially when compared with starting materials. The electrophoretic mobilities of these two cell populations did not differ significantly from one another. Cell diameter dependent migration curves were calculated and were found to be different. Families of migration curves that differ when cell size is considered as a parameter are predicted.

  17. 30 CFR 1210.155 - What reports must I submit for Federal onshore stripper oil properties?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... stripper oil properties? 1210.155 Section 1210.155 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE..., Gas, and Geothermal Resources § 1210.155 What reports must I submit for Federal onshore stripper oil... Management (BLM) under 43 CFR 3103.4-2 must submit Form ONRR-4377, Stripper Royalty Rate Reduction...

  18. 30 CFR 1210.155 - What reports must I submit for Federal onshore stripper oil properties?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... stripper oil properties? 1210.155 Section 1210.155 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE..., Gas, and Geothermal Resources § 1210.155 What reports must I submit for Federal onshore stripper oil... Management (BLM) under 43 CFR 3103.4-2 must submit Form MMS-4377, Stripper Royalty Rate Reduction...

  19. 30 CFR 1210.155 - What reports must I submit for Federal onshore stripper oil properties?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... stripper oil properties? 1210.155 Section 1210.155 Mineral Resources OFFICE OF NATURAL RESOURCES REVENUE..., Gas, and Geothermal Resources § 1210.155 What reports must I submit for Federal onshore stripper oil... Management (BLM) under 43 CFR 3103.4-2 must submit Form ONRR-4377, Stripper Royalty Rate Reduction...

  20. 21 CFR 870.1210 - Continuous flush catheter.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Diagnostic Devices § 870.1210 Continuous flush catheter. (a) Identification. A continuous flush catheter is an attachment to a catheter-transducer system...

  1. 21 CFR 870.1210 - Continuous flush catheter.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Diagnostic Devices § 870.1210 Continuous flush catheter. (a) Identification. A continuous flush catheter is an attachment to a catheter-transducer system...

  2. 21 CFR 870.1210 - Continuous flush catheter.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Diagnostic Devices § 870.1210 Continuous flush catheter. (a) Identification. A continuous flush catheter is an attachment to a catheter-transducer system...

  3. 7 CFR 1210.311 - Programs and projects.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.311 Programs and projects. Programs and projects mean those research, development, advertising, or promotion programs or projects...

  4. DNA-protein crosslinking by trans-platinum(II)diamminedichloride in mammalian cells, a new method of analysis.

    PubMed

    Kohn, K W; Ewig, R A

    1979-03-28

    DNA-protien crosslinks produced in mouse leukemia L1210 cells by trans-Pt(II)diamminedichloride were quantitated using the technique of DNA alkaline elution. DNA single-strand segments that were or were not linked to protein were separable into distinct components by alkaline elution after exposure of the cells to 2--15 kR of X-ray. Protein-linked DNA strands were separated on the basis of their retention of filters at pH 12 while free DNA strands of the size generated by 2--15 kR of X-ray passed rapidly through the filters. The retention of protein-linked DNA strands was attributable to adsorption of protein to the filter under the conditions of alkaline elution. The results obeyed a simple quantitative model according to which the frequency of DNA-protein crosslinks could be calculated.

  5. BCL-x{sub L}/MCL-1 inhibition and RARγ antagonism work cooperatively in human HL60 leukemia cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Perri, Mariarita; Yap, Jeremy L.; Yu, Jianshi

    2014-10-01

    The acute promyelocytic leukemia (APL) subtype of acute myeloid leukemia (AML) is characterized by chromosomal translocations that result in fusion proteins, including the promyelocytic leukemia–retinoic acid receptor, alpha fusion protein (PML–RARα). All-trans retinoic acid (atRA) treatment is the standard drug treatment for APL yielding cure rates >80% by activating transcription and proteasomal degradation of retinoic acid receptor, alpha (RARα). Whereas combination therapy with As{sub 2}O{sub 3} has increased survival further, patients that experience relapse and are refractory to atRA and/or As{sub 2}O{sub 3} is a clinically significant problem. BCL-2 family proteins regulate apoptosis and over-expression of anti-apoptotic B-cell leukemia/lymphoma 2more » (BCL-2) family proteins has been associated with chemotherapeutic resistance in APL including impairment of the ability of atRA to induce growth arrest and differentiation. Here we investigated the novel BH3 domain mimetic, JY-1-106, which antagonizes the anti-apoptotic BCL-2 family members B-cell lymphoma-extra large (BCL-x{sub L}) and myeloid cell leukemia-1 (MCL-1) alone and in combination with retinoids including atRA, AM580 (RARα agonist), and SR11253 (RARγ antagonist). JY-1-106 reduced cell viability in HL-60 cells alone and in combination with retinoids. The combination of JY-1-106 and SR11253 had the greatest impact on cell viability by stimulating apoptosis. These studies indicate that dual BCL-x{sub L}/MCL-1 inhibitors and retinoids could work cooperatively in leukemia treatment. - Highlights: • Novel Bcl-x{sub L}/Mcl-1 inhibitor JY-1-106 reduces HL60 cell viability. • JY-1-106 is investigated in combination with retinoic acid, AM580, and SR11253. • AM580 is an RARα agonist; SR11253 is an RARγ antagonist. • Combined use of JY-1-106/SR11253 exhibited the greatest cell viability reduction. • JY-1-106 alone or in combination with retinoids induces apoptosis.« less

  6. 7 CFR 1210.330 - Policy and objective.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... research, development, advertising, and promotion in order to: (a) Strengthen watermelons' competitive... PROMOTION PLAN Watermelon Research and Promotion Plan Research and Promotion § 1210.330 Policy and objective...

  7. 16 CFR 1210.11 - General.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... CIGARETTE LIGHTERS Certification Requirements § 1210.11 General. Section 14(a) of the Consumer Product... certify that their products comply with the Safety Standard for Cigarette Lighters. This subpart B..., recordkeeping, and reporting pursuant to sections 14, 16(b), 17(g), and 27(e) of the CPSA, 15 U.S.C. 2063, 2065...

  8. 16 CFR 1210.11 - General.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... CIGARETTE LIGHTERS Certification Requirements § 1210.11 General. Section 14(a) of the Consumer Product... certify that their products comply with the Safety Standard for Cigarette Lighters. This subpart B..., recordkeeping, and reporting pursuant to sections 14, 16(b), 17(g), and 27(e) of the CPSA, 15 U.S.C. 2063, 2065...

  9. 21 CFR 1210.3 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... MILK ACT General Provisions § 1210.3 Definitions. (a) Secretary. Secretary means the Secretary of...) Milk. For the purposes of the act and of the regulations in this part: Milk is the whole, fresh, clean, lacteal secretion obtained by the complete milking of one or more healthy cows, properly fed and kept...

  10. 36 CFR § 1210.31 - Insurance coverage.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS Post-Award Requirements Property Standards § 1210.31 Insurance coverage. Recipients shall, at a minimum, provide the equivalent insurance coverage for...

  11. 20 CFR 418.1210 - What is not a major life-changing event?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false What is not a major life-changing event? 418.1210 Section 418.1210 Employees' Benefits SOCIAL SECURITY ADMINISTRATION MEDICARE SUBSIDIES Medicare Part B Income-Related Monthly Adjustment Amount Determinations Using A More Recent Tax Year's Modified...

  12. Combination Chemotherapy With or Without Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2018-04-20

    Acute Lymphoblastic Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult B Acute Lymphoblastic Leukemia; Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; Adult L1 Acute Lymphoblastic Leukemia; Adult L2 Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  13. 21 CFR 1210.28 - Permits waiving clause 4, section 2 of the Federal Import Milk Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Import Milk Act. 1210.28 Section 1210.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION REGULATIONS UNDER THE FEDERAL IMPORT MILK ACT Permit Control § 1210.28 Permits...

  14. 21 CFR 1210.28 - Permits waiving clause 4, section 2 of the Federal Import Milk Act.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Import Milk Act. 1210.28 Section 1210.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION REGULATIONS UNDER THE FEDERAL IMPORT MILK ACT Permit Control § 1210.28 Permits...

  15. A Major Binding Protein for Leukemia Inhibitory Factor in Normal Mouse Serum: Identification as a Soluble Form of the Cellular Receptor

    NASA Astrophysics Data System (ADS)

    Layton, Meredith J.; Cross, Bronwyn A.; Metcalf, Donald; Ward, Larry D.; Simpson, Richard J.; Nicola, Nicos A.

    1992-09-01

    A protein that specifically binds leukemia inhibitory factor (LIF) has been isolated from normal mouse serum by using four successive fractionation steps: chromatography on a LIF affinity matrix, anion-exchange chromatography, size-exclusion chromatography, and preparative native gel electrophoresis. The purified LIF-binding protein (LBP) is a glycoprotein with an apparent molecular mass of 90 kDa that specifically binds 125I-labeled murine LIF with an affinity comparable to that of the low-affinity cellular LIF receptor (K_d = 600 pM). N-terminal sequencing has identified this protein as a soluble truncated form of the α chain of the cellular LIF receptor. LBP is present in normal mouse serum at high levels (1 μg/ml) and these levels are elevated in pregnant mice and reduced in neonatal mice. Since normal serum concentrations of LBP can block the biological actions of LIF in culture, LBP may serve as an inhibitor of the systemic effects of locally produced LIF.

  16. 19 CFR 12.10 - Regulations and orders of the Department of Agriculture.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Agriculture. 12.10 Section 12.10 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND... Regulations and orders of the Department of Agriculture. The importation into the United States of plants and plant products is subject to regulations and orders of the Department of Agriculture restricting or...

  17. 19 CFR 12.10 - Regulations and orders of the Department of Agriculture.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Agriculture. 12.10 Section 12.10 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND... Regulations and orders of the Department of Agriculture. The importation into the United States of plants and plant products is subject to regulations and orders of the Department of Agriculture restricting or...

  18. 19 CFR 12.10 - Regulations and orders of the Department of Agriculture.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Agriculture. 12.10 Section 12.10 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND... Regulations and orders of the Department of Agriculture. The importation into the United States of plants and plant products is subject to regulations and orders of the Department of Agriculture restricting or...

  19. 19 CFR 12.10 - Regulations and orders of the Department of Agriculture.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Agriculture. 12.10 Section 12.10 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND... Regulations and orders of the Department of Agriculture. The importation into the United States of plants and plant products is subject to regulations and orders of the Department of Agriculture restricting or...

  20. 19 CFR 12.10 - Regulations and orders of the Department of Agriculture.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Agriculture. 12.10 Section 12.10 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND... Regulations and orders of the Department of Agriculture. The importation into the United States of plants and plant products is subject to regulations and orders of the Department of Agriculture restricting or...

  1. 30 CFR 1210.53 - When are my royalty reports and payments due?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false When are my royalty reports and payments due? 1210.53 Section 1210.53 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR Natural Resources Revenue FORMS AND REPORTS Royalty Reports-Oil, Gas, and...

  2. 5 CFR 630.1210 - Greater leave entitlements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND LEAVE Family and Medical Leave § 630.1210 Greater leave entitlements. (a) An agency shall comply... greater family or medical leave entitlements to employees than those provided under this subpart. Nothing...

  3. Growth inhibitory and proapoptotic effects of l-asparaginase from Fusarium culmorum ASP-87 on human leukemia cells (Jurkat).

    PubMed

    Meghavarnam, Anil K; Salah, Maryam; Sreepriya, Meenakshisundaram; Janakiraman, Savitha

    2017-06-01

    The objective of this study was to evaluate the anticancer properties of l-asparaginase purified from fungal isolate Fusarium culmorum ASP-87 against human T-cell leukemia cell line (Jurkat). The growth inhibitory and proapoptotic effects of purified l-asparaginase on Jurkat cell lines were investigated by determining its influence on cell viability, colony formation, DNA fragmentation, and cell cycle progression. The results revealed that purified l-asparaginase showed significant decrease in cell survival with IC 50 value of 90 μg/mL (9 IU/mL). The enzyme inhibited colony formation and showed characteristic laddering pattern on agarose gel thereby confirming the induction of apoptosis. Further, cell cycle analysis revealed that the enzyme induced apoptotic cell death by arresting the growth of cells at G 2 -M phase. However, the enzyme did not elicit any toxic effects on human erythrocytes. l-asparaginase purified from F. culmorum ASP-87 showed significant and selective cytotoxic and apoptotic effects on human T-cell leukemic cells in dose-dependent manner. Results of the study give leads for the anticancer effects of fungal l-asparaginase and its potential usefulness in the chemotherapy of leukemia. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  4. 36 CFR 1210.32 - Real property.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Section 1210.32 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION GENERAL... Government after it compensates the Federal Government for that percentage of the current fair market value... that percentage of the current fair market value of the property attributable to the Federal...

  5. 33 CFR 154.1210 - Purpose and applicability.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Fats and Vegetable Oils Facilities § 154.1210 Purpose and applicability. (a) The requirements of this... fats or vegetable oils including— (1) A fixed MTR facility capable of transferring oil in bulk, to or...

  6. 33 CFR 154.1210 - Purpose and applicability.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Fats and Vegetable Oils Facilities § 154.1210 Purpose and applicability. (a) The requirements of this... fats or vegetable oils including— (1) A fixed MTR facility capable of transferring oil in bulk, to or...

  7. 33 CFR 154.1210 - Purpose and applicability.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Fats and Vegetable Oils Facilities § 154.1210 Purpose and applicability. (a) The requirements of this... fats or vegetable oils including— (1) A fixed MTR facility capable of transferring oil in bulk, to or...

  8. 34 CFR 12.10 - How is a Public Benefit Allowance (PBA) calculated?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... proposing to use the surplus Federal real property to add a new physical education program. Entity A would... 34 Education 1 2010-07-01 2010-07-01 false How is a Public Benefit Allowance (PBA) calculated? 12.10 Section 12.10 Education Office of the Secretary, Department of Education DISPOSAL AND UTILIZATION...

  9. 34 CFR 12.10 - How is a Public Benefit Allowance (PBA) calculated?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false How is a Public Benefit Allowance (PBA) calculated? 12.10 Section 12.10 Education Office of the Secretary, Department of Education DISPOSAL AND UTILIZATION... under appendix A: (1) Entity A is a specialized school that has had a building destroyed by fire, and...

  10. 21 CFR 1210.24 - Temporary permits.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... FEDERAL IMPORT MILK ACT Permit Control § 1210.24 Temporary permits. A temporary permit will be granted... inspections required by the applicable provisions of section 2 of the Federal Import Milk Act. Temporary...

  11. 21 CFR 1210.24 - Temporary permits.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... FEDERAL IMPORT MILK ACT Permit Control § 1210.24 Temporary permits. A temporary permit will be granted... inspections required by the applicable provisions of section 2 of the Federal Import Milk Act. Temporary...

  12. 45 CFR 1210.3-3 - Suspension.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early Termination § 1210.3-3 Suspension. (a) The ACTION State Director may suspend a Volunteer for up to 30 days in order... Volunteer. Suspension is not warranted if the State Director determines that sufficient grounds already...

  13. 45 CFR 1210.3-3 - Suspension.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early Termination § 1210.3-3 Suspension. (a) The ACTION State Director may suspend a Volunteer for up to 30 days in order... Volunteer. Suspension is not warranted if the State Director determines that sufficient grounds already...

  14. 45 CFR 1210.3-3 - Suspension.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early Termination § 1210.3-3 Suspension. (a) The ACTION State Director may suspend a Volunteer for up to 30 days in order... Volunteer. Suspension is not warranted if the State Director determines that sufficient grounds already...

  15. 45 CFR 1210.3-3 - Suspension.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early Termination § 1210.3-3 Suspension. (a) The ACTION State Director may suspend a Volunteer for up to 30 days in order... Volunteer. Suspension is not warranted if the State Director determines that sufficient grounds already...

  16. 45 CFR 1210.3-3 - Suspension.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early Termination § 1210.3-3 Suspension. (a) The ACTION State Director may suspend a Volunteer for up to 30 days in order... Volunteer. Suspension is not warranted if the State Director determines that sufficient grounds already...

  17. 33 CFR 155.1210 - Purpose and applicability.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... requirements for vessels carrying animal fats and vegetable oils as a primary cargo § 155.1210 Purpose and... vessel carrying animal fats and vegetable oils as a primary cargo. The requirements of this subpart are...

  18. 33 CFR 155.1210 - Purpose and applicability.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... requirements for vessels carrying animal fats and vegetable oils as a primary cargo § 155.1210 Purpose and... vessel carrying animal fats and vegetable oils as a primary cargo. The requirements of this subpart are...

  19. 33 CFR 155.1210 - Purpose and applicability.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... requirements for vessels carrying animal fats and vegetable oils as a primary cargo § 155.1210 Purpose and... vessel carrying animal fats and vegetable oils as a primary cargo. The requirements of this subpart are...

  20. Retroviral insertions in the VISION database identify molecular pathways in mouse lymphoid leukemia and lymphoma

    PubMed Central

    Weiser, Keith C.; Liu, Bin; Hansen, Gwenn M.; Skapura, Darlene; Hentges, Kathryn E.; Yarlagadda, Sujatha; Morse III, Herbert C.

    2007-01-01

    AKXD recombinant inbred (RI) strains develop a variety of leukemias and lymphomas due to somatically acquired insertions of retroviral DNA into the genome of hematopoetic cells that can mutate cellular proto-oncogenes and tumor suppressor genes. We generated a new set of tumors from nine AKXD RI strains selected for their propensity to develop B-cell tumors, the most common type of human hematopoietic cancers. We employed a PCR technique called viral insertion site amplification (VISA) to rapidly isolate genomic sequence at the site of provirus insertion. Here we describe 550 VISA sequence tags (VSTs) that identify 74 common insertion sites (CISs), of which 21 have not been identified previously. Several suspected proto-oncogenes and tumor suppressor genes lie near CISs, providing supportive evidence for their roles in cancer. Furthermore, numerous previously uncharacterized genes lie near CISs, providing a pool of candidate disease genes for future research. Pathway analysis of candidate genes identified several signaling pathways as common and powerful routes to blood cancer, including Notch, E-protein, NFκB, and Ras signaling. Misregulation of several Notch signaling genes was confirmed by quantitative RT-PCR. Our data suggest that analyses of insertional mutagenesis on a single genetic background are biased toward the identification of cooperating mutations. This tumor collection represents the most comprehensive study of the genetics of B-cell leukemia and lymphoma development in mice. We have deposited the VST sequences, CISs in a genome viewer, histopathology, and molecular tumor typing data in a public web database called VISION (Viral Insertion Sites Identifying Oncogenes), which is located at http://www.mouse-genome.bcm.tmc.edu/vision. PMID:17926094

  1. Retroviral insertions in the VISION database identify molecular pathways in mouse lymphoid leukemia and lymphoma.

    PubMed

    Weiser, Keith C; Liu, Bin; Hansen, Gwenn M; Skapura, Darlene; Hentges, Kathryn E; Yarlagadda, Sujatha; Morse Iii, Herbert C; Justice, Monica J

    2007-10-01

    AKXD recombinant inbred (RI) strains develop a variety of leukemias and lymphomas due to somatically acquired insertions of retroviral DNA into the genome of hematopoetic cells that can mutate cellular proto-oncogenes and tumor suppressor genes. We generated a new set of tumors from nine AKXD RI strains selected for their propensity to develop B-cell tumors, the most common type of human hematopoietic cancers. We employed a PCR technique called viral insertion site amplification (VISA) to rapidly isolate genomic sequence at the site of provirus insertion. Here we describe 550 VISA sequence tags (VSTs) that identify 74 common insertion sites (CISs), of which 21 have not been identified previously. Several suspected proto-oncogenes and tumor suppressor genes lie near CISs, providing supportive evidence for their roles in cancer. Furthermore, numerous previously uncharacterized genes lie near CISs, providing a pool of candidate disease genes for future research. Pathway analysis of candidate genes identified several signaling pathways as common and powerful routes to blood cancer, including Notch, E-protein, NFkappaB, and Ras signaling. Misregulation of several Notch signaling genes was confirmed by quantitative RT-PCR. Our data suggest that analyses of insertional mutagenesis on a single genetic background are biased toward the identification of cooperating mutations. This tumor collection represents the most comprehensive study of the genetics of B-cell leukemia and lymphoma development in mice. We have deposited the VST sequences, CISs in a genome viewer, histopathology, and molecular tumor typing data in a public web database called VISION (Viral Insertion Sites Identifying Oncogenes), which is located at http://www.mouse-genome.bcm.tmc.edu/vision .

  2. Cell death sensitization of leukemia cells by opioid receptor activation

    PubMed Central

    Friesen, Claudia; Roscher, Mareike; Hormann, Inis; Fichtner, Iduna; Alt, Andreas; Hilger, Ralf A.; Debatin, Klaus-Michael; Miltner, Erich

    2013-01-01

    Cyclic AMP (cAMP) regulates a number of cellular processes and modulates cell death induction. cAMP levels are altered upon stimulation of specific G-protein-coupled receptors inhibiting or activating adenylyl cyclases. Opioid receptor stimulation can activate inhibitory Gi-proteins which in turn block adenylyl cyclase activity reducing cAMP. Opioids such as D,L-methadone induce cell death in leukemia cells. However, the mechanism how opioids trigger apoptosis and activate caspases in leukemia cells is not understood. In this study, we demonstrate that downregulation of cAMP induced by opioid receptor activation using the opioid D,L-methadone kills and sensitizes leukemia cells for doxorubicin treatment. Enhancing cAMP levels by blocking opioid-receptor signaling strongly reduced D,L-methadone-induced apoptosis, caspase activation and doxorubicin-sensitivity. Induction of cell death in leukemia cells by activation of opioid receptors using the opioid D,L-methadone depends on critical levels of opioid receptor expression on the cell surface. Doxorubicin increased opioid receptor expression in leukemia cells. In addition, the opioid D,L-methadone increased doxorubicin uptake and decreased doxorubicin efflux in leukemia cells, suggesting that the opioid D,L-methadone as well as doxorubicin mutually increase their cytotoxic potential. Furthermore, we found that opioid receptor activation using D,L-methadone alone or in addition to doxorubicin inhibits tumor growth significantly in vivo. These results demonstrate that opioid receptor activation via triggering the downregulation of cAMP induces apoptosis, activates caspases and sensitizes leukemia cells for doxorubicin treatment. Hence, opioid receptor activation seems to be a promising strategy to improve anticancer therapies. PMID:23633472

  3. 7 CFR 1210.364 - Proceedings after termination.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ....364 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Miscellaneous § 1210.364 Proceedings...

  4. 36 CFR 1210.32 - Real property.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Real property. 1210.32....32 Real property. The NHPRC shall prescribe requirements for recipients concerning the use and disposition of real property acquired in whole or in part under awards. Unless otherwise provided by statute...

  5. 36 CFR 1210.32 - Real property.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false Real property. 1210.32....32 Real property. The NHPRC shall prescribe requirements for recipients concerning the use and disposition of real property acquired in whole or in part under awards. Unless otherwise provided by statute...

  6. 36 CFR 1210.32 - Real property.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false Real property. 1210.32....32 Real property. The NHPRC shall prescribe requirements for recipients concerning the use and disposition of real property acquired in whole or in part under awards. Unless otherwise provided by statute...

  7. 20 CFR 655.1210 - What penalties and other remedies may the Administrator impose?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false What penalties and other remedies may the Administrator impose? 655.1210 Section 655.1210 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION... also may impose appropriate remedies, including the payment of back wages, the performance of attested...

  8. 20 CFR 655.1210 - What penalties and other remedies may the Administrator impose?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 3 2013-04-01 2013-04-01 false What penalties and other remedies may the Administrator impose? 655.1210 Section 655.1210 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION... also may impose appropriate remedies, including the payment of back wages, the performance of attested...

  9. 20 CFR 655.1210 - What penalties and other remedies may the Administrator impose?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false What penalties and other remedies may the Administrator impose? 655.1210 Section 655.1210 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION... also may impose appropriate remedies, including the payment of back wages, the performance of attested...

  10. 20 CFR 655.1210 - What penalties and other remedies may the Administrator impose?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 3 2014-04-01 2014-04-01 false What penalties and other remedies may the Administrator impose? 655.1210 Section 655.1210 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION... also may impose appropriate remedies, including the payment of back wages, the performance of attested...

  11. Structural features of a close homologue of L1 (CHL1) in the mouse: a new member of the L1 family of neural recognition molecules.

    PubMed

    Holm, J; Hillenbrand, R; Steuber, V; Bartsch, U; Moos, M; Lübbert, H; Montag, D; Schachner, M

    1996-08-01

    We have identified a close homologue of L1 (CHL1) in the mouse. CHL1 comprises an N-terminal signal sequence, six immunoglobulin (Ig)-like domains, 4.5 fibronectin type III (FN)-like repeats, a transmembrane domain and a C-terminal, most likely intracellular domain of approximately 100 amino acids. CHL1 is most similar in its extracellular domain to chicken Ng-CAM (approximately 40% amino acid identity), followed by mouse L1, chicken neurofascin, chicken Nr-CAM, Drosophila neuroglian and zebrafish L1.1 (37-28% amino acid identity), and mouse F3, rat TAG-1 and rat BIG-1 (approximately 27% amino acid identity). The similarity with other members of the Ig superfamily [e.g. neural cell adhesion molecule (N-CAM), DCC, HLAR, rse] is 16-11%. The intracellular domain is most similar to mouse and chicken Nr-CAM, mouse and rat neurofascin (approximately 60% amino acid identity) followed by chicken neurofascin and Ng-CAM, Drosophila neuroglian and zebrafish L1.1 and L1.2 (approximately 40% amino acid identity). Besides the high overall homology and conserved modular structure among previously recognized members of the L1 family (mouse/human L1/rat NILE; chicken Ng-CAM; chicken/mouse Nr-CAM; Drosophila neuroglian; zebrafish L1.1 and L1.2; chicken/mouse neurofascin/rat ankyrin-binding glycoprotein), criteria characteristic of L1 were identified with regard to the number of amino acids between positions of conserved amino acid residues defining distances within and between two adjacent Ig-like domains and FN-like repeats. These show a collinearity in the six Ig-like domains and four adjacent FN-like repeats that is remarkably conserved between L1 and molecules containing these modules (designated the L1 family cassette), including the GPI-linked forms of the F3 subgroup (mouse F3/chicken F11/human CNTN1; rat BIG-1/mouse PANG; rat TAG-1/mouse TAX-1/chicken axonin-1). The colorectal cancer molecule (DCC), previously introduced as an N-CAM-like molecule, conforms to the L1 family

  12. Protective effect of humus extract against Trypanosoma brucei infection in mice.

    PubMed

    Kodama, Hiroshi; Denso; Okazaki, Fumi; Ishida, Saeko

    2008-11-01

    Humic substances are formed during the decomposition of organic matter in humus, and are found in many natural environments in which organic materials and microorganisms are present. Oral administration of humus extract to mice successfully induced effective protection against experimental challenge by the two subspecies, Trypanosoma brucei brucei and T. brucei gambiense. Mortality was most reduced among mice who received a 3% humus extract for 21 days in drinking water ad libitum. Spleen cells from humus-administered mice exhibited significant non-specific cytotoxic activity against L1210 mouse leukemia target cells. Also, spleen cells produced significantly higher amounts of Interferon-gamma when stimulated in vitro with Concanavalin A than cells from normal controls. These results clearly show that administration to mice of humus extract induced effective resistance against Trypanosoma infection. Enhancement of the innate immune system may be involved in host defense against trypanosomiasis.

  13. Biochemical and chemical characterization of trifluoromethylglyoxal bis(guanylhydrazone), a close analog of the antileukemic drug mitoguazone.

    PubMed

    Elo, H; Mutikainen, I

    1988-01-01

    In order to study the structure-activity relationships of bis(guanylhydrazone) type polyamine antimetabolites, trifluoromethylglyoxal bis(guanylhydrazone) (CF3-GBG), a close analog of the antileukemic drug methylglyoxal bis(guanylhydrazone) (mitoguazone, MGBG) was synthesized according to a novel modification of previous methods, yielding single crystals. Single-crystal X-ray crystallography revealed the presence of an isomer different from the one detected in the case of MGBG and all other bis(guanylhydrazones) so far studied. In contrast to MGBG, CF3-GBG was shown to be a very weak inhibitor of yeast adenosylmethionine decarboxylase, being thus devoid of value as a polyamine antimetabolite. In addition, the compound did not have antiproliferative activity against mouse L1210 leukemia cells in vitro. As long as analogous isomers of the two compounds are not available, no conclusions can be drawn about the reasons lying behind the drastical differences between their biological properties.

  14. 7 CFR 1210.330 - Policy and objective.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Research and Promotion § 1210.330 Policy and objective... research, development, advertising, and promotion in order to: (a) Strengthen watermelons' competitive...

  15. Antitumor activity of ethanol extract from Hippophae rhamnoides L. leaves towards human acute myeloid leukemia cells in vitro.

    PubMed

    Zhamanbaeva, G T; Murzakhmetova, M K; Tuleukhanov, S T; Danilenko, M P

    2014-12-01

    We studied the effects of ethanol extract from Hippophae rhamnoides L. leaves on the growth and differentiation of human acute myeloid leukemia cells (KG-1a, HL60, and U937). The extract of Hippophae rhamnoides L. leaves inhibited cell growth depending on the cell strain and extract dose. In a high concentration (100 μg/ml), the extract also exhibited a cytotoxic effect on HL60 cells. Hippophae rhamnoides L. leaves extract did not affect cell differentiation and did not modify the differentiating effect of calcitriol, active vitamin D metabolite. Inhibition of cell proliferation was paralleled by paradoxical accumulation of phase S cells (synthetic phase) with a reciprocal decrease in the count of G1 cells (presynthetic phase). The extract in a concentration of 100 μg/ml induced the appearance of cells with a subdiploid DNA content (sub-G1 phase cells), which indicated induction of apoptosis. The antiproliferative effect of Hippophae rhamnoides L. extract on acute myeloid leukemia cells was at least partially determined by activation of the S phase checkpoint, which probably led to deceleration of the cell cycle and apoptosis induction.

  16. Pharmacologic inhibition of the menin-MLL interaction blocks progression of MLL leukemia in vivo

    DOE PAGES

    Borkin, Dmitry; He, Shihan; Miao, Hongzhi; ...

    2015-03-26

    Chromosomal translocations affecting mixed lineage leukemia gene ( MLL) result in acute leukemias resistant to therapy. The leukemogenic activity of MLL fusion proteins is dependent on their interaction with menin, providing basis for therapeutic intervention. In this paper, we report the development of highly potent and orally bioavailable small-molecule inhibitors of the menin-MLL interaction, MI-463 and MI-503, and show their profound effects in MLL leukemia cells and substantial survival benefit in mouse models of MLL leukemia. Finally, we demonstrate the efficacy of these compounds in primary samples derived from MLL leukemia patients. In conclusion, overall, we demonstrate that pharmacologic inhibitionmore » of the menin-MLL interaction represents an effective treatment for MLL leukemias in vivo and provide advanced molecular scaffold for clinical lead identification.« less

  17. 7 CFR 1210.331 - Programs and projects.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Research and Promotion § 1210.331 Programs and... to maintain, develop, and expand markets for watermelon; (b) Establishing and carrying out research...

  18. 7 CFR 1210.331 - Programs and projects.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Research and Promotion § 1210.331 Programs and... to maintain, develop, and expand markets for watermelon; (b) Establishing and carrying out research...

  19. 7 CFR 1210.331 - Programs and projects.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Research and Promotion § 1210.331 Programs and... to maintain, develop, and expand markets for watermelon; (b) Establishing and carrying out research...

  20. 7 CFR 1210.331 - Programs and projects.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Research and Promotion § 1210.331 Programs and... to maintain, develop, and expand markets for watermelon; (b) Establishing and carrying out research...

  1. 30 CFR 1210.20 - What if I disagree with the burden hour estimates?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false What if I disagree with the burden hour estimates? 1210.20 Section 1210.20 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT... estimates or suggestions on reducing the burden to the Bureau of Ocean Energy Management, Regulation, and...

  2. 12 CFR 611.1210 - Advance notices-commencement resolution and notice to equity holders.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Advance notices-commencement resolution and notice to equity holders. 611.1210 Section 611.1210 Banks and Banking FARM CREDIT ADMINISTRATION FARM..., within 10 days of adopting the commencement resolution, your bank and the other Farm Credit banks must...

  3. 36 CFR 1210.52 - Financial reporting.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Financial reporting. 1210.52....52 Financial reporting. (a) The following forms or such other forms as may be approved by OMB are authorized for obtaining financial information from recipients. (1) SF-269 or SF-269A, Financial Status...

  4. 36 CFR 1210.52 - Financial reporting.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Financial reporting. 1210.52....52 Financial reporting. (a) The following forms or such other forms as may be approved by OMB are authorized for obtaining financial information from recipients. (1) SF-269 or SF-269A, Financial Status...

  5. Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia

    PubMed Central

    Kharas, Michael G; Lengner, Christopher J; Al-Shahrour, Fatima; Bullinger, Lars; Ball, Brian; Zaidi, Samir; Morgan, Kelly; Tam, Winnie; Paktinat, Mahnaz; Okabe, Rachel; Gozo, Maricel; Einhorn, William; Lane, Steven W; Scholl, Claudia; Fröhling, Stefan; Fleming, Mark; Ebert, Benjamin L; Gilliland, D Gary; Jaenisch, Rudolf; Daley, George Q

    2011-01-01

    RNA-binding proteins of the Musashi (Msi) family are expressed in stem cell compartments and in aggressive tumors, but they have not yet been widely explored in the blood. Here we demonstrate that Msi2 is the predominant form expressed in hematopoietic stem cells (HSCs), and its knockdown leads to reduced engraftment and depletion of HSCs in vivo. Overexpression of human MSI2 in a mouse model increases HSC cell cycle progression and cooperates with the chronic myeloid leukemia–associated BCR-ABL1 oncoprotein to induce an aggressive leukemia. MSI2 is overexpressed in human myeloid leukemia cell lines, and its depletion leads to decreased proliferation and increased apoptosis. Expression levels in human myeloid leukemia directly correlate with decreased survival in patients with the disease, thereby defining MSI2 expression as a new prognostic marker and as a new target for therapy in acute myeloid leukemia (AML). PMID:20616797

  6. [Effect of DOT1L gene silence on proliferation of acute monocytic leukemia cell line THP-1].

    PubMed

    Zhang, Yu-Juan; Li, Hua-Wen; Chang, Guo-Qiang; Zhang, Hong-Ju; Wang, Jian; Lin, Ya-Ni; Zhou, Jia-Xi; Li, Qing-Hua; Pang, Tian-Xiang

    2013-08-01

    This study was aimed to investigate the influence of short hairpin RNA (shRNA) on proliferation of human leukemia cell line THP-1. The shRNA targeting the site 732-752 of DOT1L mRNA was designed and chemically synthesized, then a single-vector lentiviral, tet-inducible shRNA-DOT1L system (Plko-Tet-On) was generated. Thereafter, the THP-1 cells with lentivirus were infected to create stable cell line with regulatable shRNA expression. The expression of DOT1L in the THP-1 cell line was assayed by RT-PCR. Effect of shRNA-DOT1L on the proliferation of THP-1 cells was detected with MTT method,and the change of colony forming potential of THP-1 cells was analyzed by colony forming unit test. Cell cycle distribution was tested by flow cytometry. The results indicated that the expression of DOT1L was statistically lower than that in the control groups. The proliferation and colony forming capacity of THP-1 cells were significantly inhibited. The percentage of cells at G0/G1 phase increased in THP-1/shRNA cells treated with Dox while the percentage of cells at S phase significantly decreased as compared with that in the control group. It is concluded that the shRNA targeting DOT1L can effectively inhibit the proliferation of acute monocytic leukemia cell line THP-1.

  7. Synergistic Antileukemic Activity of Carnosic Acid-Rich Rosemary Extract and the 19-nor Gemini Vitamin D Analogue in a Mouse Model of Systemic Acute Myeloid Leukemia

    PubMed Central

    Shabtay, Ayelet; Sharabani, Hagar; Barvish, Zeev; Kafka, Michael; Amichay, Doron; Levy, Joseph; Sharoni, Yoav; Uskokovic, Milan R.; Studzinski, George P.; Danilenko, Michael

    2008-01-01

    Objective Differentiation therapy with the hormonal form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D3), is a promising approach to treatment of acute myeloid leukemia (AML); however, 1,25D3 induces hypercalcemia at pharmacologically active doses. We investigated the in vitro and in vivoantileukemic efficacy of combined treatment with non-toxic doses of a low-calcemic 1,25D3 analogue, 1,25-dihydroxy-21(3-hydroxy-3-methyl-butyl)-19-nor-cholecalciferol (19-nor-Gemini; Ro27-5646), and rosemary plant agents in a mouse model of AML. Methods Proliferation and differentiation of WEHI-3B D– (WEHI) murine myelomonocytic leukemia cellsin vitro were determined by standard assays. Reactive oxygen species, glutathione and protein expression levels were measured by flow cytometry, enzymatic assay and Western blotting, respectively. Systemic AML was developed by intravenous injection of WEHI cells in syngeneic Balb/c mice. Results 19-nor-Gemini had a higher potency than its parent compounds, Gemini (Ro27-2310) and 1,25D3, in the induction of differentiation (EC50 = 0.059 ± 0.011, 0.275 ± 0.093 and 0.652 ± 0.085 nM, respectively) and growth arrest (IC50 = 0.072 ± 0.018, 0.165 ± 0.061 and 0.895 ± 0.144 nM, respectively) in WEHI cells in vitro, and lower in vivo toxicity. Combined treatment of leukemia-bearing mice with 19-nor-Gemini (injected intraperitoneally) and standardized rosemary extract (mixed with food) resulted in a synergistic increase in survival (from 42.2 ± 2.5 days in untreated mice to 66.5 ± 4.2 days, n = 3) and normalization of white blood cell and differential counts. This was consistent with strong cooperative antiproliferative and differentiation effects of low concentrations of 19-nor-Gemini or 1,25D3 combined with rosemary extract or its major polyphenolic component, carnosic acid, as well as with the antioxidant action of rosemary agents and vitamin D derivatives in WEHI cell cultures. Conclusion Combined effectiveness of 1,25D3 analogues and

  8. 17 CFR 240.3a12-10 - Exemption of certain securities issued by the Resolution Funding Corporation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... securities issued by the Resolution Funding Corporation. 240.3a12-10 Section 240.3a12-10 Commodity and... Exemptions § 240.3a12-10 Exemption of certain securities issued by the Resolution Funding Corporation. Securities that are issued by the Resolution Funding Corporation pursuant to section 21B(f) of the Federal...

  9. 16 CFR 1210.18 - Refusal of importation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ....18 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR CIGARETTE LIGHTERS Certification Requirements § 1210.18 Refusal of importation. (a... in this part is violated. (b) For noncompliance with this standard and for lack of a certification...

  10. 30 CFR 1210.352 - Special forms and reports.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... INTERIOR Natural Resources Revenue FORMS AND REPORTS Geothermal Resources § 1210.352 Special forms and... conformity with the requirements of the Paperwork Reduction Act of 1980 and other applicable laws. [56 FR...

  11. 16 CFR 1210.4 - Test protocol.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... live within the United States. (4) The age and sex distribution of each 100-child panel shall be: (i... recorded for each child in the 100-child test panel: (1) Sex (male or female). (2) Date of birth (month... STANDARD FOR CIGARETTE LIGHTERS Requirements for Child Resistance § 1210.4 Test protocol. (a) Child test...

  12. 16 CFR 1210.4 - Test protocol.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... live within the United States. (4) The age and sex distribution of each 100-child panel shall be: (i... recorded for each child in the 100-child test panel: (1) Sex (male or female). (2) Date of birth (month... STANDARD FOR CIGARETTE LIGHTERS Requirements for Child Resistance § 1210.4 Test protocol. (a) Child test...

  13. 21 CFR 1210.27 - Permits waiving clauses 2 and 5, section 2 of the Federal Import Milk Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Federal Import Milk Act. 1210.27 Section 1210.27 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION REGULATIONS UNDER THE FEDERAL IMPORT MILK ACT Permit Control § 1210.27...

  14. 21 CFR 1210.27 - Permits waiving clauses 2 and 5, section 2 of the Federal Import Milk Act.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Federal Import Milk Act. 1210.27 Section 1210.27 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION REGULATIONS UNDER THE FEDERAL IMPORT MILK ACT Permit Control § 1210.27...

  15. 7 CFR 1210.342 - Exemption from assessment.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... PROMOTION PLAN Watermelon Research and Promotion Plan Expenses and Assessments § 1210.342 Exemption from assessment. (a) The Board may exempt watermelons used for nonfood purposes from the provisions of this Plan...

  16. 7 CFR 1210.331 - Programs and projects.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., effectuation and administration of appropriate programs or projects for advertising and other sales promotion...; (d) A prohibition on advertising or other promotion programs that make any reference to private brand... PROMOTION PLAN Watermelon Research and Promotion Plan Research and Promotion § 1210.331 Programs and...

  17. Structure of a gene encoding a murine thymus leukemia antigen, and organization of Tla genes in the BALB/c mouse

    PubMed Central

    1985-01-01

    We have determined the DNA sequence of a gene encoding a thymus leukemia (TL) antigen in the BALB/c mouse, and have more definitively mapped the cloned BALB/c Tla-region class I gene clusters. Analysis of the sequence shows that the Tla gene is less closely related to the H-2 genes than H-2 genes are to one another or to a Qa-2,3-region genes. The Tla gene, 17.3A, contains an apparent gene conversion. Comparison of the BALB/c Tla genes with those from C57BL shows that BALB/c has more Tla-region class I genes, and that one of the genes absent in C57BL is gene 17.3A. PMID:3894562

  18. Finding mouse models of human lymphomas and leukemia's using the Jackson laboratory mouse tumor biology database.

    PubMed

    Begley, Dale A; Sundberg, John P; Krupke, Debra M; Neuhauser, Steven B; Bult, Carol J; Eppig, Janan T; Morse, Herbert C; Ward, Jerrold M

    2015-12-01

    Many mouse models have been created to study hematopoietic cancer types. There are over thirty hematopoietic tumor types and subtypes, both human and mouse, with various origins, characteristics and clinical prognoses. Determining the specific type of hematopoietic lesion produced in a mouse model and identifying mouse models that correspond to the human subtypes of these lesions has been a continuing challenge for the scientific community. The Mouse Tumor Biology Database (MTB; http://tumor.informatics.jax.org) is designed to facilitate use of mouse models of human cancer by providing detailed histopathologic and molecular information on lymphoma subtypes, including expertly annotated, on line, whole slide scans, and providing a repository for storing information on and querying these data for specific lymphoma models. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Photoaffinity analogues of methotrexate as folate antagonist binding probes. 2. Transport studies, photoaffinity labeling, and identification of the membrane carrier protein for methotrexate from murine L1210 cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Price, E.M.; Freisheim, J.H.

    1987-07-28

    A membrane-derived component of the methotrexate/one-carbon-reduced folate transport system in murine L1210 cells has been identified by using a photoaffinity analogue of methotrexate. The compound, a radioiodinated 4-azidosalicylyl derivative of the lysine analogue of methotrexate, is transported into murine L1210 cells in a temperature-dependent, sulfhydryl reagent inhibitable manner with a K/sub t/ of 506 +/- 79 nM and a V/sub max/ of 17.9 +/- 4.2 pmol min/sup -1/ (mg of total cellular protein)/sup -1/. Uptake of the iodinated compound at 200 nM is inhibited by low amounts of methotrexate. The parent compounds of the iodinated photoprobe inhibit (/sup 3/H)methotrexate uptake,more » with the uniodinated 4-azidosalicylyl derivative exhibiting a K/sub i/ of 66 +/- 21 nM. UV irradiation, at 4 /sup 0/C, of a cell suspension that had been incubated with the probe results in the covalent modification of a 46K-48K protein. This can be demonstrated when the plasma membranes from the labeled cells are analyzed via sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Labeling of this protein occurs half-maximally at a reagent concentration that correlates with the K/sub t/ for transport of the iodinated compound. Protection against labeling of this protein by increasing amounts of methotrexate parallels the concentration dependence of inhibition of photoprobe uptake by methotrexate. Evidence that, in the absence of irradiation and at 37/sup 0/C, the iodinated probe is actually internalized is demonstrated by the labeling of two soluble proteins (M/sub r/ 38K and 21K) derived from the cell homogenate supernatant.« less

  20. Green tea, red wine and lemon extracts reduce experimental tumor growth and cancer drug toxicity.

    PubMed

    Zaletok, S P; Gulua, L; Wicker, L; Shlyakhovenko, V A; Gogol, S; Orlovsky, O; Karnaushenko, O V; Verbinenko, A; Milinevska, V; Samoylenko, O; Todor, I; Turmanidze, T

    2015-12-01

    To evaluate antitumor effect of plant polyphenol extracts from green tea, red wine lees and/or lemon peel alone and in combination with antitumor drugs on the growth of different transplanted tumors in experimental animals. Green tea extract (GTE) was prepared from green tea infusion. GTE-based composites of red wine (GTRW), lemon peel (GTRWL) and/or NanoGTE as well as corresponding nanocomposites were prepared. The total polyphenolics of the different GTE-based extracts ranged from 18.0% to 21.3%. The effects of GTE-based extracts were studied in sarcoma 180, Ehrlich carcinoma, B16 melanoma, Ca755 mammary carcinoma, P388 leukemia, L1210 leukemia, and Guerin carcinoma (original, cisplatin-resistant and doxorubicin-resistant variants). The extracts were administered as 0.1% solution in drinking water (0.6-1.0 mg by total polyphenolics per mouse per day and 4.0-6.3 mg per rat per day). Tumor growth inhibition (TGI) in mice treated with NanoGTE, cisplatin or cisplatin + NanoGTE was 27%, 55% and 78%, respectively, in Sarcoma 180%, 21%, 45% and 59%, respectively, in Ehrlich carcinoma; and 8%, 13% and 38%, respectively in B16 melanoma. Composites of NanoGTE, red wine, and lemon peel (NanoGTRWL) enhanced the antitumor effects of cyclophosphamide in mice with Ca755 mammary carcinoma. The treatment with combination of NanoGTE and inhibitors of polyamines (PA) synthesis (DFMO + MGBG) resulted in significant TGI of P388 leukemia (up to 71%) and L1210 leukemia. In rats transplanted with Guerin carcinoma (parental strain), treatment with GTRW or GTE alone resulted in 25-28% TGI vs. 55-68% TGI in cisplatin-treated animals. The inhibition observed in the case of combination of GTE or GTRW with cisplatin was additive giving 81-88% TGI. Similar effects were observed when combinations of the cytostatics with GTE (or NanoGTE) were tested against cisplatin- or doxorubicin-resistant Guerin carcinoma. Moreover, the plant extracts lowered side toxicity of the drugs. Treatment with GTE

  1. 21 CFR 1210.22 - Form of tag.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS... IMPORT MILK ACT Permit Control § 1210.22 Form of tag. Each container of milk or cream shipped or... form, bearing the required information in clear and legible type: Product (State whether raw milk...

  2. 21 CFR 1210.22 - Form of tag.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS... IMPORT MILK ACT Permit Control § 1210.22 Form of tag. Each container of milk or cream shipped or... form, bearing the required information in clear and legible type: Product (State whether raw milk...

  3. 7 CFR 1210.363 - Suspension or termination.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... suspension of this Plan. The Secretary shall suspend or terminate this Plan at the end of the marketing year... Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... PROMOTION PLAN Watermelon Research and Promotion Plan Miscellaneous § 1210.363 Suspension or termination. (a...

  4. Cooperation of MLL/AF10(OM-LZ) with PTPN11 activating mutation induced monocytic leukemia with a shorter latency in a mouse bone marrow transplantation model.

    PubMed

    Fu, Jen-Fen; Liang, Sung-Tzu; Huang, Ying-Jung; Liang, Kung-Hao; Yen, Tzung-Hai; Liang, Der-Cherng; Shih, Lee-Yung

    2017-03-01

    PTPN11 mutation, a RAS signaling pathway mutation, is associated with MLL translocations in acute leukemia. A girl with MLL/AF10 AML was found to carry PTPN11 G503A . To study the impact of PTPN11 G503A cooperating with MLL/AF10 on leukemogenesis, we established a retroviral transduction/transplantation mouse model. Compared to the MLL/AF10(OM-LZ) leukemia cells harboring PTPN11 wt , the cells harboring PTPN11 G503A were hypersensitive to GM-CSF and IL3, and more resistant to death upon treatment with daunorubicin but sensitive to cytarabine. The cells harboring PTPN11 G503A autonomously differentiated into macrophages (1.8%) in the medium containing IL3. Further studies showed that the cells had an elevated (∼2.9-fold) Csf1 transcription level and secreted more (∼4.5-fold) M-CSF to the medium which can stimulate monocyte/macrophage differentiation of BM cells. Mice transplanted with the cells harboring PTPN11 G503A had a higher concentration of M-CSF in plasma. When mixed with the MLL/AF10(OM-LZ) leukemia cells harboring PTPN11 wt , the cells harboring PTPN11 G503A had an increased competitive engraftment and clonal expansion in the BM and spleen of recipient mice, although no competitive growth advantage was observed in the in vitro co-culturing assays. The mice transplanted with the MLL/AF10(OM-LZ) cells harboring PTPN11 wt developed myelomonocytic leukemia, while those transplanted with the cells harboring PTPN11 G503A -induced monocytic leukemia in a shorter latency. Our results demonstrated that addition of PTPN11 G503A to MLL/AF10 affected cell proliferation, chemo-resistance, differentiation, in vivo BM recruitment/clonal expansion and accelerated disease progression. © 2016 UICC.

  5. 23 CFR 1210.5 - Certification requirements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... requirements of 23 U.S.C. 161, and this part. (b) The certification shall contain: (1) A copy of the State zero..., that the State has enacted and is enforcing a conforming zero tolerance law. The certifying statement... a zero tolerance law that conforms to the requirements of 23 U.S.C. 161 and 23 CFR 1210.4(c). (c) An...

  6. 23 CFR 1210.5 - Certification requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... requirements of 23 U.S.C. 161, and this part. (b) The certification shall contain: (1) A copy of the State zero..., that the State has enacted and is enforcing a conforming zero tolerance law. The certifying statement... a zero tolerance law that conforms to the requirements of 23 U.S.C. 161 and 23 CFR 1210.4(c). (c) An...

  7. 23 CFR 1210.5 - Certification requirements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... requirements of 23 U.S.C. 161, and this part. (b) The certification shall contain: (1) A copy of the State zero..., that the State has enacted and is enforcing a conforming zero tolerance law. The certifying statement... a zero tolerance law that conforms to the requirements of 23 U.S.C. 161 and 23 CFR 1210.4(c). (c) An...

  8. 23 CFR 1210.5 - Certification requirements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... requirements of 23 U.S.C. 161, and this part. (b) The certification shall contain: (1) A copy of the State zero..., that the State has enacted and is enforcing a conforming zero tolerance law. The certifying statement... a zero tolerance law that conforms to the requirements of 23 U.S.C. 161 and 23 CFR 1210.4(c). (c) An...

  9. 33 CFR 154.1210 - Purpose and applicability.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) POLLUTION FACILITIES TRANSFERRING OIL OR HAZARDOUS MATERIAL IN BULK Response Plans for Animal Fats and Vegetable Oils Facilities § 154.1210 Purpose and applicability. (a) The requirements of this... fats or vegetable oils including— (1) A fixed MTR facility capable of transferring oil in bulk, to or...

  10. 33 CFR 155.1210 - Purpose and applicability.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) POLLUTION OIL OR HAZARDOUS MATERIAL POLLUTION PREVENTION REGULATIONS FOR VESSELS Response plan requirements for vessels carrying animal fats and vegetable oils as a primary cargo § 155.1210 Purpose and... vessel carrying animal fats and vegetable oils as a primary cargo. The requirements of this subpart are...

  11. 33 CFR 154.1210 - Purpose and applicability.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) POLLUTION FACILITIES TRANSFERRING OIL OR HAZARDOUS MATERIAL IN BULK Response Plans for Animal Fats and Vegetable Oils Facilities § 154.1210 Purpose and applicability. (a) The requirements of this... fats or vegetable oils including— (1) A fixed MTR facility capable of transferring oil in bulk, to or...

  12. 33 CFR 155.1210 - Purpose and applicability.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) POLLUTION OIL OR HAZARDOUS MATERIAL POLLUTION PREVENTION REGULATIONS FOR VESSELS Response plan requirements for vessels carrying animal fats and vegetable oils as a primary cargo § 155.1210 Purpose and... vessel carrying animal fats and vegetable oils as a primary cargo. The requirements of this subpart are...

  13. 20 CFR 404.1210 - Optionally excluded services.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Section 404.1210 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND... selectively by coverage groups. They are: (a) Services in any class or classes of elective positions; (b) Services in any class or classes of part-time positions; (c) Services in any class or classes of positions...

  14. Wnt/Ca2+/NFAT signaling maintains survival of Ph+ leukemia cells upon inhibition of Bcr-Abl

    PubMed Central

    Gregory, Mark A.; Phang, Tzu L.; Neviani, Paolo; Alvarez-Calderon, Francesca; Eide, Christopher A.; O’Hare, Thomas; Zaberezhnyy, Vadym; Williams, Richard T.; Druker, Brian J.; Perrotti, Danilo; DeGregori, James

    2010-01-01

    Summary Although Bcr-Abl kinase inhibitors have proven effective in the treatment of chronic myeloid leukemia (CML), they generally fail to completely eradicate Bcr-Abl+ leukemia cells. To identify genes whose inhibition sensitizes Bcr-Abl+ leukemias to killing by Bcr-Abl inhibitors, we performed an RNAi-based synthetic lethal screen with imatinib in CML cells. This screen identified numerous components of a Wnt/Ca2+/NFAT signaling pathway. Antagonism of this pathway led to impaired NFAT activity, decreased cytokine production and enhanced sensitivity to Bcr-Abl inhibition. Furthermore, NFAT inhibition with cyclosporin A facilitated leukemia cell elimination by the Bcr-Abl inhibitor dasatinib and markedly improved survival in a mouse model of Bcr-Abl+ acute lymphoblastic leukemia (ALL). Targeting this pathway in combination with Bcr-Abl inhibition could improve treatment of Bcr-Abl+ leukemias. PMID:20609354

  15. Tumor suppressors BTG1 and IKZF1 cooperate during mouse leukemia development and increase relapse risk in B-cell precursor acute lymphoblastic leukemia patients.

    PubMed

    Scheijen, Blanca; Boer, Judith M; Marke, René; Tijchon, Esther; van Ingen Schenau, Dorette; Waanders, Esmé; van Emst, Liesbeth; van der Meer, Laurens T; Pieters, Rob; Escherich, Gabriele; Horstmann, Martin A; Sonneveld, Edwin; Venn, Nicola; Sutton, Rosemary; Dalla-Pozza, Luciano; Kuiper, Roland P; Hoogerbrugge, Peter M; den Boer, Monique L; van Leeuwen, Frank N

    2017-03-01

    Deletions and mutations affecting lymphoid transcription factor IKZF1 (IKAROS) are associated with an increased relapse risk and poor outcome in B-cell precursor acute lymphoblastic leukemia. However, additional genetic events may either enhance or negate the effects of IKZF1 deletions on prognosis. In a large discovery cohort of 533 childhood B-cell precursor acute lymphoblastic leukemia patients, we observed that single-copy losses of BTG1 were significantly enriched in IKZF1 -deleted B-cell precursor acute lymphoblastic leukemia ( P =0.007). While BTG1 deletions alone had no impact on prognosis, the combined presence of BTG1 and IKZF1 deletions was associated with a significantly lower 5-year event-free survival ( P =0.0003) and a higher 5-year cumulative incidence of relapse ( P =0.005), when compared with IKZF1 -deleted cases without BTG1 aberrations. In contrast, other copy number losses commonly observed in B-cell precursor acute lymphoblastic leukemia, such as CDKN2A/B, PAX5, EBF1 or RB1 , did not affect the outcome of IKZF1 -deleted acute lymphoblastic leukemia patients. To establish whether the combined loss of IKZF1 and BTG1 function cooperate in leukemogenesis, Btg1 -deficient mice were crossed onto an Ikzf1 heterozygous background. We observed that loss of Btg1 increased the tumor incidence of Ikzf1 +/- mice in a dose-dependent manner. Moreover, murine B cells deficient for Btg1 and Ikzf1 +/- displayed increased resistance to glucocorticoids, but not to other chemotherapeutic drugs. Together, our results identify BTG1 as a tumor suppressor in leukemia that, when deleted, strongly enhances the risk of relapse in IKZF1 -deleted B-cell precursor acute lymphoblastic leukemia, and augments the glucocorticoid resistance phenotype mediated by the loss of IKZF1 function. Copyright© Ferrata Storti Foundation.

  16. Eradication of acute promyelocytic leukemia-initiating cells through PML-RARA degradation.

    PubMed

    Nasr, Rihab; Guillemin, Marie-Claude; Ferhi, Omar; Soilihi, Hassan; Peres, Laurent; Berthier, Caroline; Rousselot, Philippe; Robledo-Sarmiento, Macarena; Lallemand-Breitenbach, Valérie; Gourmel, Bernard; Vitoux, Dominique; Pandolfi, Pier Paolo; Rochette-Egly, Cécile; Zhu, Jun; de Thé, Hugues

    2008-12-01

    Retinoic acid and arsenic trioxide target the protein stability and transcriptional repression activity of the fusion oncoprotein PML-RARA, resulting in regression of acute promyelocytic leukemia (APL). Phenotypically, retinoic acid induces differentiation of APL cells. Here we show that retinoic acid also triggers growth arrest of leukemia-initiating cells (LICs) ex vivo and their clearance in PML-RARA mouse APL in vivo. Retinoic acid treatment of mouse APLs expressing the fusion protein PLZF-RARA triggers full differentiation, but not LIC loss or disease remission, establishing that differentiation and LIC loss can be uncoupled. Although retinoic acid and arsenic synergize to clear LICs through cooperative PML-RARA degradation, this combination does not enhance differentiation. A cyclic AMP (cAMP)-dependent phosphorylation site in PML-RARA is crucial for retinoic acid-induced PML-RARA degradation and LIC clearance. Moreover, activation of cAMP signaling enhances LIC loss by retinoic acid, identifying cAMP as another potential APL therapy. Thus, whereas transcriptional activation of PML-RARA is likely to control differentiation, its catabolism triggers LIC eradication and long-term remission of mouse APL. Therapy-triggered degradation of oncoproteins could be a general strategy to eradicate cancer stem cells.

  17. Leukemia

    MedlinePlus

    ... classification is by how fast the leukemia progresses: Acute leukemia. In acute leukemia, the abnormal blood cells are immature blood ... they multiply rapidly, so the disease worsens quickly. Acute leukemia requires aggressive, timely treatment. Chronic leukemia. There ...

  18. 36 CFR § 1210.32 - Real property.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true Real property. § 1210.32....32 Real property. The NHPRC shall prescribe requirements for recipients concerning the use and disposition of real property acquired in whole or in part under awards. Unless otherwise provided by statute...

  19. 21 CFR 1210.31 - Hearing before prosecution.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ....31 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... FEDERAL IMPORT MILK ACT Hearings § 1210.31 Hearing before prosecution. Before violation of the act is referred to the Department of Justice for prosecution under section 5 of the Federal Import Milk Act, an...

  20. 21 CFR 1210.20 - Application for permit.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... FEDERAL IMPORT MILK ACT Permit Control § 1210.20 Application for permit. Application for a permit to ship or transport milk or cream into the United States shall be made by the actual shipper upon forms...

  1. 21 CFR 1210.20 - Application for permit.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... FEDERAL IMPORT MILK ACT Permit Control § 1210.20 Application for permit. Application for a permit to ship or transport milk or cream into the United States shall be made by the actual shipper upon forms...

  2. 21 CFR 1210.31 - Hearing before prosecution.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ....31 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... FEDERAL IMPORT MILK ACT Hearings § 1210.31 Hearing before prosecution. Before violation of the act is referred to the Department of Justice for prosecution under section 5 of the Federal Import Milk Act, an...

  3. 36 CFR 1210.37 - Property trust relationship.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Property trust relationship... Standards § 1210.37 Property trust relationship. Real property, equipment, intangible property and debt instruments that are acquired or improved with NHPRC funds shall be held in trust by the recipient as trustee...

  4. Effects of ubiquitin C-terminal hydrolase L1 deficiency on mouse ova.

    PubMed

    Koyanagi, Sayaka; Hamasaki, Hiroko; Sekiguchi, Satoshi; Hara, Kenshiro; Ishii, Yoshiyuki; Kyuwa, Shigeru; Yoshikawa, Yasuhiro

    2012-03-01

    Maternal proteins are rapidly degraded by the ubiquitin-proteasome system during oocyte maturation in mice. Ubiquitin C-terminal hydrolase L1 (UCHL1) is highly and specifically expressed in mouse ova and is involved in the polyspermy block. However, the role of UCHL1 in the underlying mechanism of polyspermy block is poorly understood. To address this issue, we performed a comprehensive proteomic analysis to identify maternal proteins that were relevant to the role of UCHL1 in mouse ova using UCHL1-deficient gad. Furthermore, we assessed morphological features in gad mouse ova using transmission electron microscopy. NACHT, LRR, and PYD domain-containing (NALP) family proteins and endoplasmic reticulum (ER) chaperones were identified by proteomic analysis. We also found that the 'maternal antigen that embryos require' (NLRP5 (MATER)) protein level increased significantly in gad mouse ova compared with that in wild-type mice. In an ultrastructural study, gad mouse ova contained less ER in the cortex than in wild-type mice. These results provide new insights into the role of UCHL1 in the mechanism of polyspermy block in mouse ova.

  5. Effect of Sildenafil on Pre-Eclampsia-Like Mouse Model Induced By L-Name.

    PubMed

    Motta, C; Grosso, C; Zanuzzi, C; Molinero, D; Picco, N; Bellingeri, R; Alustiza, F; Barbeito, C; Vivas, A; Romanini, M C

    2015-08-01

    N(omega)-nitro-L-arginine methyl ester (L-NAME) decreases the vasodilator effect of nitric oxide (NO) and induces pre-eclampsia in mouse. Sildenafil inhibits the degradation of nitric oxide and increases vasodilation. This study aimed to determine the effects of sildenafil citrate on angiogenesis and oxidative stress at the maternal foetal interface on pre-eclampsia-like mouse model induced by L-NAME. Twenty pregnant mice were divided into four groups: (i) vehicle control; (ii) L-NAME; (iii) sildenafil; (4) L-NAME+sildenafil. L-NAME was administered from day 7 of pregnancy and sildenafil from day 8 until day 16; animals were euthanized on day 17. Placental and foetal sizes and weights were measured; lipid peroxide levels and catalase activity in placental homogenates were determined, and placental vascular endothelia were identified by lectin-histochemistry using BSA-I lectin. Western blot analysis was used to determine VEGF expression in placental homogenates. No changes were seen in placental and foetal development in mice with normal pregnancies treated with sildenafil. Treatments with L-NAME reduced significantly the placental weight and average height and decreased the percentage of the endothelial surface. These alterations may be mediated by the reduction of NO levels in trophoblastic cells, due to the inhibitory effect of L-NAME on nitric oxide synthase (NOS) synthesis. This effect was offset by the treatment with sildenafil, with an increase in the percentage of the endothelial surface. In conclusion, our results indicate that treatment with sildenafil on pre-eclampsia mouse model can be used without adverse effects on the concept and its use in the treatment of pre-eclampsia is promising. © 2015 Blackwell Verlag GmbH.

  6. Metabolic syndrome in long-term survivors of childhood acute leukemia treated without hematopoietic stem cell transplantation: an L.E.A. study.

    PubMed

    Saultier, Paul; Auquier, Pascal; Bertrand, Yves; Vercasson, Camille; Oudin, Claire; Contet, Audrey; Plantaz, Dominique; Poirée, Marilyne; Ducassou, Stéphane; Kanold, Justyna; Tabone, Marie-Dominique; Dalle, Jean-Hugues; Lutz, Patrick; Gandemer, Virginie; Sirvent, Nicolas; Thouvenin, Sandrine; Berbis, Julie; Chambost, Hervé; Baruchel, André; Leverger, Guy; Michel, Gérard

    2016-12-01

    Cardiovascular conditions are serious long-term complications of childhood acute leukemia. However, few studies have investigated the risk of metabolic syndrome, a known predictor of cardiovascular disease, in patients treated without hematopoietic stem cell transplantation. We describe the overall and age-specific prevalence, and the risk factors for metabolic syndrome and its components in the L.E.A. (Leucémie de l'Enfant et de l'Adolescent) French cohort of childhood acute leukemia survivors treated without hematopoietic stem cell transplantation. The study included 650 adult patients (mean age at evaluation: 24.2 years; mean follow-up after leukemia diagnosis: 16.0 years). The prevalence of metabolic syndrome was 6.9% (95% CI 5.1-9.2). The age-specific cumulative prevalence at 20, 25, 30 and 35 years of age was 1.3%, 6.1%, 10.8% and 22.4%, respectively. The prevalence of decreased high-density lipoprotein cholesterol, increased triglycerides, increased fasting glucose, increased blood pressure and increased abdominal circumference was 26.8%, 11.7%, 5.8%, 36.7% and 16.7%, respectively. Risk factors significantly associated with metabolic syndrome in the multivariate analysis were male sex (OR 2.64; 95% CI 1.32-5.29), age at last evaluation (OR 1.10; 95% CI 1.04-1.17) and body mass index at diagnosis (OR 1.15; 95% CI 1.01-1.32). The cumulative steroid dose was not a significant risk factor. Irradiated and non-irradiated patients exhibited different patterns of metabolic abnormalities, with more frequent abdominal obesity in irradiated patients and more frequent hypertension in non-irradiated patients. Survivors of childhood acute leukemia are at risk of metabolic syndrome, even when treated without hematopoietic stem cell transplantation or central nervous system irradiation. A preventive approach with regular screening for cardiovascular risk factors is recommended. clinicaltrials.gov identifier:01756599. Copyright© Ferrata Storti Foundation.

  7. Antineoplastic and cytogenetic effects of complexes of Pd (II) with 4N-substituted derivatives of 2-acetyl-pyridine-thiosemicarbazone.

    PubMed

    Papageorgiou, A; Iakovidou, Z; Mourelatos, D; Mioglou, E; Boutis, L; Kotsis, A; Kovala-Demertzi, D; Domopoulou, A; West, D X; Dermetzis, M A

    1997-01-01

    The effect of novel Pd(II) complexes with derivatives of 2-acetyl-pyridinethisemicarbazone, N4-ethyl (HAc4Et) and 3-hexamethyleneiminylthiosemicarbazone (HAchexim), on Sister Chromatid Exchange (SCE) rates and human lymphocyte proliferation kinetics was studied. Also, the effect of Pd(II) complexes on DNA synthesis of P388 and L1210 cell cultures and against Leukemia P388 was investigated. Among these compounds, the compound Bis(3-hexamethyleneiminyl-2-acetylpyridine-thisemicarbazonato++ +) palladium (II) was found to be distinctly effective against Leukemia P388, in inhibiting incorporation of 3H-thymidine into DNA and in inducing SCEs and cell division delays.

  8. Pin1 inhibition exerts potent activity against acute myeloid leukemia through blocking multiple cancer-driving pathways.

    PubMed

    Lian, Xiaolan; Lin, Yu-Min; Kozono, Shingo; Herbert, Megan K; Li, Xin; Yuan, Xiaohong; Guo, Jiangrui; Guo, Yafei; Tang, Min; Lin, Jia; Huang, Yiping; Wang, Bixin; Qiu, Chenxi; Tsai, Cheng-Yu; Xie, Jane; Cao, Ziang Jeff; Wu, Yong; Liu, Hekun; Zhou, Xiaozhen; Lu, Kunping; Chen, Yuanzhong

    2018-05-30

    The increasing genomic complexity of acute myeloid leukemia (AML), the most common form of acute leukemia, poses a major challenge to its therapy. To identify potent therapeutic targets with the ability to block multiple cancer-driving pathways is thus imperative. The unique peptidyl-prolyl cis-trans isomerase Pin1 has been reported to promote tumorigenesis through upregulation of numerous cancer-driving pathways. Although Pin1 is a key drug target for treating acute promyelocytic leukemia (APL) caused by a fusion oncogene, much less is known about the role of Pin1 in other heterogeneous leukemia. The mRNA and protein levels of Pin1 were detected in samples from de novo leukemia patients and healthy controls using real-time quantitative RT-PCR (qRT-PCR) and western blot. The establishment of the lentiviral stable-expressed short hairpin RNA (shRNA) system and the tetracycline-inducible shRNA system for targeting Pin1 were used to analyze the biological function of Pin1 in AML cells. The expression of cancer-related Pin1 downstream oncoproteins in shPin1 (Pin1 knockdown) and Pin1 inhibitor all-trans retinoic acid (ATRA) treated leukemia cells were examined by western blot, followed by evaluating the effects of genetic and chemical inhibition of Pin1 in leukemia cells on transformed phenotype, including cell proliferation and colony formation ability, using trypan blue, cell counting assay, and colony formation assay in vitro, as well as the tumorigenesis ability using in vivo xenograft mouse models. First, we found that the expression of Pin1 mRNA and protein was significantly increased in both de novo leukemia clinical samples and multiple leukemia cell lines, compared with healthy controls. Furthermore, genetic or chemical inhibition of Pin1 in human multiple leukemia cell lines potently inhibited multiple Pin1 substrate oncoproteins and effectively suppressed leukemia cell proliferation and colony formation ability in cell culture models in vitro. Moreover

  9. Synthesis of Novel Chiral Sulfonamide-Bearing 1,2,4-Triazole-3-thione Analogs Derived from D- and L-Phenylalanine Esters as Potential Anti-Influenza Agents.

    PubMed

    Başaran, Eyüp; Karaküçük-Iyidoğan, Ayşegül; Schols, Dominique; Oruç-Emre, Emine Elçin

    2016-06-01

    Novel enantiopure 1,2,4-trizole-3-thiones containing a benzensulfonamide moiety were synthesized via multistep reaction sequence starting with D-phenylalanine methyl ester and L-phenylalanine ethyl ester as a source of chirality. The chemical structures of all compounds were characterized by elemental analysis, UV, IR, (1) H NMR, (13) C NMR, 2D NMR (HETCOR), and mass spectral data. All compounds were tested in vitro antiviral activity against a broad variety of DNA and RNA viruses and in vitro cytostatic activity against murine leukemia (L1210), human T-lymphocyte (CEM) and human cervix carcinoma (HeLa) cell lines. Although enantiopure 1,2,4-triazole-3-thione analogs in (R) configuration emerged as promising anti-influenza A H1N1 subtype in Madin Darby canine kidney cell cultures (MDCK), their enantiomers exhibited no activity. Especially compounds , , , , and (EC50 : 6.5, 6.1, 2.4, 1.6, 1.7 μM, respectively) had excellent activity against influenza A H1N1 subtype compared to the reference drug ribavirin (EC50 : 8.0 μM). Several compounds have been found to inhibit proliferation of L1210, CEM and HeLa cell cultures with IC50 in the 12-53 μM range. Compound and in (R) configuration were the most active compounds (IC50 : 12-22 μM for and IC50 : 19-23 μM for ). Chirality 28:495-513, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. 45 CFR 1210.3-1 - Grounds for termination.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early Termination § 1210.3-1 Grounds for termination. ACTION may terminate or suspend a Volunteer based on the Volunteer's conduct for the following reasons: (a) Conviction of any criminal offense under Federal, State...

  11. 45 CFR 1210.3-5 - Preparation for appeal.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early Termination § 1210.3-5 Preparation for appeal. (a) Entitlement to Representation. A Volunteer may be accompanied, represented and advised by a representative of the Volunteer's own choice at any stage of the...

  12. 45 CFR 1210.3-5 - Preparation for appeal.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early Termination § 1210.3-5 Preparation for appeal. (a) Entitlement to Representation. A Volunteer may be accompanied, represented and advised by a representative of the Volunteer's own choice at any stage of the...

  13. 45 CFR 1210.3-1 - Grounds for termination.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early Termination § 1210.3-1 Grounds for termination. ACTION may terminate or suspend a Volunteer based on the Volunteer's conduct for the following reasons: (a) Conviction of any criminal offense under Federal, State...

  14. 45 CFR 1210.3-5 - Preparation for appeal.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early Termination § 1210.3-5 Preparation for appeal. (a) Entitlement to Representation. A Volunteer may be accompanied, represented and advised by a representative of the Volunteer's own choice at any stage of the...

  15. 45 CFR 1210.3-1 - Grounds for termination.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early Termination § 1210.3-1 Grounds for termination. ACTION may terminate or suspend a Volunteer based on the Volunteer's conduct for the following reasons: (a) Conviction of any criminal offense under Federal, State...

  16. 45 CFR 1210.3-5 - Preparation for appeal.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early Termination § 1210.3-5 Preparation for appeal. (a) Entitlement to Representation. A Volunteer may be accompanied, represented and advised by a representative of the Volunteer's own choice at any stage of the...

  17. 45 CFR 1210.3-1 - Grounds for termination.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early Termination § 1210.3-1 Grounds for termination. ACTION may terminate or suspend a Volunteer based on the Volunteer's conduct for the following reasons: (a) Conviction of any criminal offense under Federal, State...

  18. 45 CFR 1210.3-1 - Grounds for termination.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early Termination § 1210.3-1 Grounds for termination. ACTION may terminate or suspend a Volunteer based on the Volunteer's conduct for the following reasons: (a) Conviction of any criminal offense under Federal, State...

  19. 45 CFR 1210.3-5 - Preparation for appeal.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... SERVICE VISTA TRAINEE DESELECTION AND VOLUNTEER EARLY TERMINATION PROCEDURES VISTA Volunteer Early Termination § 1210.3-5 Preparation for appeal. (a) Entitlement to Representation. A Volunteer may be accompanied, represented and advised by a representative of the Volunteer's own choice at any stage of the...

  20. Leukemia Cutis Associated with Secondary Plasma Cell Leukemia.

    PubMed

    DeMartinis, Nicole C; Brown, Megan M; Hinds, Brian R; Cohen, Philip R

    2017-05-09

    Plasma cell leukemia is an uncommon, aggressive variant of leukemia that may occur de novo or in association with multiple myeloma. Leukemia cutis is the cutaneous manifestation of leukemia, and indicates an infiltration of the skin by malignant leukocytes or their precursors. Plasma cell leukemia cutis is a rare clinical presentation of leukemia. We present a man who developed plasma cell leukemia cutis in association with multiple myeloma. Cutaneous nodules developed on his arms and legs 50 days following an autologous stem cell transplant. Histopathologic examination showed CD138-positive nodular aggregates of atypical plasma cells with kappa light chain restriction, similar to the phenotype of his myeloma. In spite of systemic treatment of his underlying disease, he died 25 days after the presentation of leukemia cutis. Pub-Med was searched for the following terms: cutaneous plasmacytomas, leukemia cutis, plasma cell leukemia nodules, plasma cell leukemia cutis, and secondary cutaneous plasmacytoma. Papers were reviewed and appropriate references evaluated. Leukemia cutis in plasma cell leukemia patients is an infrequent occurrence. New skin lesions in patients with plasma cell leukemia should be biopsied for pathology and for tissue cultures to evaluate for cancer or infection, respectively. The diagnosis plasma cell leukemia cutis is associated with a very poor prognosis.

  1. Efficacy of Oral E1210, a New Broad-Spectrum Antifungal with a Novel Mechanism of Action, in Murine Models of Candidiasis, Aspergillosis, and Fusariosis▿

    PubMed Central

    Hata, Katsura; Horii, Takaaki; Miyazaki, Mamiko; Watanabe, Nao-aki; Okubo, Miyuki; Sonoda, Jiro; Nakamoto, Kazutaka; Tanaka, Keigo; Shirotori, Syuji; Murai, Norio; Inoue, Satoshi; Matsukura, Masayuki; Abe, Shinya; Yoshimatsu, Kentaro; Asada, Makoto

    2011-01-01

    E1210 is a first-in-class, broad-spectrum antifungal with a novel mechanism of action—inhibition of fungal glycosylphosphatidylinositol biosynthesis. In this study, the efficacies of E1210 and reference antifungals were evaluated in murine models of oropharyngeal and disseminated candidiasis, pulmonary aspergillosis, and disseminated fusariosis. Oral E1210 demonstrated dose-dependent efficacy in infections caused by Candida species, Aspergillus spp., and Fusarium solani. In the treatment of oropharyngeal candidiasis, E1210 and fluconazole each caused a significantly greater reduction in the number of oral CFU than the control treatment (P < 0.05). In the disseminated candidiasis model, mice treated with E1210, fluconazole, caspofungin, or liposomal amphotericin B showed significantly higher survival rates than the control mice (P < 0.05). E1210 was also highly effective in treating disseminated candidiasis caused by azole-resistant Candida albicans or Candida tropicalis. A 24-h delay in treatment onset minimally affected the efficacy outcome of E1210 in the treatment of disseminated candidiasis. In the Aspergillus flavus pulmonary aspergillosis model, mice treated with E1210, voriconazole, or caspofungin showed significantly higher survival rates than the control mice (P < 0.05). E1210 was also effective in the treatment of Aspergillus fumigatus pulmonary aspergillosis. In contrast to many antifungals, E1210 was also effective against disseminated fusariosis caused by F. solani. In conclusion, E1210 demonstrated consistent efficacy in murine models of oropharyngeal and disseminated candidiasis, pulmonary aspergillosis, and disseminated fusariosis. These data suggest that further studies to determine E1210's potential for the treatment of disseminated fungal infections are indicated. PMID:21788462

  2. Efficacy of oral E1210, a new broad-spectrum antifungal with a novel mechanism of action, in murine models of candidiasis, aspergillosis, and fusariosis.

    PubMed

    Hata, Katsura; Horii, Takaaki; Miyazaki, Mamiko; Watanabe, Nao-Aki; Okubo, Miyuki; Sonoda, Jiro; Nakamoto, Kazutaka; Tanaka, Keigo; Shirotori, Syuji; Murai, Norio; Inoue, Satoshi; Matsukura, Masayuki; Abe, Shinya; Yoshimatsu, Kentaro; Asada, Makoto

    2011-10-01

    E1210 is a first-in-class, broad-spectrum antifungal with a novel mechanism of action-inhibition of fungal glycosylphosphatidylinositol biosynthesis. In this study, the efficacies of E1210 and reference antifungals were evaluated in murine models of oropharyngeal and disseminated candidiasis, pulmonary aspergillosis, and disseminated fusariosis. Oral E1210 demonstrated dose-dependent efficacy in infections caused by Candida species, Aspergillus spp., and Fusarium solani. In the treatment of oropharyngeal candidiasis, E1210 and fluconazole each caused a significantly greater reduction in the number of oral CFU than the control treatment (P < 0.05). In the disseminated candidiasis model, mice treated with E1210, fluconazole, caspofungin, or liposomal amphotericin B showed significantly higher survival rates than the control mice (P < 0.05). E1210 was also highly effective in treating disseminated candidiasis caused by azole-resistant Candida albicans or Candida tropicalis. A 24-h delay in treatment onset minimally affected the efficacy outcome of E1210 in the treatment of disseminated candidiasis. In the Aspergillus flavus pulmonary aspergillosis model, mice treated with E1210, voriconazole, or caspofungin showed significantly higher survival rates than the control mice (P < 0.05). E1210 was also effective in the treatment of Aspergillus fumigatus pulmonary aspergillosis. In contrast to many antifungals, E1210 was also effective against disseminated fusariosis caused by F. solani. In conclusion, E1210 demonstrated consistent efficacy in murine models of oropharyngeal and disseminated candidiasis, pulmonary aspergillosis, and disseminated fusariosis. These data suggest that further studies to determine E1210's potential for the treatment of disseminated fungal infections are indicated.

  3. 38 CFR 12.10 - Proceeds of sale.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Proceeds of sale. 12.10... Proceeds of sale. After proper notice as prescribed, sale of any such property which it is proper to sell... and place stated in the notice of sale. The property will be sold to the highest bidder (no employee...

  4. 38 CFR 12.10 - Proceeds of sale.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Proceeds of sale. 12.10... Proceeds of sale. After proper notice as prescribed, sale of any such property which it is proper to sell... and place stated in the notice of sale. The property will be sold to the highest bidder (no employee...

  5. 38 CFR 12.10 - Proceeds of sale.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Proceeds of sale. 12.10... Proceeds of sale. After proper notice as prescribed, sale of any such property which it is proper to sell... and place stated in the notice of sale. The property will be sold to the highest bidder (no employee...

  6. 38 CFR 12.10 - Proceeds of sale.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Proceeds of sale. 12.10... Proceeds of sale. After proper notice as prescribed, sale of any such property which it is proper to sell... and place stated in the notice of sale. The property will be sold to the highest bidder (no employee...

  7. 16 CFR § 1210.4 - Test protocol.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... live within the United States. (4) The age and sex distribution of each 100-child panel shall be: (i... recorded for each child in the 100-child test panel: (1) Sex (male or female). (2) Date of birth (month... STANDARD FOR CIGARETTE LIGHTERS Requirements for Child Resistance § 1210.4 Test protocol. (a) Child test...

  8. Tanespimycin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, Chronic Myelomonocytic Leukemia, or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-09-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  9. 40 CFR 147.1210 - Requirements for Indian lands.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 24 2012-07-01 2012-07-01 false Requirements for Indian lands. 147... § 147.1210 Requirements for Indian lands. (a) Purpose and scope. This section sets forth additional requirements that apply to injection activities on Indian lands in Minnesota. (b) Requirements. Notwithstanding...

  10. 40 CFR 147.1210 - Requirements for Indian lands.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 24 2013-07-01 2013-07-01 false Requirements for Indian lands. 147... § 147.1210 Requirements for Indian lands. (a) Purpose and scope. This section sets forth additional requirements that apply to injection activities on Indian lands in Minnesota. (b) Requirements. Notwithstanding...

  11. 40 CFR 147.1210 - Requirements for Indian lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Requirements for Indian lands. 147... § 147.1210 Requirements for Indian lands. (a) Purpose and scope. This section sets forth additional requirements that apply to injection activities on Indian lands in Minnesota. (b) Requirements. Notwithstanding...

  12. 40 CFR 147.1210 - Requirements for Indian lands.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false Requirements for Indian lands. 147... § 147.1210 Requirements for Indian lands. (a) Purpose and scope. This section sets forth additional requirements that apply to injection activities on Indian lands in Minnesota. (b) Requirements. Notwithstanding...

  13. 40 CFR 147.1210 - Requirements for Indian lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false Requirements for Indian lands. 147... § 147.1210 Requirements for Indian lands. (a) Purpose and scope. This section sets forth additional requirements that apply to injection activities on Indian lands in Minnesota. (b) Requirements. Notwithstanding...

  14. Oral or parenteral administration of curcumin does not prevent the growth of high-risk t(4;11) acute lymphoblastic leukemia cells engrafted into a NOD/SCID mouse model

    PubMed Central

    ZUNINO, SUSAN J.; STORMS, DAVID H.; NEWMAN, JOHN W.; PEDERSEN, THERESA L.; KEEN, CARL L.; DUCORE, JONATHAN M.

    2013-01-01

    In this study, the efficacy of orally and parenter-ally administered curcumin was evaluated in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice (NOD.CB17-Prkdcscid/J mice) engrafted with the human t(4;11) acute lymphoblastic leukemia line, SEM. SEM cells were injected into the tail vein and engraftment was monitored by flow cytometry. Once engraftment was observed, the chemotherapeutic potential was examined by injecting mice intraperitoneally with curcumin (5 mg/kg body weight) dissolved in dimethylsulfoxide (DMSO) or DMSO alone (control) every other day, or vincristine (0.5 mg/kg body weight) 3 times per week for 4 weeks (n=16 per group). The intraperitoneal administration of curcumin did not inhibit the growth of the leukemia cells. To determine the efficacy of oral curcumin, mice were fed a control diet or a diet containing 0.5% w/w curcumin 3 weeks prior to the injection of the leukemia cells and throughout the experimental period (n=16 per group). To determine whether dietary curcumin can enhance the efficacy of a conventional chemotherapeutic agent, vincristine was injected intraperitoneally into leukemic mice fed the different diets. Dietary curcumin did not delay the engraftment or growth of leukemia cells, or sensitize the cells to vincristine. Liquid chromatography-tandem mass spectrometry analyses of mouse sera showed that curcumin rapidly metabolized to glucuronidated and sulfated forms within 1 h post-injection and these were the major curcumin metabolites found in the sera of the mice fed the curcumin diet. In contrast to the findings in previous in vitro models, the current data indicate that orally or parenterally administered curcumin is not a potent preventive agent against high-risk t(4;11) acute lymphoblastic leukemia. PMID:23232667

  15. Update on the Use of l-Asparaginase in Infants and Adolescent Patients with Acute Lymphoblastic Leukemia

    PubMed Central

    Andrade, Augusto F; Borges, Kleiton S; Silveira, Vanessa S

    2014-01-01

    Great improvements have been made in acute lymphoblastic leukemia (ALL) treatment in the past decades, especially due to the use of l-asparaginase (l-ASP). Despite the significant success rate, several side effects mainly caused by toxicity, asparaginase silent inactivation, and cellular resistance, encourage an open debate regarding the optimal dosage and formulation of l-ASP. Alternative sources of asparaginases have been constantly investigated in order to overcome hypersensitivity clinical toxicity. Additionally, genomic modulation as gene expression profiling, genetic polymorphisms, and epigenetic changes is also being investigated concerning their role in cellular resistance to l-ASP. Understanding the mechanisms that mediate the resistance to l-ASP treatment may bring new insights into ALL pathobiology and contribute to the development of more effective treatment strategies. In summary, this review presents an overview on l-ASP data and focuses on cellular mechanisms underlying resistance and alternative therapies for the use of asparaginase in childhood ALL treatment. PMID:25210485

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