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  1. Article: The emerging role of the dendritic cell in novel cancer therapies.

    Hermans, I F / Moroni-Rawson, P / Ronchese, F / Ritchie, D S

    The New Zealand medical journal

    1998  Volume 111, Issue 1063, Page(s) 111–113

    Abstract: Research over the last two years has explored a number of possible approaches to applying dendritic cell immunotherapy to the treatment of human cancers. The chosen strategy in clinical situations will vary for individual patients and will depend on the ... ...

    Abstract Research over the last two years has explored a number of possible approaches to applying dendritic cell immunotherapy to the treatment of human cancers. The chosen strategy in clinical situations will vary for individual patients and will depend on the type of tumour, availability of tissue samples and potential source of dendritic cells. We believe that the isolation of fractionated tumour peptide from individual patients' tumours for use with autologous stem cell-derived dendritic cells may provide, in at least some cases, an effective and practical approach to cancer immunotherapy. This approach will provide a 'closed' system of tumour immunotherapy with all components (dendritic cells, antigen and cytotoxic T lymphocytes) being provided by the patient and applied in a tailor-made fashion to individual patients as an adjuvant to current anti-tumour therapies.
    MeSH term(s) Antigens, Neoplasm ; Dendritic Cells/immunology ; Humans ; Immunotherapy ; Neoplasms/immunology ; Neoplasms/therapy ; T-Lymphocytes/immunology
    Chemical Substances Antigens, Neoplasm
    Language English
    Publishing date 1998-04-10
    Publishing country New Zealand
    Document type Journal Article ; Review
    ZDB-ID 390590-1
    ISSN 1175-8716 ; 0028-8446 ; 0110-7704
    ISSN (online) 1175-8716
    ISSN 0028-8446 ; 0110-7704
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Tumor-peptide-pulsed dendritic cells isolated from spleen or cultured in vitro from bone marrow precursors can provide protection against tumor challenge.

    Hermans, I F / Daish, A / Moroni-Rawson, P / Ronchese, F

    Cancer immunology, immunotherapy : CII

    1997  Volume 44, Issue 6, Page(s) 341–347

    Abstract: Dendritic cells (DC) purified from murine spleen or generated in vitro from bone marrow precursors were compared for their respective abilities to stimulate T cell responses and provide tumor protection in vivo. In vitro incubation with synthetic tumor ... ...

    Abstract Dendritic cells (DC) purified from murine spleen or generated in vitro from bone marrow precursors were compared for their respective abilities to stimulate T cell responses and provide tumor protection in vivo. In vitro incubation with synthetic tumor peptide conferred on both DC populations the ability to induce proliferation of tumor-peptide-specific T cells in vitro. Spleen DC were reproducibly about twofold more effective than bone-marrow-derived DC in this assay. Both DC populations could also induce cytotoxic activity in vivo. In vitro cytoxicity assays showed that, while cytotoxic activity induced by immunization with spleen DC was clearly peptide-specific, a high non-specific cytotoxic activity was consistently observed after immunization with bone-marrow-derived DC, whether peptide-pulsed or not. Regardless of such high non-specific activity in vitro, only tumor-peptide-pulsed DC could provide protection against subsequent inoculation of tumor cells. DC not pulsed with tumor peptide were ineffective. We conclude that DC isolated from spleen or generated in vitro from bone marrow precursors are suitable reagents for use in tumor vaccination studies.
    MeSH term(s) Animals ; Antigens, Viral ; Base Sequence ; Bone Marrow/drug effects ; Bone Marrow/immunology ; Bone Marrow Cells ; Cancer Vaccines/therapeutic use ; Cells, Cultured ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Epitopes/immunology ; Female ; Glycoproteins/immunology ; Glycoproteins/pharmacology ; Immunotherapy, Active ; Lymphocyte Activation ; Male ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Neoplasm Proteins/immunology ; Neoplasm Proteins/pharmacology ; Neoplasms, Experimental/immunology ; Neoplasms, Experimental/prevention & control ; Peptide Fragments/immunology ; Peptide Fragments/pharmacology ; Spleen/cytology ; Spleen/drug effects ; Spleen/immunology ; T-Lymphocytes/immunology ; T-Lymphocytes, Cytotoxic/immunology ; Viral Proteins
    Chemical Substances Antigens, Viral ; Cancer Vaccines ; Epitopes ; Glycoproteins ; Neoplasm Proteins ; Peptide Fragments ; Viral Proteins ; glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus
    Language English
    Publishing date 1997-08
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 195342-4
    ISSN 1432-0851 ; 0340-7004
    ISSN (online) 1432-0851
    ISSN 0340-7004
    DOI 10.1007/s002620050392
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    Zs.A 1237: Show issues Location:
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  3. Article: Submitochondrial distribution and delayed proteolysis of subunit c of the H+-transporting ATP-synthase in ovine ceroid-lipofuscinosis.

    Hughes, S M / Moroni-Rawson, P / Jolly, R D / Jordan, T W

    Electrophoresis

    2001  Volume 22, Issue 9, Page(s) 1785–1794

    Abstract: The neuronal ceroid-lipofuscinose (NCL) are recessively inherited lysosomal storage diseases in children and animals. The major stored protein in many of these diseases is subunit c of the mitochondrial inner membrane H+-transporting ATP-synthase. ... ...

    Abstract The neuronal ceroid-lipofuscinose (NCL) are recessively inherited lysosomal storage diseases in children and animals. The major stored protein in many of these diseases is subunit c of the mitochondrial inner membrane H+-transporting ATP-synthase. Previous studies of naturally occurring ovine ceroid-lipofuscinosis (OCL) in South Hampshire sheep showed that the genes and transcripts for subunit c were normal and inferred that this protein was expressed normally in mitochondria prior to storage in lysosomes. Accumulation in mitochondria has not been conclusively established and we have therefore used the South Hampshire model to demonstrate approximately 1.8-fold normal levels of subunit c in mitochondrial inner membranes prepared from liver. Other mitochondrial inner membrane and ATP-synthase proteins that could be detected by mass spectrometry (MS) or two-dimensional electrophoresis (2-DE) were present in normal amounts. The accumulating subunit c showed normal post-translational modification but was abnormally resistant to proteolysis. These results are consistent with the hypothesis that OCL may result from a mitochondrial disorder that affects turnover of correctly expressed subunit c, although we cannot exclude the possibility that a postmitochondrial defect delays processing of subunit c out of mitochondria.
    MeSH term(s) Animals ; Electrophoresis, Gel, Two-Dimensional ; Mitochondria, Liver/metabolism ; Mitochondria, Liver/ultrastructure ; Neuronal Ceroid-Lipofuscinoses/metabolism ; Neuronal Ceroid-Lipofuscinoses/pathology ; Proton-Translocating ATPases/analysis ; Proton-Translocating ATPases/metabolism ; Sheep
    Chemical Substances Proton-Translocating ATPases (EC 3.6.3.14)
    Language English
    Publishing date 2001-05
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 619001-7
    ISSN 1522-2683 ; 0173-0835
    ISSN (online) 1522-2683
    ISSN 0173-0835
    DOI 10.1002/1522-2683(200105)22:9<1785::AID-ELPS1785>3.0.CO;2-L
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    Zs.A 1868: Show issues Location:
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  4. Article: Variant proteins in ovine ceroid-lipofuscinosis.

    Moroni-Rawson, P / Palmer, D N / Jolly, R D / Jordan, T W

    American journal of medical genetics

    1995  Volume 57, Issue 2, Page(s) 279–284

    Abstract: Two-dimensional polyacrylamide gel electrophoresis has been used to search for disease-related protein variation in South Hampshire sheep with ovine ceroid-lipofuscinosis. Several hundred proteins in homogenates and subcellular fractions from livers have ...

    Abstract Two-dimensional polyacrylamide gel electrophoresis has been used to search for disease-related protein variation in South Hampshire sheep with ovine ceroid-lipofuscinosis. Several hundred proteins in homogenates and subcellular fractions from livers have been examined, using isoelectric focusing as the first dimension separation, and SDS PAGE in the second dimension. Under these circumstances it was not possible to detect subunit c of the Fo region of ATP synthase, as this protein did not enter the isoelectric focusing gels. However, our studies emphasize the selective nature of misprocessing of subunit c, as we have not been able to detect any other consistent variation between affected and control animals for over 200 mitochondrial fraction proteins. Comparison of the presence or absence, and abundance, of proteins from isolated storage bodies with their counterparts in subcellular fractions from normal liver indicated that storage bodies contained a small subset of mitochondrial proteins, in addition to subunit c, with possible minor contributions from lysosomal, microsomal, and soluble proteins. Analysis of extramitochondrial proteins showed greater than 10-20-fold accumulation of ferritin light chains in microsomes, and partial loss of a putatively lysosomal protein, in ovine ceroid-lipofuscinosis. In addition, senescence marker protein was more abundant in the cytosolic fraction of controls, compared with affected individuals. We are currently investigating the basis and significance of these differences.
    MeSH term(s) Animals ; Cell Fractionation ; Crosses, Genetic ; Electrophoresis, Gel, Two-Dimensional ; Electrophoresis, Polyacrylamide Gel ; Female ; Genetic Variation ; Heterozygote ; Liver/metabolism ; Male ; Mitochondria, Liver/enzymology ; Molecular Weight ; Neuronal Ceroid-Lipofuscinoses/genetics ; Neuronal Ceroid-Lipofuscinoses/metabolism ; Neuronal Ceroid-Lipofuscinoses/veterinary ; Proton-Translocating ATPases/genetics ; Proton-Translocating ATPases/isolation & purification ; Sheep ; Sheep Diseases ; Subcellular Fractions/metabolism
    Chemical Substances Proton-Translocating ATPases (EC 3.6.3.14)
    Language English
    Publishing date 1995-06-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 133387-2
    ISSN 0148-7299
    ISSN 0148-7299
    DOI 10.1002/ajmg.1320570233
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    Zs.A 1376: Show issues Location:
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  5. Article: Functional comparison of spleen dendritic cells and dendritic cells cultured in vitro from bone marrow precursors.

    Garrigan, K / Moroni-Rawson, P / McMurray, C / Hermans, I / Abernethy, N / Watson, J / Ronchese, F

    Blood

    1996  Volume 88, Issue 9, Page(s) 3508–3512

    Abstract: We have compared dendritic cells (DC) isolated from mouse spleen, or generated in vitro from bone marrow (BM) precursors cultured in granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4), for the ability to process and ... ...

    Abstract We have compared dendritic cells (DC) isolated from mouse spleen, or generated in vitro from bone marrow (BM) precursors cultured in granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4), for the ability to process and present soluble antigen and stimulate major histocompatibility complex (MHC) Class II-restricted T cells. DC from spleen or BM cultures were equally able to stimulate the in vitro proliferation of allogeneic T cells or of antigen-specific T-cell receptor (TCR)-transgenic T cells. Both DC populations also induced comparable levels of IL-2 secretion by a T-cell hybridoma. Therefore, splenic and BM-derived DC express comparable levels of (Antigen + MHC Class II) ligands and/or costimulatory molecules and have comparable ability to stimulate T-cell responses. When presentation of a native protein antigen, rather than peptide, was evaluated, BM-derived DC were at least 50 times better than splenic DC at stimulating the proliferation of TCR-transgenic T cells. The antigen processing ability of the two populations was similar only when splenic DC were used immediately ex vivo. Therefore, unlike spleen DC, BM-derived DC maintain the capacity to process protein antigen for MHC Class II presentation during in vitro culture. Due to these characteristics, BM-derived DC may represent a useful tool in immunotherapy studies, as they combine high T-cell stimulatory properties with the capacity to process and present native antigen.
    MeSH term(s) Amino Acid Sequence ; Animals ; Bone Marrow/immunology ; Bone Marrow Cells ; Cells, Cultured ; Coculture Techniques ; Dendritic Cells/cytology ; Dendritic Cells/immunology ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Histocompatibility Antigens Class II/immunology ; Interleukin-4/pharmacology ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Molecular Sequence Data ; Organ Specificity ; Receptors, Antigen, T-Cell/immunology ; Spleen/cytology ; Spleen/immunology ; T-Lymphocytes/cytology ; T-Lymphocytes/immunology
    Chemical Substances Histocompatibility Antigens Class II ; Receptors, Antigen, T-Cell ; Interleukin-4 (207137-56-2) ; Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1)
    Language English
    Publishing date 1996-11-01
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
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