GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Adenovirus encoding vascular endothelial growth factor–D induces tissue-specific vascular patterns in vivo
    American Society of Hematology ; 2002
    In:  Blood Vol. 99, No. 12 ( 2002-06-15), p. 4434-4442
    Details
    In: Blood, American Society of Hematology, Vol. 99, No. 12 ( 2002-06-15), p. 4434-4442
    Abstract: The capacity of an adenovirus encoding the mature form of vascular endothelial growth factor (VEGF)–D, VEGF-DΔNΔC, to induce angiogenesis, lymphangiogenesis, or both was analyzed in 2 distinct in vivo models. We first demonstrated in vitro that VEGF-DΔNΔC encoded by the adenovirus (Ad-VEGF-DΔNΔC) is capable of inducing endothelial cell proliferation and migration and that the latter response is primarily mediated by VEGF receptor-2 (VEGFR-2). Second, we characterized a new in vivo model for assessing experimental angiogenesis, the rat cremaster muscle, which permits live videomicroscopy and quantitation of functional blood vessels. In this model, a proangiogenic effect of Ad-VEGF-DΔNΔC was evident as early as 5 days after injection. Immunohistochemical analysis of the cremaster muscle demonstrated that neovascularization induced by Ad-VEGF-DΔNΔC and by Ad-VEGF-A165 (an adenovirus encoding the 165 isoform of VEGF-A) was composed primarily of laminin and VEGFR-2–positive vessels containing red blood cells, thus indicating a predominantly angiogenic response. In a skin model, Ad-VEGF-DΔNΔC induced angiogenesis and lymphangiogenesis, as indicated by staining with laminin, VEGFR-2, and VEGFR-3, whereas Ad-VEGF-A165 stimulated the selective growth of blood vessels. These data suggest that the biologic effects of VEGF-D are tissue-specific and dependent on the abundance of blood vessels and lymphatics expressing the receptors for VEGF-D in a given tissue. The capacity of Ad-VEGF-DΔNΔC to induce endothelial cell proliferation, angiogenesis, and lymphangiogenesis demonstrates that its potential usefulness for the treatment of coronary artery disease, cerebral ischemia, peripheral vascular disease, restenosis, and tissue edema should be tested in preclinical models.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    URL: Article
    DOI: 10.1182/blood.V99.12.4434
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2002
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Primitive Quiescent CD34+ Cells in Chronic Myeloid Leukemia Are Targeted by In Vitro Expanded Allogeneic Natural Killer Cells, Which Are Functionally Enhanced by Bortezomib Treatment.
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 1008-1008
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 1008-1008
    Abstract: Primitive quiescent CD34+ cells in chronic myeloid leukemia (CML) are relatively resistant to the tyrosine kinase inhibitors imatinib and dasatinib, which may explain the persistence of detectable BCR-ABL transcripts following treatment with these agents. Conversely, allogeneic stem cell transplantation (SCT) can eradicate residual CML, suggesting that quiescent stem cells are eliminated by graft-versus-leukemia (GVL) effects. We studied the progeny of CD34+ cells after 4 days culture in serum-free media supplemented with interleukin-3, interleukin-6, stem cell factor, granulocyte-colony stimulating factor and Flt-3 ligand in 14 CML patients (8 chronic phase, 6 advanced phase) who subsequently received T cell depleted SCT from their HLA-identical sibling donors. Cycling CD34-negative and CD34+, and non-cycling quiescent CD34+ CML cells were isolated by fluorescence activated cell sorting. Fluorescence in situ hybridization in 4 representative CML patients revealed over 80% BCR-ABL positivity in both quiescent and cycling CD34+ and CD34-negative populations. Using real-time quantitative polymerase chain reaction, we found the expression of BCR-ABL, and leukemia-associated antigens (LAA), WT1, PR3 and ELA2, were the same in both cycling and quiescent CD34+ cell populations in CML. LAA expression was not significantly different when compared with similarly cultured CD34+ cells from healthy donors. Pre-SCT quiescent CD34+ cells from CML patients were lysed by natural killer (NK) cells from their donors but were less susceptible than their cycling CD34+ and CD34-negative counterparts. Purified donor NK cells (n=7) expanded after 11–13 days culture with interleukin-2 and irradiated EBV-LCL lysed quiescent CD34+ CML cells as well as their cycling CD34+ and CD34-negative progeny. Previous studies have demonstrated that bortezomib can sensitize malignant cells to NK-cell tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (Lundqvist et al Cancer Res. 2006 Jul 15;66(14):7317–25). Addition of bortezomib 10nM to CD34+ cell cultures enhanced cytotoxic effects of expanded donor NK cells on quiescent CD34+ CML cells. As observed with other malignancies, this enhanced sensitivity to NK-cytotoxicity correlated with increased expression of TRAIL receptors DR4 and DR5 on the surface of CD34+ quiescent cells, compared with cycling CD34+ or CD34-negative cells. Bortezomib treatment did not significantly affect the expression of MHC Class I, MIC A/B or Fas (CD95) on CD34+ quiescent or cycling cells. These results suggest that adoptive transfer of in vitro expanded donor NK cells with concomitant administration of bortezomib to the recipient may enhance cytotoxicity to quiescent CD34+ cells and may improve NK-mediated GVL effects. This may be particularly applicable to CML patients who are increasingly transplanted in more advanced stage disease, and so are at a greater risk of relapse post-SCT.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.1008.1008
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Downregulation of Antigen-Presenting Cell Functions After Administration of Mitogenic Anti-CD3 Monoclonal Antibodies in Mice
    American Society of Hematology ; 1999
    In:  Blood Vol. 94, No. 12 ( 1999-12-15), p. 4347-4357
    Details
    In: Blood, American Society of Hematology, Vol. 94, No. 12 ( 1999-12-15), p. 4347-4357
    Abstract: Antibodies against CD3ɛ are widely used as immunosuppressive agents. Although it is generally assumed that these reagents exert their immunomodulatory properties by inducing T-cell deletion and/or inactivation, their precise mechanism of action remains to be elucidated. Using a murine model, we demonstrate in this report that administration of anti-CD3ɛ antibodies causes the migration and maturation of dendritic cells (DC) in vivo, as determined by immunohistochemical analysis. This maturation/migration process was followed by selective loss of splenic DC, which resulted in a selective inhibition of antigen-presenting cell (APC) functions in vitro. Spleen cells from anti-CD3ɛ–treated animals were unable to productively stimulate naive alloreactive T cells and Th1-like clones in response to antigen, while retaining the ability to present antigen to a T-cell hybridoma and Th2 clones. Anti-CD3ɛ treatment was found to induce a selective deficiency in the ability of spleen cells to produce bioactive interleukin-12 in response to CD40 stimulation. APC dysfunction was not observed when nonmitogenic forms of anti-CD3ɛ antibodies were used, suggesting that splenic DC loss was a consequence of in vivo T-cell activation. Nonmitogenic anti-CD3ɛ monoclonal antibodies were found to be less immunosuppressive in vivo, raising the possibility that APC dysfunction contributes to anti-CD3ɛ–induced immunomodulation. Collectively, these data suggest a novel mechanism by which mitogenic anti-CD3ɛ antibodies downregulate immune responses.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    URL: Article
    DOI: 10.1182/blood.V94.12.4347.424k31_4347_4357
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 1999
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Downregulation of Antigen-Presenting Cell Functions After Administration of Mitogenic Anti-CD3 Monoclonal Antibodies in Mice
    American Society of Hematology ; 1999
    In:  Blood Vol. 94, No. 12 ( 1999-12-15), p. 4347-4357
    Details
    In: Blood, American Society of Hematology, Vol. 94, No. 12 ( 1999-12-15), p. 4347-4357
    Abstract: Antibodies against CD3ɛ are widely used as immunosuppressive agents. Although it is generally assumed that these reagents exert their immunomodulatory properties by inducing T-cell deletion and/or inactivation, their precise mechanism of action remains to be elucidated. Using a murine model, we demonstrate in this report that administration of anti-CD3ɛ antibodies causes the migration and maturation of dendritic cells (DC) in vivo, as determined by immunohistochemical analysis. This maturation/migration process was followed by selective loss of splenic DC, which resulted in a selective inhibition of antigen-presenting cell (APC) functions in vitro. Spleen cells from anti-CD3ɛ–treated animals were unable to productively stimulate naive alloreactive T cells and Th1-like clones in response to antigen, while retaining the ability to present antigen to a T-cell hybridoma and Th2 clones. Anti-CD3ɛ treatment was found to induce a selective deficiency in the ability of spleen cells to produce bioactive interleukin-12 in response to CD40 stimulation. APC dysfunction was not observed when nonmitogenic forms of anti-CD3ɛ antibodies were used, suggesting that splenic DC loss was a consequence of in vivo T-cell activation. Nonmitogenic anti-CD3ɛ monoclonal antibodies were found to be less immunosuppressive in vivo, raising the possibility that APC dysfunction contributes to anti-CD3ɛ–induced immunomodulation. Collectively, these data suggest a novel mechanism by which mitogenic anti-CD3ɛ antibodies downregulate immune responses.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    URL: Article
    DOI: 10.1182/blood.V94.12.4347
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 1999
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Telomere Elongation in Dyskeratosis Congenita Induced Pluripotent Stem Cells.
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 497-497
    Details
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 497-497
    Abstract: Abstract 497 Patients with dyskeratosis congenita (DC), a disorder of telomere maintenance, suffer premature degeneration of multiple tissues. Bone marrow failure is the principal cause of mortality, and allogeneic stem cell transplantation is limited by increased treatment-related mortality. Somatic cells can be reprogrammed using defined genetic and chemical factors, yielding “induced pluripotent stem” (iPS) cell lines which have the capacity to differentiate into any tissue. Patient-specific iPS cells therefore hold promise as therapeutic agents and disease models for human degenerative disorders like DC. A cardinal feature of iPS cells is acquisition of indefinite self-renewal capacity, and we have found that telomere length is increased in human iPS cells relative to the normal primary somatic cells from which they are derived. Here we investigated whether defects in telomerase function would limit derivation or self-renewal of iPS cells from patients with DC. We reprogrammed primary fibroblasts from patients with X-linked and autosomal dominant DC, caused by mutations in the genes encoding dyskerin and telomerase RNA component (TERC), respectively. We were able to establish multiple DC-specific iPS lines showing all hallmarks of pluripotency, including the formation of hematopoietic progenitors in vitro. Unexpectedly, DC-specific iPS cells were able to sustain continual proliferation in vitro, in contrast to the premature senescence displayed by the DC fibroblasts. Although early passage DC iPS cells had shorter telomeres than donor fibroblasts, we found that telomere length in DC iPS cells increased with continued passage in culture. To explain this finding, we discovered that steady state levels of TERC, which are critically limiting in several forms of DC, are upregulated in normal and DC iPS cells. We found that TERC upregulation is a feature of the pluripotent state, that the TERC locus is a target of pluripotency-associated transcription factors, and that transcriptional silencing accompanies a 3' deletion at the TERC locus in autosomal dominant DC. Our results demonstrate that reprogramming restores self-renewal capacity in DC cells despite genetic lesions affecting telomerase, and suggest that strategies to enhance endogenous TERC expression may be feasible and therapeutically beneficial in DC patients. The studies demonstrate the value of patient-specific iPS cells for basic and translational discovery, and further the rationale for autologous iPS based cellular therapy of genetic hematologic disorders. Disclosures: Daley: MPM Capital: Consultancy; Solasia: Consultancy; Epizyme: Consultancy; iPierian: Consultancy, Equity Ownership.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V114.22.497.497
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Dasatinib may overcome the negative prognostic impact of KIR2DS1 in newly diagnosed patients with chronic myeloid leukemia
    American Society of Hematology ; 2012
    In:  Blood Vol. 120, No. 3 ( 2012-07-19), p. 697-698
    Details
    In: Blood, American Society of Hematology, Vol. 120, No. 3 ( 2012-07-19), p. 697-698
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2012-04-421016
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Primitive quiescent CD34+ cells in chronic myeloid leukemia are targeted by in vitro expanded natural killer cells, which are functionally enhanced by bortezomib
    American Society of Hematology ; 2009
    In:  Blood Vol. 113, No. 4 ( 2009-01-22), p. 875-882
    Details
    In: Blood, American Society of Hematology, Vol. 113, No. 4 ( 2009-01-22), p. 875-882
    Abstract: Primitive quiescent CD34+ chronic myeloid leukemia (CML) cells are more biologically resistant to tyrosine kinase inhibitors than their cycling counterparts; however, graft-versus-leukemia (GVL) effects after allogeneic stem cell transplantation (SCT) probably eliminate even these quiescent cells in long-term surviving CML transplant recipients. We studied the progeny of CD34+ cells from CML patients before SCT, which were cultured 4 days in serum-free media with hematopoietic growth factors. BCR-ABL expression was similar in both cycling and quiescent noncycling CD34+ populations. Quiescent CD34+ cells from CML patients were less susceptible than their cycling CD34+ and CD34− counterparts to lysis by natural killer (NK) cells from their HLA-identical sibling donors. Compared with cycling populations, quiescent CD34+ CML cells had higher surface expression of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) receptors DR4 and DR5. Bortezomib up-regulated TRAIL receptor expression on quiescent CD34+ CML cells, and further enhanced their susceptibility to cytotoxicity by in vitro expanded donor NK cells. These results suggest that donor-derived NK cell–mediated GVL effects may be improved by sensitizing residual quiescent CML cells to NK-cell cytotoxicity after SCT. Such treatment, as an adjunct to donor lymphocyte infusions and pharmacologic therapy, may reduce the risk of relapse in CML patients who require treatment by SCT.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2008-05-158253
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Genetic and mechanistic diversity in pediatric hemophagocytic lymphohistiocytosis
    American Society of Hematology ; 2018
    In:  Blood Vol. 132, No. 1 ( 2018-07-05), p. 89-100
    Details
    In: Blood, American Society of Hematology, Vol. 132, No. 1 ( 2018-07-05), p. 89-100
    Abstract: Whole-exome sequencing may identify specific therapeutic opportunities for patients with HLH. HLH should be conceptualized as a critical illness phenotype driven by toxic activation of immune cells from different underlying mechanisms.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2017-11-814244
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...