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Antitumor effects by macrophages act...

Lum, Hillary Day.

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Antitumor effects by macrophages activated with an agonist monoclonal antibody to CD40.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Antitumor effects by macrophages activated with an agonist monoclonal antibody to CD40./
作者:	Lum, Hillary Day.
面頁冊數:	215 p.
附註:	Source: Dissertation Abstracts International, Volume: 67-06, Section: B, page: 3048.
Contained By:	Dissertation Abstracts International67-06B.
標題:	Health Sciences, Immunology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3222821
ISBN:	9780542753176

Antitumor effects by macrophages activated with an agonist monoclonal antibody to CD40.
Lum, Hillary Day.

Antitumor effects by macrophages activated with an agonist monoclonal antibody to CD40. - 215 p.

Source: Dissertation Abstracts International, Volume: 67-06, Section: B, page: 3048.

Thesis (Ph.D.)--The University of Wisconsin - Madison, 2006.

Macrophages (m&phis;) are versatile innate immune cells that are capable of exerting pro- or anti-tumor effects. The distinct phenotype and related functions of these cells is determined by how they are activated. In this thesis, I have pursued the hypothesis that ligation of CD40 molecules on the surface of m&phis; by agonist monoclonal antibodies to CD40 (alphaCD40) activates m&phis; to exert antitumor effects against well-established weakly immunogenic murine tumors.

ISBN: 9780542753176Subjects--Topical Terms:

1017716
Health Sciences, Immunology.

Antitumor effects by macrophages activated with an agonist monoclonal antibody to CD40.
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500 $a Source: Dissertation Abstracts International, Volume: 67-06, Section: B, page: 3048.
500 $a Adviser: Paul M. Sondel.
502 $a Thesis (Ph.D.)--The University of Wisconsin - Madison, 2006.
520 $a Macrophages (m&phis;) are versatile innate immune cells that are capable of exerting pro- or anti-tumor effects. The distinct phenotype and related functions of these cells is determined by how they are activated. In this thesis, I have pursued the hypothesis that ligation of CD40 molecules on the surface of m&phis; by agonist monoclonal antibodies to CD40 (alphaCD40) activates m&phis; to exert antitumor effects against well-established weakly immunogenic murine tumors.
520 $a Our laboratory had previously demonstrated T cell-independent antitumor and antimetastatic effects of CD40 ligation that involved NK cells. Here we show that alphaCD40 immunotherapy induced antitumor effects in the absence of T cells, natural killer cells, and polymorphonuclear cells. Furthermore, in vivo treatment with alphaCD40 resulted in enhanced expression of pro-inflammatory cytokines by m&phis;, as well as in vitro m&phis;-mediated tumor cell growth inhibition. A role for m&phis; in alphaCD40 immunotherapy was shown by reduction in the antitumor effects of alphaCD40 when m&phis; functions were inhibited in vivo by silica.
520 $a We also show that the cytotoxic molecules, nitric oxide (NO) and tumor necrosis factor (TNF)-alpha, are produced by alphaCD40-activated m&phis; and involved in the tumoristatic effects of these effector cells. Use of in vitro inhibitors or neutralizing mAb to block NO or TNF-alpha, as well as evaluation of m&phis; from inducible NO synthase- or TNF-alpha-KO mice following alphaCD40 activation all showed reduced tumoristatic activity. Interestingly, when alphaCD40-activated m&phis; were further stimulated with lipopolysaccharide, the resulting enhanced tumoristatic activity was much less dependent on NO or TNF-alpha.
520 $a Finally, we tested the immunotherapeutic combination of alphaCD40 and tumor-specific mAb linked to interleukin-2 (immunocytokines) in the treatment of weakly immunogenic murine tumors and found that the combination of these agents resulted in enhanced antitumor effects that also occurred in a T cell-independent manner. However, the combination of these immunotherapeutic agents did not result in complete tumor regression. Further studies are necessary to fully understand how m&phis; can be optimally activated to exert greater antitumor effects alone or following activation in combination with other immunotherapies that target them or other immune effector cells to result in potent antitumor effects.
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