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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 38 (1996), S. S22 
    ISSN: 1432-0843
    Keywords: Key words Interleukin 12 (IL-12) ; Interferon-γ (IFN-γ) ; Antitumor effect ; Antimetastatic effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Interleukin 12 (IL-12) has a pivotal role in controlling cell-mediated immunity through a number of important biological activities, such as secretion of interferon-γ (IFN-γ). In this review, we report our recent results regarding the antitumor and antimetastatic effects of IL-12. Five intraperitoneal injections of recombinant IL-12 (rIL-12) into mice bearing subcutaneous tumors (CSA1M fibrosarcoma) induced complete tumor regression, irrespective of whether tumors were at early or late stages of growth. Furthermore, IL-12-treated mice that had rejected the primary tumor exhibited complete resistance to rechallenge with the same tumor but did not reject a second syngeneic tumor. Immunohistochemical analyses following IL-12 treatment revealed that CD4+ and CD8+ T-cells had infiltrated the tumor. More importantly, IFN-γ mRNA expression was observed in fresh tumor masses from tumor-bearing mice receiving IL-12 treatment. The importance of IFN-γ was further demonstrated by the observation that systemic administration of anti-IFN-γ monoclonal antibody prior to IL-12 treatment completely abrogated the antitumor effect of IL-12. We next investigated the ability of rIL-12 to modulate the outgrowth of metastatic tumor cells in an ovarian carcinoma (OV-HM) model. This aggressive tumor showed rapid growth of the primary tumor mass, a high incidence of metastases to the lung and lymph nodes, and invasion from the primary subcutaneous site into the peritoneal cavity. At approximately 1 month after tumor implantation, primary tumors in animals without palpable lymph nodes were surgically resected. When examined 2 months later, most animals had developed lymph node and lung metastases. In contrast, rIL-12 injections following tumor resection inhibited the development of metastases in both the lung and lymph nodes. Even in mice showing signs of lymph node metastases or invasion of the abdominal wall before primary tumor resection, rIL-12 administration following tumor resection prevented further invasion into the peritoneal cavity and metastatic tumor cell growth in the lung. Our results demonstrate that administration of rIL-12 to tumor-bearing mice results in tumor regression through mechanisms involving efficient IFN-γ production by antitumor T-cells at tumor sites in situ and the establishment of a tumor-specific protective immune response. The results also indicate that IL-12 can induce a curative immune response in the face of an aggressive micrometastasizing tumor.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-069X
    Keywords: Inflammatory linear epidermal naevus ; Keratinization ; DACM ; Involucrin ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Skin lesions of three patients with inflammatory linear verrucose epidermal naevus (ILVEN) were examined. Histologically, orthokeratosis and parakeratosis were alternately seen in the acanthotic epidermis. By N-(7-dimethylamino-4-methyl-3-coumarinyl)maleimide staining, the horny cells in the parakeratotic epidermis showed a cytoplasmic SH pattern and a weak membranous SS pattern. The orthokeratotic epidermis revealed an increased involucrin expression, whereas the parakeratotic epidermis showed almost no involucrin expression. Ultrastructurally, in the parakeratotic epidermis, the living keratinocytes had prominent Golgi apparatuses and vesicles in the cytoplasm. In the intercellular spaces in the upper spinous layer through to the lower horny layer, an electron dense, homogeneous substance was deposited. The cytoplasm of the horny cells was filled with keratin filaments and contained remnants of nucleus and cytoplasmic membrane structures, and some lipid droplets. The marginal band formation was incomplete. Most of these ultrastructural abnormalities were not found in the orthokeratotic epidermis. There are both similarities and differences in histopathogenesis of the parakeratotic epidermis between ILVEN and psoriasis. A unique finding was the lack of involucrin expression in the ILVEN parakeratotic epidermis.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Development genes and evolution 210 (2000), S. 120-128 
    ISSN: 1432-041X
    Keywords: Key words Key words: Wing-deficient mutant fl ; Bombyx mori ; Wing imaginal discs ; Ecdysteroid ; Metamorphosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  The wing-deficient mutant, flügellos (fl), of the silkworm, lacks four wings in the pupa and the adult. Previous studies have suggested that the fl wing discs lose responsiveness to ecdysteroid during metamorphosis. To test this hypothesis at the molecular level we compared the expression of 12 genes when the wing discs from the wild-type (WT) and fl larvae were cultured in the presence or absence of 20-hydroxyecdysone (20E). Most of the genes tested here, ecdysteroid-inducible (EcR-A, -B1,and E75) and noninducible genes (actin A3, β-tubulin, apterous (ap), USP, and BHR38) were normally expressed in the fl wing discs. However, the amounts of mRNAs of two ecdysteroid-inducible genes, BHR3 (early-late gene; Bombyx homologue to DHR3 and MHR3) and Urbain (wing-specific late gene), were reduced to about 50% and 20% of WT in the cultured fl wing discs, respectively. We analyzed developmental profiles of these mRNAs during metamorphosis. They also demonstrated decreased BHR3 and Urbain mRNA 2 days after the onset of wandering. This reduction in transcription of BHR3 in the fl mutant was observed only in the wing disc, not in the testis and fatbody. These results imply that the aberrant expression of the fl gene affects the downstream pathway of ecdysteroid signaling specifically in the wing discs and thus leads to a deficiency in wing formation.
    Type of Medium: Electronic Resource
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