Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The anti-tumor effect of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) was examined in BALB/c mice bearing increasing burdens of a syngeneic lymphoma (YC8). A single i.p. injection of the drug resulted in over 75% of cures when given at day 3, 5, 7 or 10 after an i.v. inoculum of 10(4) YC8 cells. The efficacy of BCNU on mice bearing large tumor burdens (from day 5 on) was not only due to its tumoricidal activity, but was immunologically mediated. Residual tumorigenic cells could be recovered in the livers of 5-day tumor bearers (TB) up to 2 weeks after BCNU treatment and only a low percentage of cures could be achieved when BCNU was administered to nude mice. In addition, BCNU-cured mice specifically rejected a lethal YC8 challenge and their splenocytes developed anti-tumor cytotoxicity in response to in vitro stimulation with YC8 cells. During kinetic experiments a 2-week period elapsed after BCNU injection before an anti-tumor cytotoxic T-lymphocyte (CTL) response could be generated by spleen cells of BCNU-treated 5-day TB. This period was characterized by immunosuppression as evaluated from impairment in the generation of lymphokine-activated killer (LAK) cells or of allospecific primary CTL responses by spleen cells from BCNU-treated 5-day TB and BCNU-treated normal mice. LAK cells first recovered and could be generated 7 days later, whereas primary allospecific CTL responses could only be detected by day 14, concomitantly with the generation of anti-tumor cytotoxicity by 5-day TB. The development of secondary in vitro CTL responses, however, was permanently abrogated. Spleen cells from BALB/c mice immunized either with YC8 or with DBA/2 minor histocompatibility antigens and treated with BCNU 1 week after the last immunization failed to mount an in vitro CTL response to their immunizing antigen, even when the cultures were supplemented with recombinant interleukin-2.
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PMID:Eradication of a disseminated mouse lymphoma by 1,3-bis(2-chloroethyl)-1-nitrosourea is immunologically mediated and accompanied by de novo generation of anti-tumor cytotoxicity. 224 96

Combination therapy using reovirus type 3 and the chemo-therapeutic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) is sufficient to cure approximately 80% of EL-4 lymphoma tumor-bearing BD2F1 male mice. Cured animals can be challenged with the EL-4 tumor, in the absence of the therapy, to yield 100% survival, whereas those challenged with heterologous tumor produce 0% survival. These results strongly suggest that a host-immune response is responsible for the observed therapeutic effect. Reovirus, a double-stranded RNA virus, is an efficient inducer of type I interferon. In an effort to determine the role of virus in this therapy, we substituted interferon-alpha (IFN-alpha) for reovirus in the therapy. Doses of IFN-alpha from 1000-10,000 U were capable of replacing reovirus to produce cure rates similar to reovirus. Spleen cells isolated from therapy-treated animals demonstrated high levels of cytotoxicity against the natural killer cell-sensitive cell line YAC-1, but not against EL-4 tumor. In vitro stimulation of isolated spleen cells by IFN-alpha resulted in a high level of natural killer cell activity, but no cytotoxicity against the EL-4 tumor. A significant antiproliferative effect against the EL-4 tumor in cell culture was demonstrated by IFN-alpha. Finally, therapy-treated, tumor-bearing mice that were injected with anti-IFN-alpha + -beta antibodies had similar survival levels as control mice, indicating that other cytokines might also play a role in promoting tumor killing. These investigations suggest that IFN-alpha may be a mediator of antitumor activity in the reovirus therapy system.
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PMID:The role of interferon-alpha in a successful murine tumor therapy. 1598 24