Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of interleukin (IL)-12 to prevent tumors when administered to individuals with a genetic risk of cancer was studied in two lines of transgenic mice expressing rat HER-2/neu oncogene in the mammary gland. Female BALB/c (H-2(d)) mice carrying the activated HER-2/ neu oncogene show no morphological abnormalities of the mammary gland until 3 wk of age. They then progress through atypical hyperplasia to in situ lobular carcinoma and at 33 wk of age all 10 mammary glands display invasive carcinomas. Adult FVB mice (H-2(q)) carrying the HER-2/neu protooncogene develop mammary carcinomas with a longer latency (38-49 wk) and a lower multiplicity (mean of 2.6 tumors/mice). Treatment with IL-12 (5 daily intraperitoneal injections, 1 wk on, 3 wk off; the first course with 50 ng IL-12/day, the second with 100 ng IL-12/day) begun at 2 wk of age in BALB/c mice and at 21 wk of age in FVB mice markedly delayed tumor onset and reduced tumor multiplicity. Analogous results were obtained in immunocompetent and permanently CD8(+) T lymphocyte-depleted mice. In both transgenic lines, tumor inhibition was associated with mammary infiltration of reactive cells, production of cytokines and inducible nitric oxide synthase, and reduction in microvessel number, in combination with a high degree of hemorrhagic necrosis.
 ...
PMID:Interleukin 12-mediated prevention of spontaneous mammary adenocarcinomas in two lines of Her-2/neu transgenic mice. 968 35

The development of autochtonous mammary tumors in HER-2/neu transgenic mice is facilitated by immune tolerance to the neu-transgene. However, appropriate vaccination strategies can initiate immune system-mediated antitumor response by a process that requires IFN-gamma. We investigated the role of inducible nitric oxide synthase (iNOS) induction by IFN-gamma to promote tumor cell apoptosis. Tumors from FVBN202 mice expressing the normal neu gene under the control of the MMTV-LTR were treated in slice cultures with IFN-gamma for up to 24 hr. Apoptosis was induced, which depended on iNOS enzymatic activity. iNOS expression was predominantly found in infiltrating CD11b(+)CD11c(+) myeloid cells and at much lower levels in the tumor epithelium. By contrast, IFN-gamma treatment of explant cultures of tumor epithelial cells was not sufficient to efficiently induce iNOS, emphasizing an important role of the integrity of tumor tissue architecture, which was preserved in the slice cultures. This notion was further supported by the upregulation of iNOS costimulatory cytokines TNF-alpha and IL-1beta in slice cultures but not in explants and the capability of purified CD11b(+)CD11c(+) cells to enhance iNOS expression of tumor cells in cocultures. The findings suggest that tumor-infiltrating myeloid cells in immuno-tolerant HER-2/neu transgenic mice possess tumor killing ability via induction of iNOS and underline the capacity of antitumor strategies designed to stimulate infiltrating myeloid cells.
 ...
PMID:Infiltrating CD11b+CD11c+ cells have the potential to mediate inducible nitric oxide synthase-dependent cell death in mammary carcinomas of HER-2/neu transgenic mice. 1965 77

To date three distinct isoforms of nitric oxide synthase (NOS) have been identified. Two isoforms are considered to be expressed constitutively-neu-ronal NOS (nNOS; type I NOS) and endothelial NOS (eNOS; type III NOS). The third isoform is not generally present in normal cells and tissues but is induced in response to infection, inflammation or trauma-inducible NOS (iNOS; type II NOS). In 1990 Bredt and Synder (1) succeeded in developing antibodies to rat brain NOS (nNOS) and used immuncytochemistry subsequently to furnish one of the first anatomical descriptions of the distribution and localization of nNOS. Today numerous antibodies to all three NOS isoforms isolated from various tissues and different animal species are available and the application of immunocytochemistry is commonplace in the investigation of NOS in healthy and diseased tissues including human (2-6) (Fig. 1 Fig. 2 Fig. 3).
 ...
PMID:Immunochemical detection of nitric oxide synthase in human tissue. 2134 Sep 71