Our previous work showing that reducing M3R expression and activation attenuates intestinal epithelial cell proliferation and neoplasia in both Apc min/+ [ 4] and azoxymethane (AOM) [ 5] murine models supports a functional role for M3R expression and activation in colon cancer.
Here we described for the first time a murine model supporting the engraftment human MM cells, and allowing for the development of a disease involving multiple sites, similar to that observed in patients [ 65- 73].
Multiple in vivo MYC-overexpression cancer murine models further support MYC as a therapeutic target [ 44].
Evidence from murine models also supports an immunoregulatory role for NK cells in modulating other immune cell responses (Fig. 2b).
The behaviour of mutant BRAF melanomas in murine xenograft models supported these preclinical findings and confirmed mutant BRAF as an attractive target for melanoma therapy, particularly as it occurs in at least half the tumour population, and does not occur in normal cells.
Murine models initially lent support to FTO itself being the causal gene in the locus; an obesity protective phenotype was observed in the fto knock-out mouse [36] and a similar but lesser effect in the hypomorphic fto missense I367F mutant [37].
The paucity of clinical combination studies is surprising, in view of murine models that strongly support their rationale (Schrayer et al, 2002; Overwijk et al, 2003).
This is consistent with previous studies in the murine model and supports the view that platelets are involved in the neurovascular injury during CM [25],[25].
However, subcutaneous vaccination with genetically modified cytokine-secreting tumour cells has been demonstrated to be efficacious against intracranial tumours in a murine model, which supports the notion that an effective immune response can be generated against intracerebral tumours (Dranoff et al, 1993; Sampson et al, 1996).
