Therefore, we report that defects in expression or activation of Stat1 or Stat2 were infrequent in melanoma cell lines and tumor samples and did not correlate with IFN resistance.
A direct comparison of IFN-alpha and pegylated IFN-alpha did not reveal any significant differences in tumor growth inhibition indicating that this novel and more stable class of IFN is functionally equivalent.
Loss of heterozygosity (LOH) assays for three microsatellite polymorphic markers on chromosome 9p21 (IFNA and D9S171), regions of putative tumor suppressor gene p16, and on chromosome 17p13 (TP53), the p53 tumor suppressor gene locus, were done.
The IFN-alpha protein concentration was markedly increased in the injected subcutaneous tumour, but leakage of the potent cytokine into the systemic blood circulation was minimal.
In conclusion, our findings show that intracavitary IFN-alpha gene therapy, using a lentiviral vector, provides strong antitumor effects in murine models of ovarian cancer and reinforces the evidence that angiogenesis inhibition is a promising strategy for the treatment of localized tumors.
Elsewhere, we reported that multiple serial in vivo passage of a squamous cell carcinoma cells (SCC61) concurrent with ionizing radiation (IR) treatment resulted in the selection of radioresistant tumor (nu61) that overexpresses the signal transducer and activator of transcription 1 (Stat1)/IFN-dependent pathway.
Combination treatment and PEG-IFN monotherapy also significantly elevated the p53 protein and mRNA levels in the tumour but only combination treatment increased the degree of p53 phosphorylation at serine46 and induced p53-regulated apoptosis-inducing protein 1 (p53AIP1) expression.
Interestingly, the engagement of the receptor by TLR3 agonists can directly inhibit cell proliferation and induce tumor cell death when combined to treatment with either type I IFN or protein synthesis inhibitors.
The type I IFN response upon different gene transfer methods in human tumor and primary cell lines was studied by analysing IFN-beta mRNA expression, secretion of type I IFNs and accumulation of IFN-alpha/beta-induced MxA protein (myxovirus resistance protein A).
This study identified a novel role for IFN type 1 signaling as a positive regulator of neoplasia and suggests that IFN treatment is a less than optimal therapy for this tumor type.
Intravesical delivery of the gene encoding interferon results in an alternative strategy for IFN-based therapy of the disease, enabling sustained exposure of IFN protein that results from production by tumor and non-tumor cells in the urothelium.
IL-27 augmented the expression of IFN regulatory factor (IRF)-1 and IRF-8, which possess tumor suppressor activities, in B16F10 transfectants expressing wild-type WSX-1.
Recent studies have shown that the ubiquitin-like protein, IFN-stimulated gene 15 (ISG15), which is highly elevated in many human cancers and tumor cell lines, antagonizes the ubiquitin/proteasome pathway.
Cervical biopsy samples from control women or those without neoplasia or HPV infection displayed higher IFN-alpha receptor expression than those with CIN, while simultaneous expression of both IFN-alpha receptor subunits was found only in the control group.
IFN regulatory factor 8 (IRF8) has been shown to suppress tumor development at least partly through regulating apoptosis of tumor cells; however, the molecular mechanisms underlying IRF8 regulation of apoptosis are still not fully understood.
Targeted overexpression of hPNPase(old-35) might provide an effective therapeutic strategy for miR-221-overexpressing and IFN-resistant tumors, such as melanoma.
IFNgamma is an inflammatory cytokine that induces the expression and function of IFN regulatory factor 1 (IRF1), a tumor suppressor gene that can increase antiestrogen responsiveness.
These data show that Ad.IFN-α2b has potential therapeutic benefit in MPM and that it generates anti-tumor immune responses that may induce anatomic and/or metabolic reductions in distant tumor.