In conclusion, the frequency of genetic variants in the IL-10 gene promoter was not associated with melanoma appearance, but conditioned the age at diagnosis in males and the overall survival in patients with advanced disease.
Although our findings need to be confirmed by independent and larger multicenter studies, we have described for the first time the association of distal gene variants of the IL-10 gene as an independent risk factor for melanoma.
This meta-analysis showed that the -592A/C and 1082G/AIL-10 polymorphisms might not be risk factors for melanoma or for BCC and sSCC patients, but we obtained a correlation between skin cancer risk and the IL-10 -819T/C polymorphism.
We analyzed the frequency of the ATA haplotype formed by the alleles at -1082 (G/A), -819 (C/T), and -592 (C/A) at the promoter region of the IL-10 gene in patients with melanoma (n = 108) and healthy subjects (n = 393).
Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) is a unique member of the IL-10 gene family that displays nearly ubiquitous cancer-specific toxicity, with no harmful effects toward normal cells or tissues. mda-7/IL-24 was cloned from human melanoma cells by differentiation induction subtraction hybridization (DISH) and promotes endoplasmic reticulum (ER) stress culminating in apoptosis or toxic autophagy in a broad-spectrum of human cancers, when assayed in cell culture, in vivo in human tumor xenograft mouse models and in a Phase I clinical trial in patients with advanced cancers.
Melanoma differentiation-associated gene (MDA)-7)/interleukin (IL)-24, a member of the IL-10 family of cytokines, inhibits growth of various human cancer cells, yet the underlying mechanism is largely unknown.
The analysis of IL-10 promoter -1082 polymorphism in the sixteen patients showed a positive correlation between AA genotype, accompanied by lower in vitro IL-10 production by stimulated PBMC, and faster melanoma progression after lymph nodes surgery (p = 0.04).
The analysis of IL-10 promoter -1082 polymorphism in the sixteen patients showed a positive correlation between AA genotype, accompanied by lower in vitro IL-10 production by stimulated PBMC, and faster melanoma progression after lymph nodes surgery (p = 0.04).
Mda-7 or IL-24, a novel member of the IL-10 cytokine family has growth inhibitory effect on several human cancers including melanoma via selective apoptosis.
These data indicate that investigation of polymorphisms in the regulatory regions of IL10, IL6 and INFgamma genes does not seem to be useful for predicting the risk of development of primary cutaneous melanoma.
Melanoma differentiation associated gene-7 (<i>mda-7/IL-24</i>) is a member of the IL-10 family of cytokines, with ubiquitous direct and "bystander" tumor-selective killing properties.
We analyzed the frequency of the ATA haplotype formed by the alleles at -1082 (G/A), -819 (C/T), and -592 (C/A) at the promoter region of the IL-10 gene in patients with melanoma (n = 108) and healthy subjects (n = 393).
The treatment by gavage with a mixture of fish and soybean oils (1:1 ratio) both reduced the melanoma growth and the levels of leukotriene B<sub>4</sub> (LTB<sub>4</sub>), prostaglandin E<sub>2</sub> (PGE<sub>2</sub>), PGE<sub>2</sub>/prostaglandin E<sub>3</sub> (PGE<sub>3</sub>) ratio, and CXC ligand 1 (CXCL1) and increased the levels of interleukin 10 (IL-10) to IL-10/CXCL1 ratio in the melanoma microenvironment.
The main predisposition of PMN formation in melanoma lies in the pulmonary recruitment of granulocytic myeloid-derived suppressor cells (G-MDSCs, CD11b<sup>+</sup>Ly6G<sup>+</sup> cells) induced by tumors, which increase vascular permeability by secreting matrix metalloproteinase-9 (MMP-9) and result in immunosuppression by secreting interleukin-10 (IL-10) in premetastatic lungs.
These results indicate that Wnt/β-catenin pathways in human melanoma may be involved in immunosuppression and immunoresistance in both induction and effector phases of antitumor immunoresponses partly through IL-10 production, and they may be attractive targets for restoring immunocompetence in patients with Wnt/β-catenin-activated melanoma.
Recombinant IL-10 and melanoma supernatants were found to inhibit production of TNF-alpha, IFN-gamma, IL-2 and mixed lymphocyte reactions but reversal of these effects of melanoma supernatants by MAbs against IL-10 was only seen in the case of TNF-alpha production.
We show that IL-10 gene silenced DC produces more IL-12 and also generates a better cytolytic T cell response against the human melanoma associated epitope, MART-1(27-35), in vitro.
The tumorigenicity of the human melanoma A375SM and the murine melanoma B16-BL6 cells was also significantly inhibited when they were admixed with A375P-IL-10 but not with A375P-Hygro before s. c. injection into nude mice.
Other studies have provided evidence that interleukin-10 (IL-10) neutralizing antibodies (αIL-10) enhance immunologic melanoma therapies by modulating the tolerogenic tumor microenvironment.
Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) is a unique member of the IL-10 gene family that induces cancer-selective growth suppression and apoptosis in a wide spectrum of human cancers in cell culture and animal models.
Melanoma differentiation associated gene-7/Interleukin-24 (MDA-7/IL-24) is a novel member of the IL-10 gene family that selectively induces apoptosis and toxic autophagy in a broad spectrum of human cancers, including breast cancer, without harming normal cells or tissues.