Dataset Information

Microdistribution of MC1R-targeted polyplexes in murine melanoma tumor tissue.

ABSTRACT: Targeted sodium-iodide symporter (NIS) gene transfer can be considered as a promising approach for diagnostics of specific types of cancer. For this purpose we used targeted polyplexes based on PEI-PEG-MC1SP block-copolymer containing MC1SP-peptide, a ligand specific for melanocortin receptor-1 (MC1R) overexpressed on melanoma cells. Targeted polyplexes demonstrated enhanced NIS gene transfer compared to non-targeted (lacking MC1SP) ones in vitro. Using dorsal skinfold chamber and intravital microscopy we evaluated accumulation and microdistribution of quantum dot-labeled polyplexes in tumor and normal subcutaneous tissues up to 4 h after intravenous injection. Polyplexes demonstrated significantly higher total accumulation in tumor tissue in comparison with subcutaneous ones (control). Targeted and non-targeted polyplexes extravasated and penetrated into the tumor tissue up to 20 ?m from the vessel walls. In contrast, in normal subcutaneous tissue polyplexes penetrated not more than 3 ?m from the vessel walls with the level of extravasated polyplexes 400-fold less than in tumor. Accumulated polyplexes in tumor tissue caused NIS gene expression. Subsequent (123)I(-) intravenous injection resulted in 6.8 ± 1.1 and 4.5 ± 0.8% ID/g (p < 0.001) iodide accumulation in tumors in the case of targeted and non-targeted polyplexes, respectively, as was shown using SPECT/CT.

SUBMITTER: Durymanov MO

PROVIDER: S-EPMC3796774 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Microdistribution of MC1R-targeted polyplexes in murine melanoma tumor tissue.

Durymanov Mikhail O MO Slastnikova Tatiana A TA Kuzmich Alexey I AI Khramtsov Yuri V YV Ulasov Alexey V AV Rosenkranz Andrey A AA Egorov Sergey Y SY Sverdlov Eugene D ED Sobolev Alexander S AS

Biomaterials 20130927 38

Targeted sodium-iodide symporter (NIS) gene transfer can be considered as a promising approach for diagnostics of specific types of cancer. For this purpose we used targeted polyplexes based on PEI-PEG-MC1SP block-copolymer containing MC1SP-peptide, a ligand specific for melanocortin receptor-1 (MC1R) overexpressed on melanoma cells. Targeted polyplexes demonstrated enhanced NIS gene transfer compared to non-targeted (lacking MC1SP) ones in vitro. Using dorsal skinfold chamber and intravital mic ...[more]

PMID: 24075405

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Project description:Importance:We previously reported that survival is poorer from histopathologically amelanotic than pigmented melanoma because of more advanced stage at diagnosis. Identifying patients at risk of amelanotic melanoma might enable earlier diagnosis and improved survival; however, the phenotypic characteristics and underlying genetics associated with amelanotic melanoma are unknown. Objective:To determine whether phenotypic characteristics, carriage of MC1R variants, and history of amelanotic melanoma are associated with histopathologically amelanotic melanoma. Design, Setting, and Participants:The Genes, Environment, and Melanoma (GEM) study is an international cohort study that enrolled patients with incident primary cutaneous melanomas from population-based and hospital-based cancer registries (1998 to 2003). The GEM participants included here were 2387 patients with data for phenotypes, MC1R genotype, and primary melanomas scored for histopathologic pigmentation. Of these 2387 patients with incident melanomas scored for pigmentation, 527 had prior primary melanomas also scored for pigmentation. Main Outcomes and Measures:Associations of phenotypic characteristics (freckles, nevi, phenotypic index) and MC1R status with incident amelanotic melanomas were evaluated using logistic regression models adjusted for age, sex, study center, and primary status (single or multiple primary melanoma); odds ratios (ORs) and 95% CIs are reported. Association of histopathologic pigmentation between incident and prior melanomas was analyzed using an exact logistic regression model. Results:This study included 2387 patients (1065 women, 1322 men; mean [SD] age at diagnosis, 58.3 [16.1] years) and 2917 primary melanomas. In a multivariable model including phenotypic characteristics, absence of back nevi, presence of many freckles, and a sun-sensitive phenotypic index were independently associated with amelanotic melanoma. Carriage of MC1R variants was associated with amelanotic melanoma but lost statistical significance in a model with phenotype. Further, patients with incident primary amelanotic melanomas were more likely to have had a prior primary amelanotic melanoma (OR, 4.62; 95% CI, 1.25-14.13) than those with incident primary pigmented melanomas. Conclusions and Relevance:Absence of back nevi, presence of many freckles, a sun-sensitive phenotypic index, and prior amelanotic melanoma increase odds for development of amelanotic melanoma. An increased index of suspicion for melanoma in presenting nonpigmented lesions and more careful examination for signs of amelanotic melanoma during periodic skin examination in patients at increased odds of amelanotic melanoma might lead to earlier diagnosis and improved survival.

Dataset Information

Microdistribution of MC1R-targeted polyplexes in murine melanoma tumor tissue.

Publications

Microdistribution of MC1R-targeted polyplexes in murine melanoma tumor tissue.

Similar Datasets

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