Biological Cover Mitigates Disruption of the Dermal Structure in Mechanically Expanded Skin in a Porcine Model

Tissue expansion is an integral procedure of the vast majority of breast reconstruction and has a significant impact on the final clinical outcomes. Therefore, technological advances leading to a fewer number of unfavorable outcomes and a decrease in complication rates are imperative. In this study, using a porcine model, we investigated an effect of acellular dermal matrix (ADM) used as a tissue expander cover on the dermal changes induced by mechanical forces during tissue expansion. After 14 days of expansion, skin samples were collected from one animal, while the second animal underwent radiation, and tissue was collected 8 weeks later. Tissue expanded without the use of ADM and unexpanded skin served as the controls. Collected skin biopsies were used for histological and immunohistochemical evaluation, and for gene expression analysis. We revealed that the biological cover incorporation into host tissue is facilitated by macrophages without inducing a broad inflammatory response. The utilization of ADM mitigated disruption in the dermal structure, excessive collagen deposition, and capsule formation in non-irradiated expanded skin. The protective effect was not fully maintained in irradiated skin. These results demonstrate that tissue expansion might be improved by using the tissue expander cover

Pooled sample-based GWAS: a cost-effective alternative for identifying colorectal and prostate cancer risk variants in the Polish population.

BACKGROUND: Prostate cancer (PCa) and colorectal cancer (CRC) are the most commonly diagnosed cancers and cancer-related causes of death in Poland. To date, numerous single nucleotide polymorphisms (SNPs) associated with susceptibility to both cancer types have been identified, but their effect on disease risk may differ among populations. METHODS: To identify new SNPs associated with PCa and CRC in the Polish population, a genome-wide association study (GWAS) was performed using DNA sample pools on Affymetrix Genome-Wide Human SNP 6.0 arrays. A total of 135 PCa patients and 270 healthy men (PCa sub-study) and 525 patients with adenoma (AD), 630 patients with CRC and 690 controls (AD/CRC sub-study) were included in the analysis. Allele frequency distributions were compared with t-tests and χ(2)-tests. Only those significantly associated SNPs with a proxy SNP (p<0.001; distance of 100 kb; r(2)>0.7) were selected. GWAS marker selection was conducted using PLINK. The study was replicated using extended cohorts of patients and controls. The association with previously reported PCa and CRC susceptibility variants was also examined. Individual patients were genotyped using TaqMan SNP Genotyping Assays. RESULTS: The GWAS selected six and 24 new candidate SNPs associated with PCa and CRC susceptibility, respectively. In the replication study, 17 of these associations were confirmed as significant in additive model of inheritance. Seven of them remained significant after correction for multiple hypothesis testing. Additionally, 17 previously reported risk variants have been identified, five of which remained significant after correction. CONCLUSION: Pooled-DNA GWAS enabled the identification of new susceptibility loci for CRC in the Polish population. Previously reported CRC and PCa predisposition variants were also identified, validating the global nature of their associations. Further independent replication studies are required to confirm significance of the newly uncovered candidate susceptibility loci

The GWAS-selected SNPs association with AD, CRC or PCa, considering allelic and additive models.

<p>Bold denotes significant association (<i>p</i><0.05). G1 vs. G2; compared groups of cases and controls, respectively, MA; minor allele (+) strand, F1, F2; frequency of MA in the case and control groups, respectively, OR; odds ratio, CI; confidence interval, N; control, PCa; prostate cancer, AD; adenoma, CRC; colorectal cancer, F; female, M; male.</p>a<p>^/SNP identifier based on NCBI SNP database;</p>b<p>^/NCBI ID of genes localized in proximity to the SNPs of interest (source: HapMap).</p

The literature-selected SNPs significant associations with AD, CRC or PCa, considering allelic and additive models.

<p>Bold denotes significant association (<i>p</i>-value_cor<0.05). MA; minor allele (+) strand, G1 vs. G2; compared groups of cases and controls, respectively, OR; odds ratio, CI; confidence interval, N; control, PCa; prostate cancer, AD; adenoma, CRC; colorectal cancer, F; female, M; male.</p>a<p>^/SNP identifier based on NCBI SNP database;</p>b<p>^/NCBI ID of genes localized in proximity to the SNPs of interest (source: HapMap).</p

Pooled-DNA allelotyping GWAS and technical validation of GWAS selections using individual patient TaqMan genotyping.

<p>Technical validation was performed by individual typing of DNA samples from the same study cohorts used for pooled-DNA GWAS. The allele frequency distribution and χ²-test <i>p</i>-values were taken into account. G1 vs. G2; compared groups of cases and controls, respectively, MA; minor allele (+) strand, F1, F2; frequency of MA in the case and control groups, respectively, OR; odds ratio, CI; confidence interval, N; control, PCa; prostate cancer, AD; adenoma, CRC; colorectal cancer, F; female, M; male.</p>a<p>^/SNP identifier based on NCBI SNP database;</p>b<p>^/SNP identified in two independent comparisons.</p