Transparent PDMS Surfaces with Covalently Attached Lubricants for Enhanced Anti-adhesion Performance.

Liquid-like surfaces featuring slippery, omniphobic, covalently attached liquids (SOCALs) reduce unwanted adhesion by providing a molecularly smooth and slippery surface arising from the high mobility of the liquid chains. Such SOCALs are commonly prepared on hard substrates, such as glass, wafers, or metal oxides, despite the importance of nonpolar elastomeric substrates, such as polydimethylsiloxane (PDMS) in anti-fouling or nonstick applications. Compared to polar elastomers, hydrophobic PDMS elastomer activation and covalent functionalization are significantly more challenging, as PDMS tends to display fast hydrophobic recovery upon activation as well as superficial cracking. Through the extraction of excess PDMS oligomers and fine-tuning of plasma activation parameters, homogeneously functionalized PDMS with fluorinated polysiloxane brushes could be obtained while at the same time reducing crack formation. Polymer brush mobility was increased through the addition of a smaller molecular silane linker to exhibit enhanced dewetting properties and reduced substrate swelling compared to functionalizations featuring hydrocarbon functionalities. Linear polymer brushes were verified by thermogravimetric analysis. The optical properties of PDMS remained unaffected by the activation in high-frequency plasma but were impacted by low-frequency plasma. Drastic decreases in solid adhesion of not just complex contaminants but even ice could be shown in horizontal push tests, demonstrating the potential of SOCAL-functionalized PDMS surfaces for improved nonstick applications.

A multigenic approach to predict breast cancer risk.

In the biology of complex disorders, such as breast cancer, interactions among genetic factors may play an important role and theoretical considerations suggest that gene-gene interactions are quite common in such diseases. In this case-control study with 500 breast cancer patients and 500 population-based healthy sex- and age-matched control subjects, we applied a multigenic approach to examine the associations with breast cancer risk of a comprehensive panel of 16 selected polymorphisms in a variety of pathways using classification tree analysis (CART). Overall, 79.6% of all breast cancer patients and 80.6% of all control subjects were correctly classified on the basis of their individual genetic profile by the classification procedure. CART analysis of the data identified the heterozygous vascular endothelial growth factor (VEGF) and matrix metalloproteinase 3 (MMP3) genotype and homozygous cyclooxygenase-2 (PTGS2) mutant as the initial splits, indicating that these genotypes exert the greatest impact on the classification process. Breast cancer patients were primarily indicated by 30 distinct genetic profiles. The odds ratio of these genetic risk profiles for breast cancer was 16.12 (95% confidence interval 11.09-23.49). Five genetic profiles formed homogenous breast cancer subgroups and represented highest risk genetic profiles. This is the first comprehensive study to use a multigenic analysis for breast cancer and the data suggest that individuals with distinct genetic profiles are at an increased risk for breast cancer, confirming the importance of taking a multigenic approach for risk assessment.

Interleukin-10 [ATA] promoter haplotype and prostate cancer risk: a population-based study.

Interleukin-10 (IL-10) is a multifunctional cytokine acting as inhibitor of inflammatory and immune responses as well as tumour induced angiogenesis. A common [ATA] haplotype formed by polymorphisms at positions -1082, -819 and -592in the promoter of the IL-10 gene is a strong determinant for IL-10 expression. The presence of this haplotype can be determined by analysis of the -592C>A polymorphism. To analyse the role of the IL-10 [ATA] haplotype in prostate cancer we performed a case-control study including 561 prostate cancer patients and 561 male, age-matched, control subjects without malignant disease. The IL-10 -592C>A polymorphism was determined by a 5'-nuclease assay (TaqMan). IL-10 -592 CC, CA and AA genotype frequencies were not significantly different between patients (53.6%, 40.0%, 6.4%) and controls (54.3%, 39.6%, 6.1%; p=0.96). IL-10 genotypes were furthermore not associated with tumour characteristics such as histological grade, T stage, PSA levels at diagnosis, or age at diagnosis. Therefore we conclude that the IL-10 -592C>A promoter polymorphism, tagging the IL-10 low-producer [ATA] haplotype, is not associated with risk for prostate cancer.

The cyclooxygenase-2 (PTGS2) 8473T>C polymorphism is associated with breast cancer risk.

Cyclooxygenase-2 (COX-2) is involved in carcinogenesis, immune response suppression, apoptosis inhibition, angiogenesis, and tumor cell invasion and metastasis. The gene for COX-2, designated as PTGS2, carries a common polymorphism at position 8473 in the 3'-untranslated region (PTGS2 8473T>C), which has been associated with susceptibility to malignant disease. To investigate the role of this polymorphism for breast cancer, we determined the prevalence of PTGS2 genotypes in 500 women with breast cancer and 500 sex- and age-matched healthy control subjects. Homozygous carriers of the 8473-CC genotype were more frequent among patients (12.4%) than among controls (6.6%; P = 0.002). The odds ratio for carriers of this genotype for breast cancer was 2.1 (95% confidence interval, 1.3-3.3). Among patients, estrogen receptor positivity was less frequent among carriers of a CC genotype (63.9%) than among carriers of a TT or TC genotype (76.9%; P = 0.028). Tumor size, histologic grade, presence of primary lymph node metastases, progesterone receptor positivity, or age at diagnosis were not associated with PTGS2 genotypes. We conclude that the homozygous PTGS2 8473-CC genotype may be associated with breast cancer risk.

Integrin alpha-2 and beta-3 gene polymorphisms and breast cancer risk.

Integrins are cell surface receptors, which mediate cell-to-cell and cell-to-extracellular matrix adhesion. Some of them, e.g. alpha(V)beta(3), alpha(IIb)beta(3) and alpha(2)beta(1), have been suggested as key players for cancer development and tumor metastasis. Two polymorphisms in the gene for the alpha(2) component, ITGA2 807C>T and 1648G>A, have been associated with the cell-surface density of integrin alpha(2)beta(1). The 176T>C polymorphism in the ITGB3 gene, encoding the beta(3) subunit of integrins alpha(IIb)beta(3) and alpha(V)beta(3), modifies a variety of traits of beta(3) expressing cells. To analyze the role of ITGA2 and ITGB3 polymorphisms for breast cancer risk and prognosis, we performed a case-control study including 500 female breast cancer patients and 500 healthy female age-matched control subjects. All study participants were of Caucasian origin (Austria, Middle-Europe). The ITGA2 1648_AA genotype was significantly associated with breast cancer (odds ratio 3.12; 95% confidence interval 1.11-8.77). Carriers of the most common ITGA2 haplotype (807C_1648G, 'wildtype') were at decreased risk for breast cancer (odds ratio 0.72; 95% confidence interval 0.53-0.98). A histological grade of 3 or 4 was found more often in ITGA2 807TT subjects (p=0.039 compared to CC+CT genotypes) and carriers of an ITGA2 1648A allele (p=0.017 compared to GG genotype). Carriers of the ITGA2 807C_1648G haplotype were less likely to have a histological grade 3 or 4 compared to non-carriers (p=0.003). The ITGB3 176T>C polymorphisms was not associated with breast cancer susceptibility. In a Cox-regression analysis, carriers of the homozygous ITGB3 176-CC genotype had a higher risk for metastasis (relative risk 2.3; 95% CI 1.3-4.2; p=0.005). We conclude that functional polymorphisms in integrin genes ITGA2 and ITGB3 influence the development and progression of breast cancer, respectively. The precise mechanism remains to be determined, but likely involves dysregulated signaling pathways.

Interleukin-10 promoter polymorphism is associated with decreased breast cancer risk.

Interleukin-10 (IL-10) is an immunosuppressive cytokine which may facilitate development of cancer by supporting tumor escape from the immune response. A [TCATA] haplotype formed by polymorphisms at positions -3575, -2763, -1082, -819 and -592 in the promoter of the IL-10 gene is a strong determinant for IL-10 expression. The presence of this haplotype can be determined by analysis of the -592C > A polymorphism. Aim of the present study was to analyze the role of the IL-10 [TCATA] haplotype for breast cancer. We performed a case-control study including 500 female patients with histologically confirmed breast cancer and 500 female, age-matched, healthy control subjects from population-based screening studies. The -592C > A polymorphism was determined by a 5'-nuclease assay (TaqMan). Frequency of the homozygous -592 AA genotype, indicating homozygosity for the [TCATA] haplotype, was 4.2% among patients and 7.3% among controls (p=0.038; odds ratio 0.56; 95% confidence interval 0.32-0.97). IL-10 genotypes were not associated with tumor size, histological grading, estrogen or progesterone receptor status and age at diagnosis. Therefore we conclude that the IL-10 -592C > A promoter polymorphism may be associated with a reduced breast cancer risk.

Genetic variants of the sulfotransferase 1A1 and breast cancer risk.

Sulfotransferase 1A1 (SULT1A1), also designated as phenol-preferring sulfotransferase, is involved in the bioactivation and detoxification of a variety of potential carcinogens, including iodothyronines, hydroxylated aromatic amines, and phenolic xenobiotics. A common arginine (R) to histidine (H) polymorphism at amino acid position 213 influences SULT1A1 activity and has been suggested as risk factor for a different types of cancers. To investigate the role of this polymorphism for breast cancer risk, SULT1A1 genotype was determined in 500 women with clinically verified breast cancer and 500 female age-matched healthy control subjects. Frequencies of heterozygous (controls: 42.5% patients: 50.2%) or homozygous (controls: 12.6%; patients: 9.4%) carriers of the 213H variant were not significantly different between groups. The SULT1A1 genotype was furthermore not associated with tumor size, histological grading, estrogen or progesterone receptor status and age at diagnosis. The SULT1A1 213H variant was associated with the presence of lymph node metastases (p = 0.002). We conclude that the SULT1A1 R213H polymorphism is not a general risk factor for breast cancer, but may be involved in lymph node metastazing in breast cancer patients.