Basal cell carcinoma (BCC) environment consists of stromal and inflammatory cells which produce variety of cytokines, chemokines and growth factors that may affect the tumor behavior. One of the cytokines suggested to be involved in the pathogenesis of BCC is IL-6the upstream element of IL-6/JAK/STAT3 pathway. In the present study rs1800795 (-174 G/C) IL-6 gene polymorphism and STAT3 rs2293152 (intron 11, C/G) and rs4796793 (e1697, C/G) polymorphisms were assessed in relation to the BCC risk and clinical course. Additionally, IL-6 serum level was assessed in relation to IL-6 genotype and clinical variables. The study included 254 unrelated BCC patients (mean age 70.39AE11.43) and 198 healthy, unrelated age-and sex-matched volunteers. We have found that the presence of C allele in rs1800795 IL-6 gene polymorphism was associated with increased risk of BCC (aOR: 1.86; 95% CI¼1.22-2.84; p¼0.004). The presence of CC genotype in STAT3 rs2293152 polymorphism was associated with increased BCC risk in recessive model analysis (aOR¼3.94; 95% CI: 1.59-9.77; p¼0.003). In contrast, the presence of GC genotype in overdominant model was associated with decreased risk of BCC (aOR¼0.24; 95% CI:0.12-0.49; p<0.0001). The presence of C allele in STAT3 rs2293152 polymorphism was associated with increased risk of BCC (aOR: 1.31; 95% CI:1.01-1.69; p¼0.04). The presence of GG genotype in STAT3 rs4796793 polymorphism was associated with increased BCC risk in recessive model analysis (aOR¼3.66; 95%
Gold (Au) and silver (Ag) are known to be important contact metals on YBa2Cu3O7−x (YBCO). Both metals have been used as additives in fabricating tapes of YBCO and Bi2Sr2CaCu2O8 (BSCCO) materials, and have favorable results in improving not only the flexibility but also the weighted critical currents of the resulting composites. Previous results on superconductor/normal metal/superconductor junctions made using YBCO/Au/YBCO and YBCO/Au/Nb demonstrated that a supercurrent can be induced in the normal metal layers through the proximity effect. Our transmission electron microscopy study of the Au/YBCO interfaces shows a well-bonded interface with no extraneous phases present. Lattice fringes of the (001) plane in YBCO terminated at the interface abruptly. This observation supports previous results of contact resistance of x-ray photoelectron spectroscopy (XPS). Both (001) integral steps and multiples of 1/3 (001) steps were observed at the Au/YBCO interface. When the top gold layer was absent locally, surface degradation was observed as the (001) lattice fringes stopped short from the surface by 10 nm. Our results support that Au is a desirable contact metal and a dependable surface passivation material for YBCO.
Facial angiofibromas (AF) and fibrous cephalic plaques (FCP) are typical skin lesions in tuberous sclerosis complex (TSC) that contain TSC2-null fibroblast-like cells with overactivation of mTORC1 signaling. To identify paracrine factors important in TSC tumorigenesis, we used transcriptomic analysis of cells incubated with or without the mTOR inhibitor rapamycin (20 nM), using TSC2-null fibroblasts from AFs and FCPs with paired TSC fibroblasts from normalappearing skin from 4 patients. Unbiased hierarchical clustering identified a group of genes whose expression levels were greater in tumor than normal fibroblasts and negatively regulated by rapamycin. CXCL12 was selected for further study since CXCL12 has been implicated in angiogenesis and cancer. CXCL12 protein levels were measured using ELISA in culture supernatants of TSC2-null tumor cells derived from 4 AFs and 3 FCPs as well as the patient normal fibroblasts. CXCL12 protein released into the media by tumor cells over 24 hours averaged 4.6-fold more than patient normal fibroblasts (p¼0.03). Levels of CXCL12 released by FCP cells into media was decreased by 49% with rapamycin (20 nM) treatment for 24 hours. To further study CXCL12 in TSC, we used our mouse model with conditional knockout of Tsc2 in limb bud and ventral skin mesenchyme using homozygous Tsc2 floxed alleles and the Prrx1-cre transgene (termed here Tsc2cKO mice). Tsc2-null dermal fibroblasts isolated from ventral skin of Tsc2cKO mice released 2.9-fold more CXCL12 into media than fibroblasts from control mice. Levels of CXCL12 in the sera of 3.5 weeks old Tsc2cKO mice were 1.7-fold higher than in the sera of control mice (p¼0.01). These results suggest that CXCL12 overexpressed by TSC2-null fibroblasts may serve as a paracrine factor in TSC tumorigenesis.
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