Anti-CASP9 polyclonal antibody

Adenoid cystic carcinoma (ACC) of the head and neck is a malignant tumor with poor long-term prognosis. Besides the recently identified MYBNFIB fusion oncogene generated by a t(6;9) translocation, little is known about other genetic alterations in ACC. Using high-resolution, array-based comparative genomic hybridization, and massively paired-end sequencing, we explored genomic alterations in 40 frozen ACCs. Eighty-six percent of the tumors expressed MYBNFIB fusion transcripts and 97% overexpressed MYB mRNA, indicating that MYB activation is a hallmark of ACC. Thirty-five recurrent copy number alterations (CNAs) were detected, including losses involving 12q, 6q, 9p, 11q, 14q, 1p, and 5q and gains involving 1q, 9p, and 22q. Grade III tumors had on average a significantly higher number of CNAs/tumor compared to Grade I and II tumors (P = 0.007). Losses of 1p, 6q, and 15q were associated with high-grade tumors, whereas losses of 14q were exclusively seen in Grade I tumors. The t(6;9) rearrangements were associated with a complex pattern of breakpoints, deletions, insertions, inversions, and for 9p also gains. Analyses of fusion-negative ACCs using high-resolution arrays and massively paired-end sequencing revealed that MYB may also be deregulated by other mechanisms in addition to gene fusion. Our studies also identified several down-regulated candidate tumor suppressor genes (CTNNBIP1, CASP9, PRDM2, and SFN) in 1p36.33-p35.3 that may be of clinical significance in high-grade tumors. Further, studies of these and other potential target genes may lead to the identification of novel driver genes in ACC. (c) 2012 Wiley Periodicals, Inc.

Exposure to ZnO nanoparticles (NPs) might modulate endoplasmic reticulum (ER) stress-autophagy gene expression, but the possible influence of hydrophobic surface coating on these responses was less studied. This study used A549-macrophage co-culture as the in vitro model for lung barrier and investigated the toxicity of pristine and hydrophobic ZnO NPs. Pristine and hydrophobic NPs exhibited different Zeta potential and solubility in water, which suggested that hydrophobic surface coating might alter the colloidal aspects of ZnO NPs. However, pristine and hydrophobic ZnO NPs induced cytotoxicity and reduced the release of soluble monocyte chemotactic protein-1 (sMCP-1) in A549-macrophage co-culture to a similar extent. Exposure to pristine ZnO NPs significantly promoted the expression of ER stress-apoptosis genes, namely DDIT3, XBP-ls, CASP9, CASP12 and BAX (p < 0.05), but hydrophobic ZnO NPs only significantly promoted the expression of BAX (p < 0.05). Exposure to pristine ZnO NPs also significantly reduced the expression of autophagic gene BECN1 (p < 0.05) but not ATG7 (p > 0.05), whereas hydrophobic ZnO NPs significantly reduced the expression of ATG7 and BECN1 (p < 0.01). Moreover, the expression of XBP-ls, HSPA5, CASP9, CASP12, BAX and ATG7 in pristine ZnO NP-exposed co-culture was significantly lower than that in hydrophobic ZnO NP-exposed co-culture (p < 0.05). In conclusion, hydrophobic surface coating might influence the colloidal aspects of ZnO NPs and alter ER stress-apoptosis-autophagy gene expression pattern by pristine ZnO NPs in A549-macrophage co-culture.