Cap43 has been identified as a nickel-and calcium-induced gene, and is also known as N-myc downstream-regulated gene 1 (NDRG1), Drg-1 and rit42. It is also reported that overexpression of Cap43 suppresses metastasis of some malignancies, but its precise role remains unclear. In this study, we asked how Cap43 could modulate the tumor growth of pancreatic cancer. Stable Cap43 cDNA transfectants of pancreatic cancer cells with Cap43 overexpression showed similar growth rates in culture as their control counterparts with low Cap43 protein level. By contrast, Cap43 overexpression showed a marked decrease in tumor growth rates in vivo. Moreover, a marked reduction in tumor-induced angiogenesis was observed. Gelatinolytic activity by matrix metalloproteinase-9 and invasive ability in Matrigel invasion activity were markedly decreased in pancreatic cancer cell lines with high Cap43 expression. Cellular expression of matrix metalloproteinase-9 and two major angiogenic factors, vascular endothelial growth factor and interleukin-8, were also significantly decreased in cell lines with Cap43 overexpression as compared with their parental counterparts. Immunohistochemical analysis of specimens from 65 patients with pancreatic ductal adenocarcinoma showed a significant association between Cap43 expression and tumor microvascular density (P = 0.0001) as well as depth of invasion (P = 0.0003), histopathologic grading (P = 0.0244), and overall survival rates for patients with pancreatic cancer (P = 0.0062). Thus, Cap43 could play a key role in the angiogenic on-or offswitch of tumor stroma in pancreatic ductal adenocarcinoma.
Methylglyoxal (MG) is a physiological metabolite, but it is known to be toxic, inducing stress in cells and causing apoptosis. This study examines molecular mechanisms in the MG-induced signal transduction leading to apoptosis, focusing particularly on the role of JNK activation. We first confirmed that MG caused apoptosis in Jurkat cells and that it was cell type dependent because it failed to induce apoptosis in MOLT-4, HeLa, or COS-7 cells. A caspase inhibitor, Z-DEVD-fmk, completely blocked MG-induced poly(ADP-ribose)polymerase (PARP) cleavage and apoptosis, showing the critical role of caspase activation. Inhibition of JNK activity by a JNK inhibitor, curcumin, remarkably reduced MG-induced caspase-3 activation, PARP cleavage, and apoptosis. Stable expression of the dominant negative mutant of JNK also protected cells against apoptosis notably, although not completely. Correspondingly, loss of the mitochondrial membrane potential induced by MG was decreased by the dominant negative JNK. These results confirmed a crucial role of JNK working upstream of caspases, as well as an involvement of JNK in affecting the mitochondrial membrane potential.
A quantitative infrared spectroscopic study of a model urethane‐type compound was carried out in order to obtain basic data on hydrogen bonding in polyurethanes. First, the absolute intensity of free NH groups of N‐phenylurethane, which was adopted as the model urethane, was determined by Wilson‐Wells' method to be 3.59 × 103l./mole‐cm.2. The free NH of this urethane absorbed at 3447 cm.−1, and hydrogen‐bonded NH absorbed near 3300 cm.−1. Then, the extents of hydrogen bonding of the urethane at various concentrations were determined, and the hydrogen bonding between the urethane and ethers was studied by using the above‐mentioned absolute intensity. For comparison, diphenylamine was also used as proton donor. Di‐n‐butyl ether and poly‐(oxyethylene glycol) were examined and proved to be able to act as proton acceptors. The frequency shifts of NH stretching vibration of diphenylamine and N‐phenylurethane caused by hydrogen bonding with di‐n‐butyl ether were 96 cm.−1 and 150 cm.−1, respectively. The equilibrium constants were 4.8 × 10−1l./mole for the former system 4.6 × 10−1l./mole for the latter.
We retrospectively studied the cytological features of aspiration cytology in 12 cases of basal cell adenoma (BCA) and 5 cases mistakenly diagnosed as BCA. On macroscopic findings, the 12 cases of BCA included 7 cases of solid type and 5 cases of cystic type. The characteristic cytological features of solid type BCA were three-dimensional clusters in 71%, sharp-angle small clusters in 86%, basement membrane- like material in 71%, and cell crush in 86%. In contrast, 3 of the 5 cystic type BCA cases showed inadequate cellular components or no basaloid tumor cells, and the cytological diagnosis of BCA could not be determined. In the 5 cases misdiagnosed as BCA, there were 2 cases of pleomorphic adenoma, 2 cases of benign lymphoepithelial cyst, and 1 case of basal cell adenocarcinoma. Accurate differential cytological diagnosis of BCA is relatively easy to determine the solid type BCA, but is more difficult for cystic type BCA.
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