Long-term skeletal stability after maxillary advancement with distraction osteogenesis in cleft lip and palate patients: A systematic review

Objective:To systematically review the long-term skeletal stability after maxillary advancement with distraction osteogenesis (DO) in cleft lip and palate (CLP) patients.Materials and Methods:Electronic databases, grey literature, and reference list searches were conducted. The inclusion criteria were stability of maxillary advancement with distraction osteogenesis assessed at the posttreatment follow-up ≥ 1 year in CLP patients. Full articles were retrieved from abstracts or titles that appear to meet the inclusion criteria or lacked sufficient detail for immediate exclusion. Once full articles were collected, they were again reviewed considering more detailed inclusion criteria for a final selection decision. A methodologic quality assessment tool was utilized.Results:Thirty abstracts/titles met the initial search criteria, and 13 articles were finally selected. Overall, methodologic quality scores were high in only one randomized clinical trial. After maxillary advancement with DO in CLP patients, the long-term horizontal relapse in A-point was less than 15% in eight studies and between 20% and 25% in four studies. The study that was judged as a high-quality study reported 8.2% horizontal relapse in A-point. The relapse rate was higher in DO with external distracter device than DO with internal distracter device.Conclusions:Current evidence suggests maxillary advancement with DO has good stability in CLP patients with moderate and severe maxillary hypoplasia.     

Induction of GDF-15/NAG-1/MIC-1 in human lung carcinoma cells by retinoid-related molecules and assessment of its role in apoptosis

Growth and Differentiation Factor-15 (GDF-15, NAG-1, MIC-1) is induced by several apoptosis-inducing agents including the retinoid-related molecule (RRM) 6-[3-(1-adamantyl-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437). It has been suggested that GDF-15 may be involved in the induction of apoptosis by CD437 in H460 lung cancer cells. The present study was designed to probe this hypothesis more directly. Several RRMs (CD437, ST1926 and MX3350-1) but not the retinoids all-trans- retinoic acid and 4HPR were able to induce GDF-15 in H460 cells. A similar differential effect of these retinoids was observed for the induction of p53, which has been reported to regulate GDF-15 expression. In H460 cells transfected with a neo vector control (H460-Neo), treatment with RRMs but not ATRA or 4HPR resulted in increases in p53, GDF-15 and apoptosis evidenced by poly(ADP ribose) polymerase (PARP) cleavage. In contrast, RRMs failed to increase p53 or induce apoptosis in H460 cells in which p53 was inactivated by transfection of the human papillomavirus E6-6 (H460-E6-6). The increase in GDF-15 by RRMs was also compromised in the H460-E6-6 cells. Because PARP cleavage was only evident when GDF-15 levels where elevated it appeared that GDF-15 was mediating the pro-apoptotic effects of RRMs. However, silencing of GDF-15 induction by RNA interference failed to decrease the ability of CD437 and ST1926 to induce apoptosis. These results demonstrate that GDF-15 is dispensable for the pro-apoptotic activity of CD437 and ST1926.     

Involvement of Rac in fenretinide-induced apoptosis

The synthetic retinoid N-(4-hydroxyphenyl)retinamide (4HPR) has shown potential as a chemopreventive and therapeutic agent. The ability of 4HPR to enhance production of reactive oxygen species (ROS) leading to apoptosis has been suggested as a possible mechanism underlying these effects. We explored the possibility that ROS induction by 4HPR involves the small GTPase Ras-related C3 botulinum toxin substrate (Rac), a regulatory subunit of the NADPH oxidase complex. Rac was activated in human head and neck squamous cell carcinoma (HNSCC) cells as early as 5 minutes following 4HPR exposure. Moreover, inhibition of Rac activity or silencing of its expression by RNA interference decreased ROS generation in human head and neck, lung, and cervical cancer cells and murine melanoma cells. In HNSCC UMSCC-22B cells, this decrease correlated with reduction in apoptosis induction by 4HPR. Expression of a constitutive active mutant Rac increased basal and 4HPR-induced ROS generation and poly(ADP-ribose) polymerase cleavage. In addition, the metastatic DM14 cells exhibited higher Rac activation following 4HPR treatment compared with the primary Tu167-C2 cells. Furthermore, the metastatic cancer cells tested exhibited higher ROS generation and growth inhibition due to 4HPR exposure compared with their primary cancer cell counterparts. These findings show a preferential susceptibility of metastatic cells to the proapoptotic retinoid 4HPR through Rac activation and support the use of ROS-inducing agents such as 4HPR against metastatic cancer cells.     

Schizanthines N, O, and P, tropane alkaloids from the aerial parts of Schizanthus tricolor

Three tropane alkaloids, named schizanthines N, O, and P (1-3), have been isolated from the crude alkaloid extract of the endemic Chilean plant Schizanthus tricolor. On the basis of extensive NMR studies and MS fragmentation analysis, their structures were determined to be 3α-(E)-4-hydroxysenecioyloxy-6β-angeloyloxytropane (1), 3α-(E)-4-hydroxysenecioyloxy-6β-senecioyloxytropane (2), and 3α-mesaconyloxy-6β-senecioyloxytropane (3). Compounds 1 and 2 are the first isomeric alkaloids in the tropane series possessing a hydroxysenecioyl substituent as an esterifying moiety.     

Involvement of mitochondrial and Akt signaling pathways in augmented apoptosis induced by a combination of low doses of celecoxib and N-(4-hydroxyphenyl) retinamide in premalignant human bronchial epithelial cells

Celecoxib is being evaluated as a chemopreventive agent. However, its mechanism of action is not clear because high doses were used for in vitro studies to obtain antitumor effects. We found that celecoxib inhibited the growth of premalignant and malignant human bronchial epithelial cells with IC(50) values between 8.9 and 32.7 micromol/L, irrespective of cyclooxygenase-2 (COX-2) expression. Normal human bronchial epithelial cells were less sensitive to celecoxib. Because these concentrations were higher than those attainable in vivo (相似文献