Acacetin inhibits TPA-induced MMP-2 and u-PA expressions of human lung cancer cells through inactivating JNK signaling pathway and reducing binding activities of NF-kappaB and AP-1.

Acacetin (5,7-dihydroxy-4'-methoxyflavone), a flavonoid compound, has antiperoxidative and antiinflammatory effects. The effect of acacetin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMPs and u-PA expressions in human lung cancer A549 cells was investigated. First, the result demonstrated acacetin could inhibit TPA-induced the abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay and Boyden chamber assay. Data also showed acacetin could inhibit phosphorylation of c-Jun N-terminal kinase 1 and 2 (JNK1/2) involved in the down-regulating protein expressions and transcriptions of matrix metalloproteinase-2 (MMP-2) and urokinase-type plasminogen activator (u-PA) induced by TPA. Next, acacetin also strongly inhibited TPA-stimulated the nuclear levels of nuclear factor kappa B (NF-kappaB), c-Fos, and c-Jun. Also, a dose-dependent inhibition on the binding abilities of NF-kappaB and activator protein-1 (AP-1) by acacetin treatment was further observed. Further, the treatment of specific inhibitor for JNK (SP600125) to A549 cells could inhibit TPA-induced MMP-2 and u-PA expressions along with an inhibition on cell invasion and migration. Taken together, these results suggest the antimetastatic effects of acacetin on the TPA-induced A549 cells might be by reducing MMP-2 and u-PA expressions through inhibiting phosphorylation of JNK and reducing NF-kappaB and AP-1 binding activities.

Transcatheter arterial embolization for hemorrhage caused by injury of the hepatic artery.

BACKGROUND: The aims of the study were to compare (i) the effects of transcatheter arterial embolization on initial hemostasis and the control of rebleeding in the treatment of hemorrhage due to hepatic artery injury; and (ii) the outcomes of embolization by different locations. METHODS: Subjects were 32 patients with suspected hepatic artery injury who were transferred to Chi-Mei Foundation Medical Center for hepatic angiography and embolization. The causes of arterial injury included liver trauma (n = 15) and iatrogenic injury (n = 17). The sites of embolization were classified into four groups: group 1 (n = 8) was classified as 'combined outlet, target and inlet control' with embolization of the vascular lesion (target) and hepatic artery distal (outlet) and proximal (inlet) to the vascular lesion simultaneously; group 2 (n = 11) as 'combined target and inlet control'; group 3 (n = 8) as 'combined outlet and inlet control'; group 4 (n = 5) as 'inlet control' only. RESULTS: Successful initial hemostasis was achieved in 30 of the 32 patients (93.8%), with two failures, both of which were caused by liver injury and occurred in subjects in group 4. Rebleeding was seen in three patients who had successful initial hemostasis: two of them in group 4 (66.7%) and one in group 1 (12.5%). All rebleedings were successfully managed by repeat embolization. Abscess formation was found in two group 1 patients, and both were successfully managed by percutaneous drainage. CONCLUSIONS: Transcatheter arterial embolization is an effective method for hemostasis in hepatic artery hemorrhage for both patients with liver trauma and patients with iatrogenic injuries to the hepatic artery. Based on this experience, embolization of the vascular lesion and/or the arterial lumen distal to the vascular lesion combined with inlet control is recommended for preventing recurrent hemorrhage, but studies with larger sample sizes will be required to validate this conclusion.

Complete laryngotracheal disruption caused by blunt injury.

BACKGROUND: We reviewed the clinical courses and evaluated the surgical results of 7 patients with complete laryngotracheal disruption caused by blunt injury. METHODS: Seven patients with complete laryngotracheal disruption caused by blunt injury were successfully treated in a 13-year period. Six of the seven incidents involved men younger than 30 years on motorcycles. All but one had intact cutaneous tissue of the neck. Six of seven laryngotracheal disruptions were at the cricotracheal junction and the other was at the junction of second and third tracheal ring. In the emergency departments, 4 of these 7 patients underwent endotracheal intubation and three others underwent tracheostomy after failed intubation. Two of 7 patients underwent delayed surgery (posttrauma day 3 and day 5) because of delayed diagnosis. All patients underwent laryngotracheoplasty with (n = 3) or without (n = 4) concomitant tracheostomy. RESULTS: Total hospital stays ranged from 9 to 28 days (average 15 days). Intensive care unit stay ranged from 2 to 10 days (average 5.8 days). All 7 patients had paralysis of bilateral vocal cords that were revealed by postoperative bronchoscopy. In 3 patients who underwent concomitant tracheostomy, the tracheostomy tubes were removed within 3 to 5 months after surgery. In the other 4 patients who underwent laryngotracheoplasty only, the endotracheal tube was used as an airway support for 2 to 6 days (average 3.5 days). All patients had patent airways. Vocal cord function partially recovered in one side (n = 6) or both sides (n = 1). Their voices were audible but still husky 5 months or 1 year later. CONCLUSIONS: Complete laryngotracheal disruption can be treated by laryngotracheoplasty with or without concomitant tracheostomy, and phonation can be partially recovered.

Activation of human telomerase reverse transcriptase expression by some new symmetrical bis-substituted derivatives of the anthraquinone.

As a part of our program aimed at exploring the biological activity of symmetrical substitution of side chains into the anthracene-9,10-dione chromophore, we have synthesized a series of 1,5-bisthioanthraquinones 2 and 1,5-bisacyloxyanthraquinones 3 that are related to the antitumor agent mitoxantrone. Since the telomerase enzyme is a novel target for potential anticancer therapy and stem cell expansion, we explore the biological effects of these compounds by evaluating their effects on telomerase activity and telomerase expression. Telomerase is required for telomere maintenance and is active in most human cancers and in germinal cells but not in most of the normal human somatic tissues. We found that most of the 1,5-disubstituted anthraquinones did not exhibit inhibitory activity at the concentration ranging from 20 to 30 microM. To facilitate the analysis of the expression of telomerase, we used cancer and normal cell lines that carry secreted alkaline phosphatase (SEAP) gene under the control of human telomerase reverse transcriptase (hTERT). The effects of these compounds on the expression of telomerease were analyzed using the cell-based reporter systems. While most of these compounds did not appear to selectively repress the expression of hTERT in cancer cells, compounds 3a, 3d, and 3i activated hTERT expression in normal cells. The effects of these three compounds on hTERT expression appear to be specific because they did not increase the expression of a CMV promoter-driven SEAP. Thus, in addition to anticancer functions, our finding raises the possibility that these compounds might also have a role in cell immortalization. The application of these anthraquinone derivatives in stem cell research and tissue engineering is also discussed.