AMPK activation by GSK621 inhibits human melanoma cells in vitro and in vivo.

Recent studies suggest that forced activation of AMP-activated protein kinase (AMPK) could inhibit melanoma cell proliferation. In this report, we evaluated the anti-melanoma cell activity by a novel small-molecular AMPK activator, GSK621. Treatment of GSK621 decreased survival and proliferation of human melanoma cells (A375, WM-115 and SK-Mel-2 lines), which was accompanied by activation of caspase-3/-9 and apoptosis. Reversely, caspase inhibitors attenuated GSK621-induced cytotoxicity against melanoma cells. Significantly, GSK621 was more potent than other AMPK activators (A769662, Compound 13 and AICAR) in inhibiting melanoma cells. Intriguingly, same GSK621 treatment was non-cytotoxic or pro-apoptotic against human melanocytes. Molecularly, we showed that activation of AMPK mediated GSK621's activity against melanoma cells. AMPKα1 shRNA knockdown or dominant negative mutation (T172A) dramatically attenuated GSK621-induced melanoma cell lethality. Further studies revealed that MEK-ERK activation might be the primary resistance factor of GSK621. MEK-ERK inhibition, either genetically or pharmacologically, significantly sensitized melanoma cells to GSK-621. Remarkably, intraperitoneal (i.p.) injection of GSK621 inhibited A375 tumor growth in SCID mice. Co-administration of MEK-ERK inhibitor MEK162 further sensitized GSK621-induced anti-A375 tumor activity in vivo. Together, the results imply that targeted activation of AMPK by GSK621 inhibits melanoma cell survival and proliferation. MEK-ERK inhibition may further sensitize GSK621's anti-melanoma cell activity in vitro and in vivo.

[Repair and reconstruction of femoral pseudoaneurysm caused by drug injection].

OBJECTIVE: To evaluate repair and reconstruction of the femoral pseudoaneurysm caused by drug injection. METHODS: From May 2000 to May 2005, 15 cases of femoral pseudoaneurysm caused by drug injection underwent operation treatment. All patients were male, aging 20-36 years. The disease course was 18-52 days (mean 35 days) and the course of drug injection was 3-17 months. The locations were the left side in 5 cases and the right side in 10 cases. After having been bandaged with pressure and supported with nutrition, they had been all operated. One case received fistula repair, and 14 cases received vascular grafting with ePTFE man-made blood vessel. RESULTS: The wounds healed by the first intention in 14 cases. All limbs survived. The complexion, temperature and response of involved leg were in gear. The postoperative color ultrasound Doppler detection showed that all the vascular grafts were of patency. The function of the involved limbs restored to normal. CONCLUSION: Complete debridement, vascular reconstruction and better microsurgery skill were the key factors of treating successfully the femoral pseudoaneurysm caused by drug injection.

[Reconstruction of infected median sternotomy wound dehiscence after coronary artery revascularization].

OBJECTIVE: To introduce the experience about the reconstruction of median sternotomy wound dehiscence. METHODS: From February 2002 to October 2004, 10 patients with median sternotomy wound dehiscence due to coronary artery revascularization were treated. There were 7 males and 3 females, aging from 68 to 76 years. The sizes of defects ranged from 3 cm x 5 cm to 5 cm x 15 cm. After debridement of necrotic soft tissue, sternum and rib, infected median sternotomy wound was reconstructed with rectus abdominis myocutaneous flap, pectoralis major myocutaneous flap and latissimus dorsi flap or single muscle flap. The sizes of flaps ranged from 3 cm x 5 cm to 5 cm x 16 cm. RESULTS: All patients were followed up from 3 to 11 months with an average of 6 months. All the patients achieved healing by first intention with normal respiration and normal function of upper limbs. The wound of donor site healed well. No abdominal hernia and other complications occurred. The wound of donor site healed well. The results were satisfactory. CONCLUSION: According to different stages of the disease and different conditions of an operation, the surgical management should vary with each individual.

[Repair the infra-orbital defect with a rotation flap after basal cell carcinoma resection].

OBJECTIVE: To explore the method repairing the infra-orbital defect after basal cell carcinoma resection. METHOD: A facial rotation flap was applied to repair the infra-orbital defects from tumor resection in 28 cases. RESULT: All defects were repaired by this one-stage method, which avoided skin graft, shortened the operation time and minimized the operation trauma. The incision sears are inconspicuous. The facial contours are more satisfactory. CONCLUSION: This technique is simple and effective in repairing the infra-orbital defects, worthy of extensive application.