Enhanced anticancer activity by the combination of vinpocetine and sorafenib via PI3K/AKT/GSK-3ß signaling axis in hepatocellular carcinoma cells.

Vinpocetine is widely used to treat cerebrovascular diseases. However, the effect of vinpocetine to treat hepatocellular carcinoma (HCC) has not been investigated. In this study, we revealed that vinpocetine was associated with antiproliferative activity in HCC cells, but induced cytoprotective autophagy, which restricted its antitumor activity. Autophagy inhibitors improved the antiproliferative activity of vinpocetine in HCC cells. Sorafenib is effective to treat advanced HCC, but the effect of autophagy induced by sorafenib is indistinct. We demonstrated vinpocetine plus sorafenib suppressed the cytoprotective autophagy activated by vinpocetine in HCC cells and significantly induced apoptosis and suppressed cell proliferation in HCC cells. In addition, vinpocetine plus sorafenib activates glycogen synthase kinase 3ß (GSK-3ß) and subsequently inhibits cytoprotective autophagy induced by vinpocetine in HCC cells. Meanwhile, overexpression of GSK-3ß was efficient to increase the apoptosis induced by vinpocetine plus sorafenib in HCC cells. Our study revealed that vinpocetine plus sorafenib could suppress the cytoprotective autophagy induced by vinpocetine and subsequently show synergistically anti-HCC activity via activating GSK-3ß and the combination of vinpocetine and sorafenib might reverse sorafenib resistance via the PI3K/protein kinase B/GSK-3ß signaling axis. Thus, vinpocetine may be a potential candidate for sorafenib sensitization and HCC treatment, and our results may help to elucidate more effective therapeutic options for HCC patients with sorafenib resistance.

[Autologous peripheral blood stem cell transplantation for the treatment of lower extremity arterial occlusive disease].

OBJECTIVE: To evaluate the safety and feasibility of autologous peripheral blood mononuclear cells (PBMNCs) implantation after granulocyte-colony stimulating factor (G-CSF)-induced mobilization in patients with lower extremity arterial occlusive disease (AOD). METHODS: A total of 12 patients with AOD were enrolled in this study. Following administration of rhG-CSF (150 microg/d) for 5 days, PBMNCs were harvested and injected intramuscularly in the diseased extremities (3 x 10(9) per limb). RESULTS: One patient received left leg amputation due to uncontrolled ulcer 15 days post PBMNCs transplantation and the symptoms and signs were improved significantly in 9 patients and the symptoms and signs remained unchanged in another 2 aged patients (> 70 years). Doppler ultrasonography measurement showed that peak systolic velocity in diseased extremities was significantly increased post transplantation [(44.55 +/- 4.13) cm/s vs. (21.32 +/- 0.63) cm/s, P < 0.01]. Contrast lower limb angiogram showed increased collateral vessels post transplantation. One aged patient (80 years) who did not respond to autologous PBMNCs received heterologous PBMNCs transplantation (PBMNCs was harvested from a young relative of him) 3 months post autologous PBMNCs transplantation and observed for another 3 months and all observed parameters improved significantly. CONCLUSION: Implantation of autologous PBMNCs collected after G-CSF administration might offer a simple, safe, and effective therapy for the AOD patients.

[The operative technique selection of lung transplantation for end-stage emphysema].

OBJECTIVE: To investigate the operation of lung transplantation for end-stage emphysema. METHODS: From September 2002 to February 2005, 9 patients with chronic obstructive pulmonary disease (COPD) underwent lung transplantation. The types of surgery included single lung transplantation in 2 patients, lung transplantation with asynchronous contralateral lung volume reduction (one week later) in 1, single lung transplantation with synchronized contralateral lung volume reduction in 4, and bilateral sequential lung transplantation without cardiopulmonary bypass in 2. RESULTS: The volume of chest drainage was more than 2000 ml at the first postoperative day in 2 patients, one was reoperated for hemostasis and another was successfully responded to conservative therapy. The ventilation time was ranged from 3 to 22 days postoperatively. Two patients were received tracheotomy. Seven patients achieved good results, two of them had returned to work, and 1 patient had lived for 30 months. One patient was died of severe acute rejection (4A) at 15th postoperative day and 1 succumbed to multisystem organ failure due to severe bacterial infection combine fungal infection. CONCLUSION: End-stage emphysema is an indication for single lung transplantation. Single lung transplantation with contralateral lung volume reduction is a good way to utilize donor. If patient suffered from infection, double-lung transplantation should be considered first.