ABSTRACT
BACKGROUND: Amputation-free survival (AFS) has been recommended as the gold standard for evaluating No-Option Critical Limb Ischemia (NO-CLI) therapy. Early-phase clinical trials suggest that autologous bone-marrow derived cells (BMCs) transplantation may have a positive effect on patients with NO-CLI, especially decreasing the incidence of amputation. However, the BMCs therapeutic efficacy remains controversial and whether BMCs therapy is suitable for all CLI patients is unclear. METHODS: We conducted a meta-analysis using data from randomized controlled trials (RCTs) by comparing autologous BMCs therapy with controls in patients with critical limb ischemia, and the primary endpoint is the incidence of amputation. Pubmed, EBSCO and the Cochrane Central Register of Controlled Trials (to approximately July 25, 2012) were searched. RESULTS: Seven RCTs with 373 patients were enrolled in the meta-analysis. Because serious disease was the main reason leading to amputation in one trial, six studies with 333 patients were finally included in the meta-analysis. Pooling the data of the final six studies, we found that BMCs therapy significantly decreased the incidence of amputation in patients with CLI (odds ratio (OR), 0.37; 95% confidence interval (CI), 0.22 to 0.62; P = 0.0002), and the efficacy had not significantly declined within 6 months after BMCs were transplanted; OR, 0.33; 95%CI, 0.16 to 0.70; P = 0.004 within 6 months and OR, 0.30; 95%CI, 0.11 to 0.79; P = 0.01 within 3 months. The rate of AFS after BMCs therapy was significantly increased in patients with Rutherford class 5 CLI (OR 3.28; 95%CI, 1.12 to 9.65; P = 0.03), while there was no significant improvement in patients with Rutherford class 4 (OR 0.35; 95%CI, 0.05 to 2.33; P = 0.28) compared with controls. The BMCs therapy also improved ulcer healing (OR, 5.83; 95%CI, 2.37 to 14.29; P = 0.0001). CONCLUSIONS: Our analysis suggests that autologous BMCs therapy has a beneficial effect in decreasing the incidence of amputation and the efficacy does not decrease significantly within 6 months after BMCs transplantation. Patients with Rutherford class 5 are suitable for BMCs therapy, while the efficiency in patients with Rutherford 4 needs further evaluation.
Subject(s)
Bone Marrow Transplantation/methods , Ischemia/therapy , Lower Extremity/pathology , Transplantation, Autologous/methods , Humans , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: Gleevec (aka STI571, Imatinib) is a recently FDA approved anti-tumor drug for chronic myelogenous leukemia. Gleevec binds specifically to BCR-ABL tyrosine kinase and inhibit the tyrosine kinase activity. It cross-reacts with another two important membrane tyrosine kinase receptors, c-kit and PDGF receptors. We sought to investigate if Gleevec has a potential role in treatment of non-small cell lung cancer. RESULTS: We have shown that Gleevec alone can inhibit the A549 lung cancer cell growth in dose-dependent manner, and the optimal concentration of Gleevec inhibition of A549 cell growth is at the range of 2-3 microM (IC50). We have also shown that A549 cells are resistant to cisplatin treatment (IC50 64 microM). Addition of Gleevec to the A549 cells treated with cisplatin resulted in a synergistic cell killing effect, suggesting that Gleevec can potentiate the effect of cisplatin on A549 cells. We also showed that the A549 lung cancer cells expresses the platelet derived growth factor receptor alpha, and the inhibitory effects of Gleevec on A549 cells is likely mediated through inhibition of PDGFR alpha phosphorylation. We further tested 33 lung cancer patients' tumor specimens to see the frequency of PDGFR-alpha expression by tissue micro-arrays and immunohistochemistry. We found that 16 of the 18 squamous carcinomas (89%), 11 of the 11 adenocarcinomas (100%), and 4 of the 4 small cell lung cancers (100%) expressed PDGFR-alpha. CONCLUSION: These results suggest a potential role of Gleevec as adjuvant therapeutic agent for treatment of non-small cell lung cancer.
