Purpose: To investigate the effect of penehyclidine hydrochloride (PHC) on interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), hypoxia inducible factor-1α (HIF-1α), and oxidative stress levels in lung tissues of acute lung injury (ALI) neonatal rats.Methods: 40 male Sprague-Dawley (SD) rats were assigned to model, low-dose PHC, high-dose PHC, and control groups (n = 10). Levels of IL-6, TNF-α and HIF-1α were evaluated by enzyme-linked immunosorbent assay (ELISA). Pulmonary lesions were determined histologically using H&E staining.Results: The lung tissue levels of IL-6, TNF-α and HIF-1α were significantly higher in model rats than in control rats, and significantly lower in PHC-treated rats than in model group, with decrease in levels as PHC dose increased (p < 0.05). The lung tissue activity of MPO and level of MDA in model rats were significantly higher than those in control rats, but significantly lower in the lung tissues of the two PHC groups than in the model group; decrease in levels occurred as PHC dose increased (p < 0.05).Conclusion: PHC decreases the lung and serum levels of IL-6, TNF-α and HIF-1α in a rat model of ALI, and mitigates pulmonary oxidative stress and lung tissue damage. Thus, penehyclidine hydrochloride may be useful to mitigate ALI-induced damage in patients. However, further studies and clinical trials are required to ascertain this Keywords: Penehyclidine hydrochloride, Alveolar septum, Acute lung injury, Inflammatory cells, IL-6, TNF-α, HIF-1α, Oxidative stress
e16011 Background: In head and neck cancer, p53 mutations are present in up 60% of head and neck cancers. Studies indicated p53 gene could increase both radio- and chemo-sensitivities. In this study, we investigate the effectiveness of recombinant adenoviral human p53 gene (rAd-p53) combined with chemoradiotherapy in treatment of advanced unresectable head and neck cancer. Methods: From May 2008 to Dec. 2011, 48 patients with an advanced unresectable head and neck cancer, 29 males and 18 females with an average of 61.3 years old, were included this study. Those patients were treated with intratumoral injection of rAd-p53 at a dose 1-3 ×1012 viral particles (VP) , once every 3 days for 6 times. Chemotherapy regimen consisted of cisplatin 60 mg/m2 on d1 and 5-Fu 600 mg/m2 on d1-5, given intravenously every 3 weeks for 3 cycles. Radiation were given at a dose of 2Gy/f, five fractions a week for a total dose 50~70Gy. Patients were monitored for response, long-term efficacy and adverse events. Results: The median follow-up time was 21.2 months (6~39 months). Overall response rate was 91.7% (44/48), 47.9% (23/48) of complete responses and 43.8% (23/48) of partial responses. One-year overall survival was 79.2% and local progression-free survival was 70.8%. At the last follow-up, the overall survival was 72.9%. Forty-six patients experienced self-limited fever after administration of p53. Conclusions: rAd-p53 gene therapy as a component of comprehensive treatment for advanced unresectable head and neck cancer showed significant beneficial effects.
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