Postoperative intensity-modulated radiation therapy reduces local recurrence and improves overall survival in III-N2 non-small-cell lung cancer: A single-center, retrospective study.

PURPOSE: To determine the postoperative effects of radiotherapy (PORT) on the local recurrence-free survival (LRFS) and overall survival (OS) of stage III-N2 non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: 183 patients with resected stage III-pN2 NSCLC from Hunan Cancer Hospital between 2013 and 2016 were divided into two groups for postoperative chemotherapy (POCT) (n = 105) or combination chemotherapy and radiotherapy (POCRT) (n = 78). The LRFS and OS were compared and the factors affecting local recurrence were illustrated in these two groups. The sites of failure based on the lobe of the primary tumor in two groups were described. RESULTS: PORT leads to a strikingly lower risk for local recurrence and brought superior OS benefit. For different pN2 Subclassification, Patients with multiple-station pN2 ± pN1 disease had the worst LRFS (11 months) and single-station pN2 + multiple station pN1 disease had a relatively short LRFS (24 months) in group POCT. Short LRFS is correlated with multiple-station pN2, older age (Y > 55), patients with a high positive LN ratio > 1/3 and a poor tumor histological differentiation degree. In group POCT, the most frequent failure site occurs at the ipsilateral hilum (21.0%), the bronchial stump (20.0%), followed by LNs4R (19.0%), LNs4L (18.1%), LNs7 (15.2%), most of left-sided tumors more frequently involved the contralateral mediastinum, whereas the ipsilateral recurrences dominated for right-sided tumors, especially for LNs4R. In group POCRT, the highest failure site was the bronchial stump (11.5%), followed by LNs4L (8.97%), LNs1 (7.69%), the ipsilateral hilum (6.41%) and LNs4R (6.41%). CONCLUSION: PORT remarkably reduced local recurrence and improved OS in stage III-pN2 NSCLC, especially in the multiple-station pN2 group.

Nanoemulsion-based delivery system for enhanced oral bioavailability and caco-2 cell monolayers permeability of berberine hydrochloride.

Berberine hydrochloride (BBH) has a variety of pharmacological activities such as antitumor, antimicrobial, anti-inflammation, and reduce irritable bowel syndrome. However, poor stability and low oral bioavailability limited its usage. Herein, an oil-in-water nanoemulsion system of BBH was developed to improve its stability and oral bioavailability. The pseudoternary phase diagrams were constructed for the determination of composition of various nanoemulsions. The nanoemulsions of BBH composed of Labrafil M 1944 CS (oil phase), RH-40 (surfactant), glycerin (co-surfactant), and water (aqueous phase). The O/W nanoemulsion of BBH showed a relative bioavailability of 440.40% compared with unencapsulated BBH and was stable in our 6-month stability study. Further, there was a significant increase in intestinal permeability of BBH as assessed by Caco-2 cell monolayers and a significant reduction in efflux of BBH by the multidrug efflux pump P-glycoprotein. This study confirmed that the nanoemulsion formulation could be used as an alternative oral formulation of BBH to improve its stability, oral bioavailability and permeability.

Long Chain Omega-3 Polyunsaturated Fatty Acid Supplementation Alleviates Doxorubicin-Induced Depressive-Like Behaviors and Neurotoxicity in Rats: Involvement of Oxidative Stress and Neuroinflammation.

Doxorubicin (DOX) is a chemotherapeutic agent widely used in human malignancies. Its long-term use can cause neurobiological side-effects associated with depression. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), the essential fatty acids found in fish oil, possess neuroprotecitve and antidepressant activities. Thus, the aim of this study was to explore the potential protective effects of ω-3 PUFAs against DOX-induced behavioral changes and neurotoxicity. ω-3 PUFAs were given daily by gavage (1.5 g/kg) over three weeks starting seven days before DOX administration (2.5 mg/kg). Open-field test (OFT) and forced swimming test (FST) were conducted to assess exploratory activity and despair behavior, respectively. Our data showed that ω-3 PUFAs supplementation significantly mitigated the behavioral changes induced by DOX. ω-3 PUFAs pretreatment also alleviated the DOX-induced neural apoptosis. Meanwhile, ω-3 PUFAs treatment ameliorated DOX-induced oxidative stress in the prefrontal cortex and hippocampus. Additionally, gene expression of pro-inflammatory cytokines, including IL-1ß, IL-6, and TNF-α, and the protein levels of NF-κB and iNOS were significantly increased in brain tissues of DOX-treated group, whereas ω-3 PUFAs supplementation significantly attenuated DOX-induced neuroinflammation. In conclusion, ω-3 PUFAs can effectively protect against DOX-induced depressive-like behaviors, and the mechanisms underlying the neuroprotective effect are potentially associated with its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.

Mechanisms of microemulsion enhancing the oral bioavailability of puerarin: comparison between oil-in-water and water-in-oil microemulsions using the single-pass intestinal perfusion method and a chylomicron flow blocking approach.

The purpose of the present work was to determine the mechanisms by which microemulsions (MEs) enhance the oral bioavailability of puerarin. The in situ perfusion method was used in rats to study the absorption mechanisms of an oil-in-water (O/W) microemulsion (O/W-ME) and a water-in-oil (W/O) microemulsion (W/O-ME). The possibility of lymphatic transport of the MEs was investigated using a chylomicron flow blocking approach. The results for the absorption mechanisms in the stomach and intestines indicated that the absorption characteristics of the O/W-ME and W/O-ME depend on the segment. The W/O-ME had higher internal membrane permeability than the O/W-ME. The results of the lymphatic transport analyses showed that both the O/W-ME and W/O-ME underwent lymphatic transport and that this pathway was a major contributor to the oral bioavailability of MEs. Furthermore, the type of ME can significantly affect the absorption of puerarin through the lymphatic system due to the oil content and the form of the microemulsion after oral administration. In conclusion, these data indicate that microemulsions are an effective and promising delivery system to enhance the oral bioavailability of poorly water-soluble drugs.