Study protocol: a multicentre, prospective, phase II trial of isotoxic hypofractionated concurrent chemoradiotherapy for non-small cell lung cancer.

INTRODUCTION: Concurrent chemoradiotherapy with conventional fractionation has been acknowledged as one of the standard treatments for locally advanced non-small cell lung cancer (NSCLC). The radiotherapy dose of 60 Gy is far from enough for local tumour control. Due to this fact, hypofractionated radiotherapy can shorten the total treatment duration, partially counteract the accelerated repopulation of tumour cells and deliver a higher biological effective dose, it has been increasingly used for NSCLC. In theory, concurrent hypofractionated chemoradiotherapy can result in an enhanced curative effect. To date, the vast majority of radiotherapy prescriptions assign a uniform radiotherapy dose to all patients. However this kind of uniform radiotherapy prescription may lead to two consequences: excess damage to normal tissues for large tumours and insufficient dose for small tumours. Our study aims to evaluate whether delivering individualised radiotherapy dose is feasible using intensity-modulated radiotherapy. METHODS AND ANALYSIS: Our study of individualised radiotherapy is a multicenter phase II trial. From April 2019, a total of 30 patients from three Chinese centres, with a proven histological or cytological diagnosis of inoperable NSCLC, will be recruited. The dose of radiation will be increased until one or more of the organs at risk tolerance or the maximum dose of 69 Gy is reached. The primary end point is feasibility, with response rates, progression-free survival and overall survival as secondary end points. The concurrent chemotherapy regimen will be docetaxel plus lobaplatin. ETHICS AND DISSEMINATION: The study has been approved by medical ethics committees from three research centres. The trial is conducted in accordance with the Declaration of Helsinki.The trial results will be disseminated through academic conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03606239.

Losartan inhibits LPS-induced GFAP expression via AMPK activation in mouse hippocampus / 中国病理生理杂志

AIM:To investigate the effects of losartan on lipopolysaccharide (LPS)-induced glial fibrillary acidic protein (GFAP) expression,and to determine whether adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) activation is involved in the mechanism.METHODS:Adult male KM mice were divided into control group,LPS model group,losartan treatment group,and losartan and Compound C co-treatment group.To establish a model of central nervous system inflammation,the mice received daily intracerebroventricular injection of LPS (24 μg/d) for 2 d.Daily losartan administration (0.5,1 or 5 mg · kg-1 · d-1,ip) initiated at 14 d prior to LPS injection.Compound C (10 mg/kg,ip),a selective AMPK inhibitor,started to be injected daily at 2 d prior to LPS injection.The hippocampal tissues in each group were isolated at 3 d after the last LPS injection,and then the protein levels of GFAP,AMPK,p-AMPK,mammalian target of rapamycin (mTOR) and p-mTOR were determined by Western blot.RESULTS:Twice LPS injections significantly increased the expression of GFAP in the hippocampus (P ＜ 0.01).Losartan inhibited LPS-induced GFAP expression in a concentration-dependent way,and losartan at 5 mg· kg-1 · d-1 significantly inhibited GFAP expression and AMPK activation (P ＜ 0.05),but it had no obvious effect on mTOR activation.Furthermore,Compound C significantly reversed the effect of losartan treatment on LPS-induced GFAP expression and AMPK phosphorylation (P ＜ 0.05).CONCLUSION:Losartan inhibits LPS-induced GFAP expression in the mouse hippocampus,and AMPK activation but not mTOR,is involved in the mechanism.

Losartan inhibits LPS-induced GFAP expression via AMPK activation in mouse hippocampus / 中国病理生理杂志

AIM:To investigate the effects of losartan on lipopolysaccharide (LPS)-induced glial fibrillary acidic protein (GFAP) expression,and to determine whether adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) activation is involved in the mechanism.METHODS:Adult male KM mice were divided into control group,LPS model group,losartan treatment group,and losartan and Compound C co-treatment group.To establish a model of central nervous system inflammation,the mice received daily intracerebroventricular injection of LPS (24 μg/d) for 2 d.Daily losartan administration (0.5,1 or 5 mg · kg-1 · d-1,ip) initiated at 14 d prior to LPS injection.Compound C (10 mg/kg,ip),a selective AMPK inhibitor,started to be injected daily at 2 d prior to LPS injection.The hippocampal tissues in each group were isolated at 3 d after the last LPS injection,and then the protein levels of GFAP,AMPK,p-AMPK,mammalian target of rapamycin (mTOR) and p-mTOR were determined by Western blot.RESULTS:Twice LPS injections significantly increased the expression of GFAP in the hippocampus (P ＜ 0.01).Losartan inhibited LPS-induced GFAP expression in a concentration-dependent way,and losartan at 5 mg· kg-1 · d-1 significantly inhibited GFAP expression and AMPK activation (P ＜ 0.05),but it had no obvious effect on mTOR activation.Furthermore,Compound C significantly reversed the effect of losartan treatment on LPS-induced GFAP expression and AMPK phosphorylation (P ＜ 0.05).CONCLUSION:Losartan inhibits LPS-induced GFAP expression in the mouse hippocampus,and AMPK activation but not mTOR,is involved in the mechanism.