In vitro study on blocking mTOR signaling pathway in EGFR-TKI resistance NSCLC

Objective:To investigate the effect and mechanism of inhibitor everolimus on EGFR-TKI resistance NSCLC.Methods:MTT assay was used to detect proliferation of human non-small cell lung cancer cell line A549.Flow cytometry was used to detect the changes of apoptosis and cycle distribution in each group after 24 h and 48 h.RT-PCR was used to detect the changes of PTEN and 4EBP1 expression levels after 48 h of monotherapy and combination therapy.Results:MTT assay showed that everolimus had dose-dependent inhibition against growth of A549 cells.Flow cytometry showed when everolimus could induce apoptosis and induce G0/G1 phase cell cycle arrest,which was time-dependent(P<0.05).RT-PCR showed everolimus could increase PTEN and 4EBP1 expression.Conclusions:mTOR inhibitor everolimus has an inhibitory effect on EGFR-TKI resistant NSCLC,which cannot reverse the resistance effect of EGFR-TKI resistant cell line A549.The relationship between EGFR/AKT signaling pathway and the mTOR signaling pathway and the mechanism in non-small cell lung cancer need further study.

A Dosimetric Comparison between Conventional Fractionated and Hypofractionated Image-guided Radiation Therapies for Localized Prostate Cancer

Background： Image-guided radiation therapy （IGRT） is the preferred method for curative treatment of localized prostate cancer, which could improve disease outcome and reduce normal tissue toxicity reaction. 1GRT using cone-beam computed tomography （CBCT） in combination with volumetric-modulated arc therapy （VMAT） potentially allows smaller treatment margins and dose escalation to the prostate. The aim of this study was to compare the difference of dos^metric diffusion in conventional IGRT using 7-field, step-and-shoot intensity-modulated radiation therapy （IMRT） and hypofractionated IGRT using VMAT for patients with localized prostate cancer. Methods： We studied 24 patients who received 78 Gy in 39 daily fractions or 70 Gy in 28 daily fractions to their prostate with/without the seminal vesicles using IMRT （n = 12） or VMAT （n = 12） for prostate cancer between November 2013 and October 2015. Image guidance was performed using kilovoltage CBCT scans equipped on the linear accelerator. Offline planning was performed using the daily treatment images registered with simulation computed tomography （CT） images. A total of 212 IMRT plans in conventional cohort and 292 VMAT plans in hypofractionated cohort were enrolled in the study. Dose distributions were recalculated on CBCT images registered with the planning CT scanner. Results： Compared with 7-field, step-and-shoot IMRT, VMAT plans resulted in improved planning target volume （PTV） D95% （7663.17 ± 69.57 cGy vs. 7789.17± 131.76 cGy, P 〈 0.001）. VMAT reduced the rectal D25 （P 〈 0.001）, D35 （P 〈 0.001）, and D50 （P 〈 0.001）, bladder V50 （P 〈 0.001）, D25 （P = 0.002）, D35 （P = 0.028）, and D50 （P = 0.029）. However, VMAT did not statistically significantly reduce the rectal V50, compared with 7-field, step-and-shoot IMRT （25.02 ± 5.54% vs. 27.43 ±8.79%, P - 0.087）. Conclusions： To deliver the hypofractionated radiotherapy in prostate cancer, VMAT significantly increased PTV D95% dose and decreased the dose of radiation delivered to adjacent normal tissues comparing to 7-field, step-and-shoot IMRT. Daily online image-guidance and better management of bladder and rectum could make a more precise treatment delivery.

Biodegradable Poly(propylene carbonate)/Layered Double Hydroxide Composite Films with Enhanced Gas Barrier and Mechanical Properties

Relatively well crystallized and high aspect ratio Mg-Al layered double hydroxides（LDHs） were prepared by coprecipitation process in aqueous solution and further rehydrated to an organic modified LDH（OLDH） in the presence of surfactant. The intercalated structure and high aspect ratio of OLDH were verified by X-ray diffraction（XRD） and scanning electron microscopy（SEM）. A series of poly（propylene carbonate）（PPC）/OLDH composite films with different contents of OLDH were prepared via a melt-blending method. Their cross section morphologies, gas barrier properties and tensile strength were investigated as a function of OLDH contents. SEM results show that OLDH platelets are well dispersed within the composites and oriented parallel to the composite sheet plane. The gas barrier properties and tensile strength are obviously enhanced upon the incorporation of OLDH. Particularly, PPC/2%OLDH film exhibits the best barrier properties among all the composite films. Compared with pure PPC, the oxygen permeability coefficient（OP） and water vapor permeability coefficient（WVP） is reduced by 54% and 17% respectively with 2% OLDH addition. Furthermore, the tensile strength of PPC/2%OLDH is 83% higher than that of pure PPC with only small lose of elongation at break. Therefore, PPC/OLDH composite films show great potential application in packaging materials due to its biodegradable properties, superior oxygen and moisture barrier characteristics.