ABSTRACT
Monoclonal antibody-based therapy has achieved great success and is now one of the most crucial therapeutic modalities for cancer therapy. The first monoclonal antibody authorized for treating human epidermal growth receptor 2 (HER2)-positive breast cancer is trastuzumab. However, resistance to trastuzumab therapy is frequently encountered and thus significantly restricts the therapeutic outcomes. To address this issue, tumor microenvironment (TME) pH-responsive nanoparticles (NPs) were herein developed for systemic mRNA delivery to reverse the trastuzumab resistance of breast cancer (BCa). This nanoplatform is comprised of a methoxyl-poly (ethylene glycol)-b-poly (lactic-co-glycolic acid) copolymer with a TME pH-liable linker (Meo-PEG-Dlink m -PLGA) and an amphiphilic cationic lipid that can complex PTEN mRNA via electrostatic interaction. When the long-circulating mRNA-loaded NPs build up in the tumor after being delivered intravenously, they could be efficiently internalized by tumor cells due to the TME pH-triggered PEG detachment from the NP surface. With the intracellular mRNA release to up-regulate PTEN expression, the constantly activated PI3K/Akt signaling pathway could be blocked in the trastuzumab-resistant BCa cells, thereby resulting in the reversal of trastuzumab resistance and effectively suppress the development of BCa.
ABSTRACT
[Objective] The retrospective study was designed to analyze the dynamic relationship between the Apolipoprotein A 1,B100 and the progression of coronary artery lesion.[Methods] Patients who underwent the second coronary angiography or coronary 320-slice CTA at a minimum review interval of 6 months after their first examinations in the Third Affiliated Hospital of Sun Yat-sen University from 2010 to 2015 (n =245),were divided into non progress group (n =114) and progress group (n =131).We compared the differences of clinical and Biochemical data between two groups,and tried to find out the relationship by Logistic Regression analysis.[Results] The baseline levels of APOA1 (1.33 ± 0.29 vs 1.24 ± 0.25,P =0.015),APOA1/AOPB100(1.56 ± 0.65 vs 1.38 ± 0.44,P =0.014)in non progress group were higher than those in progress group.The baseline levels of APOB 100 were similar in both groups.The follow-up levels of APOA1 were higher than the baseline levels in both groups,the variation was significant in progress group (1.24 -± 0.25 vs 1.31 ± 0.28,P =0.006).The levels of APOA1 and APOA1/APOB100 were correlated with progression of coronary artery lesion negatively in single-variate logistic regression analysis.The level of APOA 1 (OR =0.245,P =0.005) was correlated with progression of coronary artery lesion negatively in multivariate logistic regression analysis.[Conclusions] APOA1 may has the effect of delaying the progression of coronary artery lesion,and may predict the progression of coronary artery lesion.
ABSTRACT
<p><b>OBJECTIVE</b>To compare the vibration parameters in reducible anterior disc displacement and symptomless youth, and explore the clinical diagnostic value of frequency spectrogram of temporomandibular joint (TMJ) sounds.</p><p><b>METHODS</b>21 youth with anterior disc displacement were included as experimental group, and 26 symptomless youth were included as control group. The joint vibrations during rhythmic maximal open-close jaw movement of all subjects were recorded. The sensitivity and specificity of total integral in diagnosis of reducible anterior disc displacement were calculated.</p><p><b>RESULTS</b>All TMJ vibration parameters, include total integral, integral < 300 Hz, integral > 300 Hz, > 300/< 300 Hz radio, peak amplitude, peak frequency and median frequency, were significantly higher in experimental group than that in control group (P < 0.05). Along with the increasing of disc displacement degree, the TMJ vibration parameters were increasing, and total integral significantly increased (P < 0.05). The total integral demonstrated a high sensitivity and specificity in diagnosis of anterior disc displacement with reduction (0.86 and 0.85, respectively).</p><p><b>CONCLUSION</b>The TMJ vibration parameters are significantly higher in youth with reducible anterior disc displacement than that in symptomless youth. Different pathological stages of disc displacement show different TMJ sounds.</p>