Clinical Observation And Prognostic Analysis Of Radiotherapy Combined Long-term Endocrine Therapy In Prostate Cancer Patients With Pre-treatment PSA Greater Than 50 Ng/ml

Objective:To analysis the clinical characteristics of prostate cancer patients with pre-treatment PSA greater than 50 ng/ml.To evaluate the prognosis and side-effects of radiotherapy combined endocrine therapy for prostate cancer patients with pre-treatment PSA greater than 50 ng/ml.Methods:52 prostate cancer patients with PSA greater than 50 ng/ml aged from 52 to 88 years(mean:73 years)were enrolled,Gleason score from 7 to 10(mean:8).All patients were treated by radiotherapy combined endocrine therapy.The values were entered and evaluated by Kaplan-Meier univariate analysis,including age,PSA and Gleason score.Results:Age(p=0.036),PSA(p>0.001)and Gleason score(p>0.001)were the prognostic factors of the prostate cancer patients with pre-treatment PSA greater than 50ng/ml.Conclusion:Age,PSA and Gleason score were the prognostic factors of the prostate cancer patients with pre-treatment PSA greater than 50 ng/ml.Objective:Herein,we aim to setup a microfluidic model to mimic in vivo tumor cell local invasion microenvironment during metastasis to characterize the morphology of cell invasion,meanwhile to uncover potential targets for anti-invasion therapy.Methods:1.We designed and produced a SU-8 template to fabricate microfluidic chips.2.MDA-MB-231 cell were cultured in microfluidic chips and analyzed during subsequent observation.3.Immuno:fluorescence was conducted to identify the morphological characteristics of tumor cells during invasion and the expressive localization of a potent invasive marker,AURKA kinase during tumor collective invasion.4.We constructed a stable AURKA overexpressed MCF-10A cell line to uncover the induction of AUKRA on MCF-10A ce ll collective invasion;meanwhile,we built a stable endogenic AURKA knockdown MDA-MB-231 cell to observe the effect of down regulated AURKA protein on collective invasion.5.The phosphorylation level of ERK1/2 in leader cells was detected;the highly selective MEK1/2 inhibitor was utilized to inhibit the ERK kinase activity to verify its effect on collective invasion;overexpression and knock down assays were conducted to test AURKA kinase activity on ERK1/2(The202/Tyr204)phosphorylation level.6.The kinase inhibitor,VX680 and AKI603 were test for their ability to suppress AURKA activity and collective cell invasion in 3D microfluidic cell culture platform.Results:1.We built up a microfluidic platform to observe tumor cell local invasion in real time.2.MDA-MB-231 breast cancer cell line tends to invade into surrounding matrix in a collective manner in a 3D cell culture environment.3.AURKA is more highly expressed in leader cells than follower cells.4.Exogenous AURKA kinase induces collective invasion in non-invasive MCF-10A cells;Knocking down endogenous AURKA in MDA-MB-231 cells significantly reduces the collective cell invasion.5.ERK1/2 is highly phosphorylated in leader cells and regulated by AURKA kinase.6.Highly selective AURKA kinase inhibitor AKI603 and VX680 can effectively inhibit tumor cell collective invasion.Conclusion:The 3D microfluidic cell invasion model successfully mimicked the morphology of in vivo tumor local invasion.The key player of during cell invasion can be dynamically observed.We set up ARUKA inhibitors,AKI603 and VX680 as examples to verify the potential of this microfluidic chips in screening inhibitor inhibited tumor local invasion.