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Analytical Modeling of Flowrate and Its Maxima in Electrochemical Bioelectronics with Drug Delivery Capabilities

Research 2022年第3期2022卷 61-73页

作者： Raudel Avila Yixin Wu Rinaldo Garziera John A.Rogers Yonggang Huang Department of Mechanical Engineering Northwestern UniversityEvanstonIL 60208USA Department of Materials Science and Engineering Northwestern UniversityEvanstonIL 60208USA Querrey Simpson institute for Bioelectronics Northwestern UniversityEvanstonIL 60208USA Dipartimento di Ingegneria ed Architettura Universitàdi ParmaItaly Department of Biomedical Engineering Northwestern UniversityEvanstonIL 60208USA Department of Electrical and Computer Engineering Northwestern UniversityEvanstonIL 60208USA Department of Chemistry Northwestern UniversityEvanstonIL 60208USA Department of Neurological Surgery Northwestern UniversityFeinberg School of MedicineChicagoIL 60611USA Department of Civil and Environmental Engineering Northwestern UniversityEvanstonIL 60208USA

Flowrate control in flexible bioelectronics with targeted drug delivery capabilities is essential to ensure timely and safe *** neuroscience and pharmacogenetics studies in small animals,these flexible bioelectronic systems can be tailored to deliver small drug volumes on a controlled fashion without damaging surrounding tissues from stresses induced by excessively high *** drug delivery process is realized by an electrochemical reaction that pressurizes the internal bioelectronic chambers to deform a flexible polymer membrane that pumps the drug through a network of microchannels implanted in the small *** flowrate temporal profile and global maximum are governed and can be modeled by the ideal gas ***,we obtain an analytical solution that groups the relevant mechanical,fluidic,environmental,and electrochemical terms involved in the drug delivery process into a set of three nondimensional *** unique combinations of these three nondimensional parameters(related to the initial pressure,initial gas volume,and microfluidic resistance)can be used to model the flowrate and scale up the flexible bioelectronic design for experiments in medium and large animal *** analytical solution is divided into(1)a fast variable that controls the maximum flowrate and(2)a slow variable that models the temporal ***,the two variables detail the complete drug delivery process and control using the three nondimensional *** of the analytical model with alternative numerical models shows excellent agreement and validates the analytic modeling *** findings serve as a theoretical framework to design and optimize future flexible bioelectronic systems used in biomedical research,or related medical fields,and analytically control the flowrate and its global maximum for successful drug delivery.

关键词： governed Electrochemical Flow

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The establishment of polypeptide PSMA-targeted chimericantigen receptor-engineered natural killer cells forcastration-resistant prostate cancer and the induction of ferroptosis-related cell death

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Cancer communications 2022年第8期42卷 768-783页

作者： Liyuan Wu Fei Liu Le Yin Fangming Wang Hui Shi Qinxin Zhao Feiya Yang Dong Chen Xiying Dong Yuchun Gu Nianzeng Xing State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China Department of Urology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021P.R.China Molecular Pharmacology Laboratory Institute of Molecular MedicinePeking UniversityBeijing 100871P.R.China Translation Medicine Research Group Aston Medical SchoolAston UniversityBirminghamB47ETUnited Kingdom Research and Development Department Allife Medicine Inc.Beijing 100176P.R.China Peking Union Medical College Hospital Peking Union Medical College and Chinese Academy of Medical SciencesBeijing 100730P.R.China Department of Urology Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityTaiyuanShanxi 030013P.R.China

Background:The mortality of castration-resistant prostate cancer(CRPC)is high due to lack of an effective *** antigen receptor(CAR)-based therapy is a promising immunotherapeutic ***,we aimed to design a novel CAR-natural killer(NK)cells with a clinically significant tumoricidal effect on ***:We constructed novel CAR-NK92MI cells with a CD244-based recombinant lentiviral *** intracellular segments(CD244,NKG2D,or CD3ζ)were screened to identify the best candidate according to cell lysis assay and CD107a expression *** enhance the affinity of the CAR to the tumor antigen,we compared an antibody specific for prostate-specific membrane antigen(anti-PSMA)with PSMA-targeted polypeptide(p-PSMA),which was screened by phage display combinatorial ***,CAR-NK92MI cells with both a high affinity for PSMA and a strong tumoricidal capacity were *** addition,we verified their tumor-killing effect in vitro and in *** release of cytokine by NK92MI cells was compared with that by CAR-NK92MI cells through flow cytometry and enzyme-linked immunosorbent ***,ferroptosis-related cell death was explored as a possible underlying ***:Three different CAR intracellular regions CAR1(CD244),CAR2(CD244,NKG2D)and CAR3(CD244,NKG2D,and CD3ζ)were ***2 was chosen to confer a stronger tumoricidal ability on CAR-NK92MI *** with anti-PSMA,p-PSMA exhibited enhanced affinity for the tumor ***,p-PSMA-CAR-NK92MI cells,which expressed CAR with a polypeptide-based antigen-binding region,an intracellular CD244 and a NKG2D costimulatory domain,were *** could selectively and successfully kill PSMA+target cells and exhibited specific lysis rate of 73.19%for PSMA-positive C4-2 cells and 33.04%for PSMA-negative PC3 ***,p-PSMA-CAR-NK92MI cells had significantly higher concentrations of IFN-γ,TNF-αand granzyme B than NK92MI *** a CRPC cancer xenograft model

关键词： CAR-NK92MI chimeric antigen receptors immunotherapy prostate-specific membrane antigen ferroptosis

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TES functions as a Mena-dependent tumor suppressor in gastric cancer carcinogenesis and metastasis

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Cancer communications 2019年第1期39卷 14-27页

作者： Dan-dan Wang Yi-bing Chen Jing-jing Zhao Xiao-fei Zhang Guang-chao Zhu De-sheng Weng Ke Pan Lin Lv Qiu-zhong Pan Shan-shan Jiang Lei-lei Wang Jian-chuan Xia Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangzhou 510060GuangdongP.R.China Department of Biotherapy Sun Yat-sen University Cancer Center651 Dongfeng Road EastGuangzhou 510060GuangdongP.R.China Shandong Medicinal Biotechnology Centre Back and Neck Pain HospitalShandong Academy of Medical SciencesJinan 250062ShandongP.R.China Genetic and Prenatal Diagnosis Center Department of Gynecology and ObstetricsFirst Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052HenanP.R.China Key Laboratory for Applied Microbiology of Shandong Province Ecology Institute of Shandong Academy of SciencesJinan 250014ShandongP.R.China

Background: In our previous study, we identified a candidate tumor suppressor gene, testin LIM domain protein (TES), in primary gastric cancer (GC). TES contains three LIM domains, which are specific interacting regions for the cell adhesion and cytoskeleton regulatory proteins. Mena is a known cytoskeleton regulator that regulates the assembly of actin filaments and modulates cell adhesion and motility by interacting with Lamellipodin (Lpd). Therefore, we hypothesized that TES plays a role as tumor suppressor in GC through interacting with Mena. This study aimed to investigate the tumor suppressive functions of TES in GC. Methods: We explored the tumor suppressive effect of TES in GC by in vitro cell proliferation assay, colony formation assay, cell cycle analysis, Transwell assays, and in vivo tumorigenicity and metastasis assays. The interaction of TES and Mena was investigated through immunoprecipitation-based mass spectrometry. We also analyzed the expression of TES and Mena in 172 GC specimens using immunohistochemistry and investigated the clinicopathological and prog-nostic significance of TES and Mena in GC. Results: TES suppressed GC cell proliferation and colony formation, induced cell cycle arrest, and inhibited tumorigenicity in vitro. Additionally, it inhibited GC cell migration and invasion in vitro and suppressed metastasis in vivo. TES interacted with Mena, and inhibited the interaction of Mena with Lpd. Transwell assays suggested that TES suppressed migration and invasion of GC cells in a Mena-dependent fashion. In GC patients with high Mena expression, the expression of TES was associated with tumor infiltration (P = 0.005), lymph node metastasis (P = 0.003), TNM stage (P = 0.003), and prognosis (P = 0.010). However, no significant association was observed in GC patients with low Mena expression. Conclusions: We believe that TES functions as a Mena-dependent tumor suppressor. TES represents a valuable prog-nostic marker and potential target for GC

关键词： Gastric cancer TES Tumor suppressor Mena Lamellipodin

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Pertuzumab in combination with trastuzumab and chemotherapy for Chinese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer:a subpopulation analysis of the JACOB trial

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Cancer communications 2019年第1期39卷 354-363页

作者： Tianshu Liu Yanru Qin Jin Li Ruihua Xu Jianming Xu Shujun Yang Shukui Qin Yuxian Bai Changping Wu Yixiang Mao Haiyan Wu Yilin Ge Lin Shen Department of Oncology Zhongshan HospitalFudan UniversityShanghai 200032P.R.China Department of Clinical Oncology The First Affiliated HospitalZhengzhou UniversityZhengzhou 450052HenanP.R.China Department of Medical Oncology Fudan University Shanghai Cancer CenterShanghai 200032P.R.China Department of Oncology Tongji University Eastern HospitalShanghai 200120P.R.China Department of Medical Oncology Sun Yat-Sen University Cancer CenterGuangzhou 510060Guang-dongP.R.China Department of Oncology 307th Hospital of PLAAcademy of Military Medical SciencesBeijing 100071P.R.China Department of Medical Oncology Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhou 450008HenanP.R.China Department of Oncology People’s Liberation Army(PLA)Cancer Center81st Hospital of PLANanjing 210002JiangsuP.R.China Medical Department Harbin Medical University Cancer HospitalHarbin 150081HeilongjiangP.R.China Department of Oncology First People’s Hospital of ChangzhouChangzhou 213003JiangsuP.R.China Roche(China)Holding Co. Ltd.Shanghai 201203P.R.China Medical Division Shanghai Roche Pharmaceuticals Ltd.Shanghai 201203P.R.China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Gastrointestinal OncologyPeking University Cancer Hospital and Institute#52 Fucheng RoadHaidian DistrictBeijing 100142P.R.China

Background:The JACOB trial(NCT01774786)was a double-blinded,placebo-controlled,randomized,multicenter,international,phase III trial evaluating the efficacy and safety of adding pertuzumab to trastuzumab and chemo-therapy in first-line treatment of human epidermal growth factor receptor 2(HER2)-positive metastatic gastric cancer/gastroesophageal junction cancer(GEJC).The aim of this analysis was to investigate efficacy and safety outcomes in the Chinese subpopulation from the JACOB ***:This post hoc subpopulation analysis included all patients recruited in China's Mainland(n=163;20.9%)between June 2013 and January *** patients were randomly assigned in a 1:1 ratio to receive pertuzumab plus trastuzumab and chemotherapy(pertuzumab group;n=82)or placebo plus trastuzumab and chemotherapy(con-trol group;n=81).Intravenous pertuzumab(840 mg)and trastuzumab(8 mg/kg loading and 6 mg/kg maintenance doses)were given every 3 weeks until disease progression or unacceptable *** was given as per standard regimens/doses of capecitabine or 5-fluorouracil plus *** primary endpoint was overall survival(OS);secondary efficacy endpoints included progression-free survival(PFS),and overall objective response rate(ORR).Results:The median OS was 18.7 months in the pertuzumab group and 16.1 months in the control group(hazard ratio[HR]0.75;95%confidence interval[CI]0.49 to 1.14).The median PFS was 10.5 and 8.6 months in the pertuzumab and control groups,respectively(HR 0.85;95%CI 0.60 to 1.21),and the median ORRs were 68.9%and 55.7%,*** treatment effect in this Chinese subpopulation showed consistency with that in the global ITT population with numerically lower HR for OS and PFS compared with the control *** safety profiles of the pertuzumab and control groups in this Chinese subpopulation analysis were generally *** most common grade 3-5adverse events were neutropenia,anemia,and ***,due to the nature of

关键词： Gastric cancer Gastroesophageal junction cancer HER2 Pertuzumab Trastuzumab Chemotherapy Overall survival Progression-free survival Safety China

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Adhesive hydrogels for bioelectronics

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Biomedical Engineering communications 2023年第3期2卷 21-37页

作者： Yu-Jing Sheng Yun Chen Jian-Feng Qiu Xi Yang Ru-Liang Zhang Ying-Lun Sun institute of Medical Engineering and Interdisciplinary Research Medical Science and Technology Innovation CenterShandong First Medical University&Shandong Academy of Medical SciencesJinan 250118China School of Materials Science and Engineering Shandong University of Science and TechnologyQingdao 266590China Medical Engineering and Technology Research Center School of RadiologyShandong First Medical University&Shandong Academy of Medical SciencesTaian 271000China Department of Mathematics&Statistics Graduate School of Arts&SciencesBoston UniversityMassachusetts 02115USA

Benefiting from the unique advantages of superior biocompatibility,strong stability,good biodegradability,and adjustable mechanical properties,hydrogels have attracted extensive research interests in ***,due to the existence of an interface between hydrogels and human tissues,the transmission of electrical signals from the human tissues to the hydrogel electronic devices will be *** adhesive hydrogels with adhesive properties can tightly combine with the human tissue,which can enhance the contact between the electronic devices and human tissues and reduce the contact resistance,thereby improving the performance of hydrogel electronic *** this review,we will discuss in detail the adhesion mechanism of adhesive hydrogels and elaborate on the design principles of adhesive *** that,we will introduce some methods of performance evaluation for adhesive ***,we will provide a perspective on the development of adhesive hydrogel bioelectronics.

关键词： adhesive hydrogels bioelectronics flexible electronic devices adhesion mechanism sensors

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