1.Advances in research on tumor immunotherapy and its drug development
Xuyang XING ; Xiaochun WANG ; Wei HE
Journal of China Pharmaceutical University 2021;52(1):10-19
The progress of molecular biology and tumor biology has greatly changed the mode of cancer treatment. A large number of scientific studies have revealed the mechanism of tumor immune evasion, and a variety of new types of tumor immunotherapy have emerged, which has become another effective treatment of cancer after surgery, radiotherapy, chemotherapy and targeted therapy. This paper introduces the mechanism of tumor cell immune evasion, and focuses on the design principle, biological drugs and the latest research progress of immunotherapy, such as cytokine immunotherapies, therapeutic monoclonal antibody immunotherapy, PD-1/PD-L1 therapy, CAR-T therapy, tumor vaccine, oncolytic virus and so on. At the same time, the advantages and disadvantages of various immunotherapies are compared to provide reference for drug research and development in tumor immunotherapy.
2.Relationship between basivertebral foramen and retropulsed bone fragment in thoracolumbar burst fracture
Xuyang ZHANG ; Shengyun LI ; Tianming YU ; Xing ZHAO ; Shunwu FAN ; Fengdong ZHAO
Chinese Journal of Orthopaedics 2017;37(19):1223-1230
Objective To clarify the relationship between the basivertebral foramen (BF) and the retropulsed bone fragment (RBF) in thoracolumbar burst fracture (TLBF) and further explain the mechanism of RBF formation.Methods From June 2013 to June 2016,Sixty-two patients suffering from TLBF with RBF were collected.The characteristics of RBF as well as the parameters of vertebral body were studied using CT reconstruction imaging.In the transverse images,the lengths of RBF (RL) and vertebral body (VL) were measured.In median sagittal images,the heights and widths of RBF (RH,RW) and vertebral body (VH,VW) were also obtained.The ratios of different parameters of RBF and vertebral body (RL/VL,RW/VW,RH/VH) were calculated,and then defined the location relationship of RBF and BF.Eight frozen cadaveric spine were selected and evaluated by Micro-CT scans.Each vertebral body was divided into three layers (Superior,Middle,Inferior).Each layer was further divided into 9 regions (R1-R9),named as SR1-SR9,MR1-MR9,IR1-IR9.Microarchitecture parameters of each region in each layer,including bone volume fraction (BV/TV),bone mineral density (BMD),trabecular connectivity (Corn.D),and trabecular number (Tb.N) and thickness (Tb.Th) were calculated,and their differences were also analyzed to see if the trabecular bone distribution would be affected by BF.In vitro study,burst fractures were simulated on cadaveric spines by using bursting fracture simulator,aiming to observe the RBF morphology and imaging findings to future investigate the relationship between RBF and BF.Results The length and height of RBF were close to half of vertebral body length and height (RL/VL:0.497±0.059,RH/VH:0.485±0.036).The width of RBF was usually one-third of vertebral body width (RW/VW:0.319±0.025),which indicated that the fracture block was often located in the posterior of vertebral body above the BF.BV/TV,Tb.N in the MR2 and MR5 regions were lowest than other regions and the SMI of MR2 and MR5 was largest than others.SR5 was the lowest region in superior lawyer that was corresponded to regions most affected by burst fracture.In simulated burst fractures,the fracture line of RBF went across the vertex or upper surface of the BF and the lower boundaries of RBF were also the upper bound of the BF.Moreover,the damage sites of posterior longitudinal ligament were mainly located at the edge of the BF.Conclusion At the bone defect region,the BF is the weakest area in the vertebral body which may affect the distribution of trabecular bone surrounding it.When subjected to vertical violence,these regions undergo fracture first which impact the anterior and lower boundaries of RBF.Ultimately,RBF was produced upon the BF,involving all or part of the upper bound of the BF.
3.Alleviating experimental pulmonary hypertension via co-delivering FoxO1 stimulus and apoptosis activator to hyperproliferating pulmonary arteries.
Bingbing LI ; Chao TENG ; Huiling YU ; Xiaohong JIANG ; Xuyang XING ; Qi JIANG ; Chenshi LIN ; Zongmin ZHAO ; Ruifeng ZHANG ; Wei HE
Acta Pharmaceutica Sinica B 2023;13(6):2369-2382
Pulmonary hypertension (PH) is an insidious pulmonary vasculopathy with high mortality and morbidity and its underlying pathogenesis is still poorly delineated. The hyperproliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs) contributes to pulmonary vascular remodeling in pulmonary hypertension, which is closely linked to the downregulation of fork-head box transcriptional factor O1 (FoxO1) and apoptotic protein caspase 3 (Cas-3). Here, PA-targeted co-delivery of a FoxO1 stimulus (paclitaxel, PTX) and Cas-3 was exploited to alleviate monocrotaline-induced pulmonary hypertension. The co-delivery system is prepared by loading the active protein on paclitaxel-crystal nanoparticles, followed by a glucuronic acid coating to target the glucose transporter-1 on the PASMCs. The co-loaded system (170 nm) circulates in the blood over time, accumulates in the lung, effectively targets the PAs, and profoundly regresses the remodeling of pulmonary arteries and improves hemodynamics, leading to a decrease in pulmonary arterial pressure and Fulton's index. Our mechanistic studies suggest that the targeted co-delivery system alleviates experimental pulmonary hypertension primarily via the regression of PASMC proliferation by inhibiting cell cycle progression and promoting apoptosis. Taken together, this targeted co-delivery approach offers a promising avenue to target PAs and cure the intractable vasculopathy in pulmonary hypertension.
4.Intracellular codelivery of anti-inflammatory drug and anti-miR 155 to treat inflammatory disease.
Chao TENG ; Chenshi LIN ; Feifei HUANG ; Xuyang XING ; Shenyu CHEN ; Ling YE ; Helena S AZEVEDO ; Chenjie XU ; Zhengfeng WU ; Zhongjian CHEN ; Wei HE
Acta Pharmaceutica Sinica B 2020;10(8):1521-1533
Atherosclerosis (AS) is a lipid-driven chronic inflammatory disease occurring at the arterial subendothelial space. Macrophages play a critical role in the initiation and development of AS. Herein, targeted codelivery of anti-miR 155 and anti-inflammatory baicalein is exploited to polarize macrophages toward M2 phenotype, inhibit inflammation and treat AS. The codelivery system consists of a carrier-free strategy (drug-delivering-drug, DDD), fabricated by loading anti-miR155 on baicalein nanocrystals, named as baicalein nanorods (BNRs), followed by sialic acid coating to target macrophages. The codelivery system, with a diameter of 150 nm, enables efficient intracellular delivery of anti-miR155 and polarizes M1 to M2, while markedly lowers the level of inflammatory factors and . In particular, intracellular fate assay reveals that the codelivery system allows for sustained drug release over time after internalization. Moreover, due to prolonged blood circulation and improved accumulation at the AS plaque, the codelivery system significantly alleviates AS in animal model by increasing the artery lumen diameter, reducing blood pressure, promoting M2 polarization, inhibiting secretion of inflammatory factors and decreasing blood lipids. Taken together, the codelivery could potentially be used to treat vascular inflammation.