2.Pharmacokinetic/pharmacodynamic models of anti-tumor agents in xenograft mice: historical review, recent advances, and application in drug development
Acta Pharmaceutica Sinica 2020;55(11):2580-2594
Xenograft mice are preclinical animal models of tumors and are widely utilized in anti-tumor research. PK/PD modeling of anti-tumor agents is an approach that can capture the time profile of the "dose-plasma concentration-biomarker level-tumor volume" process based on experimental data from xenograft mice using a non-linear mixed-effect model. PK/PD modeling can help optimize the dosing regimen for anti-tumor therapy, evaluate any synergistic effect and help identify an optimal schedule for combination therapy, as well as providing a preliminary estimate of a drug's efficacy and anti-tumor potency in the human body. PK/PD modeling can also help by quantitatively explaining the mechanism of the tumor-inhibitory effect as indicated by changes in biomarker levels after a drug acts on its target. This article provides a systematic summary of the background, application range, and limitations of the mainstream anti-tumor agent PK/PD models. Recent advances in model structure development are reviewed in detail. Finally, we discuss promising applications of PK/PD models in anti-tumor medicine development from the perspective of a drug's mechanism of action, optimization of combination therapy schedules, and their clinical translation.
3.Studies on Purification and Properties of Phytase from Trichoderma viride
Yan-Ling YANG ; Shi-Hua WANG ; Kai-Hui HU ;
Microbiology 1992;0(06):-
The phytase was extracted from solid state leavening of Trichoderma Viride LH374.The crude product was purified by(NH_4)_2SO_4 precipitation,gel filtration and ion exchange chromatography.The purified phyatse was 13.3 times of the raw products,and the extraction ration was 27.1%.The study on the enzymology of phyatse showed that the optimal temperature and pH were 55℃ and 6.0,respectively.The Km value of the phytase was 0.15mmol/L.
4.Effect of Nano-?-Linolenic Acid on Expression of Cathepsin B in Mice with Viral Myocarditis
shi-kai, TAN ; yun-hua, YANG ; shuang-jie, LI
Journal of Applied Clinical Pediatrics 2003;0(10):-
Objective To investigate the effect of nano-?-linolenic acid on the expression of cathepsin B(CB) in mice with viral myocarditis(VM).Methods Eighty male Balb/c mice were randomly divided into 4 groups:control group,myocarditis group,low-dose intervention group and high-dose intervention group,each group had 20 mice.Mice in control group were inoculated introperitoneally with eagle′s solution,every mouse in the last 3 groups was treated with 0.1 mL Coxsackie B3 virus(CVB3) intraperitoneally.Then,mice in low-dose intervention group and high-dose intervention group were treated with 60 mg?kg-1and 180 mg?kg-1 nano-?-linolenic acid solution for 7 days,respectively.Mice in control group and myocarditis group were treated with 9 g?L-1 saline for 7 days.All mice were killed on the 15th day,and the specimens of hearts and serum were conserved.Myocardial histopathology was determined with hematoxylin and eosin stain.The expression levels of myocardial CB mRNA were detected by reverse transcription polymerase chain reaction.Serum CB concentration was examined by enzyme-linked immunosorbent assay.Results The mortality rate was 0,45%,30% and 20% in control group,myocarditis group,low-dose intervention group and high-dose intervention group,respectively;the mortality rate was significantly lower in high-dose intervention group compared with myocarditis group(P0.05).The expression level of CB mRNA and serum CB concentration were markedly higher in myocarditis group than those in control group(Pa
5.Minimal invasive elastic intramedullary nails and external fixation for treatment of comminuted closed fracture of tibia-fibula shaft.
Yang YU ; Wei-kai CHEN ; Wei CUI ; Yi-fei ZHOU ; Hua CHEN ; Lei YANG
China Journal of Orthopaedics and Traumatology 2015;28(5):412-416
OBJECTIVETo investigate the clinical results of external fixation and AO titanium elastic intramedullary nailing for treatment of tibia-fibula comminuted closed fractures.
METHODSFrom June 2010 to June 2012,58 patients with tibia-fibula comminuted closed fractures were treated with external fixation and AO titanium elastic intramedullary nailing, including 31 males and 27 females with an average age of 38.5 years old ranging from 21 to 57 years old. According to the system of AO Classification, the fractures were classified as type B1 in 9 cases,type B2 in 7 cases, type B3 in 10 cases, type Cl in 14 cases, type C2 in 12 cases,and type C3 in 6 cases. According to the system of Winquist-Hanson,the fractures' comminuted were classified as grade 1 in 23 cases, grade 2 in 17 cases, grade 3 in 12 cases, and grade 4 in 6 cases. According to the system of Johner-Wruhs, clinical results were compared between different type and grade groups by the time of last followed-up.
RESULTSAll 58 patients were followed up with an average time of 6.8 months (ranged from 18 to 36 weeks). All fractures had clinical healing with an average time of 28 weeks (ranged from 24 to 32 weeks). The total rate of good to excellent results was 91.4%. The rate of good to excellent in the group of grade 1 was higher than that of other grades. The complication rates and fracture healing time would increase respectively with higher Winquist-Hanson's grade. The complication rates in the group of type C3 was higher than that of other types, but the rate of good to excellent was lower than that of other types. The complication rates in the group of type B1 was lower than that of other types,but the rate of good to excellent was higher than that of other types.
CONCLUSIONMinimal invasiveusing AO titanium elastic intramedullary nailing combined with external fixation for treatment of tibia-fibula fractures especially for the multiple-segment,long spiral mild-to-moderate comminuted with hidden fracture can get satisfactory reduction and reliable fixation,it conformes to the principle of BO completely, protects the fracture end blood supply,reduces the external fixation time, has less skin soft tissue complications, postoperative function recovered satisfactorily.
Adult ; Bone Nails ; Bone Plates ; External Fixators ; Female ; Fibula ; injuries ; surgery ; Follow-Up Studies ; Fracture Fixation, Intramedullary ; instrumentation ; methods ; Fractures, Closed ; surgery ; Fractures, Comminuted ; surgery ; Humans ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures ; methods ; Tibia ; injuries ; surgery ; Young Adult
6.Stereoscopic image diagnosis and treatment of ruptured multiple intracranial aneurysm
Kai-Jian LUO ; Hua YANG ; Jian LIU ; Fang-You CAO ; Bing ZHAO ; Shi-Bin SONG ;
Chinese Journal of Emergency Medicine 2006;0(12):-
Objective To evaluate the effect of three diamension-digital subtraction angiography (3D-DSA) or computed tomography angiography (CTA) on the patients with ruptured multiple intmcranial aneurysm (MIA). Methods A retrospective study on 21 patients with MIA was performed.After scanning with 3D-DSA or 3D-CTA, three-dimensional reconstruction of MIA was carried out by 3D workstation,then the diagnosis was decided and the treatment plan (endovascular treatment or microsurgery) was selected according to stereoscopic image of MIA. Results (1) 3D-DSA or CTA was performed in 21 patients with subarachnoid hemorrhage (SAH),it was revealed these patients carried with 48 aneurysms,including 35 small aneurysms (25 mm).Not only miero-aneurysms and small aneurysms could be precisely showed,also the size of aneurysmal neck,the relationship of the aneurysm and the parent vessel and contiguous branches by stereoscopic image.(2) According to the standard of classification,9 patients with MIA for gradeⅠ(42.9%),10 for gradeⅡ(47.6%),2 for gradeⅢ(9.5%),0 for gradeⅣ.Endovascular treatment was selected prior to microsargery for those high grade patients.In this group,17 patients with 40 aneurysms underwent endovascular embolotherapy with GDC coils.Twenty four anemysms were completely occlusioned,12 beyond 90%,4 were left without treatment because of their small size.In microsurgery group,3 aneurysrus were totally clipped,1 could not be found during operation.No any treatment was accepted in 2 patients with 4 aneurysms. Conclusions 3D-DSA or CTA,which is very useful for the diagnosis and treatment of MIA,could improve the accuracy of diagnosis of MIA and clearly show the stereoscopic image of MIA,also the relation of sac and parent artery.For those patients with high grade MIA,endovascular treatment was selected prior to microsurgery,pro re nata,used to combine with mierosurgery.
7.Effects of xuefu zhuyu decoction on antioxidant and drug-metabolizing enzymes in liver of rats.
Xing-hua FAN ; Wei-Zhou SHI ; Yun-xiang CHENG ; Kai-jie ZOU ; Xiu-fen YANG
China Journal of Chinese Materia Medica 2014;39(22):4453-4458
Xuefu Zhuyu decoction (XFZYD) is a famous traditional Chinese medicine (TCM) formula, is widely used in the treatment of cardiovascular and cerebrovascular diseases in China over one hundred years. But its effect on antioxidant and drug-metabolizing enzymes are unknown. This study was to observe the effects of Xuefu Zhuyu decoction (XFZYD) on the activities of antioxidant and drug metabolism enzymes (DMEs) in liver of rats. Male SD rats, treated with XFZYD at the dosage of 3.51, 7.02 and 14.04 g x kg(-1) per day for 15 days, serum were collected, tissue fluid, cytosols and microsomes isolated from liver tissues were prepared by centrifugation according to the standard procedure, the activities of antioxidant enzymes and drug-Metabolizing Enzymes were determined by UV-V is spectrophotometer. In serum, the activities of AST was not significantly affected by the treatment with XFZYD, at the high- est dose, the levels of ALT, Cr and BUN were significantly decreased (P < 0.05). GPX were significantly increased at the dose of 7.02, 14.04 g x kg(-1) (P < 0.05), CAT were significantly increased at the highest dose (P < 0.05). T-SOD was not significantly af- fected by this treatment. In the liver tissue, GPX was significantly increased at the dose of 3.51, 7.02 g x kg(-1) (P < 0.05), GST, CAT and T-SOD were not significantly affected following this treatment. In cytosols, GST was significantly increased at the dose of 3.51 g x kg(-1) (P < 0.05), T-SOD was remarkable induced at the dose of 3.51 and 7.02 g x kg(-1) (P < 0.05). In microsomes, XFZYD had no significant effect on Cytochromeb5, NADPH-Cytochrome P450 reductase, CYP3A, CYP2E1 and UGT, XFZYD significantly in- duced GST at the dose of 3.51 and 7.02 g x kg(-1) (P < 0.05), and the level of GSH were significantly increased by XFZYD at the dose of 3.51, 7.02 and 14.04 g kg(-1) (P < 0.05). These findings suggest XFZYD can induce the activities of GPX, CAT, SOD, GST and increase GSH level in liver of rats, which indicate XFZYD may have detoxification and antioxidant functions.
Animals
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Antioxidants
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metabolism
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Drugs, Chinese Herbal
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pharmacology
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Inactivation, Metabolic
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drug effects
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Liver
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drug effects
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enzymology
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Male
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Rats
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Rats, Sprague-Dawley
8.Discussion on the Isomorphism of TCM Syndrome and Biological Entropy
Xiuxiu WANG ; Yanli LIU ; Hua FAN ; Meina YANG ; Xiaolei ZHAO ; Kai SHI ; Jinxiang HAN
Chinese Journal of Information on Traditional Chinese Medicine 2014;(12):1-4
Syndrome, a very important concept in traditional Chinese medicine (TCM), is the essence and characteristics of TCM theory. Progress of related studies on syndrome will drive the development of TCM. Therefore, clinical and basic researches on syndrome have focused on the hotspot of TCM. In recent 60 years, many scholars have discussed the concept, essence and the establishment of standardization of syndrome from different angles and layers. Although many results have been obtained, there is still a certain one sidedness and dispute. Therefore, looking for a new theoretical tool to reveal the scientific connotation of TCM syndrome is imperative. TCM syndrome and biological entropy belong to two different subject concepts, but can also reveal the physiological and pathological state in the changes of life body growth. This article discussed isomorphism of TCM syndrome and biological entropy from the concept, theoretical background and characteristics, with a purpose to provide certain guiding significance to study and promote standardized researches on TCM syndrome.
9.Effect of psoralen on TopoIIα expression in breast cancer stem cells
Chengfeng XU ; Xiaohong WANG ; Yitong HUA ; Kai CHENG ; Weiwei ZOU ; Jian LIU ; Yingzhe ZHANG ; Zhenlin YANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2017;38(5):744-748
Objective To explore the effect of psoralen on topoisomerase IIα(TopoIIα) expression of breast cancer stem cells.Methods CD44+CD24-/low breast cancer stem cells were sorted from MCF-7/ADR by magnetic-activated cell sorting(MACS).We observed the growth characteristics of these stem cells through optical microscope and detected the growth-inhibitory effects of psoralen on breast cancer stem cells by CCK-8 assay and IC50 of adriamycin and adriamycin combined with psoralen to calculate the reversal index.The mRNA and protein expressions of Topo IIα were detected using RT-PCR and Western blot, respectively.Results Under the optical microscope, breast cancer stem cells presented spheres.IC10 and IC20 of psoralen on breast cancer stem cells were (6.77±0.23)μg/mL and (10.36±0.21)μg/mL.IC50 of adriamycin and adriamycin combined with psoralen on breast cancer stem cells was (90.03±3.56)μg/mL and (21.47±0.82)μg/mL, the reversal index was 4.19.Psoralen significantly raised the expressions of Topo Ⅱα at mRNA and protein levels.Conclusion Psoralen reversed the resistance of adriamycin by increasing the gene and protein expressions of breast cancer stem cells Topo Ⅱα and the drug targets.
10.Clinical comparison of laparoscopic and open surgery for radical cystectomy
Xiaodong WANG ; Yuanlin WANG ; Hua SHI ; Shuxiong XU ; Kai LI ; Guangheng LUO ; Xiushu YANG ; Jianxin HU
China Journal of Endoscopy 2016;22(2):42-45
Objective To evaluated the clinical value of laparoscopic techniques in radical cystectomy surgery for the treatment of bladder cancer. Methods Clinical data of 49 patients underwent radical cystectomy with Bricker ileal conduit diversion were retrospectively analyzed from October 2009 to August 2014, which laparoscopic radical cystectomy with Bricker ileal conduit 20 cases (Group A), open radical cystectomy with Bricker ileal conduit 29 cas-es (Group B). The blood loss during operation, operating time, gastrointestinal function recovery after operation, hos-pital stay after operation and complications were observed between the two groups. Results The blood loss during operation was significantly lower in Group A (416.66 ± 232.73) ml than in Group B (964.16 ± 445.73) ml ( <0.05), and hospital stay after operation was significantly lower in Group A (14.93 ± 2.72) days than in Group B (19.50 ± 3.16) days ( < 0.05), complication after operation was significantly lower in Group A than in Group B ( < 0.05). The operating time and gastrointestinal function recovery has no significantly difference between the two groups. Conclusions Laparoscopic radical cystectomy have advantages of minimal invasion, less blood loss, rapid recovery and less postoperative complications. It is a safe and effective surgical method. Long term effect need evaluated by follow up.